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Sample records for cardiac action potential

  1. Role of Sodium Channel on Cardiac Action Potential

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    S. H. Sabzpoushan

    2012-06-01

    Full Text Available Sudden cardiac death is a major cause of death worldwide. In most cases, it's caused by abnormal action potential propagation that leads to cardiac arrhythmia. The aim of this article is to study the abnormal action potential propagation through sodium ion concentration variations. We use a new electrophysiological model that is both detailed and computationally efficient. This efficient model is based on the partial differential equation method. The central finite difference method is used for numerical solving of the two-dimensional (2D wave propagation equation. Simulations are implemented in two stages, as a single cardiac cell and as a two-dimensional grid of cells. In both stages, the normal action potential formation in case of a single cell and it's normal propagation in case of a two-dimensional grid of cells were simulated with nominal sodium ion conductance. Then, the effect of sodium ion concentration on the action potential signal was studied by reducing the sodium ion conductance. It is concluded that reducing the sodium ion conductance, decreases both passing ability and conduction velocity of the action potential wave front.

  2. A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

    OpenAIRE

    Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G.; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N.

    2008-01-01

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Cai) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ven...

  3. Noisy unmaskers of multistability of periodic rhythms in a model of the ventricular cardiac action potential

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    Surovyatkina, Elena; Egorchenkov, Roman; Ivanov, Guennady

    2007-06-01

    The coexistence of different dynamical regimes of cardiac cell-model at a fixed set of stimulation parameters, i.e. multistability, revealed by noise is presented in this paper. Numerical simulations are performed using Luo-Rudy (LR1) action potential model. Numerical experiments with LR1 model conducted via noisy periodical stimulation showed the coexistence of several periodic rhythms. Weak noise in period of stimulation causes a hopping process between all the (meta-) stable rhythms of cell-model. This process is reflected in several parallel branches of the bifurcation diagram: noise unveils new, invisible before, stable rhythms which could appear in this model at different initial conditions. The phenomenon of multistability is directly evidenced by other numerical experiments: we have established the multistability property of a cell consisting in the fact that different initial conditions of stimulation (different extrasystole application times) lead to different stable periodic rhythms. We have obtained the shaping of attraction basins on the action potential curves. Such basins of attraction contain a set of initial conditions which determinate a stable periodic rhythm. We have found a close association between the attraction basins of the complex rhythms on the curves of action potential and the cardiac vulnerable windows on ECG record, during which extra stimuli can induce life threatening arrhythmias. Obtained results allow us to make a conclusion that multistability is very important for the electrical conduction system of the heart from the cell level to the integrated function of the heart.

  4. Effects of Potassium Currents upon Action Potential of Cardiac Cells Exposed to External Electric fields

    Institute of Scientific and Technical Information of China (English)

    An-Ying Zhang; Xiao-Feng Pang

    2008-01-01

    Previous studies show that exposure to high-voltage electric fields would influence the electro cardiogram both in experimental animate and human beings. The effects of the external electric fields upon action potential of cardiac cells are studied in this paper based on the dynamical model, LR91. Fourth order Runger-Kuta is used to analyze the change of potassium ion channels exposed to external electric fields in detail. Results indicate that external electric fields could influence the current of potassium ion by adding an induced component voltage on membrane. This phenomenon might be one of the reasons of heart rate anomaly under the high-voltage electric fields.

  5. Anthropomorphizing the Mouse Cardiac Action Potential via a Novel Dynamic Clamp Method

    Science.gov (United States)

    Ahrens-Nicklas, Rebecca C.; Christini, David J.

    2009-01-01

    Abstract Interspecies differences can limit the translational value of excitable cells isolated from model organisms. It can be difficult to extrapolate from a drug- or mutation-induced phenotype in mice to human pathophysiology because mouse and human cardiac electrodynamics differ greatly. We present a hybrid computational-experimental technique, the cell-type transforming clamp, which is designed to overcome such differences by using a calculated compensatory current to convert the macroscopic electrical behavior of an isolated cell into that of a different cell type. We demonstrate the technique's utility by evaluating drug arrhythmogenicity in murine cardiomyocytes that are transformed to behave like human myocytes. Whereas we use the cell-type transforming clamp in this work to convert between mouse and human electrodynamics, the technique could be adapted to convert between the action potential morphologies of any two cell types of interest. PMID:19917221

  6. Computational modeling of voltage-gated Ca channels inhibition: identification of different effects on uterine and cardiac action potentials

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    Wing Chiu eTong

    2014-10-01

    Full Text Available The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs. Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models – of uterine smooth muscle cells (USMC, cardiac sinoatrial node cells (SAN and ventricular cells – to investigate the relative effects of reducing two important voltage-gated Ca currents – the L-type (ICaL and T-type (ICaT Ca currents. Reduction of ICaL (10% alone, or ICaT (40% alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine

  7. Liénard-type models for the simulation of the action potential of cardiac nodal cells

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    Podziemski, P.; Żebrowski, J. J.

    2013-10-01

    Existing models of cardiac cells which include multi-variable cardiac transmembrane current are too complex to simulate the long time dynamical properties of the heart rhythm. The large number of parameters that need to be defined and set for such models make them not only cumbersome to use but also require a large computing power. Consequently, the application of such models for the bedside analysis of heart rate of a specific patient may be difficult. Other ways of modelling need to be investigated. We consider the general problem of developing a model of cardiac pacemaker tissue that allows to combine the investigation of phenomena at a time scale of thousands of heart beats with the ability to reproduce realistic tissue-level characteristics of cell dynamics. We propose a modified van der Pol-Duffing equation-a Liénard-type oscillator-as a phenomenological model for cardiac nodal tissue, with certain important physiological similarities to ion-channel models of cardiac pacemaker cells. The model presented here is specifically designed to qualitatively reproduce mesoscopic characteristics of cell dynamics, including action potential duration (APD) restitution properties, phase response characteristics, and phase space structure. We show that these characteristics agree qualitatively with the extensive ionic models and experimental results in the literature [Anumonwo et al., 1991, [33], Cao et al., 1999, [49], Coster and Celler, 2003, [31], Qu, 2004, [45], Tsalikakis et al., 2007, [32], Inada et al., 2009, [14], Qu et al., 2010, [50

  8. Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity.

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    Natarajan, A; Molnar, P; Sieverdes, K; Jamshidi, A; Hickman, J J

    2006-04-01

    The threat of environmental pollution, biological warfare agent dissemination and new diseases in recent decades has increased research into cell-based biosensors. The creation of this class of sensors could specifically aid the detection of toxic chemicals and their effects in the environment, such as pyrethroid pesticides. Pyrethroids are synthetic pesticides that have been used increasingly over the last decade to replace other pesticides like DDT. In this study we used a high-throughput method to detect pyrethroids by using multielectrode extracellular recordings from cardiac cells. The data from this cell-electrode hybrid system was compared to published results obtained with patch-clamp electrophysiology and also used as an alternative method to further understand pyrethroid effects. Our biosensor consisted of a confluent monolayer of cardiac myocytes cultured on microelectrode arrays (MEA) composed of 60 substrate-integrated electrodes. Spontaneous activity of these beating cells produced extracellular field potentials in the range of 100 microV to nearly 1200 microV with a beating frequency of 0.5-4 Hz. All of the tested pyrethroids; alpha-Cypermethrin, Tetramethrin and Tefluthrin, produced similar changes in the electrophysiological properties of the cardiac myocytes, namely reduced beating frequency and amplitude. The sensitivity of our toxin detection method was comparable to earlier patch-clamp studies, which indicates that, in specific applications, high-throughput extracellular methods can replace single-cell studies. Moreover, the similar effect of all three pyrethroids on the measured parameters suggests, that not only detection of the toxins but, their classification might also be possible with this method. Overall our results support the idea that whole cell biosensors might be viable alternatives when compared to current toxin detection methods. PMID:16198528

  9. Variability of Action Potentials Within and Among Cardiac Cell Clusters Derived from Human Embryonic Stem Cells

    OpenAIRE

    Renjun Zhu; Millrod, Michal A.; Zambidis, Elias T.; Leslie Tung

    2016-01-01

    Electrophysiological variability in cardiomyocytes derived from pluripotent stem cells continues to be an impediment for their scientific and translational applications. We studied the variability of action potentials (APs) recorded from clusters of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using high-resolution optical mapping. Over 23,000 APs were analyzed through four parameters: APD30, APD80, triangulation and fractional repolarization. Although measures were taken to re...

  10. Variability of Action Potentials Within and Among Cardiac Cell Clusters Derived from Human Embryonic Stem Cells.

    Science.gov (United States)

    Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie

    2016-01-01

    Electrophysiological variability in cardiomyocytes derived from pluripotent stem cells continues to be an impediment for their scientific and translational applications. We studied the variability of action potentials (APs) recorded from clusters of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using high-resolution optical mapping. Over 23,000 APs were analyzed through four parameters: APD30, APD80, triangulation and fractional repolarization. Although measures were taken to reduce variability due to cell culture conditions and rate-dependency of APs, we still observed significant variability in APs among and within the clusters. However, similar APs were found in spatial locations with close proximity, and in some clusters formed distinct regions having different AP characteristics that were reflected as separate peaks in the AP parameter distributions, suggesting multiple electrophysiological phenotypes. Using a recently developed automated method to group cells based on their entire AP shape, we identified distinct regions of different phenotypes within single clusters and common phenotypes across different clusters when separating APs into 2 or 3 subpopulations. The systematic analysis of the heterogeneity and potential phenotypes of large populations of hESC-CMs can be used to evaluate strategies to improve the quality of pluripotent stem cell-derived cardiomyocytes for use in diagnostic and therapeutic applications and in drug screening. PMID:26729331

  11. Beta-adrenergic stimulation reverses the I Kr-I Ks dominant pattern during cardiac action potential.

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    Banyasz, Tamas; Jian, Zhong; Horvath, Balazs; Khabbaz, Shaden; Izu, Leighton T; Chen-Izu, Ye

    2014-11-01

    β-Adrenergic stimulation differentially modulates different K(+) channels and thus fine-tunes cardiac action potential (AP) repolarization. However, it remains unclear how the proportion of I Ks, I Kr, and I K1 currents in the same cell would be altered by β-adrenergic stimulation, which would change the relative contribution of individual K(+) current to the total repolarization reserve. In this study, we used an innovative AP-clamp sequential dissection technique to directly record the dynamic I Ks, I Kr, and I K1 currents during the AP in guinea pig ventricular myocytes under physiologically relevant conditions. Our data provide quantitative measures of the magnitude and time course of I Ks, I Kr, and I K1 currents in the same cell under its own steady-state AP, in a physiological milieu, and with preserved Ca(2+) homeostasis. We found that isoproterenol treatment significantly enhanced I Ks, moderately increased I K1, but slightly decreased I Kr in a dose-dependent manner. The dominance pattern of the K(+) currents was I Kr > I K1 > I Ks at the control condition, but reversed to I Kr Kr, and I K1 to cardiac repolarization during AP at different adrenergic states. In conclusion, the β-adrenergic stimulation fine-tunes the cardiac AP morphology by shifting the power of different K(+) currents in a dose-dependent manner. This knowledge is important for designing antiarrhythmic drug strategies to treat hearts exposed to various sympathetic tones.

  12. Markov models of use-dependence and reverse use-dependence during the mouse cardiac action potential.

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    Qinlian Zhou

    Full Text Available The fast component of the cardiac transient outward current, I(Ktof, is blocked by a number of drugs. The major molecular bases of I(Ktof are Kv4.2/Kv4.3 voltage-gated potassium channels. Drugs with similar potencies but different blocking mechanisms have differing effects on action potential duration (APD. We used in silico analysis to determine the effect of I(Ktof-blocking drugs with different blocking mechanisms on mouse ventricular myocytes. We used our existing mouse model of the action potential, and developed 4 new Markov formulations for I(Ktof, I(Ktos, I(Kur, I(Ks. We compared effects of theoretical I(Ktof-specific channel blockers: (1 a closed state, and (2 an open channel blocker. At concentrations lower or close to IC(50, the drug which bound to the open state always had a much greater effect on APD than the drug which bound to the closed state. At concentrations much higher than IC(50, both mechanisms had similar effects at very low pacing rates. However, an open state binding drug had a greater effect on APD at faster pacing rates, particularly around 10 Hz. In summary, our data indicate that drug effects on APD are strongly dependent not only on IC(50, but also on the drug binding state.

  13. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

    DEFF Research Database (Denmark)

    Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T;

    2015-01-01

    augmenting Ca(2+)-induced Ca(2+) release. Ca(2+) transients in disaggregated KChIP2(-/-) cardiomyocytes are indeed comparable to wild-type transients, corroborating the preserved contractile function and suggesting that the compensatory mechanism lies in the Ca(2+)-induced Ca(2+) release event. We next...... functionally probed dyad structure, ryanodine receptor Ca(2+) sensitivity, and sarcoplasmic reticulum Ca(2+) load and found that increased temporal synchronicity of the Ca(2+) release in KChIP2(-/-) cardiomyocytes may reflect improved dyad structure aiding the compensatory mechanisms in preserving cardiac...

  14. Repolarization of the action potential enabled by Na+ channel deactivation in PSpice simulation of cardiac muscle propagation

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    Sperelakis Nicholas

    2005-12-01

    Full Text Available Abstract Background In previous studies on propagation of simulated action potentials (APs in cardiac muscle using PSpice modeling, we reported that a second black-box (BB could not be inserted into the K+ leg of the basic membrane unit because that caused the PSpice program to become very unstable. Therefore, only the rising phase of the APs could be simulated. This restriction was acceptable since only the mechanism of transmission of excitation from one cell to the next was being investigated. Methods and results We have now been able to repolarize the AP by inserting a second BB into the Na+ leg of the basic units. This second BB effectively mimicked deactivation of the Na+ channel conductance. This produced repolarization of the AP, not by activation of K+ conductance, but by deactivation of the Na+ conductance. The propagation of complete APs was studied in a chain (strand of 10 cardiac muscle cells, in which various numbers of gap-junction (gj channels (assumed to be 100 pS each were inserted across the cell junctions. The shunt resistance across the junctions produced by the gj-channels (Rgj was varied from 100,000 M? (0 gj-channels to 10,000 M? (1 gj-channel, to 1,000 M? (10 channels, to 100 M? (100 channels, and 10 M? (1000 channels. The velocity of propagation (θ, in cm/s was calculated from the measured total propagation time (TPT, the time difference between when the AP rising phase of the first cell and the last cell crossed -20 mV, assuming a cell length of 150 μm. When there were no gj-channels, or only a few, the transmission of excitation between cells was produced by the electric field (EF, i.e. the negative junctional cleft potential, that is generated in the narrow junctional clefts (e.g. 100 A when the prejunctional membrane fires an AP. When there were many gj-channels (e.g. 1000 or 10,000, the transmission of excitation was produced by local-circuit current flow from one cell to the next through the gj

  15. Remote Monitoring of the Heart Condition of Athletes by Measuring the Cardiac Action Potential Propagation Time Using a Wireless Sensor Network

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    Amang Sudarsono

    2016-04-01

    Full Text Available Highly performing athletes are susceptible to cardiac damage of several kinds which may be irreversible. The monitoring of heart rate and ECG waveforms from such subjects by wireless sensor networks has been reported in health and sports care documents. However, a more decisive parameter for instant to instant changes would be the time of Cardiac Action Potential Propagation. This time, which can be between 15-20 ms would shoot suddenly in acute stress in highly performing athletes for short durations. Repeated incidents of such rising values will tend to cause irreversible damage to the heart. We developed the technique of measuring this time and reporting it through a wireless sensor network to monitoring station.

  16. Early Afterdepolarizations with Growing Amplitudes via Delayed Subcritical Hopf Bifurcations and Unstable Manifolds of Saddle Foci in Cardiac Action Potential Dynamics

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    Kügler, Philipp

    2016-01-01

    Early afterdepolarizations (EADs) are pathological oscillations in cardiac action potentials during the repolarization phase and may be caused by drug side effects, ion channel disease or oxidative stress. The most widely observed EAD pattern is characterized by oscillations with growing amplitudes. So far, its occurence has been explained in terms of a supercritical Hopf bifurcation in the fast subsystem of the action potential dynamics from which stable limit cycles with growing amplitudes emerge. The novel contribution of this article is the introduction of two alternative explanations of EAD genesis with growing amplitudes that do not involve stable limit cycles in fast subsystems. In particular, we demonstrate that EAD patterns with growing amplitudes may alternatively arise due to a delayed subcritical Hopf bifurcation or an unstable manifold of a saddle focus fixed point in the full fast-slow system modelling the action potential. Our work extends the list of possible dynamical EAD mechanisms and may contribute to a classification of drug effects in preclinical cardiotoxicity testing. PMID:26977805

  17. Effects of the histamine H1 receptor antagonist hydroxyzine on hERG K+ channels and cardiac action potential duration

    Institute of Scientific and Technical Information of China (English)

    Byung Hoon LEE; Seung Ho LEE; Daehyun CHU; Jin Won HYUN; Han CHOE; Bok Hee CHOI; Su-Hyun JO

    2011-01-01

    To investigate the effects of hydroxyzine on human ether-a-go-go-related gene (hERG) channels to determine the electrolphysiological basis for its proarrhythmic effects.Methods:hERG channels were expressed in Xenopus oocytes and HEK293 cells,and the effects of hydroxyzine on the channels were examined using two-microelectrode voltage-clamp and patch-clamp techniques,respectively.The effects of hydroxyzine on action potential duration were examined in guinea pig ventricular myocytes using current clamp.Results:Hydroxyzine (0.2 and 2 μmol/L) significantly increased the action potential duration at 90% repolarization (APD90) in both concentration- and time-dependent manners.Hydroxyzine (0.03-3 μmol/L) blocked both the steady-state and tail hERG currents.The block was voltage-dependent,and the values of IC50 for blocking the steady-state and tail currents at +20 mV was 0.18±0.02 μmol/L and 0.16±0.01 μmol/L,respectively,in HEK293 cells.Hydroxyzine (5 μmol/L) affected both the activated and the inactivated states of the channels,but not the closed state.The S6 domain mutation Y652A attenuated the blocking of hERG current by ~6-fold.Conclusion:The results suggest that hydroxyzine could block hERG channels and prolong APD.The tyrosine at position 652 in the channel may be responsible for the proarrhythmic effects of hydroxyzine.

  18. Mortality and Embolic Potential of Cardiac Tumors

    OpenAIRE

    Ricardo Ribeiro Dias; Fábio Fernandes; Félix José Alvarez Ramires; Charles Mady; Cícero Piva de Albuquerque; Fábio Biscegli Jatene

    2014-01-01

    Background: Cardiac tumors are rare, mostly benign with high embolic potential. Objectives: To correlate the histological type of cardiac masses with their embolic potential, implantation site and long term follow up in patients undergoing surgery. Methods: Between January 1986 and December 2011, we retrospectively analyzed 185 consecutive patients who underwent excision of intracardiac mass (119 females, mean age 48±20 years). In 145 patients, the left atrium was the origin site. 72% wer...

  19. Screening action potentials: The power of light

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    Lars eKaestner

    2011-07-01

    Full Text Available Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated readout and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for e.g. pharmacological screens the following preparatory work has to be provided: (i model cells under investigation need to represent target cells in the best possible manner; (ii optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable readout with minimal interaction with the naive behavior of the cells and (iii devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials.

  20. Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr) and modulates cardiac action potential characteristics

    DEFF Research Database (Denmark)

    Larsen, Anders Peter; Olesen, Søren-Peter

    2010-01-01

    The repolarizing cardiac rapid delayed rectifier current, I(Kr), is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr). Marked heterogeneity in the kinetic properties of native I(Kr) has been described. We hypothesized...

  1. Action of SNAIL1 in Cardiac Myofibroblasts Is Important for Cardiac Fibrosis following Hypoxic Injury

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    Biswas, Hirak; Longmore, Gregory D.

    2016-01-01

    Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level. SNAIL1 is required in cardiac fibroblasts for the adoption of myofibroblast fate, collagen I expression and expression of fibrosis-related genes. Taken together this data suggests that SNAIL1 expression is induced in the cardiac fibroblasts after hypoxic injury and contributes to myofibroblast phenotype and a fibrotic scar formation. Resultant collagen deposition in the scar can maintain elevated SNAIL1 expression in the myofibroblasts and help propagate fibrosis. PMID:27706205

  2. Cardiac gap junctions and action potential propagation

    NARCIS (Netherlands)

    Veen, Antonius Adrianus Bartholomeus van

    2002-01-01

    Described are the results, obtained from experiments on transfected cells to those on intact heart and new data are provided on connexin phosphorylation, expression and distribution. Transfected cells, regarded as the lowest level of complexity, are a very useful and reliable tool to study the effec

  3. Mortality and Embolic Potential of Cardiac Tumors

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    Ricardo Ribeiro Dias

    2014-07-01

    Full Text Available Background: Cardiac tumors are rare, mostly benign with high embolic potential. Objectives: To correlate the histological type of cardiac masses with their embolic potential, implantation site and long term follow up in patients undergoing surgery. Methods: Between January 1986 and December 2011, we retrospectively analyzed 185 consecutive patients who underwent excision of intracardiac mass (119 females, mean age 48±20 years. In 145 patients, the left atrium was the origin site. 72% were asymptomatic and prior embolization was often observed (19.8%. The diagnosis was established by echocardiography, magnetic resonance and histological examination. Results: Most tumors were located in the left side of the heart. Myxoma was the most common (72.6%, followed by fibromas (6.9%, thrombi (6.4% and sarcomas (6.4%. Ranging from 0.6cm to 15cm (mean 4.6 ± 2.5cm 37 (19.8% patients had prior embolization, stroke 10.2%, coronary 4.8%, peripheral 4.3% 5.4% of hospital death, with a predominance of malignant tumors (40% p < 0.0001. The histological type was a predictor of mortality (rhabdomyomas and sarcomas p = 0.002 and embolic event (sarcoma, lipoma and fibroelastoma p = 0.006, but not recurrence. Tumor size, atrial fibrillation, cavity and valve impairment were not associated with the embolic event. During follow-up (mean 80±63 months, there were 2 deaths (1.1% and two recurrences 1 and 11 years after the operation, to the same cavity. Conclusion: Most tumors were located in the left side of the heart. The histological type was predictor of death and preoperative embolic event, while the implantation site carries no relation with mortality or to embolic event.

  4. Mortality and Embolic Potential of Cardiac Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Ricardo Ribeiro, E-mail: ricardo.dias@incor.usp.br; Fernandes, Fábio; Ramires, Félix José Alvarez; Mady, Charles; Albuquerque, Cícero Piva; Jatene, Fábio Biscegli [Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-07-15

    Cardiac tumors are rare, mostly benign with high embolic potential. To correlate the histological type of cardiac masses with their embolic potential, implantation site and long term follow up in patients undergoing surgery. Between January 1986 and December 2011, we retrospectively analyzed 185 consecutive patients who underwent excision of intracardiac mass (119 females, mean age 48±20 years). In 145 patients, the left atrium was the origin site. 72% were asymptomatic and prior embolization was often observed (19.8%). The diagnosis was established by echocardiography, magnetic resonance and histological examination. Most tumors were located in the left side of the heart. Myxoma was the most common (72.6%), followed by fibromas (6.9%), thrombi (6.4%) and sarcomas (6.4%). Ranging from 0.6cm to 15cm (mean 4.6 ± 2.5cm) 37 (19.8%) patients had prior embolization, stroke 10.2%, coronary 4.8%, peripheral 4.3% 5.4% of hospital death, with a predominance of malignant tumors (40% p < 0.0001). The histological type was a predictor of mortality (rhabdomyomas and sarcomas p = 0.002) and embolic event (sarcoma, lipoma and fibroelastoma p = 0.006), but not recurrence. Tumor size, atrial fibrillation, cavity and valve impairment were not associated with the embolic event. During follow-up (mean 80±63 months), there were 2 deaths (1.1%) and two recurrences 1 and 11 years after the operation, to the same cavity. Most tumors were located in the left side of the heart. The histological type was predictor of death and preoperative embolic event, while the implantation site carries no relation with mortality or to embolic event.

  5. Action Principle for Potential Flows

    CERN Document Server

    Frønsdal, Christian

    2014-01-01

    The restriction of hydrodynamics to non-viscous, potential (gradient, irrotational) flows is a theory both simple and elegant; a favorite topic of introductory textbooks. It is known that this theory (under the stated limitations) can be formulated as an action principle. It finds its principle application to adiabatic systems and cannot account for viscosity or dissipation. However, it can be generalized to include non-potential flows, as this paper shows. The new theory is a combination of Eulerian and Lagrangian hydrodynamics, with an extension to thermodynamics. It describes adiabatic phenomena but does not account for viscosity or dissipation. Nevertheless, it is an approach within which quasi-static processes can be described. In the adiabatic context it appears to be an improvement of the Navier-Stokes equation, the principal advantage being a natural concept of energy in the form of a first integral of the motion, conserved by virtue of the Euler-Lagrange equations.

  6. 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.

  7. Light-triggered action potentials in plants

    OpenAIRE

    Kazimierz Trębacz

    2014-01-01

    Special attention is paid in this paper to the criteria of the light-triggered action potential, namely the all-or-none law, propagation, the occurrence of refractory periods. Such action potentials have been recorded in Acetabularia mediterranea, Asplenium trichomanes, Bryum pseudotriquetrum, Eremosphaera viridis and Concephalum conicum. In Acetabularia, action potentials are generated after sudden cessation of light stimuli of sufficient intensity. The depolarization phase of the action pot...

  8. Dynamics of the inward rectifier K+ current during the action potential of guinea pig ventricular myocytes.

    OpenAIRE

    Ibarra, J; Morley, G E; Delmar, M

    1991-01-01

    The potassium selective, inward rectifier current (IK1) is known to be responsible for maintaining the resting membrane potential of quiescent ventricular myocytes. However, the contribution of this current to the different phases of the cardiac action potential has not been adequately established. In the present study, we have used the action potential clamp (APC) technique to characterize the dynamic changes of a cesium-sensitive (i.e., Ik1) current which occur during the action potential. ...

  9. Fish oil curtails the human action potential dome in a heterogeneous manner: Implication for arrhythmogenesis

    NARCIS (Netherlands)

    A.O. Verkerk; H.M. den Ruijter; N. de Jonge; R. Coronel

    2009-01-01

    Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil modulate various ion channels, including the L-type calcium current (I(Ca,L)). As a result, fish oil shortens the cardiac action potential and may cause a loss of the dome of the action potential (AP). Under conditions of increased pre

  10. Abstract Action Potential Models for Toxin Recognition

    OpenAIRE

    Peterson, James; Khan, Taufiquar

    2005-01-01

    In this paper, we present a robust methodology using mathematical pattern recognition schemes to detect and classify events in action potentials for recognizing toxins in biological cells. We focus on event detection in action potential via abstraction of information content into a low dimensional feature vector within the constrained computational environment of a biosensor. We use generated families of action potentials from a classic Hodgkin–Huxley model to verify our methodology and build...

  11. Cenderitide-eluting film for potential cardiac patch applications.

    Directory of Open Access Journals (Sweden)

    Xu Wen Ng

    Full Text Available Cenderitide, also known as CD-NP, is a designer peptide developed by combining native mammalian c-type natriuretic peptide (CNP and the C-terminus isolated from the dendroapis natriuretic peptide (DNP of the venom from the green mamba. In early studies, intravenous and subcutaneous infusion of cenderitide was reported to reduce left ventricular (LV mass and ameliorate cardiac remodelling. In this work, biodegradable polymeric films encapsulating CD-NP were developed and were investigated for their in vitro release and degradation characteristics. Subsequently, the bioactivity of released peptide and its effects on human cardiac fibroblast (HCF were explored. We achieved sustained release from three films with low, intermediate and high release profiles for 30 days. Moreover, the bioactivity of released peptide was verified from the elevated production of cyclic guanosine monophospate (cGMP. The CD-NP released from films was able to inhibit the proliferation of hypertrophic HCF as well as suppress DNA synthesis in HCF. Furthermore, the sustained delivery from films showed comparable or superior suppressive actions on hypertrophic HCF compared to daily infusion of CD-NP. The results suggest that these films could be used to inhibit fibrosis and reduce cardiac remodelling via local delivery as cardiac patches.

  12. Correlation of action potentials in adjacent neurons

    CERN Document Server

    Shneider, M N

    2015-01-01

    A possible mechanism for the synchronization of action potential propagation along a bundle of neurons (ephaptic coupling) is considered. It is shown that this mechanism is similar to the salutatory conduction of the action potential between the nodes of Ranvier in myelinated axons. The proposed model allows us to estimate the scale of the correlation, i.e., the distance between neurons in the nervous tissue, wherein their synchronization becomes possible. The possibility for experimental verification of the proposed model of synchronization is discussed.

  13. Introducing the Action Potential to Psychology Students

    Science.gov (United States)

    Simon-Dack, Stephanie L.

    2014-01-01

    For this simple active learning technique for teaching, students are assigned "roles" and act out the process of the action potential (AP), including the firing threshold, ion-specific channels for ions to enter and leave the cell, diffusion, and the refractory period. Pre-post test results indicated that students demonstrated increased…

  14. Magnetic Imaging of Applied and Propagating Action Currents in Cardiac Tissue Slices: Determination of Anisotropic Electrical Conductivities in a Two-Dimensional Bidomain.

    Science.gov (United States)

    Staton, Daniel Joseph

    We describe the first, high-resolution magnetic images of applied currents and propagating action currents in slices of canine cardiac tissue. This tissue was maintained in vitro at 37^circC. Our main conclusions are summarized as follows: the action currents produce magnetic fields which are measurable; during the initial stages of the propagating action potential, small, expanding, quatrefoil loops of current develop; the magnetic fields produced by repolarization currents are larger than previously anticipated. Most of the current associated with the propagating action potential is confined within the wavefront and should be magnetically silent; however, differences in the intracellular and extracellular electrical conductivities, in both the longitudinal and transverse fiber directions, are great enough that expanding quatrefoil current densities are associated with the wavefront and produce measurable magnetic fields. Since action currents are affected by the electrical conductivities, it is of interest to determine their values, which depend not only upon the tissue characteristics, but also on the mathematical model used to interpret the measured data. In our analysis of current injection, we use the anisotropic bidomain model which incorporates a passive, linear membrane. We introduce theoretical techniques to calculate the anisotropic conductivities of a two-dimensional bidomain. To apply these techniques to magnetic fields resulting from current injection into cardiac tissue slices, we need to improve the higher spatial frequency content of our present measurements. This may be done by measuring the magnetic field closer to the cardiac slice (presently 2.5 mm), decreasing the sampling interval of the measurement, and increasing the sampling area of the field. Magnetic fields are produced by propagating action currents, which are in turn the result of the propagating action potential. From the magnetic field, we directly image isochronal transmembrane

  15. Triangulation of the monophasic action potential causes flattening of the electrocardiographic T-wave

    DEFF Research Database (Denmark)

    Bhuiyan, Tanveer Ahmed; Graff, Claus; Thomsen, Morten Bækgaard;

    2012-01-01

    It has been proposed that triangulation on the cardiac action potential manifests as a broadened, more flat and notched T-wave on the ECG but to what extent such morphology characteristics are indicative of triangulation is more unclear. In this paper, we have analyzed the morphological changes...

  16. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    A.S. Amin; A. Asghari-Roodsari; H.L. Tan

    2010-01-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I-Na) during phase 0 of the cardiac action potential. The importance of I-Na for normal cardiac electrical activity is reflected by the high incidence of

  17. expression, physiological actions and therapeutic potential

    OpenAIRE

    Steckelings, Ulrike

    2012-01-01

    Angiotensin II mediates its action via 2 receptor subtypes: the AT1- and AT2-receptor. The existence of more than one receptor for angiotensin II has been discovered not earlier than 1989. This "Habilitationsschrift" is based on six publications which represent mosaic stones within the growing picture of AT2-receptor expression, regulation of expression, physiological and patho-physiological function as well as potential therapeutic use. The first part is dealing with tissue specific ex...

  18. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

    Directory of Open Access Journals (Sweden)

    Hester M Den Ruijter

    2010-11-01

    Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

  19. Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

    OpenAIRE

    José Manuel Calderón-Montaño; Estefanía Burgos-Morón; Manuel Luis Orta; Dolores Maldonado-Navas; Irene García-Domínguez; Miguel López-Lázaro

    2014-01-01

    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 typ...

  20. Anthracycline-induced cardiac injury using a cardiac cell line: potential for gene therapy studies.

    Science.gov (United States)

    L'Ecuyer, T; Horenstein, M S; Thomas, R; Vander Heide, R

    2001-11-01

    Anthracyclines are effective antitumor agents whose chief limitation has been cardiotoxicity directly related to free radical production. Therefore, strategies designed to selectively overexpress antioxidant proteins in the heart could protect against drug-induced toxicity and allow higher doses of chemotherapy. However, to date an adequate cardiac model system that is susceptible to anthracycline injury and can express foreign genes in a controlled fashion has been lacking. Developing a cardiac model system would permit examination of the relationship between the expression level of a potentially protective foreign gene and the degree of protection from injury. In this study we have examined the potential of the H9C2 rat cardiac myocyte cell line in this regard. H9C2 cells differentiate in a reproducible fashion, as shown by progressive increases in muscle tropomyosin-expressing cells, the organization of this thin filament protein, and the percentage of muscle cells contained within myotubes. Exposure of this cell line to the anthracycline doxorubicin produces cell injury as indicated by release of the intracellular enzyme lactate dehydrogenase into the culture medium. This injury is preceded by generation of reactive oxygen species, indicated by fluorescence after loading with carboxy-dichlorodihydrofluorescein diacetate. Stable transfection of H9C2 cells with a plasmid producing a tetracycline transactivator protein allows foreign genes to be expressed at a level tightly controlled by the concentration of tetracycline in the culture medium. Since H9C2 cells differentiate, can be injured by anthracycline exposure, and can express foreign genes at controllable levels, this is a suitable system in which to design genetic approaches to prevent this important clinical problem. PMID:11708868

  1. Smoking cessation in cardiac patients: the influence of action plans, coping plans and self-efficacy on quitting smoking.

    Science.gov (United States)

    de Hoog, Natascha; Bolman, Catherine; Berndt, Nadine; Kers, Esther; Mudde, Aart; de Vries, Hein; Lechner, Lilian

    2016-06-01

    Smoking cessation is the most effective action for cardiac patients who smoke to improve their prognosis, yet more than one-half of cardiac patients continue to smoke after hospital admission. This study examined the influence of action plans, coping plans and self-efficacy on intention to quit and smoking cessation in cardiac patients. Cardiac patients completed a baseline questionnaire (N = 245) assessing demographic characteristics, smoking behavior, intention, self-efficacy, relapse self-efficacy and action and coping plans. Six months later (N = 184) continued abstinence from smoking was assessed. Self-efficacy predicted intention to quit smoking and was an indirect predictor of continued abstinence, through intention. Intention to quit smoking and making action plans both directly influenced continued abstinence. Future interventions to facilitate smoking cessation in cardiac patients should put strong emphasis on enhancing self-efficacy and on making specific action plans to increase the likelihood of smoking cessation.

  2. Control and monitoring of deterministic effects in interventional cardiac procedures. Action levels; Control y seguimiento de aparicion de efectos deterministas en procedimientos intervencionistas cardiacos. Niveles de accion

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Castanon, P.; Rodriguez Martin, G.; Espana Lopez, M. L.; Vega Roman, C.; Berdumez Luna, R.; Fernandez Bedoya, V.

    2011-07-01

    The aim of this study is to analyze the percentage of patients undergoing cardiac interventional procedures that could potentially suffer deterministic effects, through the application of a method for estimating the PSD from the quantities available and setting levels action for them.

  3. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz;

    2016-01-01

    cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....

  4. Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

    OpenAIRE

    Philip Gemmell; Kevin Burrage; Blanca Rodriguez; T Alexander Quinn

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A s...

  5. Potential proarrhythmic effect of cardiac resynchronization therapy during perioperative period: data from a single cardiac center

    Institute of Scientific and Technical Information of China (English)

    LUO Nian-sang; YUAN Wo-liang; LIN Yong-qing; CHEN Yang-xin; MAO Xiao-qun; XIE Shuang-lun; KONG Min-yi; ZHOU Shu-xian; WANG Jing-feng

    2010-01-01

    Background Cardiac resynchronization therapy (CRT) could improve heart function, symptom status, quality of life and reduce hospitalization and mortality in patients with severe heart failure (HF) with optimal medical management. However,the possible adverse effects of CRT are often ignored by clinicians.Method A retrospective analysis of CRT over a 6-year period was made in a single cardiac center.Results Fifty-four patients were treated with CRT(D) device, aged (57±11) years, with left ventricular ejection fraction of (32.1±9.8)%, of which 4 (7%) developed ventricular tachycardia/ventricular fibrillation (VT/VF) or junctional tachycardia after operation. Except for one with frequent ventricular premature beat before operation, the others had no previous history of ventricular arrhythmia. Of the 4 patients, 3 had dilated cardiomyopathy and 1 had ischemic cardiomyopathy,and tachycardia occurred within 3 days after operation. Sustained, refractory VT and subsequent VF occurred in one patient, frequent nonsustained VT in two patients and nonparoxysmal atrioventricular junctional tachycardia in one patient. VT was managed by amiodarone in two patients, amiodarone together with beta-blocker in one patient, and junctional tachycardia was terminated by overdrive pacing. During over 12-month follow-up, except for one patient's death due to refractory heart and respiratory failure in hospital, the others remain alive and arrhythmia-free.Conclusions New-onset VT/VF or junctional tachycardia may occur in a minority of patients with or without prior history of tachycardia after biventricular pacing. Arrhythmia can be managed by conventional therapy, but may require temporary discontinuation of pacing. More observational studies should be performed to determine the potential proarrhythmic effect of CRT.

  6. The Potential of Deweyan-Inspired Action Research

    OpenAIRE

    Stark, Jody L.

    2014-01-01

    In its broadest sense, pragmatism could be said to be the philosophical orientation of all action research. Action research is characterized by research, action, and participation grounded in democratic principles and guided by the aim of social improvement. Furthermore, action research is an active process of inquiry that does not admit separation between action and reflection or theory and practice. This paper considers the potential of action research informed specifically by Deweyan pragm...

  7. Action Potential Morphology Influences Intracellular Calcium Handling Stability and the Occurrence of Alternans

    OpenAIRE

    Jordan, Peter N; Christini, David J

    2005-01-01

    Instability in the intracellular Ca2+ handling system leading to Ca2+ alternans is hypothesized to be an underlying cause of electrical alternans. The highly coupled nature of membrane voltage and Ca2+ regulation suggests that there should be reciprocal effects of membrane voltage on the stability of the Ca2+ handling system. We investigated such effects using a mathematical model of the cardiac intracellular Ca2+ handling system. We found that the morphology of the action potential has a sig...

  8. Action potential broadening in a presynaptic channelopathy

    Science.gov (United States)

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-07-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

  9. Teachers in Action Research: Assumptions and Potentials

    Science.gov (United States)

    Li, Yuen-Ling

    2008-01-01

    Research literature has long indicated that action research may stimulate practitioners themselves to actively evaluate the quality of their practice. This study is designed to report the use of action research for the development of early years professional practice by analyzing the pre-project and the post-project video-filmed teaching events.…

  10. Action potential initiation in the hodgkin-huxley model.

    OpenAIRE

    Colwell, Lucy J; Brenner, Michael P.

    2009-01-01

    A recent paper of B. Naundorf et al. described an intriguing negative correlation between variability of the onset potential at which an action potential occurs (the onset span) and the rapidity of action potential initiation (the onset rapidity). This correlation was demonstrated in numerical simulations of the Hodgkin-Huxley model. Due to this antagonism, it is argued that Hodgkin-Huxley-type models are unable to explain action potential initiation observed in cortical neurons in vivo or in...

  11. Spectral action, Weyl anomaly and the Higgs-Dilaton potential

    OpenAIRE

    Andrianov, A.A.(V.A. Fock Department of Theoretical Physics, Saint-Petersburg State University, 1 ul. Ulyanovskaya, St. Petersburg, 198504, Russia); Kurkov, M.A.; Lizzi, Fedele

    2011-01-01

    We show how the bosonic spectral action emerges from the fermionic action by the renormalization group flow in the presence of a dilaton and the Weyl anomaly. The induced action comes out to be basically the Chamseddine-Connes spectral action introduced in the context of noncommutative geometry. The entire spectral action describes gauge and Higgs fields coupled with gravity. We then consider the effective potential and show, that it has the desired features of a broken and an unbroken phase,...

  12. Flattening of the electrocardiographic T-wave is a sign of proarrhythmic risk and a reflection of action potential triangulation

    DEFF Research Database (Denmark)

    Bhuiyan, Tanveer Ahmed; Graff, Claus; Kanters, J.K.;

    2013-01-01

    Drug-induced triangulation of the cardiac action potential is associated with increased risk of arrhythmic events. It has been suggested that triangulation causes a flattening of the electrocardiographic T-wave but the relationship between triangulation, T-wave flattening and onset of arrhythmia...

  13. Action potentials reliably invade axonal arbors of rat neocortical neurons

    OpenAIRE

    Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel

    2000-01-01

    Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon...

  14. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues

    Science.gov (United States)

    Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M.

    2016-09-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

  15. Conduction velocity of antigravity muscle action potentials.

    Science.gov (United States)

    Christova, L; Kosarov, D; Christova, P

    1992-01-01

    The conduction velocity of the impulses along the muscle fibers is one of the parameters of the extraterritorial potentials of the motor units allowing for the evaluation of the functional state of the muscles. There are no data about the conduction velocities of antigravity muscleaction potentials. In this paper we offer a method for measuring conduction velocity of potentials of single MUs and the averaged potentials of the interference electromiogram (IEMG) lead-off by surface electrodes from mm. sternocleidomastoideus, trapezius, deltoideus (caput laterale) and vastus medialis. The measured mean values of the conduction velocity of antigravity muscles potentials can be used for testing the functional state of the muscles.

  16. Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

    Directory of Open Access Journals (Sweden)

    Ken Shinmura

    2013-01-01

    Full Text Available The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

  17. Effects of acetylcholine and noradrenalin on action potentials of isolated rabbit sinoatrial and atrial myocytes

    Directory of Open Access Journals (Sweden)

    Arie O. Verkerk

    2012-05-01

    Full Text Available The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh and noradrenalin (NA as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signalling proteins (RGS proteins suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 µM ACh and 1 µM NA on the intrinsic action potentials of sinotrial (SA nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1,000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA or a combination of both and may thus guide further experiments with RGS proteins.

  18. [Individualised medicine - potentials and need for action].

    Science.gov (United States)

    Hüsing, Bärbel

    2010-01-01

    Individualised medicine aims to classify seemingly homogenous patient groups into smaller clinically relevant subgroups (stratification) in order to be able to treat them differently, thus contributing to the improvement of health care services, to the prevention of inappropriate treatments and to the reduction of adverse effects. This article summarises a report to the Office of Technology Assessment at the German Bundestag and points out the need for action for transferring individualised medicine from research to clinical application: significant incentives are required in order to prove the clinical validity of newly identified biomarkers of complex diseases. Sustainable business models for the joint development of new applications by research institutions, biotechnology companies, pharmaceuticals and medical devices companies are required. Instruments for transferring knowledge from bench to bedside (translational research) and the existing regulatory framework should be further developed in order to strike an appropriate balance between incentives for accelerating the transfer of innovative technology to the health care sector while, at the same time, ensuring patient safety, high quality and clinical utility. PMID:21147435

  19. Angle-action estimation in a general axisymmetric potential

    OpenAIRE

    Sanders, Jason

    2012-01-01

    The usefulness of angle-action variables in galaxy dynamics is well known, but their use is limited due to the difficulty of their calculation in realistic galaxy potentials. Here we present a method for estimating angle-action variables in a realistic Milky Way axisymmetric potential by locally fitting a St\\"ackel potential over the region an orbit probes. The quality of the method is assessed by comparison with other known methods for estimating angle-action variables of a range of disc and...

  20. Successful Lung Transplant From Donor After Cardiac Death: A Potential Solution to Shortage of Thoracic Organs

    OpenAIRE

    McKellar, Stephen H.; Durham, Lucian A.; Scott, John P.; Cassivi, Stephen D.

    2010-01-01

    Lung transplant is an effective treatment for patients with end-stage lung disease but is limited because of the shortage of acceptable donor organs. Organ donation after cardiac death is one possible solution to the organ shortage because it could expand the pool of potential donors beyond brain-dead and living donors. We report the preliminary experience of Mayo Clinic with donation after cardiac death, lung procurement, and transplant.

  1. Radial propagation of muscle action potential along the tubular system examined by potential-sensitive dyes

    OpenAIRE

    Nakajima, S.; Gilai, A.

    1980-01-01

    Isolated single (Xenopus) muscle fibers were stained with a non-permeant potential-probing dye, merocyanine rhodanine (WW375) or merocyanine oxazolone (NK2367). When the fiber was massively stimulated, an absorption change (wave a), which seemed to reflect the action potential, occurred. Simultaneous recording of optical changes and intracellular action potentials revealed that the time-course of wave a was slower than the action potential: the peak of wave a was attained at 1 ms, and the pea...

  2. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    Science.gov (United States)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  3. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.

    Directory of Open Access Journals (Sweden)

    Francesca Oltolina

    Full Text Available A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM. We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.

  4. Critical Utopian Action Research: The Potential of Action Research in the Democratization of Society

    DEFF Research Database (Denmark)

    Nielsen, Birger Steen; Nielsen, Kurt Aagaard

    2016-01-01

    The specific concept of critical utopian action research is presented and discussed, as to its origin, use and potentials. The inspiration from Robert Jungk and his future creating workshops is elaborated....

  5. Cardiac Repolarization Abnormalities and Potential Evidence for Loss of Cardiac Sodium Currents on ECGs of Patients with Chagas' Heart Disease

    Science.gov (United States)

    Schlegel, T. T.; Medina, R.; Jugo, D.; Nunez, T. J.; Borrego, A.; Arellano, E.; Arenare, B.; DePalma, J. L.; Greco, E. C.; Starc, V.

    2007-01-01

    Some individuals with Chagas disease develop right precordial lead ST segment elevation in response to an ajmaline challenge test, and the prevalence of right bundle branch block (RBBB) is also high in Chagas disease. Because these same electrocardiographic abnormalities occur in the Brugada syndrome, which involves genetically defective cardiac sodium channels, acquired damage to cardiac sodium channels may also occur in Chagas disease. We studied several conventional and advanced resting 12-lead/derived Frank-lead ECG parameters in 34 patients with Chagas -related heart disease (mean age 39 14 years) and in 34 age-/gender-matched healthy controls. All ECG recordings were of 5-10 min duration, obtained in the supine position using high fidelity hardware/software (CardioSoft, Houston, TX). Even after excluding those Chagas patients who had resting BBBs, tachycardia and/or pathologic arrhythmia (n=8), significant differences remained in multiple conventional and advanced ECG parameters between the Chagas and control groups (n=26/group), especially in their respective QT interval variability indices, maximal spatial QRS-T angles and low frequency HRV powers (p=0.0006, p=0.0015 and p=0.0314 respectively). In relation to the issue of potential damage to cardiac sodium channels, the Chagas patients had: 1) greater than or equal to twice the incidence of resting ST segment elevation in leads V1-V3 (n=10/26 vs. n=5/26) and of both leftward (n=5/26 versus n=0/26) and rightward (n=7/26 versus n=3/26) QRS axis deviation than controls; 2) significantly increased filtered (40-250 Hz) QRS interval durations (92.1 8.5 versus 85.3 plus or minus 9.0 ms, p=0.022) versus controls; and 3) significantly decreased QT and especially JT interval durations versus controls (QT interval: 387.5 plus or minus 26.4 versus 408.9 plus or minus 34.6 ms, p=0.013; JT interval: 290.5 plus or minus 26.3 versus 314.8 plus or minus 31.3 ms; p=0.0029). Heart rates and Bazett-corrected QTc/JTc intervals

  6. Membrane, action, and oscillatory potentials in simulated protocells

    Science.gov (United States)

    Przybylski, Aleksander T.; Stratten, Wilford P.; Syren, Robert M.; Fox, Sidney W.

    1982-12-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KCl) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

  7. Membrane, action, and oscillatory potentials in simulated protocells

    Science.gov (United States)

    Syren, R. M.; Fox, S. W.; Przybylski, A. T.; Stratten, W. P.

    1982-01-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KCl) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

  8. Theophylline-induced potentiation of the antinociceptive action of baclofen.

    OpenAIRE

    Sawynok, J

    1983-01-01

    1--Theophylline (35, 50 mg/kg) potentiated the antinociceptive action of intraperitoneally administered baclofen in the tail flick and hot plate tests. Potentiation was most marked when the pretreatment time was 1 h, but some potentiation was still apparent following a 2 h pretreatment. 2--Theophylline alone (50 mg/kg) produced only slight alterations in reaction latency in the two tests. 3--When baclofen was applied directly into the spinal subarachnoid space, a 1 h pretreatment with theophy...

  9. Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

    Science.gov (United States)

    Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

    2012-01-01

    Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

  10. [Inhibition of oxygen free radicals in potassium channels of cardiac myocytes and the action of salvianolic acid A].

    Science.gov (United States)

    Bao, G

    1993-10-01

    By using the patch clamp technique, the effect of oxygen free radicals on the single potassium channels of cardiac papillary muscle cells were studied, as well as the action of salvianolic acid A. It was found that xanthane-xanthane oxidase generated oxygen free radicals could apparently inhibited the unitary currents of the single potassium channel activity. This inhibition was reversed by salvianolic acid A, which is an effective component extracted from Salvia miltiorrhiza. PMID:8168213

  11. Action prediction based on anticipatory brain potentials during simulated driving

    Science.gov (United States)

    Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R.

    2015-12-01

    Objective. The ability of an automobile to infer the driver’s upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver’s intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. Approach. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by ‘Start’/‘Stop’ cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. Main results. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a ‘Red’ traffic light) versus events that do not require such action (No-go condition; e.g. a ‘Yellow’ light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. Significance. We show for the first time the feasibility of predicting the driver’s intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

  12. Propagation of Action Potentials: An Active Participation Exercise.

    Science.gov (United States)

    Felsten, Gary

    1998-01-01

    Describes an active participation exercise that demonstrates the propagation of action potentials (the ability to transmit information through the neural network, dependent upon chemical interactions in the brain). Students assume the structure and function of the network by lining up around the room and communicating through hand signals and…

  13. Uncertainty propagation in nerve impulses through the action potential mechanism

    NARCIS (Netherlands)

    Torres Valderrama, A.; Witteveen, J.A.S.; Navarro Jimenez, M.I.; Blom, J.G.

    2015-01-01

    We investigate the propagation of probabilistic uncertainty through the action potential mechanism in nerve cells. Using the Hodgkin-Huxley (H-H) model and Stochastic Collocation on Sparse Grids, we obtain an accurate probabilistic interpretation of the deterministic dynamics of the transmembrane po

  14. Compound muscle action potentials in newborn infants with spina bifida.

    NARCIS (Netherlands)

    Geerdink, N.; Pasman, J.W.; Rotteveel, J.J.; Roeleveld, N.; Mullaart, R.A.

    2008-01-01

    The aim of this study was to investigate the relationship between compound muscle action potentials (CMAPs) and neurological impairment in newborn infants with spina bifida. Thirty-one newborn infants (17 males, 14 females, mean gestational age 39 wks [SD 2]; mean birthweight 3336 g [SD 496]) with s

  15. Sodium and potassium conductance changes during a membrane action potential.

    Science.gov (United States)

    Bezanilla, F; Rojas, E; Taylor, R E

    1970-12-01

    1. A method for turning a membrane potential control system on and off in less than 10 musec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential.2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential.3. The total membrane conductance taken from these current-voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939).4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin-Huxley equations.5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential. PMID:5505231

  16. Action potential initiation in the hodgkin-huxley model.

    Directory of Open Access Journals (Sweden)

    Lucy J Colwell

    2009-01-01

    Full Text Available A recent paper of B. Naundorf et al. described an intriguing negative correlation between variability of the onset potential at which an action potential occurs (the onset span and the rapidity of action potential initiation (the onset rapidity. This correlation was demonstrated in numerical simulations of the Hodgkin-Huxley model. Due to this antagonism, it is argued that Hodgkin-Huxley-type models are unable to explain action potential initiation observed in cortical neurons in vivo or in vitro. Here we apply a method from theoretical physics to derive an analytical characterization of this problem. We analytically compute the probability distribution of onset potentials and analytically derive the inverse relationship between onset span and onset rapidity. We find that the relationship between onset span and onset rapidity depends on the level of synaptic background activity. Hence we are able to elucidate the regions of parameter space for which the Hodgkin-Huxley model is able to accurately describe the behavior of this system.

  17. Leptin as a cardiac pro-hypertrophic factor and its potential role in the development of heart failure.

    Science.gov (United States)

    Karmazyn, Morris; Rajapurohitam, Venkatesh

    2014-01-01

    The identification of the adipocyte as a source of production of biologically-active peptides has materialized into an active area of research related to the role of these peptides in physiology and pathophysiology. Moreover, this research has resulted in the identification of the adipocyte as an endocrine organ producing potent bioactive compounds. An increasing number of these adipokines are being identified, the first of which was leptin, a product of the obesity gene whose primary function is to act as a satiety factor but which is now known to exert a myriad of effects. It is now recognized that virtually all adipokines produce effects on numerous organ systems including the heart and many of these, including leptin, are produced by cardiac tissue. Here we focus primarily on the diverse effects of leptin on the heart especially as it pertains to hypertrophy and discuss the potential cell signaling mechanisms underlying their actions. Current evidence suggests that leptin is a cardiac hypertrophic factor and from clinical studies there is evidence that hyperleptinemia is associated with cardiovascular risk especially as it pertains to heart failure. While more substantial research needs to be carried out, leptin may represent a potential link between obesity, which is associated with hyperleptinemia, and increased cardiovascular risk.

  18. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities...... at different conduction distances are determined by summation of SFAPs of varying fiber diameters, and differ in this respect, also, from the compound muscle action potential (CMAP) for which conduction velocities are determined by the very fastest fibers in the nerve. The effect and extent of temporal......, with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers...

  19. Negative inotropic actions of nitric oxide require high doses in rat cardiac muscle.

    Science.gov (United States)

    Wyeth, R P; Temma, K; Seifen, E; Kennedy, R H

    1996-08-01

    Initial experiments were designed to determine if vasoactive concentrations of nitric oxide (NO) alter contractility in rat heart. Contractile function was monitored in left atrial and papillary muscles (30 degrees C; paced at 0.5 Hz) during cumulative addition of 3-morpholino-sydnonimine-HCl(SIN-1), an agent that releases NO. At concentrations between 10(-7) and 10(-4) M (NO concentrations of approximately 10(-8)- 3 x 10(-7) M), SIN-1 did not affect contractility in either tissue. Similarly, 10(-4) M SIN-1 did not alter the positive inotropic responses to isoproterenol or increasing extracellular [Ca+2] ([Ca+2]o). To obtain higher concentrations of NO, additional studies were conducted using authentic NO. NO-saturated stock solutions and a corresponding control solvent were adjusted to pH 1.6 with HCl. Dose-dependent effects of NO were examined by adding aliquots of the stock solutions (or control solvent) to the bathing solution. At final concentrations of 1 x 10(-5)- 5 x 10(-4) M, NO produced transient, concentration-dependent decreases in contractility that were paralleled by reductions in buffer pH. Control solvent elicited similar reductions in pHo and transient decreases in contractility; however, the negative inotropic action elicited by the NO-containing solution was approximately 20% greater than that observed in control conditions. These data demonstrate that only high concentrations of NO depress contractility in isolated rat cardiac muscle, and suggest that this effect is mediated by both acidosis and a pHo-independent mechanism.

  20. Autoantibodies enhance agonist action and binding to cardiac muscarinic receptors in chronic Chagas' disease.

    Science.gov (United States)

    Hernandez, Ciria C; Nascimento, Jose H; Chaves, Elen A; Costa, Patricia C; Masuda, Masako O; Kurtenbach, Eleonora; Campos DE Carvalho, Antonio C; Gimenez, Luis E

    2008-01-01

    Chronic Chagasic patient immunoglobulins (CChP-IgGs) recognize an acidic amino acid cluster at the second extracellular loop (el2) of cardiac M(2)-muscarinic acetylcholine receptors (M(2)AChRs). These residues correspond to a common binding site for various allosteric agents. We characterized the nature of the M(2)AChR/CChP-IgG interaction in functional and radioligand binding experiments applying the same mainstream strategies previously used for the characterization of other allosteric agents. Dose-response curves of acetylcholine effect on heart rate were constructed with data from isolated heart experiments in the presence of CChP or normal blood donor (NBD) sera. In these experiments, CChP sera but not NBD sera increased the efficacy of agonist action by augmenting the onset of bradyarrhythmias and inducing a Hill slope of 2.5. This effect was blocked by gallamine, an M(2)AChR allosteric antagonist. Correspondingly, CChP-IgGs increased acetylcholine affinity twofold and showed negative cooperativity for [(3)H]-N-methyl scopolamine ([(3)H]-NMS) in allosterism binding assays. A peptide corresponding to the M(2)AChR-el2 blocked this effect. Furthermore, dissociation assays showed that the effect of gallamine on the [(3)H]-NMS off-rate was reverted by CChP-IgGs. Finally, concentration-effect curves for the allosteric delay of W84 on [(3)H]-NMS dissociation right shifted from an IC(50) of 33 nmol/L to 78 nmol/L, 992 nmol/L, and 1670 nmol/L in the presence of 6.7 x 10(- 8), 1.33 x 10(- 7), and 2.0 x 10(- 7) mol/L of anti-el2 affinity-purified CChP-IgGs. Taken together, these findings confirmed a competitive interplay of these ligands at the common allosteric site and revealed the novel allosteric nature of the interaction of CChP-IgGs at the M(2)AChRs as a positive cooperativity effect on acetylcholine action. PMID:18702010

  1. Autoantibodies Enhance Agonist Action and Binding to Cardiac Muscarinic Receptors in Chronic Chagas’ Disease

    Science.gov (United States)

    Hernández, Ciria C.; Nascimento, José H.; Chaves, Elen A.; Costa, Patrícia C.; Masuda, Masako O.; Kurtenbach, Eleonora; Campos de Carvalho, Antônio C.; Giménez, Luis E.

    2009-01-01

    Chronic Chagasic patient immunoglobulins (CChP-IgGs) recognize an acidic amino acid cluster at the second extracellular loop (el2) of cardiac M2-muscarinic acetylcholine receptors (M2AChRs). These residues correspond to a common binding site for various allosteric agents. We characterized the nature of the M2AChR/CChP-IgG interaction in functional and radioligand binding experiments applying the same mainstream strategies previously used for the characterization of other allosteric agents. Dose-response curves of acetylcholine effect on heart rate were constructed with data from isolated heart experiments in the presence of CChP or normal blood donor (NBD) sera. In these experiments, CChP sera but not NBD sera increased the efficacy of agonist action by augmenting the onset of bradyarrhythmias and inducing a Hill slope of 2.5. This effect was blocked by gallamine, an M2AChR allosteric antagonist. Correspondingly, CChP-IgGs increased acetylcholine affinity twofold and showed negative cooperativity for [3H]-N-methyl scopolamine ([3H]-NMS) in allosterism binding assays. A peptide corresponding to the M2AChR-el2 blocked this effect. Furthermore, dissociation assays showed that the effect of gallamine on the [3H]-NMS off-rate was reverted by CChP-IgGs. Finally, concentration-effect curves for the allosteric delay of W84 on [3H]-NMS dissociation right shifted from an IC50 of 33 nmol/L to 78 nmol/L, 992 nmol/L, and 1670 nmol/L in the presence of 6.7 × 10−8, 1.33 × 10−7, and 2.0 × 10−7 mol/L of anti-el2 affinity-purified CChP-IgGs. Taken together, these findings confirmed a competitive interplay of these ligands at the common allosteric site and revealed the novel allosteric nature of the interaction of CChP-IgGs at the M2AChRs as a positive cooperativity effect on acetylcholine action. PMID:18702010

  2. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-01

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation.

  3. Cardiac differentiation potential of human induced pluripotent stem cells in a 3D self-assembling peptide scaffold.

    Science.gov (United States)

    Puig-Sanvicens, Veronica A C; Semino, Carlos E; Zur Nieden, Nicole I

    2015-01-01

    In the past decade, various strategies for cardiac reparative medicine involving stem cells from multiple sources have been investigated. However, the intra-cardiac implantation of cells with contractile ability may seriously disrupt the cardiac syncytium and de-synchronize cardiac rhythm. For this reason, bioactive cardiac implants, consisting of stem cells embedded in biomaterials that act like band aids, have been exploited to repair the cardiac wall after myocardial infarction. For such bioactive implants to function properly after transplantation, the choice of biomaterial is equally important as the selection of the stem cell source. While adult stem cells have shown promising results, they have various disadvantages including low proliferative potential in vitro, which make their successful usage in human transplants difficult. As a first step towards the development of a bioactive cardiac patch, we investigate here the cardiac differentiation properties of human induced pluripotent stem cells (hiPSCs) when cultured with and without ascorbic acid (AA) and when embedded in RAD16-I, a biomaterial commonly used to develop cardiac implants. In adherent cultures and in the absence of RAD16-I, AA promotes the cardiac differentiation of hiPSCs by enhancing the expression of specific cardiac genes and proteins and by increasing the number of contracting clusters. In turn, embedding in peptide hydrogel based on RAD16-I interferes with the normal cardiac differentiation progression. Embedded hiPSCs up-regulate genes associated with early cardiogenesis by up to 105 times independently of the presence of AA. However, neither connexin 43 nor troponin I proteins, which are related with mature cardiomyocytes, were detected and no contraction was noted in the constructs. Future experiments will need to focus on characterizing the mature cardiac phenotype of these cells when implanted into infarcted myocardia and assess their regenerative potential in vivo. PMID:26707885

  4. The mode of action of quinidine on isolated rabbit atria interpreted from intracellular potential records.

    Science.gov (United States)

    VAUGHAN WILLIAMS, E M

    1958-09-01

    An attempt has been made to show why quinidine, which has long been known not to lengthen the duration of the cardiac action potential, measured with external electrodes, and also not to lengthen, and sometimes to shorten, the absolute refractory period, nevertheless reduces the maximum frequency at which atria can respond to a stimulus. Simultaneous measurements have been made in electrically driven isolated rabbit atria of contractions, conduction velocity and intracellular potentials before and during exposure to a wide range of concentrations of quinidine sulphate. The resting potential remained undiminished, in contrast to the effect of quinidine on Purkinje fibres. In the therapeutic range of doses, up to 10 mg./l., the half-time for repolarization was either shortened or unchanged, thus providing an explanation for the failure of quinidine to prolong the absolute refractory period. In contrast, even at low concentrations of quinidine, conduction velocity and the rate of rise of the action potential were greatly slowed, and the height of the overshoot was reduced. The terminal phase of the action potential was prolonged. It is known that the rate of rise of the action potential is a function of the level of repolarization at which an impulse takes off (the more negative the take-off point, the faster the rate of rise). Normally, a stimulus introduced when repolarization has proceeded to 2/3 of the resting potential evokes a response with a rate of rise fast enough for propagation, so that the duration of the terminal 1/3 of the phase of repolarization has no influence upon the length of the effective refractory period. In the presence of quinidine, however, the rate of rise itself was directly reduced, thus repolarization had to proceed further before the critical take-off point was reached at which the rate of rise was fast enough for propagation, and the duration of the terminal phase of repolarization thus became significant. It has been concluded that

  5. Warm body temperature facilitates energy efficient cortical action potentials.

    Directory of Open Access Journals (Sweden)

    Yuguo Yu

    Full Text Available The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na(+ channel inactivation, resulting in a marked reduction in overlap of the inward Na(+, and outward K(+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na(+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37-42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code.

  6. An Excel-based implementation of the spectral method of action potential alternans analysis.

    Science.gov (United States)

    Pearman, Charles M

    2014-12-01

    Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro-arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T-wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results.

  7. Update on the Pathogenic Implications and Clinical Potential of microRNAs in Cardiac Disease

    Directory of Open Access Journals (Sweden)

    Mario Notari

    2015-01-01

    Full Text Available miRNAs, a unique class of endogenous noncoding RNAs, are highly conserved across species, repress gene translation upon binding to mRNA, and thereby influence many biological processes. As such, they have been recently recognized as regulators of virtually all aspects of cardiac biology, from the development and cell lineage specification of different cell populations within the heart to the survival of cardiomyocytes under stress conditions. Various miRNAs have been recently established as powerful mediators of distinctive aspects in many cardiac disorders. For instance, acute myocardial infarction induces cardiac tissue necrosis and apoptosis but also initiates a pathological remodelling response of the left ventricle that includes hypertrophic growth of cardiomyocytes and fibrotic deposition of extracellular matrix components. In this regard, recent findings place various miRNAs as unquestionable contributing factors in the pathogenesis of cardiac disorders, thus begging the question of whether miRNA modulation could become a novel strategy for clinical intervention. In the present review, we aim to expose the latest mechanistic concepts regarding miRNA function within the context of CVD and analyse the reported roles of specific miRNAs in the different stages of left ventricular remodelling as well as their potential use as a new class of disease-modifying clinical options.

  8. Update on the Pathogenic Implications and Clinical Potential of microRNAs in Cardiac Disease.

    Science.gov (United States)

    Notari, Mario; Pulecio, Julián; Raya, Ángel

    2015-01-01

    miRNAs, a unique class of endogenous noncoding RNAs, are highly conserved across species, repress gene translation upon binding to mRNA, and thereby influence many biological processes. As such, they have been recently recognized as regulators of virtually all aspects of cardiac biology, from the development and cell lineage specification of different cell populations within the heart to the survival of cardiomyocytes under stress conditions. Various miRNAs have been recently established as powerful mediators of distinctive aspects in many cardiac disorders. For instance, acute myocardial infarction induces cardiac tissue necrosis and apoptosis but also initiates a pathological remodelling response of the left ventricle that includes hypertrophic growth of cardiomyocytes and fibrotic deposition of extracellular matrix components. In this regard, recent findings place various miRNAs as unquestionable contributing factors in the pathogenesis of cardiac disorders, thus begging the question of whether miRNA modulation could become a novel strategy for clinical intervention. In the present review, we aim to expose the latest mechanistic concepts regarding miRNA function within the context of CVD and analyse the reported roles of specific miRNAs in the different stages of left ventricular remodelling as well as their potential use as a new class of disease-modifying clinical options. PMID:26221581

  9. PROPOSED CARDIAC STEM CELLS DERIVED FROM “CARDIOSPHERES” LACK CARDIOMYOGENIC POTENTIAL

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline

    that injuried heart tissue may be repaired by stem cell therapy using autologous CS derived cells, and pre-clinical studies have already been described in literature.    Herein, we established CSs from neonatal rats, and by immunofluorescence, qRT-PCR, and microscopic examination we demonstrated......   Recent studies have reported that clinical relevant numbers of cardiac stem cells (CSCs) with cardiomyogenic potential can be obtained from small heart tissue biopsies, by an intrinsic ability of CSCs to form beating cardiospheres (CSs) during ex vivo culture. Such data have provided optimism...... to form CSs by themselves. Phenotypically, CS cells largely resembled fibroblasts, and they lacked cardiomyogenic as well as endothelial differentiation potential.    Our data imply that at least the murine cardiosphere model seems unsuitable for enrichment of cardiac stem cells with cardiomyogenic...

  10. Latencies in action potential stimulation in a two-dimensional bidomain: A numerical simulation

    Science.gov (United States)

    Barach, John Paul

    1991-05-01

    A numerical simulation is performed in which a uniform planar slab of idealized cardiac tissue is stimulated at the center. The cardiac slab is modeled as an anisotropic bidomain; within each domain current flow is determined by a forced diffusion equation in which the transmembrane current connecting the domains provides the forcing term. An action potential (AP) propagates outward after a time latency dependent upon the stimulus size and the physiological variables. Its isochrones are elliptical with an asymmetry that is a small fraction of the imposed asymmetry in resistivity. External voltages resemble the first derivative of those in the internal domain and tests with continuing stimuli exhibit a relaxation time of about 3 ms and space constants that agree with other work. The AP latency increases very strongly near threshold stimulus and decreases as the log (stimulus) for large stimuli in the ``virtual cathode'' range. Latencies in the longitudinal, transverse, and diagonal directions are found to be the same over a wide range of stimulus size and type.

  11. Implementing participatory action research in Lithuania: potential and challenges

    Directory of Open Access Journals (Sweden)

    Gabija Jarašiūnaitė

    2015-12-01

    Full Text Available Participatory action research is a quite new approach to research in Lithuania. The aim of an article was to disscuss the potential and challenges of participatory action research while implementing it in Lithuanian organizations. The qualitative approach was chosen for the study using the method of Focus groups. 20 researchers from social and biomedicine sciences from six institutions of High education in Lithuania participated in the study. The results of the study showed that participatory action reasearch is seen as an approach with many possibilities because of a wide range of used methods, constant interactions with research participants and the lenght of the research process. Researchers value the possibility to access organization at the begining, during research process and evaluate the effectiveness of the changes after the process. The research challenges are associated with the competence of a researcher including his/her sensitivity during process, ability to involve active participation of organization members in the ongoing process by creating safe and trusting environment. Some specific challenges associated with Lithuanian organizations are organizations‘ tiredness of researches and lack of faith of the benefits of researches because of some previous experiences. Keywords: Participatory Action Research, Organization, Lithuania.

  12. Optimizing Neurologically Intact Survival from Sudden Cardiac Arrest: A Call to Action

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Goodloe

    2014-11-01

    Full Text Available The U.S. national out-of-hospital and in-hospital cardiac arrest survival rates, although improving recently, have remained suboptimal despite the collective efforts of individuals, communities, and professional societies. Only until very recently, and still with inconsistency, has focus been placed specifically on survival with pre-arrest neurologic function. The reality of current approaches to sudden cardiac arrest is that they are often lacking an integrative, multi-disciplinary approach, and without deserved funding and outcome analysis. In this manuscript, a multidisciplinary group of authors propose practice, process, technology, and policy initiatives to improve cardiac arrest survival with a focus on neurologic function. [West J Emerg Med. 2014;15(7:-0.

  13. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...

  14. Sumoylation in gene regulation and cardiac disease: potential for drug discovery

    Directory of Open Access Journals (Sweden)

    Beketaev I

    2014-11-01

    Full Text Available Ilimbek Beketaev, Jun Wang Center for Stem Cell Engineering, Department of Basic Research Laboratories, Texas Heart Institute at St Luke’s Episcopal Hospital, Houston, TX, USA Abstract: Small ubiquitin-related modifier (SUMO proteins are members of ubiquitin-like super-family proteins that can be covalently conjugated to their targets through multistep enzymatic reactions. Sumoylation has caught much attention due to its versatility, wide involvement in cellular events, and disease association. Sumoylation has been well studied at cellular and molecular levels. A newly emerging role that SUMO conjugation plays is in cardiac pathophysiology. In this review we will update new advances in the study of implications of the sumoylation pathway in the pathogenesis of cardiac diseases, discuss promise of the SUMO pathway as a potential therapeutic target, and conclude with future directions for SUMO research in the heart field. Keywords: posttranslational modification, SUMO, SENP, heart

  15. Indeterminacy of Spatiotemporal Cardiac Alternans

    CERN Document Server

    Zhao, Xiaopeng

    2007-01-01

    Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in ECG morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the US each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Usin...

  16. Flexible graphene transistors for recording cell action potentials

    Science.gov (United States)

    Blaschke, Benno M.; Lottner, Martin; Drieschner, Simon; Bonaccini Calia, Andrea; Stoiber, Karolina; Rousseau, Lionel; Lissourges, Gaëlle; Garrido, Jose A.

    2016-06-01

    Graphene solution-gated field-effect transistors (SGFETs) are a promising platform for the recording of cell action potentials due to the intrinsic high signal amplification of graphene transistors. In addition, graphene technology fulfills important key requirements for in-vivo applications, such as biocompability, mechanical flexibility, as well as ease of high density integration. In this paper we demonstrate the fabrication of flexible arrays of graphene SGFETs on polyimide, a biocompatible polymeric substrate. We investigate the transistor’s transconductance and intrinsic electronic noise which are key parameters for the device sensitivity, confirming that the obtained values are comparable to those of rigid graphene SGFETs. Furthermore, we show that the devices do not degrade during repeated bending and the transconductance, governed by the electronic properties of graphene, is unaffected by bending. After cell culture, we demonstrate the recording of cell action potentials from cardiomyocyte-like cells with a high signal-to-noise ratio that is higher or comparable to competing state of the art technologies. Our results highlight the great capabilities of flexible graphene SGFETs in bioelectronics, providing a solid foundation for in-vivo experiments and, eventually, for graphene-based neuroprosthetics.

  17. Prediction of the potential clinical outcomes for post-resuscitated patients after cardiac arrest

    Science.gov (United States)

    Hong, Sungmin; Kwon, Bojun; Yun, Il Dong; Lee, Sang Uk; Kim, Kyuseok; Kim, Joonghee

    2013-02-01

    Cerebral injuries after cardiac arrest are serious causes for morbidity. Many previous researches in the medical society have been proposed to prognosticate the functional recoveries of post-resuscitated patients after cardiac arrest, but the validity of suggested features and the automation of prognostication have not been made yet. This paper presents the automatic classification method which predicts the potential clinical outcomes of post-resuscitated patients who suffered from cardiac arrest. The global features and the local features are adapted from the researches from the medical society. The global features, which are consisted of the percentage of the partial volume under the uniformly increasing thresholds, represent the global tendency of apparent diffusion coefficient value in a DWI. The local features are localized and measured on the refined local apparent diffusion coefficient minimal points. The local features represent the ischemic change of small areas in a brain. The features are trained and classified by the random forest method, which have been widely used in the machine learning society for classification. The validity of features is automatically evaluated during the classification process. The proposed method achieved the 0.129 false-positive rate while maintaining the perfect true-positive rate. The area-under-curve of the proposed method was 0.9516, which showed the feasibility and the robustness of the proposed method.

  18. [The cardioprotective action of the anticonvulsant preparation sodium valproate in disorders of cardiac contractile function caused by acute myocardial infarct in rats].

    Science.gov (United States)

    Belkina, L M; Korchazhkina, N B; Kamskova, Iu G; Fomin, N A

    1997-01-01

    The preventive and therapeutical effects of sodium valproate (SV), 200 mg/kg, on cardiac contractile disorders (developed pressure, rate-pressure products, dp/dt) were studied in rats having 2-day myocardial infarction (MI). The postinfarction rather than preinfarction use of SV substantially restricted the depressed resting left ventricular function. Given by two regimens, SV increased cardiac resistance to the maximum isometric load induced by 60-sec ligation of the ascending aorta. The cardioprotective effect of the drug was shown due to its positive chronotropic action rather than its inotropic one. Thus, SV may be used as an effective drug for the prevention and treatment of postinfarct cardiac dysfunctions. PMID:9235532

  19. The Potential of Deweyan-Inspired Action Research

    Science.gov (United States)

    Stark, Jody L.

    2014-01-01

    In its broadest sense, pragmatism could be said to be the philosophical orientation of all action research. Action research is characterized by research, action, and participation grounded in democratic principles and guided by the aim of social improvement. Furthermore, action research is an active process of inquiry that does not admit…

  20. Pressure wave model for action potential propagation in excitable cells

    CERN Document Server

    Rvachev, M M

    2003-01-01

    Speed of propagation of small-amplitude pressure waves through the cytoplasmic interior of myelinated and unmyelinated axons of different diameters is theoretically estimated and is found to generally agree with the action potential (AP) conduction velocities. This remarkable coincidence allows to surmise a model in which AP spread along axon is propelled not by straggling ionic currents as in the widely accepted local circuit theory, but by mechanoactivation of the membrane ion channels by a traveling pressure pulse. Hydraulic pulses propagating in the viscous axoplasm are calculated to decay over ~1 mm distances, and it is further hypothesized that it is the role of influxing during the AP calcium ions to activate membrane skeletal protein network attached to the membrane cytoplasmic side for a brief radial contraction amplifying the pressure pulse and preventing its decay. The model correctly predicts that the AP conduction velocity should vary as the one-half power of axon diameter for large unmyelinated ...

  1. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    at different conduction distances are determined by summation of SFAPs of varying fiber diameters, and differ in this respect, also, from the compound muscle action potential (CMAP) for which conduction velocities are determined by the very fastest fibers in the nerve. The effect and extent of temporal...... dispersion over increasing conduction distance is greater for the SNAP than CMAP, and demonstration of conduction block is therefore difficult. In addition, the effect of temporal dispersion on amplitude and shape is strongly dependent on the number of conducting fibers and their distribution, and...... in different polyneuropathies. In this review, different factors that characterize sensory fibers and set the SNAP apart from the CMAP are discussed to emphasize the supplementary and complementary information that can be obtained from sensory conduction studies. Sensory conduction studies require particular...

  2. [11C]-Acetoacetate PET imaging: a potential early marker for cardiac heart failure

    International Nuclear Information System (INIS)

    The ketone body acetoacetate could be used as an alternate nutrient for the heart, and it also has the potential to improve cardiac function in an ischemic–reperfusion model or reduce the mitochondrial production of oxidative stress involved in cardiotoxicity. In this study, [11C]-acetoacetate was investigated as an early marker of intracellular damage in heart failure. Methods: A rat cardiotoxicity heart failure model was induced by doxorubicin, Dox(+). [14C]-Acetoacetate, a non-positron (β −) emitting radiotracer, was used to characterize the arterial blood input function and myocardial mitochondrial uptake. Afterward, [11C]-acetoacetate (β +) myocardial PET images were obtained for kinetic analysis and heart function assessment in control Dox(−) (n = 15) and treated Dox(+) (n = 6) rats. The uptake rate (K1) and myocardial clearance rate (k2or kmono) were extracted. Results: [14C]-Acetoacetate in the blood was increased in Dox(+), from 2 min post-injection until the last withdrawal point when the heart was harvested, as well as the uptake in the heart and myocardial mitochondria (unpaired t-test, p < 0.05). PET kinetic analysis of [11C]-acetoacetate showed that rate constants K1, k2 and kmono were decreased in Dox(+) (p < 0.05) combined with a reduction of 24% of the left ventricular ejection fraction (p < 0.001). Conclusion: Radioactive acetoacetate ex vivo analysis [14C], and in vivo kinetic [11C] studies provided evidence that [11C]-acetoacetate can assess heart failure Dox(+). Contrary to myocardial flow reserve (rest–stress protocol), [11C]-acetoacetate can be used to assess reduced kinetic rate constants without requirement of hyperemic stress response. The proposed [11C]-acetoacetate cardiac radiotracer in the investigation of heart disease is novel and paves the way to a potential role for [11C]-acetoacetate in cardiac pathophysiology

  3. Chagas Cardiomiopathy: The Potential of Diastolic Dysfunction and Brain Natriuretic Peptide in the Early Identification of Cardiac Damage

    OpenAIRE

    Ana Garcia-Alvarez; Marta Sitges; María-Jesús Pinazo; Ander Regueiro-Cueva; Elizabeth Posada; Silvia Poyatos; José Tomás Ortiz-Pérez; Magda Heras; Manel Azqueta; Joaquim Gascon; Ginés Sanz

    2010-01-01

    INTRODUCTION: Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the r...

  4. Optimisation of Ionic Models to Fit Tissue Action Potentials: Application to 3D Atrial Modelling

    Directory of Open Access Journals (Sweden)

    Amr Al Abed

    2013-01-01

    Full Text Available A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN, intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue.

  5. Cardiac risk stratification with myocardial perfusion imaging in potential renal-pancreas transplant recipients

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, M.C.; Larcos, G.; Chapman, J. [Westmead Hospital, Westmead, Sydney, NSW (Australia). Departments of Nuclear Medicine and Ultrasound

    1998-06-01

    Full text: Combined renal/pancreas transplantation is used in patients with severe type-1 diabetes and renal failure. Many patients have asymptomatic coronary artery disease (CAD). Thus, myocardial perfusion imaging (MPI) is widely used for preoperative risk assessment, however, its value has recently been challenged. The purpose of this study was to determine the predictive value of MPI compared to coronary angiography and/or thirty day perioperative cardiac events (cardiac death, myocardial infarction and unstable angina). We reviewed the MPI in 132 patients that were referred for possible renal pancreas transplantation during the period between 1987 - June 1997. Fifty five patients were excluded because of: still awaiting transplantation (n=19) ongoing medical assessment (n=21), received kidney only transplant (n=6) or other factors (n=9). Thus, 77 patients form the basis of this report. Seventy one patients were transplanted, 5 had coronary angiography and one died before transplantation but with coronary anatomy defined at autopsy. All patients (39 male, 38 female; mean age 37 years) had Tl-201 or Tc-99m MIBI SPECT at Westmead (n=54) or elsewhere (n=23). Patients underwent MPI, a mean of 12.1 months before transplantation and a mean of 6 months before coronary angiography or autopsy. MPI was normal in 64 (83%) and abnormal in 13 (17%) patients. Of the abnormal MPI, 7 patients had CAD and one had unstable angina post-operatively (PPV = 8/13; 61%). One patient had a fixed defect post CABG but proceeded to transplant with-out event; the other 4 patients had normal coronary anatomy. Of the normal MPIs there were no transplant related cardiac events, but one patient required CABG >12 months post MPI and a further patient died >12 months post transplant and was shown to have CAD at autopsy (NPV=62/64;97%). In conclusion we have found an excellent NPV and an acceptable PPV for MPI in potential renal pancreas graft recipients

  6. 'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells.

    Science.gov (United States)

    Okamoto, Kazuma; Miyoshi, Shunichiro; Toyoda, Masashi; Hida, Naoko; Ikegami, Yukinori; Makino, Hatsune; Nishiyama, Nobuhiro; Tsuji, Hiroko; Cui, Chang-Hao; Segawa, Kaoru; Uyama, Taro; Kami, Daisuke; Miyado, Kenji; Asada, Hironori; Matsumoto, Kenji; Saito, Hirohisa; Yoshimura, Yasunori; Ogawa, Satoshi; Aeba, Ryo; Yozu, Ryohei; Umezawa, Akihiro

    2007-07-15

    The clinical application of cell transplantation for severe heart failure is a promising strategy to improve impaired cardiac function. Recently, an array of cell types, including bone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and embryonic stem cells, have become important candidates for cell sources for cardiac repair. In the present study, we focused on the placenta as a cell source. Cells from the chorionic plate in the fetal portion of the human placenta were obtained after delivery by the primary culture method, and the cells generated in this study had the Y sex chromosome, indicating that the cells were derived from the fetus. The cells potentially expressed 'working' cardiomyocyte-specific genes such as cardiac myosin heavy chain 7beta, atrial myosin light chain, cardiac alpha-actin by gene chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin 43 by immunohistochemistry. These cells were able to differentiate into cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous pattern of localization at intercellular contact sites after cardiomyogenic differentiation, suggesting that the chorionic mesoderm contained a large number of cells with cardiomyogenic potential. The cells began spontaneously beating 3 days after co-cultivation with murine fetal cardiomyocytes and the frequency of beating cells reached a maximum on day 10. The contraction of the cardiomyocytes was rhythmical and synchronous, suggesting the presence of electrical communication between the cells. Placenta-derived human fetal cells may be useful for patients who cannot supply bone marrow cells but want to receive stem cell-based cardiac therapy.

  7. Modelling Action Potential Generation and Propagation in Fibroblastic Cells

    Science.gov (United States)

    Torres, J. J.; Cornelisse, L. N.; Harks, E. G. A.; Theuvenet, A. P. R.; Ypey, D. L.

    2003-04-01

    Using a standard Hodgkin-Huxley (HH) formalism, we present a mathematical model for action potential (AP) generation and intercellular AP propagation in quiescent (serum-deprived) normal rat kidney (NRK) fibroblasts [1], based on the recent experimental identification of the ion channels involved [2]. The principal ion channels described are those of an inwardly rectifying K+ conductance (GKIR), an L-type calcium conductance (GCaL), an intracellular calcium activated Cl- conductance (GCl(Ca)), a residual leak conductance Gleak, and gap junctional channels between the cells (Ggj). The role of each one of these components in the particular shape of the AP wave-form has been analyzed and compared with experimental observations. In addition, we have studied the role of subcellular processes like intracellular calcium dynamics and calcium buffering in AP generation. AP propagation between cells was reconstructed in a hexagonal model of cells coupled by Ggj with physiological conductance values. The model revealed an excitability mechanism of quiescent NRK cells with a particular role of intracellular calcium dynamics. It allows further explorations of the mechanism of signal generation and transmission in NRK cell cultures and its dependence on growth conditions.

  8. Pharmacological actions of statins: potential utility in COPD

    Directory of Open Access Journals (Sweden)

    T. E. Eaton

    2009-12-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-B mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1 Inhibition of cytokine production (tumour necrosis factor-, interleukin (IL-6 and IL-8 and neutrophil infiltration into the lung; 2 inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3 antioxidant and anti-inflammatory (IL-6 mediated effects on skeletal muscle; 4 reduced inflammatory response to pulmonary infection; and 5 inhibition of the development (or reversal of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD.

  9. Pharmacological actions of statins: potential utility in COPD.

    Science.gov (United States)

    Young, R P; Hopkins, R; Eaton, T E

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-κB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-α, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD. PMID:20956147

  10. Acute nerve stretch and the compound motor action potential

    Directory of Open Access Journals (Sweden)

    Wolfe Jacob

    2011-08-01

    Full Text Available Abstract In this paper, the acute changes in the compound motor action potential (CMAP during mechanical stretch were studied in hamster sciatic nerve and compared to the changes that occur during compression. In response to stretch, the nerve physically broke when a mean force of 331 gm (3.3 N was applied while the CMAP disappeared at an average stretch force of 73 gm (0.73 N. There were 5 primary measures of the CMAP used to describe the changes during the experiment: the normalized peak to peak amplitude, the normalized area under the curve (AUC, the normalized duration, the normalized velocity and the normalized velocity corrected for the additional path length the impulses travel when the nerve is stretched. Each of these measures was shown to contain information not available in the others. During stretch, the earliest change is a reduction in conduction velocity followed at higher stretch forces by declines in the amplitude of the CMAP. This is associated with the appearance of spontaneous EMG activity. With stretch forces Multiple means of predicting when a change in the CMAP suggests a significant stretch are discussed and it is clear that a multifactorial approach using both velocity and amplitude parameters is important. In the case of pure compression, it is only the amplitude of the CMAP that is critical in predicting which changes in the CMAP are associated with significant compression.

  11. Short latency compound action potentials from mammalian gravity receptor organs

    Science.gov (United States)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  12. Protection of Coronary Endothelial Function during Cardiac Surgery: Potential of Targeting Endothelial Ion Channels in Cardioprotection

    Directory of Open Access Journals (Sweden)

    Qin Yang

    2014-01-01

    Full Text Available Vascular endothelium plays a critical role in the control of blood flow by producing vasoactive factors to regulate vascular tone. Ion channels, in particular, K+ channels and Ca2+-permeable channels in endothelial cells, are essential to the production and function of endothelium-derived vasoactive factors. Impairment of coronary endothelial function occurs in open heart surgery that may result in reduction of coronary blood flow and thus in an inadequate myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion during cardioplegic intervention compromise NO and EDHF-mediated function and the impairment involves alterations of K+ channels, that is, KATP and KCa, and Ca2+-permeable TRP channels in endothelial cells. Pharmacological modulation of these channels during ischemia-reperfusion and hyperkalemic exposure show promising results on the preservation of NO and EDHF-mediated endothelial function, which suggests the potential of targeting endothelial K+ and TRP channels for myocardial protection during cardiac surgery.

  13. Assessment of potential drug-drug interactions and its associated factors in the hospitalized cardiac patients.

    Science.gov (United States)

    Murtaza, Ghulam; Khan, Muhammad Yasir Ghani; Azhar, Saira; Khan, Shujaat Ali; Khan, Tahir M

    2016-03-01

    Drug-drug interactions (DDIs) may result in the alteration of therapeutic response. Sometimes they may increase the untoward effects of many drugs. Hospitalized cardiac patients need more attention regarding drug-drug interactions due to complexity of their disease and therapeutic regimen. This research was performed to find out types, prevalence and association between various predictors of potential drug-drug interactions (pDDIs) in the Department of Cardiology and to report common interactions. This study was performed in the hospitalized cardiac patients at Ayub Teaching Hospital, Abbottabad, Pakistan. Patient charts of 2342 patients were assessed for pDDIs using Micromedex® Drug Information. Logistic regression was applied to find predictors of pDDIs. The main outcome measure in the study was the association of the potential drug-drug interactions with various factors such as age, gender, polypharmacy, and hospital stay of the patients. We identified 53 interacting-combinations that were present in total 5109 pDDIs with median number of 02 pDDIs per patient. Overall, 91.6% patients had at least one pDDI; 86.3% were having at least one major pDDI, and 84.5% patients had at least one moderate pDDI. Among 5109 identified pDDIs, most were of moderate (55%) or major severity (45%); established (24.2%), theoretical (18.8%) or probable (57%) type of scientific evidence. Top 10 common pDDIs included 3 major and 7 moderate interactions. Results obtained by multivariate logistic regression revealed a significant association of the occurrence of pDDIs in patient with age of 60 years or more (p Older patients, patients with longer hospital stay and with elevated number of prescribed drugs were at higher risk of pDDIs. PMID:27013915

  14. Significance of classifying antiarrhythmic actions since the cardiac arrhythmia suppression trial.

    Science.gov (United States)

    Vaughan Williams, E M

    1991-02-01

    The Cardiac Antiarrhythmic Suppression Trial (CAST) showed flecainide and encainide induced excess mortality compared with placebo. Labeling drugs as Class 1C is based on clinical observations, comprising measurements of the electrocardiographic parameters QRS. H-V and J-T intervals and of effective refractory period (ERP) as follows: 1--(QRS) wide, 2--(HV) long, 3--(ERP) unchanged, 4--(JT) unchanged. In vitro electrophysiology helped to explain the clinical findings. Flecainide and encainide rendered Na channels as nonconducting, but F and E were only slowly released from the channels after repolarization. At any given drug concentration, a proportion of total channels were eliminated, and the steady-state proportion increased at rising heart rate. It is not proven that the properties that lead to classification of a drug as 1C were those that caused excess deaths in the CAST. The proarrhythmic tendency of 1C drugs can be reduced by beta-blockade, and the mechanisms of adrenergic arrhythmogenicity are discussed. Propafenone is both a 1C drug and a beta-blocker, and its pharmacologic profile is reviewed to illustrate how it resembles and differs from flecainide and encainide. Some features of the CAST are assessed with particular reference to the extent to which conclusions drawn from the results may be justifiably extrapolated to other drugs classified as 1C.

  15. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    Science.gov (United States)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  16. Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult.

    Science.gov (United States)

    Silva, A C; Rodrigues, S C; Caldeira, J; Nunes, A M; Sampaio-Pinto, V; Resende, T P; Oliveira, M J; Barbosa, M A; Thorsteinsdóttir, S; Nascimento, D S; Pinto-do-Ó, P

    2016-10-01

    A main challenge in cardiac tissue engineering is the limited data on microenvironmental cues that sustain survival, proliferation and functional proficiency of cardiac cells. The aim of our study was to evaluate the potential of fetal (E18) and adult myocardial extracellular matrix (ECM) to support cardiac cells. Acellular three-dimensional (3D) bioscaffolds were obtained by parallel decellularization of fetal- and adult-heart explants thereby ensuring reliable comparison. Acellular scaffolds retained main constituents of the cardiac ECM including distinctive biochemical and structural meshwork features of the native equivalents. In vitro, fetal and adult ECM-matrices supported 3D culture of heart-derived Sca-1(+) progenitors and of neonatal cardiomyocytes, which migrated toward the center of the scaffold and displayed elongated morphology and excellent viability. At the culture end-point, more Sca-1(+) cells and cardiomyocytes were found adhered and inside fetal bioscaffolds, compared to the adult. Higher repopulation yields of Sca-1(+) cells on fetal ECM relied on β1-integrin independent mitogenic signals. Sca-1(+) cells on fetal bioscaffolds showed a gene expression profile that anticipates the synthesis of a permissive microenvironment for cardiomyogenesis. Our findings demonstrate the superior potential of the 3D fetal microenvironment to support and instruct cardiac cells. This knowledge should be integrated in the design of next-generation biomimetic materials for heart repair. PMID:27424216

  17. Scaling of the quark-antiquark potential and improved actions in SU(2) lattice gauge theory

    International Nuclear Information System (INIS)

    The scaling behaviour of the quark-antiquark potential is investigated by a high statistics Monte Carlo calculation in SU(2) lattice gauge theory. Besides the standard one-plaquette action we also use Symanzik's tree-level improved action and Wilson's block-spin improved action. No significant differences between Symanzik's action and the standard action have been observed. For small β Wilson's action scales differently. The string tension value chi extracted from the data corresponds to Λsub(latt) = (0.018 +- 0.001) √chi for the one-plaquette action. (orig.)

  18. Circadian- and Light-Dependent Regulation of Resting Membrane Potential and Spontaneous Action Potential Firing of Drosophila Circadian Pacemaker Neurons

    OpenAIRE

    Sheeba, Vasu; Gu, Huaiyu; Sharma, Vijay K.; O'Dowd, Diane K.; Holmes, Todd C.

    2007-01-01

    The ventral lateral neurons (LNvs) of adult Drosophila brain express oscillating clock proteins and regulate circadian behavior. Whole cell current-clamp recordings of large LNvs in freshly dissected Drosophila whole brain preparations reveal two spontaneous activity patterns that correlate with two underlying patterns of oscillating membrane potential: tonic and burst firing of sodium-dependent action potentials. Resting membrane potential and spontaneous action potential firing are rapidly ...

  19. Effects of thallium on membrane currents at diastolic potentials in canine cardiac Purkinje strands.

    Science.gov (United States)

    Cohen, I S; Mulrine, N K

    1986-01-01

    A two-micro-electrode voltage-clamp technique was used to record membrane currents from canine cardiac Purkinje strands during hyperpolarizing steps to potentials between -70 and -150 mV in Tyrode solutions containing K+ and/or Tl+. Complete replacement of external K+ by equimolar Tl+ increases the instantaneous inwardly rectifying current. The inwardly rectifying region of the instantaneous I-V relation is shifted to more positive potentials and its slope is increased. The diastolic time-dependent current is reduced or reversed. Partial substitution of equimolar Tl+ for K+ reduces the diastolic time-dependent current. The instantaneous I-V relation is shifted inward for molar fractions of Tl+ (YTl) greater than 0.5, and is slightly more inward or unchanged for YTl less than or equal to 0.5. Addition of small amounts of Tl+ shifts the instantaneous I-V relation inward and reduces the diastolic time-dependent current. Addition of Tl+ in solutions containing Ba2+ to block the background inward rectifier has no effect on the instantaneous I-V relation; the diastolic time-dependent (pace-maker) current is reduced. Block of the pace-maker current by Tl+ is largely independent of potential in Ba2+ Tyrode solution. Since Tl+ has opposite effects on the pace-maker current and the inward rectifier, these findings support other evidence that the pace-maker current is not part of the background inward rectifier.

  20. Ontogeny of vestibular compound action potentials in the domestic chicken

    Science.gov (United States)

    Jones, S. M.; Jones, T. A.

    2000-01-01

    Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

  1. Distribution of Action Potential Duration and T-wave Morphology: a Simulation Study

    CERN Document Server

    Ryzhii, Elena; Wei, Daming

    2009-01-01

    The results of a simulation study of the action potential duration (APD) distribution and T-wave morphology taking into account the midmyocardial cells (M-cells) concept are described. To investigate the effect of M-cells we present a computer model in which ion channel action potential formulations are incorporated into three-dimensional whole heart model. We implemented inhomogeneous continuous action potential duration distribution based on different distributions of maximal slow delayed rectifier current conductance. Using the proposed action potential distribution procedure midmural zeniths with longest action potential length were created as islands of model cells in the depth of thickest areas of ventricular tissue. Different spatial functions on layer indexes were simulated and their influences on electrocardiogram waveforms were analyzed. Changing parameters of ion channel model we varied duration of minimal and maximal action potential and investigated T-wave amplitude, Q-Tpeak and QT intervals vari...

  2. Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

    Science.gov (United States)

    Rodriguez-Falces, Javier

    2015-01-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

  3. Mathematical Distinction in Action Potential between Primo-Vessels and Smooth Muscle

    OpenAIRE

    Seong-Jin Cho; Sang-Hun Lee; Wenji Zhang; Sae-Bhom Lee; Kwang-Ho Choi; Sun-Mi Choi; Yeon-Hee Ryu

    2012-01-01

    We studied the action potential of Primo-vessels in rats to determine the electrophysiological characteristics of these structures. We introduced a mathematical analysis method, a normalized Fourier transform that displays the sine and cosine components separately, to compare the action potentials of Primo-vessels with those for the smooth muscle. We found that Primo-vessels generated two types of action potential pulses that differed from those of smooth muscle: (1) Type I pulse had rapid de...

  4. Distribution of Action Potential Duration and T-wave Morphology: a Simulation Study

    OpenAIRE

    Ryzhii, Elena; Ryzhii, Maxim; Wei, Daming

    2009-01-01

    The results of a simulation study of the action potential duration (APD) distribution and T-wave morphology taking into account the midmyocardial cells (M-cells) concept are described. To investigate the effect of M-cells we present a computer model in which ion channel action potential formulations are incorporated into three-dimensional whole heart model. We implemented inhomogeneous continuous action potential duration distribution based on different distributions of maximal slow delayed r...

  5. Bortezomib-Induced Complete Heart Block and Myocardial Scar: The Potential Role of Cardiac Biomarkers in Monitoring Cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Sachin Diwadkar

    2016-01-01

    Full Text Available Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. Traditionally, bortezomib was thought to have little cardiovascular toxicity; however, there is increasing evidence that bortezomib can lead to cardiac complications including left ventricular dysfunction and atrioventricular block. We present the case of a 66-year-old man with multiple myeloma and persistent asymptomatic elevations of cardiac biomarkers who developed complete heart block and evidence of myocardial scar after his eighth cycle of bortezomib, requiring permanent pacemaker placement. In addition to discussing the cardiovascular complications of bortezomib therapy, we propose a potential role for biomarkers in the prediction and monitoring of bortezomib cardiotoxicity.

  6. Consumer-Related Food Waste: Causes and Potential for Action

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Hooge, Ilona de; Amani, Pegah;

    2015-01-01

    interviews on factors causing consumer-related food waste in households and supply chains. Results show that consumers’ motivation to avoid food waste, their management skills of food provisioning and food handling and their trade-offs between priorities have an extensive influence on their food waste...... behaviors. We identify actions that governments, societal stakeholders and retailers can undertake to reduce consumer-related food waste, highlighting that synergistic actions between all parties are most promising. Further research should focus on exploring specific food waste contexts and interactions...

  7. Effect of a prenylamine analog (MG8926) on spontaneous action potentials in isolated rabbit sinoatrial node.

    Science.gov (United States)

    Nakanishi, H; Matsuoka, I; Ono, T; Yoshida, H; Uchibori, T; Kogi, K

    1996-12-01

    Effects of verapamil, prenylamine and a prenylamine analog, MG8926 on the intracellular spontaneous action potentials recorded from the isolated rabbit sinoatrial (SA) node were studied. Verapamil (1 microM), a selective inhibitor for slow Ca2+ channels, prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential, the amplitude of action potential and the maximal diastolic potential, and usually arrested showing subthreshold fluctuation of the membrane potential within several ten min. Prenylamine (10 microM), a nonselective inhibitor for slow Ca2+ channels, tended to prolong the cycle length to decrease the diastolic depolarization, the rate of rise of action potential, the amplitude of action potential. However, these changes were statistically insignificant. Prenylamine at the concentration of 10 microM had no effect on the maximal diastolic potential. MG8926 (10 microM) prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential and tended to decrease the amplitude of action potential. MG8926 at the concentration of 10 microM had almost no effect on the maximal diastolic potential. The present findings may indicate that replacement of phenyl residue of prenylamine by cyclohexyl residue increases the inhibitory action on the slow Ca2+ channels in rabbit SA node.

  8. Mechanisms of action and potential therapeutic uses of thalidomide.

    Science.gov (United States)

    Mujagić, Hamza; Chabner, Bruce A; Mujagić, Zlata

    2002-06-01

    Thalidomide was first introduced to the market in Germany under the brand name of Contergan in 1956, as a non-barbiturate hypnotic, advocated to ensure a good nights sleep and to prevent morning sickness in pregnancy. It was advertised for its prompt action, lack of hangover, and apparent safety. It has been banned from the market since 1963 after it caused the worldwide teratogenic disaster: babies exposed to thalidomide in utero during the first 34-50 days of pregnancy were born with severe life-threatening birth defects. Despite its unfortunate history, thalidomide has attracted scientific interest again because of its recently discovered action against inflammatory diseases and cancer. Its broad range of biological activities stems from its ability to moderate cytokine action in cancer and inflammatory diseases. Early studies examined its anxiolytic, mild hypnotic, antiemetic, and adjuvant analgesic properties. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy, being superior to Aspirin in controlling leprosy-associated fever. Recent research has shown promising results with thalidomide in patients with myeloma, myelodysplastic syndrome, a variety of infectious diseases, autoimmune diseases, cancer, and progressive body weight loss related to advanced cancer and AIDS. Here we review the history of its development, pharmacokinetics, metabolism, biologic effects, and the results of clinical trials conducted thus far. Further research in this field should be directed towards better understanding of thalidomide metabolism, its mechanism of action, and the development of less toxic and more active analogs. PMID:12035132

  9. Assessment of potential drug–drug interactions and its associated factors in the hospitalized cardiac patients

    Directory of Open Access Journals (Sweden)

    Ghulam Murtaza

    2016-03-01

    Full Text Available Drug–drug interactions (DDIs may result in the alteration of therapeutic response. Sometimes they may increase the untoward effects of many drugs. Hospitalized cardiac patients need more attention regarding drug–drug interactions due to complexity of their disease and therapeutic regimen. This research was performed to find out types, prevalence and association between various predictors of potential drug–drug interactions (pDDIs in the Department of Cardiology and to report common interactions. This study was performed in the hospitalized cardiac patients at Ayub Teaching Hospital, Abbottabad, Pakistan. Patient charts of 2342 patients were assessed for pDDIs using Micromedex® Drug Information. Logistic regression was applied to find predictors of pDDIs. The main outcome measure in the study was the association of the potential drug–drug interactions with various factors such as age, gender, polypharmacy, and hospital stay of the patients. We identified 53 interacting-combinations that were present in total 5109 pDDIs with median number of 02 pDDIs per patient. Overall, 91.6% patients had at least one pDDI; 86.3% were having at least one major pDDI, and 84.5% patients had at least one moderate pDDI. Among 5109 identified pDDIs, most were of moderate (55% or major severity (45%; established (24.2%, theoretical (18.8% or probable (57% type of scientific evidence. Top 10 common pDDIs included 3 major and 7 moderate interactions. Results obtained by multivariate logistic regression revealed a significant association of the occurrence of pDDIs in patient with age of 60 years or more (p < 0.001, hospital stay of 7 days or longer (p < 0.001 and taking 7 or more drugs (p < 0.001. We found a high prevalence for pDDIs in the Department of Cardiology, most of which were of moderate severity. Older patients, patients with longer hospital stay and with elevated number of prescribed drugs were at higher risk of pDDIs.

  10. Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery.

    Directory of Open Access Journals (Sweden)

    Costanza Emanueli

    Full Text Available Exosome nanoparticles carry a composite cargo, including microRNAs (miRs. Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG surgery, we investigated if: 1 exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2 circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn, the current "gold standard" surrogate biomarker of myocardial damage.The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210, non-cardiovascular (miR-122 and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

  11. On the excitation of action potentials by protons and its potential implications for cholinergic transmission

    CERN Document Server

    Fillafer, Christian

    2014-01-01

    One of the most conserved mechanisms for transmission of a nerve pulse across a synapse relies on acetylcholine. Ever since the Nobel-prize winning works of Dale and Loewi, it has been assumed that acetylcholine - subsequent to its action on a postsynaptic cell - is split into inactive by-products by acetylcholinesterase. Herein, this widespread assumption is falsified. Excitable cells (Chara australis internodes), which had previously been unresponsive to acetylcholine, became acetylcholine-sensitive in presence of acetylcholinesterase. The latter was evidenced by a striking difference in cell membrane depolarisation upon exposure to 10 mM intact acetylcholine (deltaV=-2plus/minus5 mV) and its hydrolysate respectively (deltaV=81plus/minus19 mV) for 60 sec. This pronounced depolarization, which also triggered action potentials, was clearly attributed to one of the hydrolysis products: acetic acid (deltaV=87plus/minus9 mV at pH 4.0; choline ineffective in range 1-10 mM). In agreement with our findings, numerou...

  12. Potential involvement of serotonergic signaling in ketamine's antidepressant actions

    DEFF Research Database (Denmark)

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina;

    2016-01-01

    A single i.v. infusion of ketamine, classified as an N-methyl-D-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic...... properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5......-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms...

  13. Heterogeneity in SDF-1 expression defines the vasculogenic potential of adult cardiac progenitor cells.

    Directory of Open Access Journals (Sweden)

    Claudia O Rodrigues

    Full Text Available RATIONALE: The adult myocardium has been reported to harbor several classes of multipotent progenitor cells (CPCs with tri-lineage differentiation potential. It is not clear whether c-kit+CPCs represent a uniform precursor population or a more complex mixture of cell types. OBJECTIVE: To characterize and understand vasculogenic heterogeneity within c-kit+presumptive cardiac progenitor cell populations. METHODS AND RESULTS: c-kit+, sca-1+ CPCs obtained from adult mouse left ventricle expressed stem cell-associated genes, including Oct-4 and Myc, and were self-renewing, pluripotent and clonogenic. Detailed single cell clonal analysis of 17 clones revealed that most (14/17 exhibited trilineage differentiation potential. However, striking morphological differences were observed among clones that were heritable and stable in long-term culture. 3 major groups were identified: round (7/17, flat or spindle-shaped (5/17 and stellate (5/17. Stellate morphology was predictive of vasculogenic differentiation in Matrigel. Genome-wide expression studies and bioinformatic analysis revealed clonally stable, heritable differences in stromal cell-derived factor-1 (SDF-1 expression that correlated strongly with stellate morphology and vasculogenic capacity. Endogenous SDF-1 production contributed directly to vasculogenic differentiation: both shRNA-mediated knockdown of SDF-1 and AMD3100, an antagonist of the SDF-1 receptor CXC chemokine Receptor-4 (CXCR4, reduced tube-forming capacity, while exogenous SDF-1 induced tube formation by 2 non-vasculogenic clones. CPCs producing SDF-1 were able to vascularize Matrigel dermal implants in vivo, while CPCs with low SDF-1 production were not. CONCLUSIONS: Clonogenic c-kit+, sca-1+ CPCs are heterogeneous in morphology, gene expression patterns and differentiation potential. Clone-specific levels of SDF-1 expression both predict and promote development of a vasculogenic phenotype via a previously unreported autocrine

  14. Making Class Actions Work: The Untapped Potential of the Internet

    Directory of Open Access Journals (Sweden)

    Robert H. Klonoff

    2008-04-01

    Full Text Available Over twenty years ago, the Supreme Court recognized that in class action litigation, absent class members “must receive notice plus an opportunity to be heard and participate in the litigation, whether in person or through counsel.” Although the absent class members’ rights to receive notice and an opportunity to opt out are of vital importance, the ability to be heard and participate in the litigation are also important.

  15. Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

    Directory of Open Access Journals (Sweden)

    Fabián Muñoz

    Full Text Available Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

  16. Fibroblast growth factor homologous factors in the heart: a potential locus for cardiac arrhythmias.

    Science.gov (United States)

    Wei, Eric Q; Barnett, Adam S; Pitt, Geoffrey S; Hennessey, Jessica A

    2011-10-01

    The four fibroblast growth factor homologous factors (FHFs; FGF11-FGF14) are intracellular proteins that bind and modulate voltage-gated sodium channels (VGSCs). Although FHFs have been well studied in neurons and implicated in neurologic disease, their role in cardiomyocytes was unclear until recently. This review discusses the expression profile and function of FHFs in mouse and rat ventricular cardiomyocytes. Recent data show that FGF13 is the predominant FHF in the murine heart, directly binds the cardiac VGSC α subunit, and is essential for normal cardiac conduction. FHF loss-of-function mutations may be unrecognized causes of cardiac arrhythmias, such as long QT and Brugada syndromes.

  17. Sodium Channel (Dys)Function and Cardiac Arrhythmias

    NARCIS (Netherlands)

    C.A. Remme; C.R. Bezzina

    2010-01-01

    P>Cardiac voltage-gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation an

  18. Analysis of toxin induced changes in action potential shape for drug development

    OpenAIRE

    Akanda, Nesar; Molnar, Peter; Stancescu, Maria; Hickman, James J.

    2009-01-01

    The generation of an action potential is a complex process in excitable cells which involves the temporal opening and closing of several voltage-dependent ion channels in the cell membrane. The shape of an action potential can carry information concerning the state of the involved ion channels and their relationship to cellular processes. Alteration of these ion channels by the administration of toxins, drugs, and biochemicals can change the action potential’s shape in a specific way which ca...

  19. Consumer-Related Food Waste: Causes and Potential for Action

    Directory of Open Access Journals (Sweden)

    Jessica Aschemann-Witzel

    2015-05-01

    Full Text Available In the past decade, food waste has received increased attention on both academic and societal levels. As a cause of negative economic, environmental and social effects, food waste is considered to be one of the sustainability issues that needs to be addressed. In developed countries, consumers are one of the biggest sources of food waste. To successfully reduce consumer-related food waste, it is necessary to have a clear understanding of the factors influencing food waste-related consumer perceptions and behaviors. The present paper presents the results of a literature review and expert interviews on factors causing consumer-related food waste in households and supply chains. Results show that consumers’ motivation to avoid food waste, their management skills of food provisioning and food handling and their trade-offs between priorities have an extensive influence on their food waste behaviors. We identify actions that governments, societal stakeholders and retailers can undertake to reduce consumer-related food waste, highlighting that synergistic actions between all parties are most promising. Further research should focus on exploring specific food waste contexts and interactions more in-depth. Experiments and interventions in particular can contribute to a shift from analysis to solutions.

  20. Time-Dependent Action in φ~6 Potential

    Institute of Scientific and Technical Information of China (English)

    Hatem Widyan; Mashhoor Al-Wardat

    2012-01-01

    The false vacuum decay in field theory from a coherently oscillating initial state is studied for φ6 potential. An oscillating bubble solution is obtained. The instantaneous bubble nucleation rate is calculated.

  1. Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

    OpenAIRE

    Connors, S. P.; Gill, E. W.; Terrar, D. A.

    1992-01-01

    1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the s...

  2. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

    Energy Technology Data Exchange (ETDEWEB)

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj [Department of Physiology, University of Tübingen, Tübingen (Germany); Schönberger, Tanja [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Noegel, Angelika A. [Center for Biochemistry, Institute of Biochemistry I, University of Cologne, Köln (Germany); Gawaz, Meinrad [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology, University of Tübingen, Tübingen (Germany)

    2014-02-28

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca{sup 2+} signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7{sup −/−}) and wild-type mice (anxa7{sup +/+}) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7{sup −/−} mice than in anxa7{sup +/+} mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions.

  3. A model for thermal exchange in axons during action potential propagation.

    OpenAIRE

    Masson, Jean-Baptiste; Gallot, Guilhem

    2008-01-01

    International audience Several experiments have shown that during propagation of the action potential in axons, thermal energy is locally exchanged. In this paper, we use a simple model based on statistical physics to show that an important part of this exchange comes from the physics of the effusion. We evaluate, during the action potential propagation, the variation of internal energy and of the energy associated with the chemical potential of the effusion of water and ions to extract th...

  4. Potential synergy of phytochemicals in cancer prevention: mechanism of action.

    Science.gov (United States)

    Liu, Rui Hai

    2004-12-01

    Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer and cardiovascular disease. It is now widely believed that the actions of the antioxidant nutrients alone do not explain the observed health benefits of diets rich in fruits and vegetables, because taken alone, the individual antioxidants studied in clinical trials do not appear to have consistent preventive effects. Work performed by our group and others has shown that fruits and vegetable phytochemical extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. We proposed that the additive and synergistic effects of phytochemicals in fruits and vegetables are responsible for these potent antioxidant and anticancer activities and that the benefit of a diet rich in fruits and vegetables is attributed to the complex mixture of phytochemicals present in whole foods. This explains why no single antioxidant can replace the combination of natural phytochemicals in fruits and vegetables to achieve the health benefits. The evidence suggests that antioxidants or bioactive compounds are best acquired through whole-food consumption, not from expensive dietary supplements. We believe that a recommendation that consumers eat 5 to 10 servings of a wide variety of fruits and vegetables daily is an appropriate strategy for significantly reducing the risk of chronic diseases and to meet their nutrient requirements for optimum health.

  5. Cardiac Adipose-Derived Stem Cells Exhibit High Differentiation Potential to Cardiovascular Cells in C57BL/6 Mice.

    Science.gov (United States)

    Nagata, Hiroki; Ii, Masaaki; Kohbayashi, Eiko; Hoshiga, Masaaki; Hanafusa, Toshiaki; Asahi, Michio

    2016-02-01

    Adipose-derived stem cells (AdSCs) have recently been shown to differentiate into cardiovascular lineage cells. However, little is known about the fat tissue origin-dependent differences in AdSC function and differentiation potential. AdSC-rich cells were isolated from subcutaneous, visceral, cardiac (CA), and subscapular adipose tissue from mice and their characteristics analyzed. After four different AdSC types were cultured with specific differentiation medium, immunocytochemical analysis was performed for the assessment of differentiation into cardiovascular cells. We then examined the in vitro differentiation capacity and therapeutic potential of AdSCs in ischemic myocardium using a mouse myocardial infarction model. The cell density and proliferation activity of CA-derived AdSCs were significantly increased compared with the other adipose tissue-derived AdSCs. Immunocytochemistry showed that CA-derived AdSCs had the highest appearance rates of markers for endothelial cells, vascular smooth muscle cells, and cardiomyocytes among the AdSCs. Systemic transfusion of CA-derived AdSCs exhibited the highest cardiac functional recovery after myocardial infarction and the high frequency of the recruitment to ischemic myocardium. Moreover, long-term follow-up of the recruited CA-derived AdSCs frequently expressed cardiovascular cell markers compared with the other adipose tissue-derived AdSCs. Cardiac adipose tissue could be an ideal source for isolation of therapeutically effective AdSCs for cardiac regeneration in ischemic heart diseases. Significance: The present study found that cardiac adipose-derived stem cells have a high potential to differentiate into cardiovascular lineage cells (i.e., cardiomyocytes, endothelial cells, and vascular smooth muscle cells) compared with stem cells derived from other adipose tissue such as subcutaneous, visceral, and subscapular adipose tissue. Notably, only a small number of supracardiac adipose-derived stem cells that were

  6. LMI1195 PET imaging in evaluation of regional cardiac sympathetic denervation and its potential role in antiarrhythmic drug treatment

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Ming; Bozek, Jody; Lamoy, Melanie; Kagan, Mikhail; Benites, Pedro; Onthank, David; Robinson, Simon P. [Lantheus Medical Imaging, Discovery Research, N. Billerica, MA (United States)

    2012-12-15

    Regional cardiac sympathetic denervation (RCSD) associated with reduced noradrenaline transporter (NAT) function has been linked to cardiac arrhythmia. This study examined the association of LMI1195, an {sup 18}F-labeled NAT substrate developed for positron emission tomography (PET) imaging, with NAT in vitro, and its imaging to detect RCSD and guide antiarrhythmic drug treatment in vivo. LMI1195 association with NAT was assessed in comparison with other substrates, noradrenaline (NA) and {sup 123}I-metaiodobenzylguanidine (MIBG), in NAT-expressing cells. LMI1195 cardiac imaging was performed for evaluation of RCSD in a rabbit model surgically developed by regional phenol application on the left ventricular (LV) wall. The normal LV areas in images were quantified as regions with radioactivity {>=}50 % maximum. Potential impact of RCSD on dofetilide, an antiarrhythmic drug, induced ECG changes was assessed. NAT blockade with desipramine reduced LMI1195 cell uptake by 90 {+-} 3 %, similar to NA and MIBG. NA, MIBG, or self inhibited LMI1195 cell uptake concentration-dependently with comparable IC{sub 50} values (1.09, 0.21, and 0.90 {mu}M). LMI1195 cardiac imaging differentiated innervated and denervated areas in RCSD rabbits. The surgery resulted in a large denervated LV area at 2 weeks which was partially recovered at 12 weeks. Myocardial perfusion imaging with flurpiridaz F 18 showed normal perfusion in RCSD areas. Dofetilide induced more prominent QTc prolongation in RCSD than control animals. However, changes in heart rate were comparable. LMI1195 exhibits high association with NAT and can be used for imaging RCSD. The detected RCSD increases cardiac risks to the antiarrhythmic drug, dofetilide, by inducing more QTc prolongation. (orig.)

  7. Cardiac effects of vasopressin.

    Science.gov (United States)

    Pelletier, Jean-Sébastien; Dicken, Bryan; Bigam, David; Cheung, Po-Yin

    2014-07-01

    Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although difficult to separate from its powerful vascular effects in the clinical setting, a better understanding of vasopressin's direct cardiac effects could lead to its more effective clinical use for a variety of shock states by maximizing its therapeutic benefit. The cardiac-specific effects of vasopressin are complex and require further elucidation. Complicating our understanding include the various receptors and secondary messengers involved in vasopressin's effects, which may lead to various results based on differing doses and varying environmental conditions. Thus, there have been contradictory reports on vasopressin's action on the coronary vasculature and on its effect on inotropy. However, beneficial results have been found and warrant further study to expand the potential therapeutic role of vasopressin. This review outlines the effect of vasopressin on the coronary vasculature, cardiac contractility, and on hypertrophy and cardioprotection. These cardiac-specific effects of vasopressin represent an interesting area for further study for potentially important therapeutic benefits. PMID:24621650

  8. Neuronal oscillations enhance stimulus discrimination by ensuring action potential precision

    DEFF Research Database (Denmark)

    Schaefer, Andreas T; Angelo, Kamilla; Spors, Hartwig;

    2006-01-01

    Although oscillations in membrane potential are a prominent feature of sensory, motor, and cognitive function, their precise role in signal processing remains elusive. Here we show, using a combination of in vivo, in vitro, and theoretical approaches, that both synaptically and intrinsically......--permitted accurate discernment of up to 1,000 different stimuli. At low oscillation frequencies, stimulus discrimination showed a clear phase dependence whereby inputs arriving during the trough and the early rising phase of an oscillation cycle were most robustly discriminated. Thus, by ensuring AP precision...

  9. Consequences of converting graded to action potentials upon neural information coding and energy efficiency.

    Science.gov (United States)

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na(+) and K(+) channels, with generator potential and graded potential models lacking voltage-gated Na(+) channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na(+) channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a 'footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation.

  10. More evidence for a refined Gribov-Zwanziger action based on an effective potential approach

    OpenAIRE

    Vandersickel, N.; Dudal, D.; Sorella, S.P.

    2011-01-01

    The purpose of this proceeding is twofold. Firstly, we shall make the refining of the Gribov-Zwanziger action more complete by taking into account more condensates than considered so far. Secondly, we shall provide more evidence for the refined Gribov-Zwanziger action based on an effective potential approach.

  11. Action potential detection by non-linear microscopy

    Science.gov (United States)

    Sacconi, Leonardo; Lotti, Jacopo; O'Connor, Rodney P.; Mapelli, Jonathan; Gandolfi, Daniela; D'Angelo, Egidio; Pavone, Francesco S.

    2009-02-01

    In this work, we combined the advantages of second-harmonic generation (SHG) with a random access (RA) excitation scheme to realize a new microscope (RA-SHG) capable of optically recording fast membrane potential events occurring in a wide-field configuration. The RA-SHG microscope in combination with a bulk staining method with FM4-64 was used to simultaneously record electrical activity from clusters of Purkinje cells (PCs) in acute cerebellar slices. Spontaneous electrical activity was also monitored simultaneously in pairs of neurons, where APs were recorded in a single trial without averaging. These results show the strength of this technique to describe the temporal dynamics of neuronal assemblies.

  12. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid...

  13. Spatial and frequency domain ring source models for the single muscle fiber action potential

    DEFF Research Database (Denmark)

    Henneberg, Kaj-åge; R., Plonsey

    1994-01-01

    In the paper, single-fibre models for the extracellular action potential are developed that will allow the potential to the evaluated at an arbitrary field point in the extracellular space. Fourier-domain models are restricted in that they evaluate potentials at equidistant points along a line...

  14. Control of Secretion by Encodes of Action Potentials in Neuronal Cells

    Institute of Scientific and Technical Information of China (English)

    Kailai Duan; Zhuan Zhou

    2003-01-01

    @@ Action potentials (APs) are principle physiological stimuli of neurotransmitter secretion or synaptic transmis sion. Most studies on stimulus-secretion-coupling have been performed under voltage clamp using artificial electric stimulations.

  15. Culture conditions affect cardiac differentiation potential of human pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Marisa Ojala

    Full Text Available Human pluripotent stem cells (hPSCs, including human embryonic stem cells (hESCs and human induced pluripotent stem cells (hiPSCs, are capable of differentiating into any cell type in the human body and thus can be used in studies of early human development, as cell models for different diseases and eventually also in regenerative medicine applications. Since the first derivation of hESCs in 1998, a variety of culture conditions have been described for the undifferentiated growth of hPSCs. In this study, we cultured both hESCs and hiPSCs in three different culture conditions: on mouse embryonic fibroblast (MEF and SNL feeder cell layers together with conventional stem cell culture medium containing knockout serum replacement and basic fibroblast growth factor (bFGF, as well as on a Matrigel matrix in mTeSR1 medium. hPSC lines were subjected to cardiac differentiation in mouse visceral endodermal-like (END-2 co-cultures and the cardiac differentiation efficiency was determined by counting both the beating areas and Troponin T positive cells, as well as studying the expression of OCT-3/4, mesodermal Brachyury T and NKX2.5 and endodermal SOX-17 at various time points during END-2 differentiation by q-RT-PCR analysis. The most efficient cardiac differentiation was observed with hPSCs cultured on MEF or SNL feeder cell layers in stem cell culture medium and the least efficient cardiac differentiation was observed on a Matrigel matrix in mTeSR1 medium. Further, hPSCs cultured on a Matrigel matrix in mTeSR1 medium were found to be more committed to neural lineage than hPSCs cultured on MEF or SNL feeder cell layers. In conclusion, culture conditions have a major impact on the propensity of the hPSCs to differentiate into a cardiac lineage.

  16. Cardiac Electrophysiology Laboratories: A Potential Target for Antimicrobial Stewardship and Quality Improvement?

    Science.gov (United States)

    Branch-Elliman, Westyn; Stanislawski, Maggie; Strymish, Judith; Barón, Anna E; Gupta, Kalpana; Varosy, Paul D; Gold, Howard S; Ho, P Michael

    2016-09-01

    following cardiac device interventions may be a potential target for quality improvement programs and antimicrobial stewardship. Infect Control Hosp Epidemiol 2016;37:1005-1011. PMID:27322021

  17. Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

    OpenAIRE

    Fabián Muñoz; Pablo Fuentealba

    2012-01-01

    Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the th...

  18. Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics

    OpenAIRE

    Yu, Yuguo; Shu, Yousheng; McCormick, David A.

    2008-01-01

    Neocortical action potential responses in vivo are characterized by considerable threshold variability, and thus timing and rate variability, even under seemingly identical conditions. This finding suggests that cortical ensembles are required for accurate sensorimotor integration and processing. Intracellularly, trial-to-trial variability results not only from variation in synaptic activities, but also in the transformation of these into patterns of action potentials. Through simultaneous ax...

  19. NeuroGrid: recording action potentials from the surface of the brain

    OpenAIRE

    Khodagholy, Dion; Gelinas, Jennifer N.; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G.; Buzsáki, György

    2014-01-01

    Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) that can record both LFP and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneous...

  20. Detection of Variability of the Motor Unit Action Potential Shape by Means of the Firing Patterns

    DEFF Research Database (Denmark)

    Krarup, Christian; Nikolic, Mile; Dahl, Kristian;

    1997-01-01

    The motor unit action potential is a summation of the potentials of the individual muscle fibers from the same motor unit.By using a newly developed automatic EMG decomposition system, variability of the firing patterns of the muscle fibers are analyzed.......The motor unit action potential is a summation of the potentials of the individual muscle fibers from the same motor unit.By using a newly developed automatic EMG decomposition system, variability of the firing patterns of the muscle fibers are analyzed....

  1. Distinct electrophysiological potentials for intention in action and prior intention for action

    DEFF Research Database (Denmark)

    Vinding, Mikkel C; Jensen, Mads; Overgaard, Morten

    2014-01-01

    The role of conscious intention in relation to motoric movements has become a major topic of investigation in neuroscience. Traditionally, reports of conscious intention have been compared to various features of the readiness-potential (RP) – an electrophysiological signal that appears before...... voluntary movements. Experiments, however, tend to study intentions in immediate relation to movements (proximal intentions), thus ignoring other aspects of intentions such as planning or deciding in advance of movement (distal intentions). The current study examines the difference in electrophysiological...... activity between proximal intention and distal intention, using electroencephalography (EEG). Participants had to form an intention to move and then wait 2.5 sec before performing the actual movement. In this way, the electrophysiological activity related to forming a conscious intention was separated from...

  2. Preparation and evaluation of technetium-99m labeled cardiac glycoside derivatives as potential myocardial imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Misra, Mridula; Sarkar, H.S.; Chatterjee, Mita; Banerjee, Somenath

    1988-01-01

    Three cardiac glycosides, two natural, cymarin and convallotoxin and one synthetic, strophanthidin-..beta..-D-glucoside were converted to their thiosemicarbazone and subsequently radiolabeled with sup(99m)Tc by chelation. The resulting radioactive chelate complexes were evaluated in animals to determine the suitability of this class of compounds for myocardial imaging. It was observed from the animal biodistribution data of the three radioactive compounds that there was a considerable variation in the heart to non-target organ uptake ratio. A possible explanation of this variation was offered in the light of their lipophilic character, protein binding ability and affinity towards non-target receptors. It is anticipated that this study may help to develop a sup(99m)Tc-cardiac glycoside complex with better distribution characteristics, and such a compound may offer a suitable alternative to /sup 201/Tl, which is at present used for myocardial imaging.

  3. Controlled delivery of sonic hedgehog morphogen and its potential for cardiac repair.

    Directory of Open Access Journals (Sweden)

    Noah Ray Johnson

    Full Text Available The morphogen Sonic hedgehog (Shh holds great promise for repair or regeneration of tissues suffering ischemic injury, however clinical translation is limited by its short half-life in the body. Here, we describe a coacervate delivery system which incorporates Shh, protects it from degradation, and sustains its release for at least 3 weeks. Shh released from the coacervate stimulates cardiac fibroblasts to upregulate the expression of multiple trophic factors including VEGF, SDF-1α, IGF-1, and Shh itself, for at least 48 hours. Shh coacervate also demonstrates cytoprotective effects for cardiomyocytes in a hydrogen peroxide-induced oxidative stress environment. In each of these studies the bioactivity of the Shh coacervate is enhanced compared to free Shh. These results warrant further investigation of the in vivo efficacy of Shh coacervate for cardiac repair.

  4. Controlled delivery of sonic hedgehog morphogen and its potential for cardiac repair.

    Science.gov (United States)

    Johnson, Noah Ray; Wang, Yadong

    2013-01-01

    The morphogen Sonic hedgehog (Shh) holds great promise for repair or regeneration of tissues suffering ischemic injury, however clinical translation is limited by its short half-life in the body. Here, we describe a coacervate delivery system which incorporates Shh, protects it from degradation, and sustains its release for at least 3 weeks. Shh released from the coacervate stimulates cardiac fibroblasts to upregulate the expression of multiple trophic factors including VEGF, SDF-1α, IGF-1, and Shh itself, for at least 48 hours. Shh coacervate also demonstrates cytoprotective effects for cardiomyocytes in a hydrogen peroxide-induced oxidative stress environment. In each of these studies the bioactivity of the Shh coacervate is enhanced compared to free Shh. These results warrant further investigation of the in vivo efficacy of Shh coacervate for cardiac repair.

  5. Design of a Pulsatile Flow Facility to Evaluate Thrombogenic Potential of Implantable Cardiac Devices

    OpenAIRE

    Arjunon, Sivakkumar; Ardana, Pablo Hidalgo; Saikrishnan, Neelakantan; Madhani, Shalv; Foster, Brent; Glezer, Ari; Yoganathan, Ajit P.

    2015-01-01

    Due to expensive nature of clinical trials, implantable cardiac devices should first be extensively characterized in vitro. Prosthetic heart valves (PHVs), an important class of these devices, have been shown to be associated with thromboembolic complications. Although various in vitro systems have been designed to quantify blood-cell damage and platelet activation caused by nonphysiological hemodynamic shear stresses in these PHVs, very few systems attempt to characterize both blood damage a...

  6. Copper deficiency: A potential model for determining the role of mitochondria in cardiac aging

    OpenAIRE

    Johnson, W. Thomas; Newman, Samuel M.

    2003-01-01

    Heart mitochondria experience age-related declines in cytochrome c oxidase (CCO) activity and increases in the generation of reactive oxygen species (ROS) that may contribute to loss of cardiac function and the development of disease that occur with advancing age. In a manner similar to aging, copper deficiency also suppresses heart CCO activity and has cardiovascular consequences related to increased peroxidation. Food restriction is often used as a tool to study oxidative mechanisms of agin...

  7. Cardiac MRI of ischemic heart disease at 3 T: Potential and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Wieben, Oliver [Department of Radiology, University of Wisconsin, Madison, WI 53792-3252 (United States); Department of Medical Physics, University of Wisconsin, Madison, WI 53792-3252 (United States)], E-mail: owieben@wisc.edu; Francois, Christopher [Department of Radiology, University of Wisconsin, Madison, WI 53792-3252 (United States)], E-mail: cfrancois@uwhealth.org; Reeder, Scott B. [Department of Radiology, University of Wisconsin, Madison, WI 53792-3252 (United States); Department of Medical Physics, University of Wisconsin, Madison, WI 53792-3252 (United States); Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53792-3252 (United States); Department of Medicine, University of Wisconsin, Madison, WI 53792-3252 (United States)], E-mail: sreeder@wisc.edu

    2008-01-15

    Cardiac MRI has become a routinely used imaging modality in the diagnosis of cardiovascular disease and is considered the clinically accepted gold standard modality for the assessment of cardiac function and myocardial viability. In recent years, commercially available clinical scanners with a higher magnetic field strength (3.0 T) and dedicated multi-element coils have become available. The superior signal-to-noise ratio (SNR) of these systems has lead to their rapid acceptance in cranial and musculoskeletal MRI while the adoption of 3.0 T for cardiovascular imaging has been somewhat slower. This review article describes the benefits and pitfalls of magnetic resonance imaging of ischemic heart disease at higher field strengths. The fundamental changes in parameters such as SNR, transversal and longitudinal relaxation times, susceptibility artifacts, RF (B{sub 1}) inhomogeneity, and specific absorption rate are discussed. We also review approaches to avoid compromised image quality such as banding artifacts and inconsistent or suboptimal flip angles. Imaging sequences for the assessment of cardiac function with CINE balanced SSFP imaging and MR tagging, myocardial perfusion, and delayed enhancement and their adjustments for higher field imaging are explained in detail along with several clinical examples. We also explore the use of parallel imaging at 3.0 T to improve cardiac imaging by trading the SNR gain for higher field strengths for acquisition speed with increased coverage or improved spatial and temporal resolution. This approach is particularly useful for dynamic applications that are usually limited to the duration of a single breath-hold.

  8. FGF21 and cardiac physiopathology

    Directory of Open Access Journals (Sweden)

    Anna ePlanavila

    2015-08-01

    Full Text Available The heart is not traditionally considered either a target or a site of fibroblast growth factor-21 (FGF21 production. However, recent findings indicate that FGF21 can act as a cardiomyokine; that is, it is produced by cardiac cells at significant levels and acts in an autocrine manner on the heart itself. The heart is sensitive to the effects of FGF21, both systemic and locally generated, owing to the expression in cardiomyocytes of β-Klotho, the key co-receptor known to confer specific responsiveness to FGF21 action. FGF21 has been demonstrated to protect against cardiac hypertrophy, cardiac inflammation, and oxidative stress. FGF21 expression in the heart is induced in response to cardiac insults, such as experimental cardiac hypertrophy and myocardial infarction in rodents, as well as in failing human hearts. Intracellular mechanisms involving PPARα and Sirt1 mediate transcriptional regulation of the FGF21 gene in response to exogenous stimuli. In humans, circulating FGF21 levels are elevated in coronary heart disease and atherosclerosis, and are associated with a higher risk of cardiovascular events in patients with type 2 diabetes. These findings provide new insights into the role of FGF21 in the heart and may offer potential therapeutic strategies for cardiac disease.

  9. 76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

    Science.gov (United States)

    2011-04-19

    ... Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and... Administration (FAA), Department of Transportation (DOT). ACTION: Notice of availability of a final EA and FONSI/ROD for the evaluation of the potential environmental impacts associated with the proposed Runway...

  10. Perturbation analysis of spontaneous action potential initiation by stochastic ion channels

    KAUST Repository

    Keener, James P.

    2011-07-01

    A stochastic interpretation of spontaneous action potential initiation is developed for the Morris-Lecar equations. Initiation of a spontaneous action potential can be interpreted as the escape from one of the wells of a double well potential, and we develop an asymptotic approximation of the mean exit time using a recently developed quasistationary perturbation method. Using the fact that the activating ionic channel\\'s random openings and closings are fast relative to other processes, we derive an accurate estimate for the mean time to fire an action potential (MFT), which is valid for a below-threshold applied current. Previous studies have found that for above-threshold applied current, where there is only a single stable fixed point, a diffusion approximation can be used. We also explore why different diffusion approximation techniques fail to estimate the MFT. © 2011 American Physical Society.

  11. Cardiac MRI. Diagnostic gain of an additional axial SSFP chest sequence for the detection of potentially significant extracardiac findings in the cardiac MRI examination setting

    Energy Technology Data Exchange (ETDEWEB)

    Roller, F.C.; Schneider, C.; Krombach, G.A. [University Hospital Giessen (Germany). Dept. Radiology; Schuhbaeck, A. [University Hospital Giessen (Germany). Dept. Cardiology; Rolf, A. [Kerckhoff Hospital Bad Nauheim (Germany). Dept. Cardiology

    2014-01-15

    Purpose: Cardiac MRI (CMRI) is an effective method for imaging of the heart. The aim of our study was to assess whether an axial chest sequence in addition to the standard CMR examination setting has advantages in the detection of potentially significant extracardiac findings (PSEF). Materials and Methods: 400 consecutive patients were imaged at 1.5 T for clinical reasons. In addition to the standard long and short-axis views, an axial SSFP sequence was obtained covering the thorax from the lung apex to the diaphragm. All sequences were separately evaluated for PSEF. Results: A total of 25 PSEF were diagnosed in 400 patients, including 16 pleural effusions, a pulmonary fibrosis, a spondylodiscitis, ascites, lymphadenopathies, relapse of a mamma carcinoma, growth of adrenal glands metastases and diaphragmatic elevation. All 25 PSEF were detected by reading survey sequences. 24 of the 25 PSEF were detected by the additional SSFP chest sequence as well as the CINE sequences. Conclusion: In our study the additional axial SSFP chest sequence didn't show a benefit in the detection of PSEF. With the survey sequences we were able to detect all PSEF. We conclude that survey images should be assessed for additional findings. (orig.)

  12. Sodium and calcium currents shape action potentials in immature mouse inner hair cells.

    Science.gov (United States)

    Marcotti, Walter; Johnson, Stuart L; Rusch, Alfons; Kros, Corne J

    2003-11-01

    Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both alpha1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at -71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency.

  13. Docosahexaenoic acid has influence on action potentials and transient outward potassium currents of ventricular myocytes

    Directory of Open Access Journals (Sweden)

    Yang Zhen-Yu

    2010-04-01

    Full Text Available Abstract Background There are many reports about the anti-arrhythmic effects of ω-3 polyunsaturated fatty acids, however, the mechanisms are still not completely delineated. The purpose of this study was to investigate the characteristics of action potentials and transient outward potassium currents (Ito of Sprague-Dawley rat ventricular myocytes and the effects of docosahexaenoic acid (DHA on action potentials and Ito. Methods The calcium-tolerant rat ventricular myocytes were isolated by enzyme digestion. Action potentials and Ito of epicardial, mid-cardial and endocardial ventricular myocytes were recorded by whole-cell patch clamp technique. Results 1. Action potential durations (APDs were prolonged from epicardial to endocardial ventricular myocytes (P 2. Ito current densities were decreased from epicardial to endocardial ventricular myocytes, which were 59.50 ± 15.99 pA/pF, 29.15 ± 5.53 pA/pF, and 12.29 ± 3.62 pA/pF, respectively at +70 mV test potential (P 3. APDs were gradually prolonged with the increase of DHA concentrations from 1 μmol/L to 100 μmol/L, however, APDs changes were not significant as DHA concentrations were in the range of 0 μmol/L to 1 μmol/L. 4. Ito currents were gradually reduced with the increase of DHA concentrations from 1 μmol/L to 100 μmol/L, and its half-inhibited concentration was 5.3 μmol/L. The results showed that there were regional differences in the distribution of action potentials and Ito in rat epicardial, mid-cardial and endocardial ventricular myocytes. APDs were prolonged and Ito current densities were gradually reduced with the increase of DHA concentrations. Conclusion The anti-arrhythmia mechanisms of DHA are complex, however, the effects of DHA on action potentials and Ito may be one of the important causes.

  14. Optical magnetic detection of single-neuron action potentials using NV-diamond

    Science.gov (United States)

    Turner, Matthew; Barry, John; Schloss, Jennifer; Glenn, David; Walsworth, Ron

    2016-05-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential dynamics in whole organisms with single-neuron resolution. Here, we report a new approach to this problem: using nitrogen-vacancy (NV) color centers in diamond to measure the time-dependent magnetic fields produced by single-neuron action potentials. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional mammalian neuronal networks.

  15. Modeling and simulation of ion channels and action potentials in taste receptor cells

    Institute of Scientific and Technical Information of China (English)

    CHEN PeiHua; LIU Xiaodong; ZHANG Wei; ZHOU Jun; WANG Ping; YANG Wei; LUO JianHong

    2009-01-01

    Based on patch clamp data on the ionic currents of rat taste receptor cells,a mathematical model of mammalian taste receptor cells was constructed to simulate the action potentials of taste receptor cells and their corresponding ionic components,including voltage-gated Na~+ currents and outward delayed rectifier K~+ currents.Our simulations reproduced the action potentials of taste receptor cells in response to electrical stimuli or sour tastants.The kinetics of ion channels and their roles in action potentials of taste receptor cells were also analyzed.Our prototype model of single taste receptor cell and simulation results presented in this paper provide the basis for the further study of taste information processing in the gustatory system.

  16. Phase lagging model of brain response to external stimuli - modeling of single action potential

    CERN Document Server

    Seetharaman, Karthik; Kulish, Vladimir V

    2012-01-01

    In this paper we detail a phase lagging model of brain response to external stimuli. The model is derived using the basic laws of physics like conservation of energy law. This model eliminates the paradox of instantaneous propagation of the action potential in the brain. The solution of this model is then presented. The model is further applied in the case of a single neuron and is verified by simulating a single action potential. The results of this modeling are useful not only for the fundamental understanding of single action potential generation, but also they can be applied in case of neuronal interactions where the results can be verified against the real EEG signal.

  17. Modeling and simulation of ion channels and action potentials in taste receptor cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Based on patch clamp data on the ionic currents of rat taste receptor cells, a mathematical model of mammalian taste receptor cells was constructed to simulate the action potentials of taste receptor cells and their corresponding ionic components, including voltage-gated Na+ currents and outward delayed rectifier K+ currents. Our simulations reproduced the action potentials of taste receptor cells in response to electrical stimuli or sour tastants. The kinetics of ion channels and their roles in action potentials of taste receptor cells were also analyzed. Our prototype model of single taste receptor cell and simulation results presented in this paper provide the basis for the further study of taste information processing in the gustatory system.

  18. A phantom axon setup for validating models of action potential recordings.

    Science.gov (United States)

    Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %. PMID:27016364

  19. The Debate in Cuba's Scientific Community on Sudden Cardiac Death.

    Science.gov (United States)

    Vilches, Ernesto; Ochoa, Luis A; Ramos, Lianne

    2015-10-01

    Sudden cardiac death poses a challenge to modern medicine because of its high incidence, the unexpected and dramatic nature of the event, and years of potential life lost. What's more, despite modest decreases in global mortality attributed to cardiovascular diseases, incidence of sudden cardiac death has not declined. Cuba, like most of the Americas, suffers from knowledge gaps that hamper adequate strategies to address sudden cardiac death as a population health problem. We suggest that a generally accepted operational definition of sudden cardiac death be agreed upon, and a national registry developed that recognizes this cause of death on death certificates. These two actions will enable Cuba's public health authorities to assess the extent of the problem and to design intervention strategies for the population with intermediate and lower cardiovascular risk, the group in which most cases occur. KEYWORDS Sudden cardiac death, cardiovascular disease, sudden death, sudden cardiac arrest, risk reduction, prevention and control, Cuba.

  20. Differential effects of thioridazine enantiomers on action potential duration in rabbit papillary muscle

    DEFF Research Database (Denmark)

    Jensen, Ask Schou; Pennisi, Cristian Pablo; Sevcencu, Cristian;

    2015-01-01

    with (+)-thioridazine. In this study we for the first time investigate the cardiotoxicity of the isolated thioridazine enantiomers and show their effects on ventricular repolarization. The effects of (+)-thioridazine, (-)-thioridazine, and racemate on the rabbit ventricular action potential duration (APD) were...... investigated in a randomized controlled blinded experiment. Action potentials were measured in papillary muscles isolated from 21 female rabbits, and the drug effect on 90% APD in comparison with control (DeltaDelta-APD90) was evaluated. Increasing concentrations of (+)-thioridazine and the racemate caused...

  1. Nonaccidental Out-of-Hospital Cardiac Arrest in an Urban Area as a Potential Source of Uncontrolled Organ Donors.

    Science.gov (United States)

    Pabisiak, Krzysztof; Krejczy, Arkadiusz; Dutkiewicz, Grażyna; Safranow, Krzysztof; Sienko, Jerzy; Bohatyrewicz, Romuald; Ciechanowski, Kazimierz

    2016-09-15

    BACKGROUND Donation after cardiac death offers the possibility of increasing the pool of organs for transplantation by up to 30%. Maastricht category type 3 (M3) dominates in most countries with active DCD programs. During preparations to introduce a permanent program for uncontrolled donation after circulatory death in Szczecin, Poland, the donor pool has been estimated. In Poland, Maastricht category type 2 (M2) is considered a basic source for organ recovery. MATERIAL AND METHODS This was a retrospective cohort study of out-of-hospital cardiac arrests (OHCA) reported to local Emergency Medical Services (EMS) between 1 December 2014 and 30 November 2015. The following inclusion criteria were used in the analysis: demographic (age 18-60 years, known identity), clinical (no chest or abdominal injury, no cachexia as an equivalent of wasting diseases), and organizational (weekdays from 8:00 am to 3:00 pm). RESULTS During 12-month period, 118 EMS interventions were recorded in response to sudden cardiac arrest. The stratification process mentioned above used criteria to establish potential, eligible, qualified, and actual donor pools (27 (30.3%), 24 (26.4%), 7 (7.3%), and 6 (6.7%), respectively). To establish a "virtual" actual number of uDCD, the nationwide average level of lack of authorization for donation was 12%. CONCLUSIONS Activation of a permanent program of organ recovery from uDCD would increase the donor pool by 6 cases. Compared to the number of brain-dead donors referred from regional hospitals, this increase would be equivalent to the formation of a new reporting center. The number of transplantable organs could increase by 22% per year.

  2. Chagas cardiomyopathy: the potential of diastolic dysfunction and brain natriuretic peptide in the early identification of cardiac damage.

    Directory of Open Access Journals (Sweden)

    Ana Garcia-Alvarez

    Full Text Available INTRODUCTION: Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP in the early identification of cardiac involvement in Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-four patients divided into 3 groups--group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32, group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14, and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction 37 pg/ml were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27 ± 26 vs. 11 ± 8 pg/ml, p = 0.03. CONCLUSION/SIGNIFICANCE: In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease.

  3. Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects.

    Science.gov (United States)

    Enomoto, Riyo; Koshiba, Chika; Suzuki, Chie; Lee, Eibai

    2011-05-01

    Wogonin, a flavone in the roots of Scutellaria baicalensis, reduced etoposide-induced apoptotic cell death in normal cells, such as bone marrow cells and thymocytes. On the other hand, wogonin potentiated the proapoptotic or cytotoxic action of etoposide in tumor cells, such as Jurkat, HL-60, A549, and NCI-H226. These contradictory actions of wogonin on apoptosis are distinguished by normal or cancer cell types. Wogonin had no effect on apoptosis induced by other anticancer agents in the tumor cells. Thus, the potentiation effect of wogonin was observed only in etoposide-induced apoptosis in tumor cells. In a functional assay for P-glycoprotein (P-gp), wogonin suppressed excretion of calcein, a substrate for P-gp, in these tumor cells. Moreover, wogonin decreased the excretion of radiolabeled etoposide and accordingly increased intracellular content of this agent in the cells. P-gp inhibitors showed a similar potentiation effect on etoposide-induced apoptosis in these tumor cells. Thus, wogonin is likely to potentiate the anticancer action of etoposide due to P-gp inhibition and accumulation of this agent. These findings suggest that wogonin may be a useful chemotherapeutic adjuvant to potentiate the pharmacological action of etoposide and ameliorate its adverse effects. PMID:20658136

  4. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    Science.gov (United States)

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected. PMID:26686984

  5. Insulin-like growth factors and their potential role in cardiac epigenetics.

    Science.gov (United States)

    Iosef Husted, Cristiana; Valencik, Maria

    2016-08-01

    Cardiovascular disease (CVD) constitutes a major public health threat worldwide, accounting for 17.3 million deaths annually. Heart disease and stroke account for the majority of healthcare costs in the developed world. While much has been accomplished in understanding the pathophysiology, molecular biology and genetics underlying the diagnosis and treatment of CVD, we know less about the role of epigenetics and their molecular determinants. The impact of environmental changes and epigenetics in CVD is now emerging as critically important in understanding the origin of disease and the development of new therapeutic approaches to prevention and treatment. This review focuses on the emerging role of epigenetics mediated by insulin like-growth factors-I and -II in major CVDs such as heart failure, cardiac hypertrophy and diabetes. PMID:27061217

  6. Prediction of time of death after withdrawal of life-sustaining treatment in potential donors after cardiac death

    NARCIS (Netherlands)

    Wind, Jentina; Snoeijs, Maarten G. J.; Brugman, Cees A.; Vervelde, Janneke; Zwaveling, Janharm; van Mook, Walther N.; van Heurn, Ernest L.

    2012-01-01

    Objective: Organ donation after cardiac death increases the number of donor organs. In controlled donation after cardiac death donors, the period between withdrawal of life-sustaining treatment and cardiac arrest is one of the parameters used to assess whether organs are suitable for transplantation

  7. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    International Nuclear Information System (INIS)

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC50 values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC50 = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other

  8. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  9. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M;

    2002-01-01

    to support the back-propagation of the evoked somatic action potential to produce the second dendritic spike. In summary, the balance of spatially distributed excitatory and inhibitory inputs can dynamically switch the mitral cell firing among four different modes: axo-somatic initiation with back...

  10. Quantitative analysis of single muscle fibre action potentials recorded at known distances

    NARCIS (Netherlands)

    Albers, B.A.; Put, J.H.M.; Wallinga, W.; Wirtz, P.

    1989-01-01

    In vivo records of single fibre action potentials (SFAPs) have always been obtained at unknown distance from the active muscle fibre. A new experimental method has been developed enabling the derivation of the recording distance in animal experiments. A single fibre is stimulated with an intracellu

  11. Youth Participatory Action Research and Educational Transformation: The Potential of Intertextuality as a Methodological Tool

    Science.gov (United States)

    Bertrand, Melanie

    2016-01-01

    In this article, Melanie Bertrand explores the potential of using the concept of intertextuality--which captures the way snippets of written or spoken text from one source become incorporated into other sources--in the study and practice of youth participatory action research (YPAR). Though this collective and youth-centered form of research…

  12. ACTION OF PROGESTERONE ON THE DEPOLARIZATION OF THE MEMBRANE POTENTIAL IN TOAD OOCYTES INDUCED BY LEUCINE

    Institute of Scientific and Technical Information of China (English)

    WANGYu-Feng

    1989-01-01

    The depolarization of the membrane potential in toad oocytes induced by leucine was found in our previous experiment. In this paper, a possible action or progesterone in the process was further investigated. After oocytes had been incubated for 16 to 24 hours with

  13. Design of a pulsatile flow facility to evaluate thrombogenic potential of implantable cardiac devices.

    Science.gov (United States)

    Arjunon, Sivakkumar; Ardana, Pablo Hidalgo; Saikrishnan, Neelakantan; Madhani, Shalv; Foster, Brent; Glezer, Ari; Yoganathan, Ajit P

    2015-04-01

    Due to expensive nature of clinical trials, implantable cardiac devices should first be extensively characterized in vitro. Prosthetic heart valves (PHVs), an important class of these devices, have been shown to be associated with thromboembolic complications. Although various in vitro systems have been designed to quantify blood-cell damage and platelet activation caused by nonphysiological hemodynamic shear stresses in these PHVs, very few systems attempt to characterize both blood damage and fluid dynamics aspects of PHVs in the same test system. Various numerical modeling methodologies are also evolving to simulate the structural mechanics, fluid mechanics, and blood damage aspects of these devices. This article presents a completely hemocompatible small-volume test-platform that can be used for thrombogenicity studies and experimental fluid mechanics characterization. Using a programmable piston pump to drive freshly drawn human blood inside a cylindrical column, the presented system can simulate various physiological and pathophysiological conditions in testing PHVs. The system includes a modular device-mounting chamber, and in this presented case, a 23 mm St. Jude Medical (SJM) Regents® mechanical heart valve (MHV) in aortic position was used as the test device. The system was validated for its capability to quantify blood damage by measuring blood damage induced by the tester itself (using freshly drawn whole human blood). Blood damage levels were ascertained through clinically relevant assays on human blood while fluid dynamics were characterized using time-resolved particle image velocimetry (PIV) using a blood-mimicking fluid. Blood damage induced by the tester itself, assessed through Thrombin-anti-Thrombin (TAT), Prothrombin factor 1.2 (PF1.2), and hemolysis (Drabkins assay), was within clinically accepted levels. The hydrodynamic performance of the tester showed consistent, repeatable physiological pressure and flow conditions. In addition, the

  14. Effects of benactyzine on action potentials and contractile force of guinea pig papillary muscles

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Aim:To explore the effects of benactyzine (BEN) on the action potential and contractile force in guinea pig papillary muscles.Methods:Conventional microelectrode technique was used to record the fast action potentials (FAP) and slow action potentials (SAP) of guinea pig papillary muscles.Results:Benactyzine 5,10,50 μmol·L-1 suppressed the maximal upstroke velocity (vmax) of FAP and contractile force (Fc) concentration-dependently while prolonged the action potential duration at 50%,90% repolarization (APD50,APD90) and effective refractory period (ERP) of FAP.The suppression on the vmax was frequency-dependent.Benactyzine 5,10,50μmol·L-1 lengthened the APD50,APD90 of SAP induced by isoprenaline or histamine when perfused with KCl 22 mmol·L-1 Tyrode's solution.The vmax of the SAP was not decreased by benactyzine 5,10 μmol·L-1 but by 50 μmol·L-1.The effects on the SAP were antagonized by elevation of the extracellular calcium from 2.0 to 5.6 mmol·L-1.The effects of benactyzine on SAP elicited by tetrodotoxin resembled that by isoprenaline or histamine except the more pronounced suppression on vmax and action potential amplitude (APA).The persistent rapid spontaneous activity and triggered tachyarrhythmia induced by ouabain were also abolished immediately by benactyzine 5 μmol·L-1.Conclusion:Benactyzine can inhibit Na+,K+,Ca2+ transmembrane movement and intracellular Ca2+ mobilization in the myocardium,and this may be the electrophysiological basis of its effects against experimental arrhythmias.

  15. Cardiac Alternans Arising from an Unfolded Border-Collision Bifurcation

    CERN Document Server

    Zhao, Xiaopeng; Berger, Carolyn M; Krassowska, Wanda; Gauthier, Daniel J

    2007-01-01

    Following an electrical stimulus, the transmembrane voltage of cardiac tissue rises rapidly and remains at a constant value before returning to the resting value, a phenomenon known as an action potential. When the pacing rate of a periodic train of stimuli is increased above a critical value, the action potential undergoes a period-doubling bifurcation, where the resulting alternation of the action potential duration is known as alternans in the medical literature. Existing cardiac models treat alternans either as a smooth or as a border-collision bifurcation. However, recent experiments in paced cardiac tissue reveal that the bifurcation to alternans exhibits hybrid smooth/nonsmooth behaviors, which can be qualitatively described by a model of so-called unfolded border-collision bifurcation. In this paper, we obtain analytical solutions of the unfolded border-collision model and use it to explore the crossover between smooth and nonsmooth behaviors. Our analysis shows that the hybrid smooth/nonsmooth behavi...

  16. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats

    DEFF Research Database (Denmark)

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens J;

    2009-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral nutrition (PN)-induced mucosal hypoplasia. The objective was to determine what enteral...... was associated with decreased DPP-IV activity in ileum and colon compared with casein, soy, or PN+GLP-2 alone, P action of GLP-2 to reverse PN-induced mucosal hypoplasia in association with decreased intestinal DPP-IV activity....

  17. 'Catching the waves' - slow cortical potentials as moderator of voluntary action.

    Science.gov (United States)

    Schmidt, Stefan; Jo, Han-Gue; Wittmann, Marc; Hinterberger, Thilo

    2016-09-01

    The readiness potential is an ongoing negativity in the EEG preceding a self-initiated movement by approximately 1.5s. So far it has predominantly been interpreted as a preparatory signal with a causal link to the upcoming movement. Here a different hypothesis is suggested which we call the selective slow cortical potential sampling hypothesis. In this review of recent research results we argue that the initiation of a voluntary action is more likely during negative fluctuations of the slow cortical potential and that the sampling and averaging of many trials leads to the observed negativity. That is, empirical evidence indicates that the early readiness potential is not a neural correlate of preconscious motor preparation and thus a determinant of action. Our hypothesis thereafter challenges the classic interpretation of the Libet experiment which is often taken as proof that there is no free will. We furthermore suggest that slow cortical potentials are related to an urge to act but are not a neural indicator of the decision process of action initiation.

  18. Acute NMDA receptor antagonism disrupts synchronization of action potential firing in rat prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Leonardo A Molina

    Full Text Available Antagonists of N-methyl-D-aspartate receptors (NMDAR have psychotomimetic effects in humans and are used to model schizophrenia in animals. We used high-density electrophysiological recordings to assess the effects of acute systemic injection of an NMDAR antagonist (MK-801 on ensemble neural processing in the medial prefrontal cortex of freely moving rats. Although MK-801 increased neuron firing rates and the amplitude of gamma-frequency oscillations in field potentials, the synchronization of action potential firing decreased and spike trains became more Poisson-like. This disorganization of action potential firing following MK-801 administration is consistent with changes in simulated cortical networks as the functional connections among pyramidal neurons become less clustered. Such loss of functional heterogeneity of the cortical microcircuit may disrupt information processing dependent on spike timing or the activation of discrete cortical neural ensembles, and thereby contribute to hallucinations and other features of psychosis induced by NMDAR antagonists.

  19. Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells

    OpenAIRE

    Liu Jinxu; Tu Huiyin; Zhang Dongze; Zheng Hong; Li Yu-Long

    2012-01-01

    Abstract Background The generation of action potential is required for stimulus-evoked neurotransmitter release in most neurons. Although various voltage-gated ion channels are involved in action potential production, the initiation of the action potential is mainly mediated by voltage-gated Na+ channels. In the present study, differentiation-induced changes of mRNA and protein expression of Na+ channels, Na+ currents, and cell membrane excitability were investigated in NG108-15 cells. Result...

  20. Simulation and calculation of the contribution of hyperpolarization-activated cyclic nucleotide-gated channels to action potentials

    OpenAIRE

    Liao Liping; Lin Xianguang; Hu Jielin; Wu Xin; Yang Xiaofei; Wang Wei; Li Chenhong

    2016-01-01

    The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel, which mediates the influx of cations, has an important role in action potential generation. In this article, we describe the contribution of the HCN channel to action potential generation. We simulated several common ion channels in neuron membranes based on data from rat dorsal root ganglion cells and modeled the action potential. The ion channel models employed in this paper were based...

  1. An experimental study on a function of the cupula. Effect of cupula removal on the ampullary nerve action potential.

    Science.gov (United States)

    Suzuki, M; Harada, Y; Sugata, Y

    1984-01-01

    We used a posterior semicircular canal that had been isolated from a frog. From the utricular side the ampulla was cut open at a position one third of the way along the long axis. The cupula was removed through this opening using a glass micropipette. The action potential from the posterior ampullary nerve was recorded before and after removal of the cupula. After removal, the action potential disappeared almost completely. When the cupula was put back on the crista, the action potential was restored. When the cupula was put back upside down, the action potential recovered, but to a lesser extent.

  2. The DBI Action, Higher-derivative Supergravity, and Flattening Inflaton Potentials

    CERN Document Server

    Bielleman, Sjoerd; Pedro, Francisco G; Valenzuela, Irene; Wieck, Clemens

    2016-01-01

    In string theory compactifications it is common to find an effective Lagrangian for the scalar fields with a non-canonical kinetic term. We study the effective action of the scalar position moduli of Type II D$p$-branes. In many instances the kinetic terms are in fact modified by a term proportional to the scalar potential itself. This can be linked to the appearance of higher-dimensional supersymmetric operators correcting the K\\"ahler potential. We identify the supersymmetric dimension-eight operators describing the $\\alpha'$ corrections captured by the D-brane Dirac-Born-Infeld action. Our analysis then allows an embedding of the D-brane moduli effective action into an $\\mathcal N = 1$ supergravity formulation. The effects of the potential-dependent kinetic terms may be very important if one of the scalars is the inflaton, since they lead to a flattening of the scalar potential. We analyze this flattening effect in detail and compute its impact on the CMB observables for single-field inflation with monomia...

  3. Potentiators of Defective ΔF508-CFTR Gating that Do Not Interfere with Corrector Action.

    Science.gov (United States)

    Phuan, Puay-Wah; Veit, Guido; Tan, Joseph A; Finkbeiner, Walter E; Lukacs, Gergely L; Verkman, A S

    2015-10-01

    Combination drug therapies under development for cystic fibrosis caused by the ∆F508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR) include a "corrector" to improve its cellular processing and a "potentiator" to improve its chloride channel function. Recently, it was reported that the approved potentiator N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (Ivacaftor) reduces ∆F508-CFTR cellular stability and the efficacy of investigational correctors, including 3-(6-[([1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl) amino]-3-methyl-2-pyridinyl)-benzoic acid and 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(2-hydroxy-1,1-dimethylethyl)-1H-indol-5-yl), which might contribute to the modest reported efficacy of combination therapy in clinical trials. Here, we report the identification and characterization of potentiators that do not interfere with ∆F508-CFTR stability or corrector action. High-throughput screening and structure-activity analysis identified several classes of potentiators that do not impair corrector action, including tetrahydrobenzothiophenes, thiooxoaminothiazoles, and pyrazole-pyrrole-isoxazoles. The most potent compounds have an EC(50) for ∆F508-CFTR potentiation down to 18 nM and do not reduce corrector efficacy in heterologous ∆F508-CFTR-expressing cells or primary cultures of ∆F508/∆F508 human bronchial epithelia. The ΔF508-CFTR potentiators also activated wild-type and G551D CFTR, albeit weakly. The efficacy of combination therapy for cystic fibrosis caused by the ∆F508 mutation may be improved by replacement of Ivacaftor with a potentiator that does not interfere with corrector action. PMID:26245207

  4. Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms.

    Directory of Open Access Journals (Sweden)

    Belén Picatoste

    Full Text Available BACKGROUND: Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1 enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart. METHODS: Goto-Kakizaki (GK rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin or vehicle (n=10, each. After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays. RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36, alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells. CONCLUSIONS: Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36 promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actions.

  5. Application of Emergency Action Levels from Potential Release at Research Reactor HANARO

    International Nuclear Information System (INIS)

    Execution of the protective action promptly is possible that Emergency Action Levels (EALs) must be established for a radiological release from nuclear facility. The EALs for electric power reactor are already developed and applied to recognize an emergency situation rapidly. Recently the IAEA published the safety report including the EALs for research reactor. This paper describes the EALs to apply for a potential release pathway at the research reactor HANARO. The results of table 1 and 2 will be higher than actual because the weather condition in real situation is difference. However, the EALs applying the potential stack release, ground release and site can be useful for research reactor HANARO making the emergency declaration. The EALs at the site boundary of the table 3 can be applied to protect the off-site public

  6. Bimodal action of menthol on the transient receptor potential channel TRPA1

    OpenAIRE

    Karashima, Yuji; Damann, Nils; Prenen, Jean; Talavera Pérez, Karel; Segal Stanciu, Andrei; Voets, Thomas; Nilius, Bernd

    2007-01-01

    TRPA1 is a calcium-permeable nonselective cation transient receptor potential (TRP) channel that functions as an excitatory ionotropic receptor in nociceptive neurons. TRPA1 is robustly activated by pungent substances in mustard oil, cinnamon, and garlic and mediates the inflammatory actions of environmental irritants and proalgesic agents. Here, we demonstrate a bimodal sensitivity of TRPA1 to menthol, a widely used cooling agent and known activator of the related cold receptor TRPM8. In who...

  7. Depth-Resolved Measurement of Transient Structural Changes during Action Potential Propagation

    OpenAIRE

    Akkin, T.; Joo, C.; Boer

    2007-01-01

    We report noncontact optical measurement of fast transient structural changes in the crustacean nerve during action potential propagation without the need for exogenous chemicals or reflection coatings. The technique, spectral domain optical coherence tomography, provides real-time cross-sectional images of the nerve with micron-scale resolution to select a specific region for functional assessment and interferometric phase sensitivity for subnanometer-scale motion detection. Noncontact optic...

  8. Action Potential Energy Efficiency Varies Among Neuron Types in Vertebrates and Invertebrates

    OpenAIRE

    Biswa Sengupta; Martin Stemmler; Simon B Laughlin; Niven, Jeremy E.

    2010-01-01

    The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant ...

  9. Variety of the Wave Change in Compound Muscle Action Potential in an Animal Model

    OpenAIRE

    ITO, ZENYA; Imagama, Shiro; Ando, Kei; Muramoto, Akio; Kobayashi, Kazuyoshi; Hida, Tetsuro; Ito, Kenyu; Ishikawa, Yoshimoto; Tsushima, Mikito; Matsumoto, Akiyuki; Tanaka, Satoshi; Morozumi, Masayoshi; Matsuyama, Yukihiro; Ishiguro, Naoki

    2015-01-01

    Study Design Animal study. Purpose To review the present warning point criteria of the compound muscle action potential (CMAP) and investigate new criteria for spinal surgery safety using an animal model. Overview of Literature Little is known about correlation palesis and amplitude of spinal cord monitoring. Methods After laminectomy of the tenth thoracic spinal lamina, 2-140 g force was delivered to the spinal cord with a tension gage to create a bilateral contusion injury. The study morpho...

  10. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools

    OpenAIRE

    Frey, Scott H.; POVINELLI, DANIEL J.

    2012-01-01

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of ...

  11. ER Stress-Mediated Signaling: Action Potential and Ca2+ as Key Players

    Science.gov (United States)

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-01-01

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca2+) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca2+ regulates cell death both at the early and late stages of apoptosis. Severe Ca2+ dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca2+ (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca2+ and action potential in ER stress-mediated apoptosis. PMID:27649160

  12. Compound action potentials recorded in the human spinal cord during neurostimulation for pain relief.

    Science.gov (United States)

    Parker, John L; Karantonis, Dean M; Single, Peter S; Obradovic, Milan; Cousins, Michael J

    2012-03-01

    Electrical stimulation of the spinal cord provides effective pain relief to hundreds of thousands of chronic neuropathic pain sufferers. The therapy involves implantation of an electrode array into the epidural space of the subject and then stimulation of the dorsal column with electrical pulses. The stimulation depolarises axons and generates propagating action potentials that interfere with the perception of pain. Despite the long-term clinical experience with spinal cord stimulation, the mechanism of action is not understood, and no direct evidence of the properties of neurons being stimulated has been presented. Here we report novel measurements of evoked compound action potentials from the spinal cords of patients undergoing stimulation for pain relief. The results reveal that Aβ sensory nerve fibres are recruited at therapeutic stimulation levels and the Aβ potential amplitude correlates with the degree of coverage of the painful area. Aβ-evoked responses are not measurable below a threshold stimulation level, and their amplitude increases with increasing stimulation current. At high currents, additional late responses are observed. Our results contribute towards efforts to define the mechanism of spinal cord stimulation. The minimally invasive recording technique we have developed provides data previously obtained only through microelectrode techniques in spinal cords of animals. Our observations also allow the development of systems that use neuronal recording in a feedback loop to control neurostimulation on a continuous basis and deliver more effective pain relief. This is one of numerous benefits that in vivo electrophysiological recording can bring to a broad range of neuromodulation therapies. PMID:22188868

  13. Elevated heart rate triggers action potential alternans and sudden death. translational study of a homozygous KCNH2 mutation.

    Directory of Open Access Journals (Sweden)

    Ulrich Schweigmann

    Full Text Available BACKGROUND: Long QT syndrome (LQTS leads to arrhythmic events and increased risk for sudden cardiac death (SCD. Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed "human HERG knockout" and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness. METHODS AND RESULTS: Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in silico mathematical modelling, protein biochemistry, confocal microscopy were performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation (p.R835Q in the index patient (QTc ∼506 ms with notched T waves. Parents were I° cousins - both heterozygous for the mutation and clinically unremarkable (QTc ∼447 ms, father and ∼396 ms, mother. Heterologous expression of KCNH2-R835Q showed mildly reduced current amplitudes. Biophysical properties of ionic currents were also only nominally changed with slight acceleration of deactivation and more negative V50 in R835Q-currents. Protein biochemistry and confocal microscopy revealed similar expression patterns and trafficking of WT and R835Q, even at elevated temperature. In silico analysis demonstrated mildly prolonged ventricular action potential duration (APD compared to WT at a cycle length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT, but displayed APD alternans in R835Q. CONCLUSION: Kv11.1 channels affected by the C-terminal R835Q mutation display mildly modified biophysical properties, but leads to M-cell APD alternans with elevated heart rate and could precipitate SCD under specific clinical circumstances associated with high heart rates.

  14. Membrane potential hyperpolarization in Mammalian cardiac cells by synchronization modulation of Na/K pumps.

    Science.gov (United States)

    Chen, Wei; Dando, Robin

    2008-02-01

    In previously reported work, we developed a new technique, synchronization modulation, to electrically activate Na/K pump molecules. The fundamental mechanism involved in this technique is a dynamic entrainment procedure of the pump molecules, carried out in a stepwise pattern. The entrainment procedure consists of two steps: synchronization and modulation. We theoretically predicted that the pump functions can be activated exponentially as a function of the membrane potential. We have experimentally demonstrated synchronization of the Na/K pump molecules and acceleration of their pumping rates by many fold through use of voltage-clamp techniques, directly monitoring the pump currents. We further applied this technique to intact skeletal muscle fibers from amphibians and found significant effects on the membrane resting potential. Here, we extend our study to intact mammalian cardiomyocytes. We employed a noninvasive confocal microscopic fluorescent imaging technique to monitor electric field-induced changes in ionic concentration gradient and membrane resting potential. Our results further confirm that the well-designed synchronization modulation electric field can effectively accelerate the Na/K pumping rate, increasing the ionic concentration gradient across the cell membrane and hyperpolarizing the membrane resting potential.

  15. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential.

    Science.gov (United States)

    Desbois, Andrew P; Smith, Valerie J

    2010-02-01

    Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.

  16. Pharmacological blockade of voltage-gated calcium channels as a potential cardioprotective strategy

    OpenAIRE

    Pushparaj, Charumathi

    2014-01-01

    Voltage-gated Ca2+ channels (VGCCs) are essential for initiating and regulating cardiac function. During the cardiac action potential, Ca2+ influx through L-type channels triggers the sarcoplasmic reticulum Ca2+ release that enables the EC coupling. Ca2+ can also enter cardiac myocytes through low-voltage-activated T-type channels, which are expressed throughout cardiac development until the end of the neonatal period, and can contribute to pacemaker activity as well as EC coupling to some ex...

  17. High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Jon-Jon Santiago

    Full Text Available Fibroblast growth factor 2 (FGF-2 is a multifunctional protein synthesized as high (Hi- and low (Lo- molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD and 68% (±25 SD of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2 reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes

  18. Effects of terpineol on the compound action potential of the rat sciatic nerve

    OpenAIRE

    M.R. Moreira; G.M.P. Cruz; Lopes, M S; A.A.C. Albuquerque; J.H. Leal-Cardoso

    2001-01-01

    Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the perfumery industry. It is an important chemical constituent of the essential oil of many plants with widespread applications in folk medicine and in aromatherapy. The effects of terpineol on the compound action potential (CAP) of rat sciatic nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At 100 µM, terpineol had no demonstrable effect. At 300 µM terpineol, peak-to-peak amplitude and con...

  19. On modelling of physical effects accompanying the propagation of action potentials in nerve fibres

    CERN Document Server

    Engelbrecht, Jüri; Tamm, Kert; Laasmaa, Martin; Vendelin, Marko

    2016-01-01

    The recent theoretical and experimental studies have revealed many details of signal propagation in nervous systems. In this paper an attempt is made to unify various mathematical models which describe the signal propagation in nerve fibres. The analysis of existing single models permits to select the leading physiological effects. As a result, a more general mathematical model is described based on the coupling of action potentials with mechanical waves in a nerve fibre. The crucial issue is how to model coupling effects which are strongly linked to the ion currents through biomembranes.

  20. The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

    Institute of Scientific and Technical Information of China (English)

    Yongping Li; Jie Lao; Xin Zhao; Dong Tian; Yi Zhu; Xiaochun Wei

    2014-01-01

    The distance between the two electrode tips can greatly inlfuence the parameters used for record-ing compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spac-ings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance be-tween two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed signiifcantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no signiifcant change. Different distances between recording and stimulating sites did not produce signiifcant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential.

  1. 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.

  2. Potential synergy between lipid-lowering and blood-pressure-lowering in the Anglo-Scandinavian Cardiac Outcomes Trial

    DEFF Research Database (Denmark)

    Sever, Peter; Dahlöf, Björn; Poulter, Neil;

    2006-01-01

    A prespecified objective of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was to assess whether any synergistic effects were apparent between the lipid-lowering and blood-pressure-lowering regimens in preventing cardiovascular events.......A prespecified objective of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was to assess whether any synergistic effects were apparent between the lipid-lowering and blood-pressure-lowering regimens in preventing cardiovascular events....

  3. Anion channelrhodopsins for inhibitory cardiac optogenetics.

    Science.gov (United States)

    Govorunova, Elena G; Cunha, Shane R; Sineshchekov, Oleg A; Spudich, John L

    2016-01-01

    Optical control of the heart muscle is a promising strategy for cardiology because it is more specific than traditional electrical stimulation, and allows a higher temporal resolution than pharmacological interventions. Anion channelrhodopsins (ACRs) from cryptophyte algae expressed in cultured neonatal rat ventricular cardiomyocytes produced inhibitory currents at less than one-thousandth of the light intensity required by previously available optogenetic tools, such as the proton pump archaerhodopsin-3 (Arch). Because of their greater photocurrents, ACRs permitted complete inhibition of cardiomyocyte electrical activity under conditions in which Arch was inefficient. Most importantly, ACR expression allowed precisely controlled shortening of the action potential duration by switching on the light during its repolarization phase, which was not possible with previously used optogenetic tools. Optical shortening of cardiac action potentials may benefit pathophysiology research and the development of optogenetic treatments for cardiac disorders such as the long QT syndrome. PMID:27628215

  4. Anion channelrhodopsins for inhibitory cardiac optogenetics

    Science.gov (United States)

    Govorunova, Elena G.; Cunha, Shane R.; Sineshchekov, Oleg A.; Spudich, John L.

    2016-01-01

    Optical control of the heart muscle is a promising strategy for cardiology because it is more specific than traditional electrical stimulation, and allows a higher temporal resolution than pharmacological interventions. Anion channelrhodopsins (ACRs) from cryptophyte algae expressed in cultured neonatal rat ventricular cardiomyocytes produced inhibitory currents at less than one-thousandth of the light intensity required by previously available optogenetic tools, such as the proton pump archaerhodopsin-3 (Arch). Because of their greater photocurrents, ACRs permitted complete inhibition of cardiomyocyte electrical activity under conditions in which Arch was inefficient. Most importantly, ACR expression allowed precisely controlled shortening of the action potential duration by switching on the light during its repolarization phase, which was not possible with previously used optogenetic tools. Optical shortening of cardiac action potentials may benefit pathophysiology research and the development of optogenetic treatments for cardiac disorders such as the long QT syndrome. PMID:27628215

  5. Identifying potential functional impact of mutations and polymorphisms: Linking heart failure, increased risk of arrhythmias and sudden cardiac death.

    Directory of Open Access Journals (Sweden)

    BENOIT eJAGU

    2013-09-01

    Full Text Available Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behaviour has been the identification of single mutations that greatly increase the risk for arrhythmias and sudden cardiac death by changing channel-gating characteristics. Indeed, mutations in several genes encoding ion channels, such as SCN5A, which encodes the major cardiac Na+ channel, have emerged as the basis for a variety of inherited cardiac arrhythmias such as long QT syndrome, Brugada syndrome, progressive cardiac conduction disorder, sinus node dysfunction or sudden infant death syndrome. In addition, genes encoding ion channel accessory proteins, like anchoring or chaperone proteins, which modify the expression, the regulation of endocytosis and the degradation of ion channel α-subunits have also been reported as susceptibility genes for arrhythmic syndromes. The regulation of ion channel protein expression also depends on a fine-tuned balance among different other mechanisms, such as gene transcription, RNA processing, post-transcriptional control of gene expression by miRNA, protein synthesis, assembly and post-translational modification and trafficking.

  6. Characterization of action potential-triggered [Ca2+]i transients in single smooth muscle cells of guinea-pig ileum

    OpenAIRE

    Kohda, M.; Komori, S.; Unno, T; Ohashi, H

    1997-01-01

    To characterize increases in cytosolic free Ca2+ concentration ([Ca2+]i) associated with discharge of action potentials, membrane potential and [Ca2+]i were simultaneously recorded from single smooth muscle cells of guinea-pig ileum by use of a combination of nystatin-perforated patch clamp and fura-2 fluorimetry techniques.A single action potential in response to a depolarizing current pulse elicited a transient rise in [Ca2+]i. When the duration of the current pulse was prolonged, action po...

  7. Action of hallucinogens on raphe-evoked dorsal root potentials (DRPs) in the cat.

    Science.gov (United States)

    Larson, A A; Anderson, E G

    1986-02-01

    The dorsal root potential (DRP) evoked by stimulation of the inferior central nucleus (ICN) of the cat is affected by administration of a variety of hallucinogenic agents. It has been previously shown that a single low dose of LSD is unique in that it potentiates this DRP, while injections of 5-methoxy-N,N- dimethyltryptamine (5-MeODMT), ketamine or phencyclidine (PCP) inhibit its production. Tolerance develops to the facilitatory effect of low doses of LSD on the DRP, but not to the inhibitory action of 5-MeODMT. Repeated injections of ketamine every 30 minutes also fail to produce tachyphylaxis to the inhibitory effect of this dissociative anesthetic. The raphe-evoked DRP is a long latency potential that is inhibited by a wide variety of putative serotonin antagonists and has therefore been traditionally thought to be mediated by serotonin. However, in light of the inability of either tryptophan or fluoxetine to potentiate this DRP, and the resistance of this DRP to blockade by parachlorophenylalanine, reserpine or intrathecally administered 5,7-dihydroxytryptamine, it appears that this potential may in fact be mediated, at least in part, by a non-serotonergic transmitter. PMID:3952125

  8. The characteristics of action potential and nonselective cation current of cardiomyocytes in rabbit superior vena cava

    Institute of Scientific and Technical Information of China (English)

    WANG Pan; YANG XinChun; LIU XiuLan; BAO RongFeng; LIU TaiFeng

    2008-01-01

    As s special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cavs (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may increase or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can increase or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyocytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.

  9. Quantitative assessment of the distributions of membrane conductances involved in action potential backpropagation along basal dendrites.

    Science.gov (United States)

    Acker, Corey D; Antic, Srdjan D

    2009-03-01

    Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites is therefore likely to play an important role in cortical information processing. Both synaptic integration and synaptic plasticity depend crucially on dendritic membrane excitability and the backpropagation of action potentials. We carried out multisite voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium, or I(h) conductance had little effect on dendritic AP propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a nonuniform sodium channel distribution with decreasing conductance with distance from the soma, together with a nonuniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high-frequency trains of APs and the local generation of sodium spikelets. We also explored the conditions under which I(A) down-regulation would produce branch strength potentiation in the proposed model. Finally, we discuss the hypothesis that a fraction of basal branches may have different membrane properties compared with sister branches in the same dendritic tree. PMID:19118105

  10. Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Yang Xia

    Full Text Available GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb of the main axon trunk of layer -5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

  11. The Belem Framework for Action: Harnessing the Power and Potential of Adult Learning and Education for a Viable Future

    Science.gov (United States)

    Adult Learning, 2012

    2012-01-01

    This article presents the Belem Framework for Action. This framework focuses on harnessing the power and potential of adult learning and education for a viable future. This framework begins with a preamble on adult education and towards lifelong learning.

  12. Mechanistically based mapping of human cardiac fibrillation.

    Science.gov (United States)

    Narayan, Sanjiv M; Zaman, Junaid A B

    2016-05-01

    The mechanisms underpinning human cardiac fibrillation remain elusive. In his 1913 paper 'On dynamic equilibrium in the heart', Mines proposed that an activation wave front could propagate repeatedly in a circle, initiated by a stimulus in the vulnerable period. While the dynamics of activation and recovery are central to cardiac fibrillation, these physiological data are rarely used in clinical mapping. Fibrillation is a rapid irregular rhythm with spatiotemporal disorder resulting from two fundamental mechanisms - sources in preferred cardiac regions or spatially diffuse self-sustaining activity, i.e. with no preferred source. On close inspection, however, this debate may also reflect mapping technique. Fibrillation is initiated from triggers by regional dispersion in repolarization, slow conduction and wavebreak, then sustained by non-uniform interactions of these mechanisms. Notably, optical mapping of action potentials in atrial fibrillation (AF) show spiral wave sources (rotors) in nearly all studies including humans, while most traditional electrogram analyses of AF do not. Techniques may diverge in fibrillation because electrograms summate non-coherent waves within an undefined field whereas optical maps define waves with a visually defined field. Also fibrillation operates at the limits of activation and recovery, which are well represented by action potentials while fibrillatory electrograms poorly represent repolarization. We conclude by suggesting areas for study that may be used, until such time as optical mapping is clinically feasible, to improve mechanistic understanding and therapy of human cardiac fibrillation. PMID:26607671

  13. Introduction to cardiac imaging in infants and children: Techniques, potential, and role in the imaging work-up of various cardiac malformations and other pediatric heart conditions

    International Nuclear Information System (INIS)

    The increasing prevalence of congenital heart disease (CHD) can be attributed to major improvements in diagnosis and treatment. Although echocardiography is the most commonly used imaging modality for diagnosis and follow-up of subjects with CHD, the evolution of cardiovascular magnetic resonance (MR) imaging and increasingly computed tomography (CT) does offer new ways to visualize the heart and the great vessels. The development of cardiovascular MR techniques allows for a comprehensive assessment of cardiac anatomy and function. This provides information about the long-term sequlae of the underlying complex anatomy, hemodynamic assessment of residual post-operative lesions and complications of surgery. As much of the functional data in CHD patients is usually acquired with invasive X-ray angiography, non-invasive alternatives such as cardiovascular MR (and CT) are desirable. This review evaluates the role of MR imaging in the management of subjects with CHD, particularly detailing recent developments in imaging techniques as they relate to the various CHD diagnoses we commonly encounter in our practice

  14. Cardiac voltage-gated calcium channel macromolecular complexes.

    Science.gov (United States)

    Rougier, Jean-Sébastien; Abriel, Hugues

    2016-07-01

    Over the past 20years, a new field of research, called channelopathies, investigating diseases caused by ion channel dysfunction has emerged. Cardiac ion channels play an essential role in the generation of the cardiac action potential. Investigators have largely determined the physiological roles of different cardiac ion channels, but little is known about the molecular determinants of their regulation. The voltage-gated calcium channel Cav1.2 shapes the plateau phase of the cardiac action potential and allows the influx of calcium leading to cardiomyocyte contraction. Studies suggest that the regulation of Cav1.2 channels is not uniform in working cardiomyocytes. The notion of micro-domains containing Cav1.2 channels and different calcium channel interacting proteins, called macro-molecular complex, has been proposed to explain these observations. The objective of this review is to summarize the currently known information on the Cav1.2 macromolecular complexes in the cardiac cell and discuss their implication in cardiac function and disorder. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26707467

  15. Action potential-simulated weak electric fields can directly initiate myelination

    Institute of Scientific and Technical Information of China (English)

    Lei Liu; Shifu Zhao; Haiming Wang

    2008-01-01

    BACKGROUND: Myelination is a process whereby glial cells identify, adhere, wrap and enclose axons to form a spiral myelin sheath.OBJECTIVE: To investigate the effects of action potential-simulated weak electric fields on myelination in the central nervous system.DESIGN AND SETTING: This single-sample observation study was performed at the 324 Hospital of Chinese PLA.MATERIALS: Two 5 μm carbon fibers were provided by the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. One Sprague Dawley rat, aged 1 day, was used.METHODS: Cerebral cortex was harvested from the rat to prepare a suspension [(1-2)×105/mL] containing neurons and glial cells. To simulate the axon, carbon fibers were placed at the bottom of the neuron-glial cell coculture dish, and were electrified with a single phase square wave current, 1×10-2, 1×10-3, 1×10-4, and 1×10-5 seconds, 1 Hz, 40 mV, and 10 μA, 30 minutes each, once aday for 10 consecutive days to simulate weak negative electric fields during action potential conduction.MAIN OUTCOME MEASURES: Glial cell growth and wrapping of carbon fibers were observed by phase contrast microscopy and immunohistochemistry.RESULTS: On culture day 7, cell groups were found to adhere to negative carbon fibers in the 1×10-3 seconds square wave group. Cell membrane-like substances grew out of cell groups, wrapped the carbon fibers, and stretched to the ends of carbon fibers. Only some small and round cells close to negative carbon fibers were found on culture day 12. In the 1×10-4 and 1×10-3 seconds square wave groups, the negative carbon fibers were wrapped by oligodendrocytes or their progenitor cells.CONCLUSION: The local negative electric field which is generated by action potentials at 1×(10-4-10-3)seconds, 40 mV can directly initiate and participate in myelination in the central nervous system.

  16. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor

    Science.gov (United States)

    Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M.

    2012-03-01

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be

  17. A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty.

    Science.gov (United States)

    Dixon, David; Coates, Jonathon; del Carpio Pons, Alicia; Horabin, Joanna; Walker, Andrew; Abdul, Nicole; Kalson, Nicholas S; Brewster, Nigel T; Weir, David J; Deehan, David J; Mann, Derek A; Borthwick, Lee A

    2015-01-01

    Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1α/β will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL-1α/β induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infra-patellar fat pad. IL-1α/β treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1α/β availability and not their ability to respond to it. PMID:26553966

  18. Cancer Driver Log (CanDL): Catalog of Potentially Actionable Cancer Mutations.

    Science.gov (United States)

    Damodaran, Senthilkumar; Miya, Jharna; Kautto, Esko; Zhu, Eliot; Samorodnitsky, Eric; Datta, Jharna; Reeser, Julie W; Roychowdhury, Sameek

    2015-09-01

    Massively parallel sequencing technologies have enabled characterization of genomic alterations across multiple tumor types. Efforts have focused on identifying driver mutations because they represent potential targets for therapy. However, because of the presence of driver and passenger mutations, it is often challenging to assign the clinical relevance of specific mutations observed in patients. Currently, there are multiple databases and tools that provide in silico assessment for potential drivers; however, there is no comprehensive resource for mutations with functional characterization. Therefore, we created an expert-curated database of potentially actionable driver mutations for molecular pathologists to facilitate annotation of cancer genomic testing. We reviewed scientific literature to identify variants that have been functionally characterized in vitro or in vivo as driver mutations. We obtained the chromosome location and all possible nucleotide positions for each amino acid change and uploaded them to the Cancer Driver Log (CanDL) database with associated literature reference indicating functional driver evidence. In addition to a simple interface, the database allows users to download all or selected genes as a comma-separated values file for incorporation into their own analysis pipeline. Furthermore, the database includes a mechanism for third-party contributions to support updates for novel driver mutations. Overall, this freely available database will facilitate rapid annotation of cancer genomic testing in molecular pathology laboratories for mutations. PMID:26320871

  19. Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.

    Science.gov (United States)

    Arnold, W David; Sheth, Kajri A; Wier, Christopher G; Kissel, John T; Burghes, Arthur H; Kolb, Stephen J

    2015-01-01

    Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons. PMID:26436455

  20. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Wentao Li

    2016-08-01

    Full Text Available Fingolimod (FTY720 is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke

  1. Effect of sampling frequency on the measurement of phase-locked action potentials.

    Directory of Open Access Journals (Sweden)

    Go eAshida

    2010-09-01

    Full Text Available Phase-locked spikes in various types of neurons encode temporal information. To quantify the degree of phase-locking, the metric called vector strength (VS has been most widely used. Since VS is derived from spike timing information, error in measurement of spike occurrence should result in errors in VS calculation. In electrophysiological experiments, the timing of an action potential is detected with finite temporal precision, which is determined by the sampling frequency. In order to evaluate the effects of the sampling frequency on the measurement of VS, we derive theoretical upper and lower bounds of VS from spikes collected with finite sampling rates. We next estimate errors in VS assuming random sampling effects, and show that our theoretical calculation agrees with data from electrophysiological recordings in vivo. Our results provide a practical guide for choosing the appropriate sampling frequency in measuring VS.

  2. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond

    CERN Document Server

    Barry, J F; Schloss, J M; Glenn, D R; Song, Y; Lukin, M D; Park, H; Walsworth, R L

    2016-01-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential (AP) dynamics in whole organisms with single-neuron resolution. Here, we present a new approach to this problem: using nitrogen-vacancy (NV) quantum defects in diamond to measure the time-dependent magnetic fields produced by single-neuron APs. Our technique has a unique combination of features: (i) it is noninvasive, as the light that probes the NV sensors stays within the biocompatible diamond chip and does not enter the organism, enabling activity monitoring over extended periods; (ii) it is label-free and should be widely applicable to most organisms; (iii) it provides high spatial and temporal resolution, allowing precise measurement of the AP waveforms and conduction velocities of individual neurons; (iv) it directly determines AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector; (v) it is applicable to neurons located within optically opaque tissue or whole org...

  3. RXP-E: a connexin43-binding peptide that prevents action potential propagation block

    DEFF Research Database (Denmark)

    Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi;

    2008-01-01

    Gap junctions provide a low-resistance pathway for cardiac electric propagation. The role of GJ regulation in arrhythmia is unclear, partly because of limited availability of pharmacological tools. Recently, we showed that a peptide called "RXP-E" binds to the carboxyl terminal of connexin43 and ...... junctions in the function of multicellular systems, including the heart.......Gap junctions provide a low-resistance pathway for cardiac electric propagation. The role of GJ regulation in arrhythmia is unclear, partly because of limited availability of pharmacological tools. Recently, we showed that a peptide called "RXP-E" binds to the carboxyl terminal of connexin43...

  4. BK channels regulate spontaneous action potential rhythmicity in the suprachiasmatic nucleus.

    Directory of Open Access Journals (Sweden)

    Jack Kent

    Full Text Available BACKGROUND: Circadian ( approximately 24 hr rhythms are generated by the central pacemaker localized to the suprachiasmatic nucleus (SCN of the hypothalamus. Although the basis for intrinsic rhythmicity is generally understood to rely on transcription factors encoded by "clock genes", less is known about the daily regulation of SCN neuronal activity patterns that communicate a circadian time signal to downstream behaviors and physiological systems. Action potentials in the SCN are necessary for the circadian timing of behavior, and individual SCN neurons modulate their spontaneous firing rate (SFR over the daily cycle, suggesting that the circadian patterning of neuronal activity is necessary for normal behavioral rhythm expression. The BK K(+ channel plays an important role in suppressing spontaneous firing at night in SCN neurons. Deletion of the Kcnma1 gene, encoding the BK channel, causes degradation of circadian behavioral and physiological rhythms. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that loss of robust behavioral rhythmicity in Kcnma1(-/- mice is due to the disruption of SFR rhythms in the SCN, we used multi-electrode arrays to record extracellular action potentials from acute wild-type (WT and Kcnma1(-/- slices. Patterns of activity in the SCN were tracked simultaneously for up to 3 days, and the phase, period, and synchronization of SFR rhythms were examined. Loss of BK channels increased arrhythmicity but also altered the amplitude and period of rhythmic activity. Unexpectedly, Kcnma1(-/- SCNs showed increased variability in the timing of the daily SFR peak. CONCLUSIONS/SIGNIFICANCE: These results suggest that BK channels regulate multiple aspects of the circadian patterning of neuronal activity in the SCN. In addition, these data illustrate the characteristics of a disrupted SCN rhythm downstream of clock gene-mediated timekeeping and its relationship to behavioral rhythms.

  5. Potential Beneficiaries of the Obama Administration’s Executive Action Programs Deeply Embedded in US Society

    Directory of Open Access Journals (Sweden)

    Donald Kerwin

    2016-03-01

    Full Text Available The Obama administration has developed two broad programs to defer immigration enforcement actions against undocumented persons living in the United States: (1 Deferred Action for Parents of Americans and Lawful Permanent Residents (DAPA; and (2 Deferred Action for Childhood Arrivals (DACA. The DACA program, which began in August 2012, was expanded on November 20, 2014. DAPA and the DACA expansion (hereinafter referred to as “DACA-plus” are currently under review by the US Supreme Court and subject to an active injunction.This paper offers a statistical portrait of the intended direct beneficiaries of DAPA, DACA, and DACA-plus. It finds that potential DAPA, DACA, and DACA-plus recipients are deeply embedded in US society, with high employment rates, extensive US family ties, long tenure, and substantial rates of English-language proficiency. The paper also notes various groups that would benefit indirectly from the full implementation of DAPA and DACA or, conversely, would suffer from the removal of potential beneficiaries of these programs. For example, all those who would rely on the retirement programs of the US government will benefit from the high employment rates and relative youth of the DACA population, while many US citizens who rely on the income of a DAPA-eligible parent would fall into poverty or extreme poverty should that parent be removed from the United States.This paper offers an analysis of potential DAPA and DACA beneficiaries. In an earlier study, the authors made the case for immigration reform based on long-term trends related to the US undocumented population, including potential DAPA and DACA beneficiaries (Warren and Kerwin 2015. By contrast, this paper details the degree to which these populations have become embedded in US society. It also compares persons eligible for the original DACA program with those eligible for DACA-plus.As stated, the great majority of potential DAPA and DACA recipients enjoy strong family

  6. Cardiac Acceleration at the Onset of Exercise : A Potential Parameter for Monitoring Progress During Physical Training in Sports and Rehabilitation

    NARCIS (Netherlands)

    Hettinga, Florentina J.; Monden, Paul G.; van Meeteren, Nico L. U.; Daanen, Hein A. M.

    2014-01-01

    There is a need for easy-to-use methods to assess training progress in sports and rehabilitation research. The present review investigated whether cardiac acceleration at the onset of physical exercise (HRonset) can be used as a monitoring variable. The digital databases of Scopus and PubMed were se

  7. Incorporated sarcolemmal fish oil fatty acids shorten pig ventricular action potentials

    NARCIS (Netherlands)

    Verkerk, A.O.; Ginneken, van A.C.G.; Berecki, G.; Ruijter, den H.M.; Schumacher, C.A.; Veldkamp, M.W.; Baartscheer, A.; Casini, S.; Opthof, T.; Hovenier, R.; Fiolet, J.W.T.; Zock, P.L.; Coronel, R.

    2006-01-01

    Background: Omega-3 polyunsaturated fatty acids (W-PUFAs) from fish oil reduce the risk of sudden death presumably by preventing life-threatening arrhythmias. Acutely administered omega 3-PUFAs modulate the activity of several cardiac ion channels, but the chronic effects of a diet enriched with fis

  8. Cardiac acceleration at the onset of exercise: a potential parameter for monitoring progress during physical training in sports and rehabilitation.

    Science.gov (United States)

    Hettinga, Florentina J; Monden, Paul G; van Meeteren, Nico L U; Daanen, Hein A M

    2014-05-01

    There is a need for easy-to-use methods to assess training progress in sports and rehabilitation research. The present review investigated whether cardiac acceleration at the onset of physical exercise (HRonset) can be used as a monitoring variable. The digital databases of Scopus and PubMed were searched to retrieve studies investigating HRonset. In total 652 studies were retrieved. These articles were then classified as having emphasis on HRonset in a sports or rehabilitation setting, which resulted in 8 of 112 studies with a sports application and 6 of 68 studies with a rehabilitation application that met inclusion criteria. Two co-existing mechanisms underlie HRonset: feedforward (central command) and feedback (mechanoreflex, metaboreflex, baroreflex) control. A number of studies investigated HRonset during the first few seconds of exercise (HRonsetshort), in which central command and the mechanoreflex determine vagal withdrawal, the major mechanism by which heart rate (HR) increases. In subsequent sports and rehabilitation studies, interest focused on HRonset during dynamic exercise over a longer period of time (HRonsetlong). Central command, mechanoreflexes, baroreflexes, and possibly metaboreflexes contribute to HRonset during the first seconds and minutes of exercise, which in turn leads to further vagal withdrawal and an increase in sympathetic activity. HRonset has been described as the increase in HR compared with resting state (delta HR) or by exponential modeling, with measurement intervals ranging from 0-4 s up to 2 min. Delta HR was used to evaluate HRonsetshort over the first 4 s of exercise, as well as for analyzing HRonsetlong. In exponential modeling, the HR response to dynamic exercise is biphasic, consisting of fast (parasympathetic, 0-10 s) and slow (sympathetic, 1-4 min) components. Although available studies differed largely in measurement protocols, cross-sectional and longitudinal training studies showed that studies analyzing HRonset

  9. Optophysiological approach to resolve neuronal action potentials with high spatial and temporal resolution in cultured neurons

    Directory of Open Access Journals (Sweden)

    Stephane ePages

    2011-10-01

    Full Text Available Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm. Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (> 10 % of fluorescence change for 100 mV depolarization and time response (submillisecond of the dye allows the robust detection of action potentials (APs even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms resolution and high spatial (µm resolution.

  10. Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Poulet, Claire; Diness, Jonas Goldin;

    2014-01-01

    (+) currents by ∼15% and prolonged action potential duration (APD), but no effect was observed in myocytes from AF patients. In trabeculae muscle strips from right atrial appendages of SR patients, both compounds increased APD and effective refractory period, and depolarized the resting membrane potential...

  11. Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review.

    Science.gov (United States)

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina; Dale, Elena; Wegener, Gregers; Sanchez, Connie

    2016-11-01

    A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not

  12. Surface electrocardiogram and action potential in mice lacking urea transporter UT-B

    Institute of Scientific and Technical Information of China (English)

    MENG Yan; ZHAO ChunYan; ZHANG XueXin; ZHAO HuaShan; GUO LiRong; Lü Bin; ZHAO XueJian; YANG BaoXue

    2009-01-01

    UT-B is a urea transporter protein expressed in the kidney and in many non-renal tissues including erythrocytes, brain, heart, bladder and the testis. The objective of this study was to determine the phenotype of UT-B deletion in the heart. UT-B expression in the heart was studied in wild-type mice vs UT-B null mice by utilizing RT-PCR and Western blot. A surface electrocardiogram (ECG) recording (lead Ⅱ) was measured in wild-type mice and UT-B null mice at the ages of 6, 16 and 52 weeks. For the action potential recording, the ventricular myocytes of 16 w mice were isolated and recorded by float-ing microelectrode method. The sodium current was recorded by the patch clamp technique. RT-PCR and Western blot showed the UT-B expression in the heart of wild-type mice. No UT-B transcript and protein was found in UT-B null mice. The ECG recording showed that the P-R interval was significantly prolonged in UT-B null mice ((43.5±4.2), (45.5±6.9) and (43.8±7.6) ms at ages of 6, 16 and 52 weeks) vs wild-type mice ((38.6±2.9), (38.7±5.6) and (38.2±7.3) ms, P<0.05). The atrial ventricular heart block type Ⅱ and Ⅲ only appeared in the aging UT-B null mice (52 w old). The amplitude of action potential and Vmax decreased significantly in UT-B null mice ((92.17±10.56) and (101.89±9.54) mV/s) vs those in wild-type mice (vs (110.51±10.38) and (109.53±10.64) mV/s, P<0.05). The action potential duration at 50% and 90% (APD50 and APD90) was significantly prolonged in UT-B null mice ((123.83±11.17) and (195.43±16.41) ms) vs that in wild-type mice ((108.27±10.85) and (171.00±15.53) ms, P<0.05). The maximal sodium current decreased significantly in UT-B null mice (-8.80±0.92) nA vs that in wild-type mice ((-5.98±1.07) nA, P<0.05). These results provide the first evidence that UT-B deletion causes progressive heart block in mice.

  13. Surface electrocardiogram and action potential in mice lacking urea transporter UT-B

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    UT-B is a urea transporter protein expressed in the kidney and in many non-renal tissues including erythrocytes, brain, heart, bladder and the testis. The objective of this study was to determine the phenotype of UT-B deletion in the heart. UT-B expression in the heart was studied in wild-type mice vs UT-B null mice by utilizing RT-PCR and Western blot. A surface electrocardiogram (ECG) recording (lead II) was measured in wild-type mice and UT-B null mice at the ages of 6, 16 and 52 weeks. For the action potential recording, the ventricular myocytes of 16 w mice were isolated and recorded by floating microelectrode method. The sodium current was recorded by the patch clamp technique. RT-PCR and Western blot showed the UT-B expression in the heart of wild-type mice. No UT-B transcript and protein was found in UT-B null mice. The ECG recording showed that the P-R interval was significantly prolonged in UT-B null mice ((43.5 ± 4.2), (45.5 ± 6.9) and (43.8 ± 7.6) ms at ages of 6, 16 and 52 weeks) vs wild-type mice ((38.6 ± 2.9), (38.7 ± 5.6) and (38.2 ± 7.3) ms, P<0.05). The atrial ventricular heart block type II and III only appeared in the aging UT-B null mice (52 w old). The amplitude of action potential and Vmax decreased significantly in UT-B null mice ((92.17 ± 10.56) and (101.89 ± 9.54) mV/s) vs those in wild-type mice (vs (110.51 ± 10.38) and (109.53 ± 10.64) mV/s, P<0.05). The action potential duration at 50% and 90% (APD50 and APD90) was significantly prolonged in UT-B null mice ((123.83 ± 11.17) and (195.43 ± 16.41) ms) vs that in wild-type mice ((108.27 ± 10.85) and (171.00 ± 15.53) ms, P<0.05). The maximal sodium current decreased significantly in UT-B null mice (-8.80 ± 0.92) nA vs that in wild-type mice ((-5.98 ± 1.07) nA, P<0.05). These results provide the first evidence that UT-B deletion causes progressive heart block in mice.

  14. An experimental study on the physical properties of the cupula. Effect of cupular sectioning on the ampullary nerve action potential.

    Science.gov (United States)

    Suzuki, M; Harada, Y; Kishimoto, A

    1985-01-01

    The frog posterior semicircular canal (PSC) was isolated and a part of the ampullary wall was cut to allow removal of the cupula from the crista. The cupula was replaced on the crista and the PSC ampullary action potential was recorded. The cupula was again removed and was sectioned in half, either in the plane vertical to the crista (vertical sectioning), or in the plane parallel to the crista (horizontal sectioning). The sectioned half of the cupula was then replaced on the crista. The action potentials after replacement of the vertical or horizontal segments of the cupula were compared to those achieved when the entire cupula was replaced. After vertical sectioning, the action potentials were significantly reduced; they were 50.3% of the completely replaced cupula when a small stimulus was used and 79.1% when a large stimulus was used. A reduced attachment surface between the cupular base and the crista is possibly responsible for the decreased action potential in the vertically sectioned specimen. After horizontal sectioning, the action potentials were 64.5% for the small stimulus and 108.2% for the large stimulus. These results indicate that elicited responses are related to the height of the cupula and the deflection angle. This further suggests that the movement of the cupula is represented by that of the elastic system.

  15. CLINICAL AND EXPERIMENTAL STUDIES OF LARGE AMPLITUDE ACTION POTENTIAL OF THE SUFFERED FACIAL MUSCLES IN INTRATEMPORAL FACIAL NERVE PARALYSIS

    Institute of Scientific and Technical Information of China (English)

    任重; 惠莲

    1999-01-01

    Objctive. To testify the phenomenon that large amplitude action potential appears at the early stage oil facial paralysis, and to search for the mechanism through clinical and experimental studies. Patients(aninmls) and methods. The action potentials of the orbicular ocular and oral museles were recorded in 34 normal persons by electromyogram instrtiments. The normal range of amplitude percentage was found out according to the normal distribution, One hundred patients with facial paralysis were also studied. The action potentials of facial muscles were recorded ia 17 guinea pigs before and after the facial nerve was comp~ and the facial nerve was examined under electromicroscope before and after the compression.Results. The amplitude percentage of the suffered side to the healthy side was more than 153 percent in 6 of the 100 patients. Large amplitude action potential occured in 35 per cent guinea pigs which were performed the experiment of facial nerve compression. Electromicroscopic examination revealed separation of the lammae of the facial nerve's myelin sheath in the guinea pigs which exhibited large amplitude action potential Conclusion. The facial nerve exhibited a temporary over-excitability at the early stage of facial nerve injury in scane patients and guinea pigs. If the injury was limited in the myelin sheath, the prognods was relatively good.

  16. CLINICAL AND EXPERIMENTAL STUDIES OF LARGE AMPLITUDE ACTION POTENTIAL OF THE SUFFERED FACIAL MUSCLES IN INTRATEMPORAL FACIAL NERVE PARALYSIS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Ojective. To testify the phenomenon that large amplitude action potential appears at the early stage of facial paralysis, and to search for the mechanism through clinical and experimental studies. Patients(animals) and methods. The action potentials of the orbicular ocular and oral muscles were recorded in 34 normal persons by electromyogram instruments. The normal range of amplitude percentage was found out according to he normal distribution. One hundred patients with facial paralysis were also studied. The action potentials of facial muscles were recorded in 17 guinea pigs before and after the facial nerve was compressed and the facial nerve was examined under electromicroscope before and after the compression.Results. The amplitude percentage of the suffered ide to the healthy side was more than 153 percent in 6 of the 100 patients. Lare amplitude action potential ocured in 35 per cent guinea pigs which were performed the experiment of facial nrve compression. Electromicroscopic examination revealed separation of the lammae of the facial nerve's myelin sheath in the guinea pigs which exhibited large amplitude action potential.Conclusion. The facial nerve exhibited a temporary over-exciability at the early stage of facial nerve injury in some patients and guinea pigs. If the injury waslimited in the myelin sheath, te prognosis was relatively good.

  17. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  18. Generation of cardiac pacemaker cells by programming and differentiation.

    Science.gov (United States)

    Husse, Britta; Franz, Wolfgang-Michael

    2016-07-01

    A number of diseases are caused by faulty function of the cardiac pacemaker and described as "sick sinus syndrome". The medical treatment of sick sinus syndrome with electrical pacemaker implants in the diseased heart includes risks. These problems may be overcome via "biological pacemaker" derived from different adult cardiac cells or pluripotent stem cells. The generation of cardiac pacemaker cells requires the understanding of the pacing automaticity. Two characteristic phenomena the "membrane-clock" and the "Ca(2+)-clock" are responsible for the modulation of the pacemaker activity. Processes in the "membrane-clock" generating the spontaneous pacemaker firing are based on the voltage-sensitive membrane ion channel activity starting with slow diastolic depolarization and discharging in the action potential. The influence of the intracellular Ca(2+) modulating the pacemaker activity is characterized by the "Ca(2+)-clock". The generation of pacemaker cells started with the reprogramming of adult cardiac cells by targeted induction of one pacemaker function like HCN1-4 overexpression and enclosed in an activation of single pacemaker specific transcription factors. Reprogramming of adult cardiac cells with the transcription factor Tbx18 created cardiac cells with characteristic features of cardiac pacemaker cells. Another key transcription factor is Tbx3 specifically expressed in the cardiac conduction system including the sinoatrial node and sufficient for the induction of the cardiac pacemaker gene program. For a successful cell therapeutic practice, the generated cells should have all regulating mechanisms of cardiac pacemaker cells. Otherwise, the generated pacemaker cells serve only as investigating model for the fundamental research or as drug testing model for new antiarrhythmics. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  19. Generation of cardiac pacemaker cells by programming and differentiation.

    Science.gov (United States)

    Husse, Britta; Franz, Wolfgang-Michael

    2016-07-01

    A number of diseases are caused by faulty function of the cardiac pacemaker and described as "sick sinus syndrome". The medical treatment of sick sinus syndrome with electrical pacemaker implants in the diseased heart includes risks. These problems may be overcome via "biological pacemaker" derived from different adult cardiac cells or pluripotent stem cells. The generation of cardiac pacemaker cells requires the understanding of the pacing automaticity. Two characteristic phenomena the "membrane-clock" and the "Ca(2+)-clock" are responsible for the modulation of the pacemaker activity. Processes in the "membrane-clock" generating the spontaneous pacemaker firing are based on the voltage-sensitive membrane ion channel activity starting with slow diastolic depolarization and discharging in the action potential. The influence of the intracellular Ca(2+) modulating the pacemaker activity is characterized by the "Ca(2+)-clock". The generation of pacemaker cells started with the reprogramming of adult cardiac cells by targeted induction of one pacemaker function like HCN1-4 overexpression and enclosed in an activation of single pacemaker specific transcription factors. Reprogramming of adult cardiac cells with the transcription factor Tbx18 created cardiac cells with characteristic features of cardiac pacemaker cells. Another key transcription factor is Tbx3 specifically expressed in the cardiac conduction system including the sinoatrial node and sufficient for the induction of the cardiac pacemaker gene program. For a successful cell therapeutic practice, the generated cells should have all regulating mechanisms of cardiac pacemaker cells. Otherwise, the generated pacemaker cells serve only as investigating model for the fundamental research or as drug testing model for new antiarrhythmics. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel

  20. Cardiac arrest during gamete release in chum salmon regulated by the parasympathetic nerve system.

    Directory of Open Access Journals (Sweden)

    Yuya Makiguchi

    Full Text Available Cardiac arrest caused by startling stimuli, such as visual and vibration stimuli, has been reported in some animals and could be considered as an extraordinary case of bradycardia and defined as reversible missed heart beats. Variability of the heart rate is established as a balance between an autonomic system, namely cholinergic vagus inhibition, and excitatory adrenergic stimulation of neural and hormonal action in teleost. However, the cardiac arrest and its regulating nervous mechanism remain poorly understood. We show, by using electrocardiogram (ECG data loggers, that cardiac arrest occurs in chum salmon (Oncorhynchus keta at the moment of gamete release for 7.39+/-1.61 s in females and for 5.20+/-0.97 s in males. The increase in heart rate during spawning behavior relative to the background rate during the resting period suggests that cardiac arrest is a characteristic physiological phenomenon of the extraordinarily high heart rate during spawning behavior. The ECG morphological analysis showed a peaked and tall T-wave adjacent to the cardiac arrest, indicating an increase in potassium permeability in cardiac muscle cells, which would function to retard the cardiac action potential. Pharmacological studies showed that the cardiac arrest was abolished by injection of atropine, a muscarinic receptor antagonist, revealing that the cardiac arrest is a reflex response of the parasympathetic nerve system, although injection of sotalol, a beta-adrenergic antagonist, did not affect the cardiac arrest. We conclude that cardiac arrest during gamete release in spawning release in spawning chum salmon is a physiological reflex response controlled by the parasympathetic nervous system. This cardiac arrest represents a response to the gaping behavior that occurs at the moment of gamete release.

  1. Short-term inspiratory muscle training potentiates the benefits of aerobic and resistance training in patients undergoing CABG in phase II cardiac rehabilitation program

    Directory of Open Access Journals (Sweden)

    Bárbara Maria Hermes

    2015-08-01

    Full Text Available Abstract Objective: To investigate the efficiency of short-term inspiratory muscle training program associated with combined aerobic and resistance exercise on respiratory muscle strength, functional capacity and quality of life in patients who underwent coronary artery bypass and are in the phase II cardiac rehabilitation program. Methods: A prospective, quasi-experimental study with 24 patients who underwent coronary artery bypass and were randomly assigned to two groups in the Phase II cardiac rehabilitation program: inspiratory muscle training program associated with combined training (aerobic and resistance group (GCR + IMT, n=12 and combined training with respiratory exercises group (GCR, n=12, over a period of 12 weeks, with two sessions per week. Before and after intervention, the following measurements were obtained: maximal inspiratory and expiratory pressures (PImax and PEmax, peak oxygen consumption (peak VO2 and quality of life scores. Data were compared between pre- and post-intervention at baseline and the variation between the pre- and post-phase II cardiac rehabilitation program using the Student's t-test, except the categorical variables, which were compared using the Chi-square test. Values of P<0.05 were considered statistically significant. Results: Compared to GCR, the GCR + IMT group showed larger increments in PImax (P<0.001, PEmax (P<0.001, peak VO2 (P<0.001 and quality of life scores (P<0.001. Conclusion: The present study demonstrated that the addition of inspiratory muscle training, even when applied for a short period, may potentiate the effects of combined aerobic and resistance training, becoming a simple and inexpensive strategy for patients who underwent coronary artery bypass and are in phase II cardiac rehabilitation.

  2. Abnormal cardiac autonomic regulation in mice lacking ASIC3.

    Science.gov (United States)

    Cheng, Ching-Feng; Kuo, Terry B J; Chen, Wei-Nan; Lin, Chao-Chieh; Chen, Chih-Cheng

    2014-01-01

    Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3) is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3(-/-) mice. Asic3(-/-) mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3(-/-) mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3(-/-) mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases. PMID:24804235

  3. Abnormal Cardiac Autonomic Regulation in Mice Lacking ASIC3

    Directory of Open Access Journals (Sweden)

    Ching-Feng Cheng

    2014-01-01

    Full Text Available Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3 is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3−/− mice. Asic3−/− mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3−/− mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3−/− mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.

  4. Control of spiral waves and turbulent states in a cardiac model by travelling-wave perturbations

    Institute of Scientific and Technical Information of China (English)

    王鹏业; 谢平; 尹华伟

    2003-01-01

    We propose a travelling-wave perturbation method to control the spatiotemporal dynamics in a cardiac model.It is numerically demonstrated that the method can successfully suppress the wave instability(alternans in action potential duration) in the one-dimensional case and convert spiral waves and turbulent states to the normal travelling wave states in the two-dimensional case.An experimental scheme is suggested which may provide a new design for a cardiac defibrillator.

  5. Multislice Cardiac CT-Angiography; A Review on Accepted Indications and Potentials for Other Applications Regarding the Newest Development

    Directory of Open Access Journals (Sweden)

    M. Motevalli

    2007-05-01

    Full Text Available There were not any clear-cut criteria available for clinical use of cardiac CT-angiography (CCTA up to October 2006 in which the American College of Car-diology (ACC, American College of Radiology (ACR and six other medical institutions released a joint consensus on clinical indications of cardiac CT and MRI. A statement was released by the American Heart Association together with two other radiology and cardiology institutions in the same month on the same matter. An illustrated review will be presented on the newly accepted indications of cardiac CT, especially CCTA. Some prominent indications are as follow: 1. Evaluation of chest pain syndrome in patient with intermediate pretest probability of coronary artery disease (CAD when exercise test is not feasible. 2. Evaluation of acute chest pain in patient with in-termediate pretest probability of CAD and negative ECG and enzymes. 3. Uninterpretable or equivocal stress test (exercise, perfusion scan, or stress echo. 4. Evaluation of coronary arteries in patients with new onset heart failure. 5. Assessment of congenital coronary and cardiac anomalies. 6. Noninvasive coronary vein mapping prior to placement of biventricular pacemaker. 7. Noninvasive coronary arterial mapping, including internal mammary artery prior to repeat cardiac sur-gical revascularization. Some recent research indicated that CCTA is useful in some other specific situations too, like evaluating in-stent re-stenosis for stainless steel or cobalt stents more than 3mm in diameter and has also some roles in the evaluation of coronary bypass grafts, etc. Fi-nally, the newer progressions in the field of multislice CT are promising of even better performance which may widen the scope of its indications. Dual-source CT scanners have shown better performance com-pared with 64-slice CT scanners in the preliminary studies, namely slice-thickness of 0.25mm vs. 0.4mm, temporal resolution of 83ms vs.165ms, assessable segments of 98.6% vs. 97

  6. The transformative potential of action research and ICT in the Second Language (L2 classroom

    Directory of Open Access Journals (Sweden)

    Farren Margaret

    2015-12-01

    Full Text Available This study shows the transformative potential of action research and information and communications technology (ICT in the second language (L2 classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT creatively in their classroom. Gee (2008 advocates the use of the preferred media of our classroom students in order to address their learning. Prensky (2001 urges us to feel the fear and do it anyway with our digital native classes. A post-primary teacher and a primary teacher show us how they felt the fear, did it and transformed aspects of their own teaching in the process. The Masters programme required the teachers to engage with innovative practices, informed by their own values, and integrate technologies that were new to them into their repertoire of classroom strategies. Peer validation meetings with colleagues enabled meaningful insights to emerge from the research. The teachers improve and transform their second language (L2 practice in collaboration and validation with others.

  7. Effects of terpineol on the compound action potential of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    M.R. Moreira

    2001-10-01

    Full Text Available Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the perfumery industry. It is an important chemical constituent of the essential oil of many plants with widespread applications in folk medicine and in aromatherapy. The effects of terpineol on the compound action potential (CAP of rat sciatic nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At 100 µM, terpineol had no demonstrable effect. At 300 µM terpineol, peak-to-peak amplitude and conduction velocity of CAP were significantly reduced at the end of 180-min exposure of the nerve to the drug, from 3.28 ± 0.22 mV and 33.5 ± 7.05 m/s, respectively, to 1.91 ± 0.51 mV and 26.2 ± 4.55 m/s. At 600 µM, terpineol significantly reduced peak-to-peak amplitude and conduction velocity from 2.97 ± 0.55 mV and 32.8 ± 3.91 m/s to 0.24 ± 0.23 mV and 2.72 ± 2.72 m/s, respectively (N = 5. All these effects developed slowly and were reversible upon 180-min washout.

  8. Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.

    Science.gov (United States)

    Fabbro, Alessandra; Sucapane, Antonietta; Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.

  9. Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

    Science.gov (United States)

    Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B; Niven, Jeremy E

    2010-01-01

    The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+) and K(+) currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+) and K(+) channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost. PMID:20617202

  10. Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

    Directory of Open Access Journals (Sweden)

    Biswa Sengupta

    Full Text Available The initiation and propagation of action potentials (APs places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+ and K(+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+ and K(+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost.

  11. Dispersion of compound muscle action potential in hereditary neuropathies and chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Stanton, Michael; Pannoni, Valerie; Lewis, Richard A; Logigian, Eric L; Naguib, Demian; Shy, Michael E; Cleland, James; Herrmann, David N

    2006-10-01

    Distal compound muscle action potential (DCMAP) dispersion, defined as a DCMAP duration > or = 9 ms, and proximal-distal (P-D) CMAP dispersion are considered useful in the electrodiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Distal and P-D CMAP dispersion have not been fully studied in hereditary neuropathies, and it is not known whether these measures distinguish hereditary from acquired demyelination. We compared DCMAP duration and P-D CMAP dispersion in 91 genetically characterized hereditary neuropathies and 33 subjects with CIDP. DCMAP dispersion was more frequent in nerves affected by CIDP (41.5%) than in Charcot-Marie-Tooth disease (CMT)1A (24.4%), CMT1B (7.4%), hereditary neuropathy with liability to pressure palsies (HNPP) (10.5%), or CMTX (9.8%). P-D CMAP dispersion was more frequent in CIDP (27.7% of nerves) than in hereditary neuropathies (16.3%) when applying American Academy of Neurology (AAN) criteria; however, its frequency was similar in CIDP and the hereditary neuropathies using the more restrictive criteria of the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). Although dispersion is more common in CIDP than in the hereditary neuropathies, DCMAP and P-D dispersion occur in at least one motor nerve in a significant proportion of hereditary neuropathies, and cannot be used in isolation to distinguish acquired from hereditary demyelination.

  12. Sensitivity analysis of potential events affecting the double-shell tank system and fallback actions

    Energy Technology Data Exchange (ETDEWEB)

    Knutson, B.J.

    1996-09-27

    Sensitivity analyses were performed for fall-back positions (i.e., management actions) to accommodate potential off-normal and programmatic change events overlaid on the waste volume projections and their uncertainties. These sensitivity analyses allowed determining and ranking tank system high-risk parameters and fall- back positions that will accommodate the respective impacts. This quantification of tank system impacts shows periods where tank capacity is sensitive to certain variables that must be carefully managed and/or evaluated. Identifying these sensitive variables and quantifying their impact will allow decision makers to prepare fall-back positions and focus available resources on the highest impact parameters where technical data are needed to reduce waste projection uncertainties. For noncomplexed waste, the period of capacity vulnerability occurs during the years of single-shell tank (SST) retrieval (after approximately 2009) due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate and 200-East SST solids transfer volume. For complexed waste, the period of capacity vulnerability occurs during the period after approximately 2005 due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate. 200-East SST solids transfer volume. complexed waste reduction factor using evaporation, and 200-west saltwell liquid porosity.

  13. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics

    Directory of Open Access Journals (Sweden)

    Fikret Emre eKapucu

    2012-06-01

    Full Text Available In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESC, exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI histograms. Moreover, the algorithm calculates interspike interval thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  14. Antifungal potential of Sideroxylon obtusifolium and Syzygium cumini and their mode of action against Candida albicans.

    Science.gov (United States)

    Pereira, Jozinete Vieira; Freires, Irlan Almeida; Castilho, Aline Rogéria; da Cunha, Marcos Guilherme; Alves, Harley da Silva; Rosalen, Pedro Luiz

    2016-10-01

    Context The emergence of resistant pathogens and toxicity of antifungals have encouraged an active search for novel candidates to manage Candida biofilms. Objective In this study, the little known species Sideroxylon obtusifolium T.D. Penn (Sapotacea) and Syzygium cumini (L.) Skeels (Myrtaceae), from the Caatinga biome in Brazil were chemically characterized and explored for their antifungal potential against C. albicans. Materials and methods We determined the effects of hydroalcoholic extracts/fractions upon fungal growth (minimum inhibitory and fungicidal concentrations, MIC/MFC), biofilm morphology (scanning electron microscopy) and viability (confocal laser scanning microscopy), proposed their mode of action (sorbitol and ergosterol assays), and finally investigated their effects against macrophage and keratinocyte cells in a cell-based assay. Data were analysed using one-way analysis of variance with Tukey-Kramer post-test (α = 0.05). Results The n-butanol (Nb) fraction from S. obtusifolium and S. cumini extract (Sc) showed flavonoids (39.11 ± 6.62 mg/g) and saponins (820.35 ± 225.38 mg/g), respectively, in their chemical composition and demonstrated antifungal activity, with MICs of 62.5 and 125 μg/mL, respectively. Nb and Sc may complex with ergosterol as there was a 4-16-fold increase in MICs in the presence of exogenous ergosterol, leading to disrupted permeability of cell membrane. Deleterious effects were observed on morphology and viability of treated biofilms from concentrations as low as their MICs and higher. Sc was not toxic to macrophages and keratinocytes at these concentrations (p > 0.05), unlike Nb. Conclusions Nb and Sc demonstrated considerable antifungal activity and should be further investigated as potential alternative candidates to treat Candida biofilms. PMID:26987037

  15. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake.

    Science.gov (United States)

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A S; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-02-01

    Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant. PMID:26804557

  16. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake.

    Science.gov (United States)

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A S; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-02-01

    Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant.

  17. Ionic mechanisms maintaining action potential conduction velocity at high firing frequencies in an unmyelinated axon.

    Science.gov (United States)

    Cross, Kevin P; Robertson, R Meldrum

    2016-05-01

    The descending contralateral movement detector (DCMD) is a high-performance interneuron in locusts with an axon capable of transmitting action potentials (AP) at more than 500 Hz. We investigated biophysical mechanisms for fidelity of high-frequency transmission in this axon. We measured conduction velocities (CVs) at room temperature during exposure to 10 mmol/L cadmium, a calcium current antagonist, and found significant reduction in CV with reduction at frequencies >200 Hz of ~10%. Higher temperatures induced greater CV reductions during exposure to cadmium across all frequencies of ~20-30%. Intracellular recordings during 15 min of exposure to cadmium or nickel, also a calcium current antagonist, revealed an increase in the magnitude of the afterhyperpolarization potential (AHP) and the time to recover to baseline after the AHP (Medians for Control: -19.8%; Nickel: 167.2%; Cadmium: 387.2%), that could be due to a T-type calcium current. However, the removal of extracellular calcium did not mimic divalent cation exposure suggesting calcium currents are not the cause of the AHP increase. Computational modeling showed that the effects of the divalent cations could be modeled with a persistent sodium current which could be blocked by high concentrations of divalent cations. Persistent sodium current shortened the AHP duration in our models and increased CV for high-frequency APs. We suggest that faithful, high-frequency axonal conduction in the DCMD is enabled by a mechanism that shortens the AHP duration like a persistent or resurgent sodium current. PMID:27225630

  18. MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro

    Directory of Open Access Journals (Sweden)

    F Woodward Hopf

    2013-04-01

    Full Text Available The MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the expression of cocaine self-administration. A recent report (Chung et al., 2011a showed that the DA1/DA2 dopamine receptor activator apomorphine suppresses pre-pulse inhibition, a preclinical model for some aspects of schizophrenia. Importantly, MCH can enhance the effects of lower doses of apomorphine, suggesting that co-modulation of dopamine and MCH receptors might alleviate some symptoms of schizophrenia with a lower dose of dopamine receptor modulator and thus fewer potential side effects. Here, we investigated whether MCH and apomorphine could enhance action potential firing in vitro in the nucleus accumbens shell (NAshell, a region which has previously been shown to mediate some behavioral effects of MCH. Using whole-cell patch-clamp electrophysiology, we found that MCH, which has no effect on firing on its own, was able to increase NAshell firing when combined with a subthreshold dose of apomorphine. Further, this MCH/apomorphine increase in firing was prevented by an antagonist of either a DA1 or a DA2 receptor, suggesting that apomorphine acts through both receptor types to enhance NAshell firing. The MCH/apomorphine-mediated firing increase was also prevented by an MCH receptor antagonist or a PKA inhibitor. Taken together, our results suggest that MCH can interact with lower doses of apomorphine to enhance NAshell firing, and thus that MCH and apomorphine might interact in vivo within the NAshell to suppress pre-pulse inhibition.

  19. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics.

    Science.gov (United States)

    Kapucu, Fikret E; Tanskanen, Jarno M A; Mikkonen, Jarno E; Ylä-Outinen, Laura; Narkilahti, Susanna; Hyttinen, Jari A K

    2012-01-01

    In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESCs), exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI) histograms. Moreover, the algorithm calculates ISI thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average (CMA) and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA) data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  20. Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Galpin, Jason D; Frankel, Adam;

    2011-01-01

    -Williams classification system into classes Ia-c based on their distinct effects on the electrocardiogram. How can these drugs elicit distinct effects on the cardiac action potential by binding to a common receptor? Here we use fluorinated phenylalanine derivatives to test whether the electronegative surface potential...

  1. Risk factors and the effect of cardiac resynchronization therapy on cardiac and non-cardiac mortality in MADIT-CRT

    DEFF Research Database (Denmark)

    Perkiomaki, Juha S; Ruwald, Anne-Christine; Kutyifa, Valentina;

    2015-01-01

    causes, 108 (63.9%) deemed cardiac, and 61 (36.1%) non-cardiac. In multivariate analysis, increased baseline creatinine was significantly associated with both cardiac and non-cardiac deaths [hazard ratio (HR) 2.97, P ...AIMS: To understand modes of death and factors associated with the risk for cardiac and non-cardiac deaths in patients with cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) vs. implantable cardioverter-defibrillator (ICD) therapy, which may help clarify...... the action and limitations of cardiac resynchronization therapy (CRT) in relieving myocardial dysfunction. METHODS AND RESULTS: In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), during 4 years of follow-up, 169 (9.3%) of 1820 patients died of known...

  2. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    Science.gov (United States)

    Elskus, Adria A.

    2012-01-01

    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to

  3. Facilitating Youth to Take Sustainability Actions: The Potential of Peer Education

    Science.gov (United States)

    de Vreede, Catherine; Warner, Alan; Pitter, Robert

    2014-01-01

    Peer education is an understudied yet valuable strategy for sustainability educators in shifting youth to take action for sustainability. This case study conceptualizes the change process in facilitating youth to take sustainability actions, and explores the benefits, dynamics, and challenges of peer education as a strategy in facilitating change.…

  4. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    Science.gov (United States)

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

    2016-06-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  5. HERG channel (dys)function revealed by dynamic action potential clamp technique

    OpenAIRE

    Berecki, G; Zegers, J.G.; Verkerk, A.O.; Bhuiyan, Z.A.; Jonge, de, M.J.I.; Veldkamp, M.W.; Wilders, R; Ginneken, van, CJJM Kees

    2005-01-01

    The human ether-a-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier potassium current (IKr). Per-Arnt-Sim domain mutations of the HERG channel are linked to type 2 long-QT syndrome. We studied wild-type and/or type 2 long-QT syndrome-associated mutant (R56Q) HERG current (IHERG) in HEK-293 cells, at both 23 and 36°C. Conventional voltage-clamp analysis revealed mutation-induced changes in channel kinetics. To assess functional implication(s) of the mutatio...

  6. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons.

    Science.gov (United States)

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C

    2016-08-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca(2+) entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca(2+) buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca(2+)-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca(2+) elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377724

  7. Effects of estragole on the compound action potential of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    J.H. Leal-Cardoso

    2004-08-01

    Full Text Available Estragole, a relatively nontoxic terpenoid ether, is an important constituent of many essential oils with widespread applications in folk medicine and aromatherapy and known to have potent local anesthetic activity. We investigated the effects of estragole on the compound action potential (CAP of the rat sciatic nerve. The experiments were carried out on sciatic nerves dissected from Wistar rats. Nerves, mounted in a moist chamber, were stimulated at a frequency of 0.2 Hz, with electric pulses of 50-100-µs duration at 10-20 V, and evoked CAP were monitored on an oscilloscope and recorded on a computer. CAP control parameters were: peak-to-peak amplitude (PPA, 9.9 ± 0.55 mV (N = 15, conduction velocity, 92.2 ± 4.36 m/s (N = 15, chronaxy, 45.6 ± 3.74 µs (N = 5, and rheobase, 3.9 ± 0.78 V (N = 5. Estragole induced a dose-dependent blockade of the CAP. At 0.6 mM, estragole had no demonstrable effect. At 2.0 and 6.0 mM estragole, PPA was significantly reduced at the end of 180-min exposure of the nerve to the drug to 85.6 ± 3.96 and 13.04 ± 1.80% of control, respectively. At 4.0 mM, estragole significantly altered PPA, conduction velocity, chronaxy, and rheobase (P <= 0.05, ANOVA; N = 5 to 49.3 ± 6.21 and 77.7 ± 3.84, 125.9 ± 10.43 and 116.7 ± 4.59%, of control, respectively. All of these effects developed slowly and were reversible upon a 300-min wash-out. The data show that estragole dose-dependently blocks nerve excitability.

  8. Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential.

    Science.gov (United States)

    Chang, C L T; Chen, Yi-Ching; Chen, Hui-Ming; Yang, Ning-Sun; Yang, Wen-Chin

    2013-01-01

    Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers. Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide. This disease is caused by autoimmunity-mediated destruction of pancreatic β-cells, leading to insulin deficiency, hyperglycemia and complications. Currently, there is no cure for type 1 diabetes. Insulin injection is the only medication; however, it accompanies serious medical complications. Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy. Despite recent advances in anti-diabetic strategies, no strategy is clinically successful. How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development. Plants provide an extraordinary source of natural medicines for different diseases. Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry. Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives. In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type-1 diabetes. Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic β-cells. We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes. New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed. PMID:23210779

  9. Inter-subject variability in human atrial action potential in sinus rhythm versus chronic atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Carlos Sánchez

    Full Text Available Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR and chronic atrial fibrillation (cAF patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP recorded in 363 patients both under SR and cAF conditions.Human AP recordings in atrial trabeculae (n = 469 from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in G(K1, G(Kur and G(to, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in I(K1 and I(NaK underlies variability in APD90, variability in I(Kur, I(CaL and I(NaK modulates variability in APD50 and combined variability in Ito and I(Kur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by I(K1 and either I(NaK or I(NaCa depending on the model.Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP

  10. Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs:An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery

    OpenAIRE

    Emanueli, Costanza; Shearn, Andrew I. U.; Laftah, Abas; Fiorentino, Francesca; Reeves, Barnaby C.; Beltrami, Cristina; Mumford, Andrew; Clayton, Aled; Gurney, Mark; Shantikumar, Saran; Angelini, Gianni D.

    2016-01-01

    INTRODUCTION: Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac mi...

  11. Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery

    OpenAIRE

    Emanueli, Costanza; Shearn, Andrew I. U.; Laftah, Abas; Fiorentino, Francesca; Reeves, Barnaby C.; Beltrami, Cristina; Mumford, Andrew; Clayton, Aled; Gurney, Mark; Shantikumar, Saran; Angelini, Gianni D.

    2016-01-01

    Introduction Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miR...

  12. Synthesis of a dendritic estrogen cluster: A potential tool for studies of nuclear versus extranuclear pathways of estrogen actions

    Institute of Scientific and Technical Information of China (English)

    Jian Chen; Hu Zheng; Yan Song; Yu Feng Liang; Qing Rong Qi

    2012-01-01

    A novel estrogen dendrimer has been synthesized through a combination of divergent and convergent approaches in 9 practical steps and in good yields.It was characterized and confirmed by elemental analysis,FT-IR,MS,1H NMR,13C NMR.The dendrimer contains 16 estrone units and is potentially a useful tool for the studies of estrogen actions.

  13. Predictive value of local and core laboratory echocardiographic assessment of cardiac function in patients with chronic stable angina: The ACTION study

    NARCIS (Netherlands)

    A.M. Dart (Anthony); J.E. Otterstad (Jan Erik); B.A. Kirwan (Bridget Anne); J.D. Parker (John); S. de Brouwer (Sophie); P. Poole-Wilson (Philip); J. Lubsen (Jacobus)

    2007-01-01

    textabstractAims: To evaluate the relationship between echocardiographic cardiac function and outcome in patients with stable symptomatic angina. Methods: Baseline echo left ventricular ejection fraction and volume data measured in a central laboratory was available for 7016 patients (92% of the tot

  14. Determination of the onset of beta-methyl-digoxin action by potentiation of the adenosine response in guinea pigs.

    Directory of Open Access Journals (Sweden)

    Fukuda,Tamotsu

    1985-06-01

    Full Text Available The onset of beta-methyl-digoxin action was investigated by the potentiation of the adenosine response in guinea pigs and rats, and compared with that of digoxin and dipyridamole. A number of i.v. infusions of adenosine were given to determine the mean control adenosine response and its 95% confidence limits. After oral administration of the drugs, successive infusions of adenosine were continued until a drug-induced potentiation of the adenosine response was observed. The time of appearance of the potentiated adenosine response was marked as the onset of action of the drugs. The onset of action in guinea pigs was 9 to 12 min for 0.2 to 0.4 mg/kg of beta-methyl-digoxin, 90 to 100 min for 0.2 mg/kg of digoxin and 25 min for 5 mg/kg of dipyridamole. The maximal potentiation was 48.8 to 53.8% at 18 to 21 min for beta-methyl-digoxin, 74.5% at 130 min for digoxin and 74.8% at 80 min for dipyridamole. Adenosine infused i.v. into rats produced heart block, as in guinea pigs. However, in rats, the adenosine response was not potentiated by beta-methyl-digoxin and digoxin. Dipyridamole at a dose as high as 200 mg/kg produced 25.8% potentiation at 36 min after oral administration to rats.

  15. Assessing the Potential Impact of a Nationwide Class-Based Affirmative Action System

    OpenAIRE

    Xiang, Alice; Rubin, Donald B.

    2015-01-01

    We examine the possible consequences of a change in law school admissions in the United States from an affirmative action system based on race to one based on socioeconomic class. Using data from the 1991-1996 Law School Admission Council Bar Passage Study, students were reassigned attendance by simulation to law school tiers by transferring the affirmative action advantage for black students to students from low socioeconomic backgrounds. The hypothetical academic outcomes for the students w...

  16. Antibacterial free fatty acids : activities, mechanisms of action and biotechnological potential

    OpenAIRE

    Desbois, Andrew Paul; Smith, Valerie Jane

    2010-01-01

    Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy ...

  17. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control

    OpenAIRE

    Bravo, Alejandra; Gill, Sarjeet S.; Soberón, Mario

    2006-01-01

    Bacillus thuringiensis Cry and Cyt protein families are a diverse group of proteins with activity against insects of different orders - Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as nematodes. Their primary action is to lyse midgut epithelial cells by inserting into the target membrane and forming pores. Among this group of proteins, members of the 3-Domain Cry family are used worldwide for insect control, and their mode of action has been characterized in some...

  18. The afterhyperpolarizing potential following a train of action potentials is suppressed in an acute epilepsy model in the rat Cornu Ammonis 1 area.

    Science.gov (United States)

    Kernig, K; Kirschstein, T; Würdemann, T; Rohde, M; Köhling, R

    2012-01-10

    In hippocampal Cornu Ammonis 1 (CA1) neurons, a prolonged depolarization evokes a train of action potentials followed by a prominent afterhyperpolarizing potential (AHP), which critically dampens neuronal excitability. Because it is not known whether epileptiform activity alters the AHP and whether any alteration of the AHP is independent of inhibition, we acutely induced epileptiform activity by bath application of the GABA(A) receptor blocker gabazine (5 μM) in the rat hippocampal slice preparation and studied its impact on the AHP using intracellular recordings. Following 10 min of gabazine wash-in, slices started to develop spontaneous epileptiform discharges. This disinhibition was accompanied by a significant shift of the resting membrane potential of CA1 neurons to more depolarized values. Prolonged depolarizations (600 ms) elicited a train of action potentials, the number of which was not different between baseline and gabazine treatment. However, the AHP following the train of action potentials was significantly reduced after 20 min of gabazine treatment. When the induction of epileptiform activity was prevented by co-application of 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, 10 μM) and D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 μM) to block α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors, respectively, the AHP was preserved despite of GABA(A) receptor inhibition suggesting that the epileptiform activity was required to suppress the AHP. Moreover, the AHP was also preserved when the slices were treated with the protein kinase blockers H-9 (100 μM) and H-89 (1 μM). These results demonstrate that the AHP following a train of action potentials is rapidly suppressed by acutely induced epileptiform activity due to a phosphorylation process-presumably involving protein kinase A.

  19. Exercise-induced intra-ventricular gradients as a frequent potential cause of myocardial ischemia in cardiac syndrome X patients

    Directory of Open Access Journals (Sweden)

    Almeida Ana G

    2008-01-01

    Full Text Available Abstract Background The development of intra-ventricular gradients (IVG during dobutamine or exercise stress is not infrequent, and can be associated to symptoms during stress. The purpose of this study was to assess the occurrence of IVG during exercise stress echocardiography in cardiac syndrome X patients. Methods We prospectively evaluated 91 patients (pts mean aged 51 ± 12 years (age ranged 20 to 75 years old, 44 of whom were women. All pts had angina, positive exercise ECG treadmill testing, normal rest echocardiogram and no coronary artery disease on coronary angiogram (cardiac X syndrome. After complete Doppler echocardiographic evaluation with determination of left ventricular outflow tract index (LVOTi, relative left ventricular wall thickness (RLVWT and left ventricular end-diastolic volume index (LVDVi, all patients underwent stress echocardiography with two-dimensional and Doppler echographic evaluation during and after treadmill exercise. Results For analysis purpose patients were divided in 2 groups, according to the development of IVG. Doppler evidence of IVG was found in 33 (36% of the patients (Group A, with mean age 47 ± 14 years old (age ranged 20 to 72 years and with a mean end-systolic peak gradient of 86 ± 34 mmHg (ranging from 30 to 165 mmHg. The IVG development was accompanied by SAM of the mitral valve in 23 pts. Three of these pts experienced symptomatic hypotension. Ten were women (30% pts. 58 pts in group B, 34 of whom were women (59% (p = 0,01 vs group A, mean aged 53,5 ± 10,9 years old (age ranged 34 to 75 years (p = 0,03 vs group A, did not develop IVG. LVOTi was 10,29 ± 0,9 mm/m2 in group A and 11,4 ± 1 mm/m2 in group B (p 2 in group A and 56 ± 11,6 ml/m2 in group B (p = 0,000. Conclusion 1. A significant number of patients with cardiac X syndrome developed IVG during upright exercise in treadmill. These pts (group A are mainly males and younger than those who did not develop IVG. 2. The development of IVG

  20. Left Ventricular Assist Device and Resident Cardiac Stem Cells in Heart Failure: Human Heart’s Potential Matter

    Directory of Open Access Journals (Sweden)

    Mariangela Peruzzi

    2014-01-01

    Full Text Available Heart disease is the leading cause of mortality in Western countries, accounting for 17.3 million deaths per year. The impact of cardiovascular diseases is influenced by the ability to treat and assist patients surviving acute myocardial infarction (AMI, which has resulted in a nearly epidemic of chronic heart failure (HF, with roughly 5.8 million people with this diagnosis and about 500,000 new cases every year in the U.S.A. Irrespective of the etiology and despite the fact that recent advances in medical and surgical treatments of HF have led to better treatments, 50% of patients die within a month after AMI, and 50% of those with severe HF die within a year. From a pathophysiologic point of view the hemodynamic overload generated by AMI imposes mechanical and neurohormonal challenges on cardiac walls, initially triggering compensatory left ventricular hypertrophy, but eventually activating complex biological responses evolving into maladaptive remodeling, untreatable with conventional therapy.

  1. Governance issues, potentials and failures of participative collective action in the Kafue Flats, Zambia

    Directory of Open Access Journals (Sweden)

    Harry Nixon Chabwela

    2010-09-01

    2004 for creating by-laws based on initiatives of local staff of the Department of Fisheries, local interest groups and researchers. A broad local debate on how to manage the fisheries in a sustainable way and develop locally based by-laws for joint management of fisheries gives good potential for success and appears promising for the future of fisheries in Kafue Flats. Despite many difficulties it is an example of local collective action in order to scale up governance of common-pool resources.

  2. Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Yun-Feng Lan; Yang Li; Jian-Cheng Zhang; Jin-Lao Gao; Xue-Ping Wang; Zhou Fang; Yi-Cheng Fu; Mei-Yan Chen; Min Lin; Qiao Xue

    2013-01-01

    Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action.

  3. A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

    Science.gov (United States)

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

    Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle. PMID:27087101

  4. Electropharmacological effects of berberine on canine cardiac Purkinje fibres and ventricular muscle and atrial muscle of the rabbit.

    OpenAIRE

    Riccioppo Neto, F.

    1993-01-01

    1. Conventional microelectrode techniques were used for intracellular recordings of the transmembrane electrical potentials, the effects of berberine were studied on canine cardiac Purkinje and ventricular muscle fibres and on rabbit atrial fibres. 2. Berberine (3-30 microM) increased in a concentration-dependent manner, the action potential duration (APD) in canine Purkinje and ventricular muscle without affecting other parameters of the action potential. 3. The berberine-induced enlargement...

  5. The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages.

    Science.gov (United States)

    Masumoto, Hidetoshi; Nakane, Takeichiro; Tinney, Joseph P; Yuan, Fangping; Ye, Fei; Kowalski, William J; Minakata, Kenji; Sakata, Ryuzo; Yamashita, Jun K; Keller, Bradley B

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs. We then determined the impact of cell composition on ECT structural and functional properties. In vitro force measurement showed that CM+EC+MC ECTs possessed preferential electromechanical properties versus ECTs without vascular cells indicating that incorporation of vascular cells augmented tissue maturation and function. The inclusion of MCs facilitated more mature CM sarcomeric structure, preferential alignment, and activated multiple tissue maturation pathways. The CM+EC+MC ECTs implanted onto infarcted, immune tolerant rat hearts engrafted, displayed both host and graft-derived vasculature, and ameliorated myocardial dysfunction. Thus, a composition of CMs and multiple vascular lineages derived from hiPSCs and incorporated into ECTs promotes functional maturation and demonstrates myocardial replacement and perfusion relevant for clinical translation. PMID:27435115

  6. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  7. Potentiating action of propofol at GABAA receptors of retinal bipolar cells

    DEFF Research Database (Denmark)

    Yue, Lan; Xie, An; Bruzik, Karol S;

    2011-01-01

    specific retinal neurons. The authors investigated the action of propofol on GABA-elicited membrane current responses of retinal bipolar cells, which have both GABA(A) and GABA(C) receptors. Methods. Single, enzymatically dissociated bipolar cells obtained from rat retina were treated with propofol...

  8. Preparing Social Justice Oriented Teachers: The Potential Role of Action Research in the PDS

    Science.gov (United States)

    Dodman, Stephanie L.; Lai, Kerri; Campet, Melissa; Cavallero-Lotocki, Renee; Hopkins, Aaron; Onidi, Christine

    2014-01-01

    Deliberate investigation into practice is an essential of the National Association for Professional Development Schools' defining elements of a Professional Development School (PDS). This article reports on the pilot efforts of one PDS as it initiated deliberate investigation through action research with a small group of teacher candidates.…

  9. The Potential of General Classroom Observation: Turkish EFL Teachers' Perceptions, Sentiments, and Readiness for Action

    Science.gov (United States)

    Merç, Ali

    2015-01-01

    The purpose of this study was to determine Turkish EFL teachers' attitudes towards classroom observation. 204 teachers from different school settings responded to an online questionnaire. Data were analyzed according to three types of attitudes towards classroom observation: perceptions, sentiments, and readiness for action. The findings revealed…

  10. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control.

    Science.gov (United States)

    Bravo, Alejandra; Gill, Sarjeet S; Soberón, Mario

    2007-03-15

    Bacillus thuringiensis Crystal (Cry) and Cytolitic (Cyt) protein families are a diverse group of proteins with activity against insects of different orders--Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as nematodes. Their primary action is to lyse midgut epithelial cells by inserting into the target membrane and forming pores. Among this group of proteins, members of the 3-Domain Cry family are used worldwide for insect control, and their mode of action has been characterized in some detail. Phylogenetic analyses established that the diversity of the 3-Domain Cry family evolved by the independent evolution of the three domains and by swapping of domain III among toxins. Like other pore-forming toxins (PFT) that affect mammals, Cry toxins interact with specific receptors located on the host cell surface and are activated by host proteases following receptor binding resulting in the formation of a pre-pore oligomeric structure that is insertion competent. In contrast, Cyt toxins directly interact with membrane lipids and insert into the membrane. Recent evidence suggests that Cyt synergize or overcome resistance to mosquitocidal-Cry proteins by functioning as a Cry-membrane bound receptor. In this review we summarize recent findings on the mode of action of Cry and Cyt toxins, and compare them to the mode of action of other bacterial PFT. Also, we discuss their use in the control of agricultural insect pests and insect vectors of human diseases. PMID:17198720

  11. Doubts about actions and flanker incongruity-related potentials and performance

    NARCIS (Netherlands)

    Tops, Mattie; Wijers, Albertus A.

    2012-01-01

    The brain networks that are involved in flanker incongruity and error processing are also consistently implicated in mental disorders such as obsessive compulsive disorder (OCD) that feature increased "Doubts about Actions" (DaA) scores. In the present study we investigated whether DaA scores, simil

  12. Mesenchymal stem cells promote matrix metalloproteinase secretion by cardiac fibroblasts and reduce cardiac ventricular fibrosis after myocardial infarction.

    Science.gov (United States)

    Mias, Céline; Lairez, Olivier; Trouche, Elodie; Roncalli, Jérome; Calise, Denis; Seguelas, Marie-Hélène; Ordener, Catherine; Piercecchi-Marti, Marie-Dominique; Auge, Nathalie; Salvayre, Anne Negre; Bourin, Philippe; Parini, Angelo; Cussac, Daniel

    2009-11-01

    Recent studies showed that mesenchymal stem cells (MSCs) transplantation significantly decreased cardiac fibrosis; however, the mechanisms involved in these effects are still poorly understood. In this work, we investigated whether the antifibrotic properties of MSCs involve the regulation of matrix metalloproteinases (MMPs) and matrix metalloproteinase endogenous inhibitor (TIMP) production by cardiac fibroblasts. In vitro experiments showed that conditioned medium from MSCs decreased viability, alpha-smooth muscle actin expression, and collagen secretion of cardiac fibroblasts. These effects were concomitant with the stimulation of MMP-2/MMP-9 activities and membrane type 1 MMP expression. Experiments performed with fibroblasts from MMP2-knockout mice demonstrated that MMP-2 plays a preponderant role in preventing collagen accumulation upon incubation with conditioned medium from MSCs. We found that MSC-conditioned medium also decreased the expression of TIMP2 in cardiac fibroblasts. In vivo studies showed that intracardiac injection of MSCs in a rat model of postischemic heart failure induced a significant decrease in ventricular fibrosis. This effect was associated with the improvement of morphological and functional cardiac parameters. In conclusion, we showed that MSCs modulate the phenotype of cardiac fibroblasts and their ability to degrade extracellular matrix. These properties of MSCs open new perspectives for understanding the mechanisms of action of MSCs and anticipate their potential therapeutic or side effects.

  13. Quantum entanglement in the voltage dependent sodium channel can reproduce the salient features of neuronal action potential initiation

    CERN Document Server

    Summhammer, Johann

    2007-01-01

    We investigate the effects of a quantum entanglement regime within an ion conducting molecule (ion channel) of the neuronal plasma membrane on the onset dynamics of propagating nerve pulses (action potentials). In particular, we model the onset parameters of the sodium current in the Hodgkin Huxley equation as three similar but independent probabilistic mechanisms which become quantum entangled. The underlying physics is general and can involve entanglement between various degrees of freedom underlaying ion transition states or 'gating states' during conduction, e.g. Na$^+$ ions in different channel locations, or different 'affinity' states of ions with atoms lining the sub-regions of the channel protein ('filter-states'). We find that the 'quantum corrected' Hodgkin Huxley equation incorporating entangled systems states can reproduce action potential pulses with the critical onset dynamics observed recently in neocortical neurons in vivo by Naundorf et al. [Nature {\\bf 440}, 1060 (20 April 2006)]. Interestin...

  14. Back-propagation of physiological action potential output in dendrites of slender-tufted L5A pyramidal neurons

    OpenAIRE

    Grewe, Benjamin F.; Audrey Bonnan; Andreas Frick

    2010-01-01

    Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signalling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related &...

  15. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

    Science.gov (United States)

    Herde, Michel K; Herbison, Allan E

    2015-11-01

    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  16. Neural Networks for Template Matching: Application to Real-Time Classification of the Action Potentials of Real Neurons

    OpenAIRE

    Wong, Yiu-fai; Banik, Jashojiban; Bower, James M.

    1988-01-01

    Much experimental study of real neural networks relies on the proper classification of extracellulary sampled neural signals (i .e. action potentials) recorded from the brains of experimental animals. In most neurophysiology laboratories this classification task is simplified by limiting investigations to single, electrically well-isolated neurons recorded one at a time. However, for those interested in sampling the activities of many single neurons simultaneously, waveform cla...

  17. Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis

    Directory of Open Access Journals (Sweden)

    Burchfield Jana S

    2008-10-01

    Full Text Available Abstract A new era has begun in the treatment of ischemic disease and heart failure. With the discovery that stem cells from diverse organs and tissues, including bone marrow, adipose tissue, umbilical cord blood, and vessel wall, have the potential to improve cardiac function beyond that of conventional pharmacological therapy comes a new field of research aiming at understanding the precise mechanisms of stem cell-mediated cardiac repair. Not only will it be important to determine the most efficacious cell population for cardiac repair, but also whether overlapping, common mechanisms exist. Increasing evidence suggests that one mechanism of action by which cells provide tissue protection and repair may involve paracrine factors, including cytokines and growth factors, released from transplanted stem cells into the surrounding tissue. These paracrine factors have the potential to directly modify the healing process in the heart, including neovascularization, cardiac myocyte apoptosis, inflammation, fibrosis, contractility, bioenergetics, and endogenous repair.

  18. Spironolactone pharmacokinetics and actions in the dog: Influence on the potential spironolactone-digoxin interaction

    Energy Technology Data Exchange (ETDEWEB)

    Beck, B.L.

    1988-01-01

    This study was designed to determine if administration of spironolactone to achieve steady-state concentrations to dogs at steady-state digoxin concentration resulted in an increased serum digoxin concentration in dogs. Serum digoxin concentration and AcS tolerance were measured in dogs at steady-state spironolactone-digoxin concentration to determine if an increase in serum digoxin concentration resulted from spironolactone administration and if this resulted in increased cardiac effects of digoxin. To determine if a spironolactone-digoxin interaction occurred at the canine myocardial digitalis receptor in vitro, the effects of spironolactone and its metabolites on Na{sup +},K{sup +}-ATPase activity and ({sup 3}H)ouabain binding were studied. Spironolactone, canrenone, or K{sup +} canrenoate did not inhibit canine myocardial K{sup +}-dependent MFPase activity or the concentration-response curve for digoxin inhibition of K{sup +}-dependent MFPase. In contrast, 0.1 mM spironolactone or canrenone competitively antagonized ({sup 3}H)ouabain binding to canine myocardium. Neither 0.24 {mu}M spironolactone, 0.59 {mu}M canrenone, or 1.27 {mu}M 7{alpha}-thiomethylspirolactone, concentrations of spironolactone and its metabolites found after a therapeutic dose of spironolactone in man, altered ({sup 3}H)ouabain binding to canine myocardium.

  19. Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

    Science.gov (United States)

    Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M; Shepherd, Samantha; Lemon, Roger N

    2009-12-24

    The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation.

  20. Potential pathways of pesticide action on erectile function-a contributory factor in male infertility

    Institute of Scientific and Technical Information of China (English)

    RP Kaur; V Gupta; AF Christopher; P Bansal

    2015-01-01

    One of the important objectives of this manuscript is to focus on the place of erectile dysfunction as an important factor for infertility. The review is about correlating the indiscriminate use of pesticides and to find out and highlight the evidences for mechanism of action of these pesticides for erectile dysfunction and find out the most used and most dangerous pesticide from erectile dysfunction point of view. The review suggests that erectile dysfunction is having a significant place as a causal factor for infertility. Study infers that pesticides are having multiple mechanisms of action through which these cause erectile dysfunction. It also reflects that acetamiprid is having most devastating effect causing erectile dysfunction as it acts through multiple inhibitory pathways. The review successfully highlights the indiscriminate regional use of pesticides.

  1. Cardiac ion channels and mechanisms for protection against atrial fibrillation

    DEFF Research Database (Denmark)

    Grunnet, Morten; Bentzen, Bo Hjorth; Sørensen, Ulrik S;

    2011-01-01

    Atrial fibrillation (AF) is recognised as the most common sustained cardiac arrhythmia in clinical practice. Ongoing drug development is aiming at obtaining atrial specific effects in order to prevent pro-arrhythmic, devastating ventricular effects. In principle, this is possible due to a different...... the recent discovery that Ca(2+)-activated small conductance K(+) channels (SK channels) are important for the repolarisation of atrial action potentials. Finally, an overview of current pharmacological treatment of AF is included....

  2. Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

    OpenAIRE

    Hipkiss, Alan R; Cartwright, Stephanie P.; Bromley, Clare; Gross, Stephane R.; Bill, Roslyn M.

    2013-01-01

    The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide’s ...

  3. A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty

    OpenAIRE

    David Dixon; Jonathon Coates; Alicia del Carpio Pons; Joanna Horabin; Andrew Walker; Nicole Abdul; Kalson, Nicholas S; Brewster, Nigel T.; Weir, David J.; Deehan, David J; Mann, Derek A.; Lee A Borthwick

    2015-01-01

    Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hyp...

  4. Reading Humboldt through the theory of communicative action: the democratic potential of symbolic interaction

    OpenAIRE

    McLuskie, Ed

    2015-01-01

    Wilhelm von Humboldt's studies of language during the nineteenth century anticipated twentieth-century symbolic interactionism, suggesting a two-century intellectual history stressing the communicating subject as an intersubjective actor. Jürgen Habermas's theory of communicative action, well known for its inclusion of George Herbert Mead's symbolic interactionism, appeals in the same breath to von Humboldt's work, thus inviting a critical re-appropriation of Mead beyond the social-psychologi...

  5. Reading Humboldt through the theory of communicative action: the democratic potential of symbolic interaction:

    OpenAIRE

    McLuskie, Ed

    2003-01-01

    Wilhelm von Humboldt's studies of language during the nineteenth century anticipated twentieth-century symbolic interactionism, suggesting a two-century intellectual history stressing the communicating subject as an intersubjective actor. Jürgen Habermas's theory of communicative action, well known for its inclusion of George Herbert Mead's symbolic interactionism, appeals in the same breath to von Humboldt's work, thus inviting a critical re-appropriation of Mead beyond the social-psychologi...

  6. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy:an analysis of 500 cases

    Institute of Scientific and Technical Information of China (English)

    Yunqian Zhang; Jintao Li; Tingjuan Wang; Jianlin Wang

    2014-01-01

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Afifl-iated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control sub-jects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were signiifcantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. More-over, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The ampli-tude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, as-ymptomatic stage of diabetic peripheral neuropathy.

  7. Complex Dynamic Thresholds and Generation of the Action Potentials in the Neural-Activity Model

    Science.gov (United States)

    Kirillov, S. Yu.; Nekorkin, V. I.

    2016-05-01

    This work is devoted to studying the processes of activation of the neurons whose excitation thresholds are not constant and vary in time (the so-called dynamic thresholds). The neuron dynamics is described by the FitzHugh-Nagumo model with nonlinear behavior of the recovery variable. The neuron response to the external pulsed activating action in the presence of a slowly varying synaptic current is studied within the framework of this model. The structure of the dynamic threshold is studied and its properties depending on the external-action parameters are established. It is found that the formation of the "folds" in the separatrix threshold manifold in the model phase space is a typical feature of the complex dynamic threshold. High neuron sensitivity to the action of the comparatively weak slow control signals is established. This explains the capability of the neurons to perform flexible tuning of their selective properties for detecting various external signals in sufficiently short times (of the order of duration of several spikes).

  8. T-wave Alternans and Arrhythmogenesis in Cardiac Diseases

    Directory of Open Access Journals (Sweden)

    Zhilin eQu

    2010-11-01

    Full Text Available T-wave alternans, a manifestation of repolarization alternans at the cellular level, is associated with lethal cardiac arrhythmias and sudden cardiac death. At the cellular level, several mechanisms can produce repolarization alternans, including: 1 electrical restitution resulting from collective ion channel recovery, which usually occurs at fast heart rates but can also occur at normal heart rates when action potential is prolonged resulting in a short diastolic interval; 2 the transient outward current, which tends to occur at normal or slow heart rates; 3 the dynamics of early afterdepolarizations, which tends to occur during bradycardia; and 4 intracellular calcium cycling alternans through its interaction with membrane voltage. In this review, we summarize the cellular mechanisms of alternans arising from these different mechanisms, and discuss their roles in arrhythmogenesis in the setting of cardiac disease.

  9. Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Nan Cao; Bin Wei; Liu Wang; Ying Jin; Huang-Tian Yang; Zumei Liu; Zhongyan Chen; Jia Wang; Taotao Chen; Xiaoyang Zhao; Yu Ma; Lianju Qin; Jiuhong Kang

    2012-01-01

    Generation of induced pluripotent stem cells (iPSCs) has opened new avenues for the investigation of heart diseases,drug screening and potential autologous cardiac regeneration.However,their application is hampered by inefficient cardiac differentiation,high interline variability,and poor maturation of iPSC-derived cardiomyoeytes (iPS-CMs).To identify efficient inducers for cardiac differentiation and maturation of iPSCs and elucidate the mechanisms,we systematically screened sixteen cardiomyocyte inducers on various murine (m) iPSCs and found that only ascorbic acid (AA) consistently and robustly enhanced the cardiac differentiation of eleven lines including eight without spontaneous cardiogenic potential.We then optimized the treatment conditions and demonstrated that differentiation day 2-6,a period for the specification of cardiac progenitor cells (CPCs),was a critical time for AA to take effect.This was further confirmed by the fact that AA increased the expression of cardiovascular but not mesodermal markers.Noteworthily,AA treatment led to approximately 7.3-fold (miPSCs) and 30.2-fold (human iPSCs) augment in the yield of iPS-CMs.Such effect was attributed to a specific increase in the proliferation of CPCs via the MEK-ERK1/2 pathway by promoting collagen synthesis.In addition,AA-induced cardiomyocytes showed better sareomerie organization and enhanced responses of action potentials and calcium transients to β-adrenergic and muscarinic stimulations.These findings demonstrate that AA is a suitable cardiomyocyte inducer for iPSCs to improve cardiac differentiation and maturation simply,universally,and efficiently.These findings also highlight the importance of stimulating CPC proliferation by manipulating extracellular microenvironment in guiding cardiac differentiation of the pluripotent stem cells.

  10. An overview of cardiac morphogenesis.

    Science.gov (United States)

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-11-01

    Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In this article we review the different steps of heart development, focusing on the processes of alignment and septation. We also show, as often as possible, the links between abnormalities of cardiac development and the main congenital heart defects. The development of animal models has permitted the unraveling of many mechanisms that potentially lead to cardiac malformations. A next step towards a better knowledge of cardiac development could be multiscale cardiac modelling. PMID:24138816

  11. Effects of nicorandil on cardiac plasma membrane and cardiac mitochondrial membrane potential of guinea-pig%尼可地尔对豚鼠心肌细胞膜及线粒体膜电位的影响

    Institute of Scientific and Technical Information of China (English)

    冯力; 刘伊丽; 刘杰; 金春华

    2001-01-01

    研究KATP通道开放剂尼可地尔(Nic)对豚鼠心肌细胞膜和线粒体膜电位的影响.用激光共聚焦显微镜和特异性荧光探针,观察不同剂量的Nic及KATP通道阻滞剂格列本脲(Gli)引起急性分离的豚鼠心肌细胞膜电位,线粒体膜电位荧光值的变化.Nic1mmol.L-1引起细胞膜电位在1min内迅速超极化〔膜电位荧光值减少(75±12)%〕,Gli3μmol.L-1可阻断其变化;0.1和1mmol.L-1Nic可使线粒体膜电位去极化和膜电位荧光值在1,2,5min分别增加(12±3)%和(32±8)%,(25±6)%和(39±9)%,(34±6)%和(45±12)%;3μmol.L-1Gli可抑制其变化.结果说明低浓度Nic只引起线粒体膜电位去极化,高浓度Nic还可使细胞膜电位发生超极化,引起KATP通道开放.%With digital imaging techniques of advanced laser confocalmicroscope, effects of KATP channel opener nicorandil(Nic) on cardiac plasma membrane(CPM) and cardiac mitochondrial membrane(CMM) potential of guinea-pig were studied. It was found that Nic 1 mmol.L-1 caused the potential of CPM more negative (hyperpolarization), fluorescence intensity(FI) decreased by (75±12)% of baseline within 1 min, but no effect at 0.1 mmol.L-1. CMM was depolarized by 0.1 mmol.L-1 Nic〔FI increased by (12±3)%, (25±6)%, (34±6)% of baseline within 1, 2, 5 min〕, and by 1 mmol.L-1 Nic〔FI remarkably increased by (32±8)%, (39±9)%, (45±12)% of baseline〕. KATP channel blocker glibenclamide 3 μmol.L-1 itself caused no effect on potential of CPM and CMM, but blocked the above effect on potential of CPM and CMM induced by Nic. The results suggest that KATP channel of CMM is activated by low dose of Nic, and the high dose of Nic activate both KATP channels of CPM and CMM.

  12. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    Science.gov (United States)

    Straus, D. M.

    1983-01-01

    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eliassen-Palm flux are also discussed.

  13. Cardiac rehabilitation

    Science.gov (United States)

    ... attack or other heart problem. You might consider cardiac rehab if you have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery Heart transplant Procedures such as angioplasty and stenting In some ...

  14. Early reperfusion hemodynamics predict recovery in rat hearts: a potential approach towards evaluating cardiac grafts from non-heart-beating donors.

    Directory of Open Access Journals (Sweden)

    Monika Dornbierer

    Full Text Available AIMS: Cardiac grafts from non-heartbeating donors (NHBDs could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs. METHODS AND RESULTS: Hearts (n = 31 isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001. Coronary flow and the production of lactate and lactate dehydrogenase (LDH also correlated significantly with outcomes after 60 min reperfusion (p<0.05. Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR, developed pressure (DP and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *10(3 mmHg*beats*min(-1 (p<0.01. CONCLUSION: Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation.

  15. Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials.

    Directory of Open Access Journals (Sweden)

    Jason Robert Potas

    Full Text Available Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for

  16. Modulatory action of acetylcholine on the Na+-dependent action potentials in Kenyon cells isolated from the mushroom body of the cricket brain.

    Science.gov (United States)

    Terazima, E; Yoshino, M

    2010-12-01

    Kenyon cells, intrinsic neurons of the insect mushroom body, have been assumed to be a site of conditioning stimulus (CS) and unconditioned stimulus (US) association in olfactory learning and memory. Acetylcholine (ACh) has been implicated to be a neurotransmitter mediating CS reception in Kenyon cells, causing rapid membrane depolarization via nicotinic ACh receptors. However, the long-term effects of ACh on the membrane excitability of Kenyon cells are not fully understood. In this study, we examined the effects of ACh on Na(+) dependent action potentials (Na(+) spikes) elicited by depolarizing current injection and on net membrane currents under the voltage clamp condition in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Current-clamp studies using amphotericin B perforated-patch recordings showed that freshly dispersed cricket Kenyon cells could produce repetitive Na(+) spikes in response to prolonged depolarizing current injection. Bath application of ACh increased both the instantaneous frequency and the amplitudes of Na(+) spikes. This excitatory action of ACh on Kenyon cells is attenuated by the pre-treatment of the cells with the muscarinic receptor antagonists, atropine and scopolamine, but not by the nicotinic receptor antagonist mecamylamine. Voltage-clamp studies further showed that bath application of ACh caused an increase in net inward currents that are sensitive to TTX, whereas outward currents were decreased by this treatment. These results indicate that in order to mediate CS, ACh may modulate the firing properties of Na(+) spikes of Kenyon cells through muscarinic receptor activation, thus increasing Na conductance and decreasing K conductance.

  17. Opposing actions of chronic Δ9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation

    OpenAIRE

    Hoffman, Alexander F; Oz, Murat; Yang, Ruiqin; Lichtman, Aron H.; Carl R Lupica

    2007-01-01

    Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation (LTP), a potential substrate for learning and memory, the consequences of prolonged exposure to Δ9-THC for hippocampal function are poorly understood. Rats were injected with Δ9-THC (10 mg/kg, i.p., q.d.) for 1, 3, or ...

  18. Characterising action potential in virtual game worlds applied with the mind module

    OpenAIRE

    Eladhari, Mirjam Palosaari

    2009-01-01

    Because games set in persistent virtual game worlds (VGWs) have massive numbers of players, these games need methods of characterisation for playable characters (PCs) that differ from the methods used in traditional narrative media. VGWs have a number of particularly interesting qualities. Firstly, VGWs are places where players interact with and create elements carrying narrative potential. Secondly, players add goals, motives and driving forces to the narrative potential of a VGW, which some...

  19. Assessing potential targets of calcium action in light-modulated gravitropism

    Science.gov (United States)

    Roux, S. J.

    1995-01-01

    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

  20. Generation of slow wave type action potentials in the mouse small intestine involves a non-L-type calcium channel.

    Science.gov (United States)

    Malysz, J; Richardson, D; Farraway, L; Christen, M O; Huizinga, J D

    1995-10-01

    Intrinsic electrical activities in various isolated segments of the mouse small intestine were recorded (i) to characterize action potential generation and (ii) to obtain a profile on the ion channels involved in initiating the slow wave type action potentials (slow waves). Gradients in slow wave frequency, resting membrane potential, and occurrence of spiking activity were found, with the proximal intestine exhibiting the highest frequency, the most hyperpolarized cell membrane, and the greatest occurrence of spikes. The slow waves were only partially sensitive to L-type calcium channel blockers. Nifedipine, verapamil, and pinaverium bromide abolished spikes that occurred on the plateau phase of the slow waves in all tissues. The activity that remained in the presence of L-type calcium channel blockers, the upstroke potential, retained a similar amplitude to the original slow wave and was of identical frequency. The upstroke potential was not sensitive to a reduction in extracellular chloride or to the sodium channel blockers tetrodotoxin and mexiletine. Abolishment of the Na+ gradient by removal of 120 mM extracellular Na+ reduced the upstroke potential frequency by 13 - 18% and its amplitude by 50 - 70% in the ileum. The amplitude was similarly reduced by Ni2+ (up to 5 mM), and by flufenamic acid (100 mu M), a nonspecific cation and chloride channel blocker. Gadolinium, a nonspecific blocker of cation and stretch-activated channels, had no effect. Throughout these pharmacological manipulations, a robust oscillation remained at 5 - 10 mV. This oscillation likely reflects pacemaker activity. It was rapidly abolished by removal of extracellular calcium but not affected by L-type calcium channel blockers. In summary, the mouse small intestine has been established as a model for research into slow wave generation and electrical pacemaker activity. The upstroke part of the slow wave has two components, the pacemaker component involves a non-L-type calcium channel

  1. Cardiac pacemaker power sources

    International Nuclear Information System (INIS)

    A review of chemical and radioisotope batteries used in cardiac pacemakers is presented. The battery systems are examined in terms of longevity, reliability, cost, size and shape, energy density, weight, internal resistance versus time, end-of-life voltage, chemical compatibility, and potential failure mechanisms

  2. Bursting regimes in a reaction-diffusion system with action potential-dependent equilibrium.

    Directory of Open Access Journals (Sweden)

    Stephen R Meier

    Full Text Available The equilibrium Nernst potential plays a critical role in neural cell dynamics. A common approximation used in studying electrical dynamics of excitable cells is that the ionic concentrations inside and outside the cell membranes act as charge reservoirs and remain effectively constant during excitation events. Research into brain electrical activity suggests that relaxing this assumption may provide a better understanding of normal and pathophysiological functioning of the brain. In this paper we explore time-dependent ionic concentrations by allowing the ion-specific Nernst potentials to vary with developing transmembrane potential. As a specific implementation, we incorporate the potential-dependent Nernst shift into a one-dimensional Morris-Lecar reaction-diffusion model. Our main findings result from a region in parameter space where self-sustaining oscillations occur without external forcing. Studying the system close to the bifurcation boundary, we explore the vulnerability of the system with respect to external stimulations which disrupt these oscillations and send the system to a stable equilibrium. We also present results for an extended, one-dimensional cable of excitable tissue tuned to this parameter regime and stimulated, giving rise to complex spatiotemporal pattern formation. Potential applications to the emergence of neuronal bursting in similar two-variable systems and to pathophysiological seizure-like activity are discussed.

  3. Adaptation decision-making in the Nordic Countries: assessing the potential for joint action

    DEFF Research Database (Denmark)

    Juhola, Sirkku; Goodsite, Michael Evan; Davis, Marion;

    2014-01-01

    and in precipitation, although regional variations can be significant. The countries’ robust institutions and economies give them a strong capacity to adapt to these changes. Still, the need for adaptation to the changing climate has been and still is substantial, and in most of the region, there has been progress...... on the issue. This paper explores the potential for Nordic cooperation on adaptation; specifically, for the development of a regional adaptation strategy. In particular, it addresses two questions (1) What is the current state of adaptation in the Nordic countries? and (2) What are the potential benefits...... and weaknesses of a Nordic strategy for adaptation? In order to answer these two questions, this paper examines reviews the current national adaptation policies of each Nordic country and discusses the challenges facing a Nordic strategy and finally assesses the potential for common Nordic adaptation policy...

  4. EFFECTS OF DESENSITIZATION AND REBOUND TO ADENOSINE ON ACTION POTENTIAL AND CONTRACTILITY IN ATRIAL CELLS IN GUINEA-PIGS

    Institute of Scientific and Technical Information of China (English)

    张凤杰; 臧伟进; 于晓江; 胡浩; 张春虹; 孙强; 吕军

    2002-01-01

    Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using standard intracellular microelectrode technique and contractility was recorded using. We studied the effects of adenosine on the action potential and desensitization of contractility and rebound of contractility. Results The results showed that action potential duration were shortened by 1,10,100μmol*L-1Ado, the ratio of shortened APD was (9.58±1.40)%,(13.80±2.26)%,(24.80±3.19)%, respectively. 1μmol*L-1Ado had no desensitization (P>0.05), but the time of desensitization of 10μmol*L-1 Ado and 100μmol*L-1 Ado was 1 minute(P<0.05) and 5 minutes(P<0.05), respectively. The desensitization of contractility of 10*!μmol*L-1 Ado was obvious in atrial cells, the decrease of contractility of 10*!μmol*L-1 Ado was obvious in atrial cells, the decrease of contractility was changed from (31.4±16.04)%(2 minutes) to (50.60±15.87)% (4 minutes), compared with control. After washing out Ado, contractility was shown to rebound, the ratio of increase of contractility by 1,10,100μmol*L-1 Ado was (12.38±7.50)%,(19.00±8.14)% and (27.60±13.44)%, respectively. Conclusion Ado can abbreviate APD in atrial cells. The desensitization of Ado on APD is characterized by concentration-dependent and time-dependent in atrial cells, and the desensitization of contractility of Ado is obvious and contractility was shown to rebound after washing out Ado.

  5. Tracking motor unit action potentials in the tibialis anterior during fatigue.

    NARCIS (Netherlands)

    Beck, R.B.; O'Malley, M.J.; Stegeman, D.F.; Houtman, C.J.; Connolly, S.; Zwarts, M.J.

    2005-01-01

    New surface electromyogram (SEMG) techniques offer the potential to advance knowledge of healthy and diseased motor units. Conduction velocity (CV) estimates, obtained from indwelling electrodes, may provide diagnostic information, but the standard method of CV estimation from SEMG may be of only li

  6. Potential food applications of biobased materials. An EU- concerted action project

    DEFF Research Database (Denmark)

    Haugaard, V.K.; Udsen, A.M.; Mortensen, G.;

    2001-01-01

    The objective of the study was to ascertain the state of the art with regard to the applicability of biobased packaging materials to foods and to identify potential food applications for biobased materials. The study revealed relatively few examples of biobased materials used as primary, secondary...

  7. Motor unit action potential topography and its use in motor unit number estimation.

    NARCIS (Netherlands)

    Blok, J.H.; Dijk, J.P. van; Zwarts, M.J.; Stegeman, D.F.

    2005-01-01

    High-density multichannel electromyography (EMG) recordings add spatial information to the temporal information content of the surface EMG (sEMG) signal. This study explores the potential value of such multichannel information at a single motor unit level, in particular for the improvement of motor

  8. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    Science.gov (United States)

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present. PMID:26644208

  9. Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation

    Institute of Scientific and Technical Information of China (English)

    Yong-nan FU; Han XIAO; Xiao-wei MA; Sheng-yang JIANG; Ming XU; You-yi ZHANG

    2011-01-01

    Aim: To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect.Methods: Wild type and AMPKα2 knockout (AMPKα2-/-) littermates were subjected to left ventricular pressure overload caused by evaluated using echocardiography and anatomic and histological methods. The antihypertrophic mechanism of metformin was analyzed using Western blotting.Results: Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKx2-/- mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKα2-/-mice.Conclusion: Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.

  10. Qualitative and quantitative analyses of the morphological-dynamics of early cardiac pump action using video densidometry and optical coherence tomography (OCT)

    DEFF Research Database (Denmark)

    Männer, Jörg; Thrane, Lars; Thommes, Jan;

    2010-01-01

    During the initial phase of its pump action, vertebrate embryonic hearts are seen as valveless tubular pumps. It was traditionally thought that these tubular hearts generate unidirectional blood flow via peristalsis. Recently, however, the pumping mechanism of early embryonic hearts has become a ...

  11. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

    OpenAIRE

    Chiu, Chi-Tso; Chuang, De-Maw

    2010-01-01

    Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium’s therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurotrophic properties against various insults, and considerable clinical potential for the treatment of several neurodegenerative conditions. Evidence from pharmacological and gene m...

  12. 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.)

  13. 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.

  14. The characteristics of action potential and nonselec-tive cation current of cardiomyocytes in rabbit superior vena cava

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    As a special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cava (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may in-crease or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can in-crease or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyo-cytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.

  15. Effects of rapid and slow potassium repolarization currents and calcium dynamics on hysteresis in restitution of action potential duration.

    Science.gov (United States)

    Wu, Runze; Patwardhan, Abhijit

    2007-04-01

    We used a mathematical model to investigate effects of repolarizing currents I(kr) and I(ks), calcium (Ca) current I(CaL), and Ca dynamics in network sarcoplasmic reticulum and junctional sarcoplasmic reticulum (JSR) on hysteresis in restitution of action potential duration. Enhanced I(kr) increased slope of restitution, hysteresis loop thickness, and delay between peaks of diastolic intervals and action potential duration. Increase in I(ks) decreased loop thickness and peak delay. Decrease in I(CaL) had effects similar to increasing I(kr), except slope of restitution decreased markedly. Uptake of Ca into the network sarcoplasmic reticulum had less effect on hysteresis than transfer of Ca into JSR. Faster transfer of Ca into JSR markedly decreased loop thickness and peak delay. Our results provide insight into mechanisms responsible for this newly identified property of restitution. Such information will be valuable in studies where modification of hysteresis is used to investigate its role in arrhythmogenesis. PMID:16895773

  16. Effects of imidapril on heterogeneity of action potential and calcium current of ventriclar myocytes in infarcted rabbits

    Institute of Scientific and Technical Information of China (English)

    YangLI; QiaoXUE; JieMA; Cun-taiZHANG; PingQIU; LinWANG; WeiGAO; ReiCHENG; Zai-yinLU; Shi-wenWANG

    2004-01-01

    AIM: To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy. METHODS: Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks. Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique. RESULTS: The action potential duration of repolarization 90 % (APD90) was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of/Ca-L was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of calcium currents among subepicardium, midmyocardium, and subendocardium were also discovered. Normalization of heterogeneous changes in repolarization after treatment with imidapril was observed and decrease of TDR in noninfarcted area was measured. Early after depolarization (EAD) events of noninfarcted midmyocardium were markedly decreased by imidapril. CONCLUSION: Imidapril reduced the electrophysiologic heterogeneities in noninfarcted area in rabbits after myocardial infarction. This ability of imidapril may contribute to its antiarrhythmic efficacy.

  17. Effects of imidapril on heterogeneity of action potential and calcium current of ventriclar myocytes in infarcted rabbits

    Institute of Scientific and Technical Information of China (English)

    Yang LI; Shi-wen WANG; Qiao XUE; Jie MA; Cun-tai ZHANG; Ping QIU; Lin WANG; Wei GAO; Rei CHENG; Zai-ying LU

    2004-01-01

    AIM: To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy. METHODS: Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks.Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique.RESULTS: The action potential duration of repolarization 90 % (APD90)was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of ICa-L was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of calcium currents among subepicardium, midmyocardium, and subendocardium were also discovered. Normalization of heterogeneous changes in repolarization after treatment with imidapril was observed and decrease of TDR in noninfarcted area was measvred. Early after depolarization (EAD) events of noninfarcted midmyocardium were markedly decreased by imidapril. CONCLUSION: Imidapril reduced the electrophysiologic heterogeneities in noninfarcted area in rabbits after myocardial infarction. This ability of imidapril may contribute to its antiarrhythmic efficacy.

  18. Effects of changes in frequency on guinea pig ventricular action potential duration and on QT interval under different experimental conditions.

    Science.gov (United States)

    von Savigny, L; Hohnloser, S; Antoni, H

    1981-01-01

    Isolated perfused guinea pig hearts (Langendorff preparation) were arrested by carbachol (0.1-0.2 mg/l) and electrically stimulated in the region of the av-conducting system. The QT interval was determined by means of extracellular electrodes at different driving frequencies. Separate experiments were performed on papillary muscles from the right ventricle to measure the duration of the transmembrane action potential under comparable conditions. At 35 degrees C (Ke+ 5.4 mmol/l) increasing the frequency of stimulation (range 12-120/min) caused the action potential duration (APD) to decrease to a greater extent than the QT interval. Stepwise rising of the external K+ concentration up to 16.2 mmol/l produced a nearly parallel shift to the APD-frequency relation to lower values. Again, the QT interval was less affected by increasing the external K+ concentration than the APD. Stepwise reduction of the temperature down to 20 degrees C prolonged the APD as well as the QT interval, the effects being more pronounced at lower than at higher stimulation frequencies. Under all examined experimental conditions, the APD proved to be markedly shorter than the QT interval even when the latter is diminished by the duration of QRS. The results suggest that no close relation exists between the APD and the QT interval. The observed divergencies may be due to functional differences among various parts of the ventricles.

  19. Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

    Directory of Open Access Journals (Sweden)

    Yuan Hung Lo

    2013-01-01

    Full Text Available Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004 to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.

  20. MIF-1 potentiates the action of tricyclic antidepressants in an animal model of depression.

    Science.gov (United States)

    Kostowski, W; Danysz, W; Dyr, W; Jankowska, E; Krzaścik, P; Pałejko, W; Stefański, R; Płaźnik, A

    1991-01-01

    In the present paper, the effect of simultaneous treatment of rats with low doses of MIF-1 and tricyclic antidepressants on rat behavior in the forced swim test was studied. It was found that MIF-1 stimulated in a dose-dependent manner "active" behavior of animals in this paradigm. The effect of MIF-1 appeared to be independent of changes in rats' locomotion in the open field test. The combined treatment of rats with MIF-1 (0.01 mg/kg IP) and amitriptyline (5 mg/kg IP) or desipramine (1.25 mg/kg) IP) significantly stimulated active behavior in the forced swim test above the level obtained with each of the drugs given separately. The present data suggest the potential clinical efficacy of a combined therapy of depressive patients with MIF-1 and small doses of tricyclic antidepressants.

  1. [Cardiac amyloidosis].

    Science.gov (United States)

    Hoyer, Caroline; Angermann, Christiane E; Knop, Stefan; Ertl, Georg; Störk, Stefan

    2008-03-15

    Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment. PMID:18344065

  2. Methanol extract of Tephrosia vogelii leaves potentiates the contractile action of acetylcholine on isolated rabbit jejunum

    Institute of Scientific and Technical Information of China (English)

    Tavershima Dzenda; Joseph Olusegun Ayo; Alexander Babatunde Adelaiye; Ambrose Osemattah Adaudi

    2015-01-01

    To investigate the modulating role of methanol extract of Tephrosia vogelii leaves on acetylcholine (ACh)-induced contraction of isolated rabbit jejunum. Methods: Rabbit jejunum segment was removed and placed in an organ bath containing Tyrode’s solution, and its contractions were recorded isometrically. Results: ACh (2.0 × 10-10 g/mL) and the extract (2.0 × 10-4 g/mL) individually increased the frequency of contraction (mean ± SEM) of the isolated smooth muscle tissue by 47.6% ± 9.5%and 77.8% ± 66.5%, respectively. When ACh and the extract were combined, the frequency of contraction of the tissue was increased by 222.2% ± 25.9%, representing a 366.7% increase (P < 0.001) over the effect of ACh alone. Similarly, ACh (2.0 × 10-9 g/mL) and the extract individually increased significantly (P < 0.001) the amplitude of contraction of the tissue by 685.7% ± 61.1% and 455.2% ± 38.1%, respectively. When ACh and the extract were combined, the amplitude of contraction of the tissue rose by 1263.8% ± 69.0%, representing 84.3% increase over the effect of ACh alone. Conclusions: The findings demonstrate that methanol extract of Tephrosia vogelii leaves potentiates the contractile effect of ACh on intestinal smooth muscle, supporting the traditional claim that the plant is purgative.

  3. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action

    Directory of Open Access Journals (Sweden)

    Rae-Dong Jeong

    2016-04-01

    Full Text Available Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc. Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika.

  4. Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells

    Directory of Open Access Journals (Sweden)

    János Brunner

    2014-03-01

    Full Text Available Backpropagating action potentials (bAPs and local calcium signals that they trigger are fundamental for dendritic functions. Here we addressed the question what extent the changes of local dendritic membrane properties can contribute to the shaping of the coupling between dendritic action potentials and the local calcium responses. Using a combination of in vitro electrophysiological and confocal imaging techniques we found that activation of dendritic GIRK channels via mGlu2 or GABAB receptors enhanced the bAP¬-triggered calcium signals in the dendrites of dentate gyrus granule cells (GCs. The enhancement of calcium signals was significant only in those dendritic regions, where these receptors are predominantly expressed. Similarly to GIRK channel activation, somatic hyperpolarization by DC current injection (from -64 mV to -77 mV, significantly increased bAP-associated calcium signals in the proximal dendrites. The hyperpolarization was associated with a decrease in the input resistance due to the rectification of the membrane potential of GCs. The effect of hyperpolarization on the calcium signals was maintained when T-type calcium currents were blocked but it decreased when GIRK channels were inhibited. Simultaneous dual somato-dendritic recordings from GCs showed that somatic hyperpolarization accelerated the repolarization phase of dendritic bAP in the proximal region whereas the rising phase and peak amplitude was not affected. We hypothesize that the larger driving force for calcium ions during the faster repolarization can contribute to the increasing in calcium signals. Employment of previously recorded dendritic bAP waveforms from hyperpolarized membrane potential as voltage command evoked larger calcium currents in nucleated patches compared to bAP waveform from the same recording at depolarized membrane potential. Furthermore, addition of native, high-voltage activated, inactivating potassium conductance by somatic dynamic clamp

  5. Methanol extract of Tephrosia vogelii leaves potentiates the contractile action of acetylcholine on isolated rabbit jejunum

    Institute of Scientific and Technical Information of China (English)

    Tavershima; Dzenda; Joseph; Olusegun; Ayo; Alexander; Babatunde; Adelaiye; Ambrose; Osemattah; Adaudi

    2015-01-01

    Objective:To investigate the modulating role of methanol extract of Tephrosia vogelii leaves on acetylcholine(ACh)-induced contraction of isolated rabbit jejunum.Methods: Rabbit jejunum segment was removed and placed in an organ bath containing Tyrode’s solution, and its contractions were recorded isometrically.Results: ACh(2.0 × 10-10 g/m L) and the extract(2.0 × 10-4 g/m L) individually increased the frequency of contraction(mean ± SEM) of the isolated smooth muscle tissue by 47.6% ± 9.5% and 77.8% ± 66.5%, respectively. When ACh and the extract were combined, the frequency of contraction of the tissue was increased by 222.2% ± 25.9%, representing a 366.7% increase(P < 0.001) over the effect of ACh alone. Similarly, ACh(2.0 × 10-9 g/m L) and the extract individually increased significantly(P < 0.001) the amplitude of contraction of the tissue by 685.7% ± 61.1% and 455.2% ± 38.1%, respectively. When ACh and the extract were combined, the amplitude of contraction of the tissue rose by 1263.8% ± 69.0%, representing 84.3% increase over the ef ect of ACh alone. Conclusions: The findings demonstrate that methanol extract of Tephrosia vogelii leaves potentiates the contractile ef ect of ACh on intestinal smooth muscle, supporting the traditional claim that the plant is purgative.

  6. CXCR4 Antagonism Attenuates the Development of Diabetic Cardiac Fibrosis.

    Directory of Open Access Journals (Sweden)

    Po-Yin Chu

    Full Text Available Heart failure (HF is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice or type II diabetes (Israeli Sand-rats and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.

  7. Cardiac imaging with multi-sector data acquisition in volumetric CT: variation of effective temporal resolution and its potential clinical consequences

    Science.gov (United States)

    Tang, Xiangyang; Hsieh, Jiang; Taha, Basel H.; Vass, Melissa L.; Seamans, John L.; Okerlund, Darin R.

    2009-02-01

    With increasing longitudinal detector dimension available in diagnostic volumetric CT, step-and-shoot scan is becoming popular for cardiac imaging. In comparison to helical scan, step-and-shoot scan decouples patient table movement from cardiac gating/triggering, which facilitates the cardiac imaging via multi-sector data acquisition, as well as the administration of inter-cycle heart beat variation (arrhythmia) and radiation dose efficiency. Ideally, a multi-sector data acquisition can improve temporal resolution at a factor the same as the number of sectors (best scenario). In reality, however, the effective temporal resolution is jointly determined by gantry rotation speed and patient heart beat rate, which may significantly lower than the ideal or no improvement (worst scenario). Hence, it is clinically relevant to investigate the behavior of effective temporal resolution in cardiac imaging with multi-sector data acquisition. In this study, a 5-second cine scan of a porcine heart, which cascades 6 porcine cardiac cycles, is acquired. In addition to theoretical analysis and motion phantom study, the clinical consequences due to the effective temporal resolution variation are evaluated qualitative or quantitatively. By employing a 2-sector image reconstruction strategy, a total of 15 (the permutation of P(6, 2)) cases between the best and worst scenarios are studied, providing informative guidance for the design and optimization of CT cardiac imaging in volumetric CT with multi-sector data acquisition.

  8. Cardiac contraction induces discordant alternans and localized block

    Science.gov (United States)

    Radszuweit, M.; Alvarez-Lacalle, E.; Bär, M.; Echebarria, B.

    2015-02-01

    In this paper we use a simplified model of cardiac excitation-contraction coupling to study the effect of tissue deformation on the dynamics of alternans, i.e., alternations in the duration of the cardiac action potential, that occur at fast pacing rates and are known to be proarrhythmic. We show that small stretch-activated currents can produce large effects and cause a transition from in-phase to off-phase alternations (i.e., from concordant to discordant alternans) and to conduction blocks. We demonstrate numerically and analytically that this effect is the result of a generic change in the slope of the conduction velocity restitution curve due to electromechanical coupling. Thus, excitation-contraction coupling can potentially play a relevant role in the transition to reentry and fibrillation.

  9. Cordycepin Decreases Compound Action Potential Conduction of Frog Sciatic Nerve In Vitro Involving Ca2+-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Li-Hua Yao

    2015-01-01

    Full Text Available Cordycepin has been widely used in oriental countries to maintain health and improve physical performance. Compound nerve action potential (CNAP, which is critical in signal conduction in the peripheral nervous system, is necessary to regulate physical performance, including motor system physiological and pathological processes. Therefore, regulatory effects of cordycepin on CNAP conduction should be elucidated. In this study, the conduction ability of CNAP in isolated frog sciatic nerves was investigated. Results revealed that cordycepin significantly decreased CNAP amplitude and conductive velocity in a reversible and concentration-dependent manner. At 50 mg/L cordycepin, CNAP amplitude and conductive velocity decreased by 62.18 ± 8.06% and 57.34% ± 6.14% compared with the control amplitude and conductive velocity, respectively. However, the depressive action of cordycepin on amplitude and conductive velocity was not observed in Ca2+-free medium or in the presence of Ca2+ channel blockers (CdCl2/LaCl3. Pretreatment with L-type Ca2+ channel antagonist (nifedipine/deltiazem also blocked cordycepin-induced responses; by contrast, T-type and P-type Ca2+ channel antagonists (Ni2+ failed to block such responses. Therefore, cordycepin decreased the conduction ability of CNAP in isolated frog sciatic nerves via L-type Ca2+ channel-dependent mechanism.

  10. Potential Causes of Significant Inventory Differences at Bulk Handling Facilities and the Importance of Inventory Difference Action Levels

    International Nuclear Information System (INIS)

    Accountancy for nuclear material can be split into two categories. Firstly, where possible, accountancy should be in terms of items that can be transferred as discrete packages and their contents fixed at the time of their creation. All items must remain accounted for at all times, and a single missing item is considered significant. Secondly, where nuclear material is unconstrained, for example in a reprocessing plant where it can change form, there is an uncertainty that relates to the amount of material present in any location. Cumulatively, these uncertainties can be summed and provide a context for any estimate of material in a process. Any apparent loss or gain between what has been physically measured within a facility during its physical inventory take and what is reported within its nuclear material accounts is known as an inventory difference. The cumulative measurement uncertainties can be used to set an action level for the inventory difference so that if an inventory difference is observed outside of such action levels, the difference is classified as significant and an investigation to find the root cause(s) is required. The purpose of this paper is to explore the potential causes of significant inventory differences and to provide a framework within which an inventory difference investigation can be carried out.

  11. Promoting HIV Vaccine Research in African American Communities: Does the Theory of Reasoned Action Explain Potential Outcomes of Involvement?

    Science.gov (United States)

    Frew, Paula M; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J

    2007-01-01

    The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (>/= 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research.

  12. Dendritic Na(+) spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons.

    Science.gov (United States)

    Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

    2014-01-01

    Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na(+) spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na(+) spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow.

  13. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

    Directory of Open Access Journals (Sweden)

    Galati Gaspare

    2009-07-01

    Full Text Available Abstract Background Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of Vitis vinifera. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA. Methods The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols. Results Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6 as well as a tumor-line (HL60. Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA. Conclusion Resveratrol is

  14. The effects of propofol on local field potential spectra, action potential firing rate, and their temporal relationship in humans and felines

    Directory of Open Access Journals (Sweden)

    Sara eHanrahan

    2013-04-01

    Full Text Available Propofol is an intravenous sedative hypnotic, which, acting as a GABAA agonist, results in neocortical inhibition. While propofol has been well studied at the molecular and clinical level, less is known about the effects of propofol at the level of individual neurons and local neocortical networks. We used Utah Electrode Arrays (UEAs to investigate the effects of propofol anesthesia on action potentials (APs and local field potentials (LFPs. UEAs were implanted into the neocortex of two humans and three felines. The two human patients and one feline received propofol by bolus injection, while the other two felines received target-controlled infusions. We examined the changes in LFP power spectra and AP firing at different levels of anesthesia. Increased propofol concentration correlated with decreased high-frequency power in LFP spectra and decreased AP firing rates, and the generation of large amplitude spike-like LFP activity; however, the temporal relationship between APs and LFPs remained relatively consistent at all levels of propofol. The probability that an AP would fire at this local minimum of the LFP increased with propofol administration. The propofol-induced suppression of neocortical network activity allowed LFPs to be dominated by low-frequency spike-like activity, and correlated with sedation and unconsciousness. As the low-frequency spike-like activity increased and the AP-LFP relationship became more predictable firing rate encoding capacity is impaired. This suggests a mechanism for decreased information processing in the neocortex that accounts for propofol-induced unconsciousness.

  15. Cardiac rhabdomyosarcoma

    OpenAIRE

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical stain...

  16. Cardiac developmental toxicity

    OpenAIRE

    Mahler, Gretchen J.; Jonathan T Butcher

    2011-01-01

    Congenital heart disease is a highly prevalent problem with mostly unknown origins. Many cases of CHD likely involve an environmental exposure coupled with genetic susceptibility, but practical and ethical considerations make nongenetic causes of CHD difficult to assess in humans. The development of the heart is highly conserved across all vertebrate species, making animal models an excellent option for screening potential cardiac teratogens. This review will discuss exposures known to cause ...

  17. Effect of microbial action on the corrosion potential of austenitic alloy containers for high-level nuclear waste

    International Nuclear Information System (INIS)

    The safe disposal of high-level nuclear waste (HLW) entails the ability to ensure the integrity of waste containers for prolonged time periods. It is generally accepted that under certain conditions, microbial action may change local benign environments to those in which localized corrosion can be actively promoted. The use of repassivation potential (Erp) in relation to the value of the corrosion potential (Ecorr) has been proposed as a means of assessing the propensity of a metallic material to localized corrosion. Microbial activity is known to influence Ecorr however, the precise mechanism is unresolved. Shewanella putrefaciens, a bacteria with many of the characteristics of sulfate-reducing bacteria (SRB), are being grown under controlled conditions on 316L stainless steel (SS) surfaces to understand the relationship between Ecorr and metabolic activity. It has been observed that the growth of the bacteria under aerobic conditions, without the production of metabolic sulfide, leads to only minor variation in Ecorr. These changes possibly correlate to the periods of active bacterial growth

  18. Effect of microbial action on the corrosion potential of austenitic alloy containers for high-level nuclear waste

    Energy Technology Data Exchange (ETDEWEB)

    Angell, P.; Dunn, D.S.; Cragnolino, G.A. [Southwest Research Inst., San Antonio, TX (United States). Center for Nuclear Waste Regulatory Analyses

    1996-08-01

    The safe disposal of high-level nuclear waste (HLW) entails the ability to ensure the integrity of waste containers for prolonged time periods. It is generally accepted that under certain conditions, microbial action may change local benign environments to those in which localized corrosion can be actively promoted. The use of repassivation potential (E{sub rp}) in relation to the value of the corrosion potential (E{sub corr}) has been proposed as a means of assessing the propensity of a metallic material to localized corrosion. Microbial activity is known to influence E{sub corr} however, the precise mechanism is unresolved. Shewanella putrefaciens, a bacteria with many of the characteristics of sulfate-reducing bacteria (SRB), are being grown under controlled conditions on 316L stainless steel (SS) surfaces to understand the relationship between E{sub corr} and metabolic activity. It has been observed that the growth of the bacteria under aerobic conditions, without the production of metabolic sulfide, leads to only minor variation in E{sub corr}. These changes possibly correlate to the periods of active bacterial growth.

  19. Assessment of cardiac conduction: basic principles of optical mapping.

    Science.gov (United States)

    Ding, Chunhua; Everett, Thomas H

    2010-01-01

    Extracellular recordings acquired from electrodes placed on the surface of cardiac tissue have traditionally been used to study the electrophysiological properties of the tissue. While this technique has been used in several studies that have increased our understanding of cardiac arrhythmias and action potential propagation, there are several limitations that have prevented us from seeing a bigger picture of arrhythmia mechanisms. These limitations include the limited number of electrodes and unstable recordings. Optical mapping was developed to increase the temporal and spatial resolution over traditional electrode recordings and ultimately the accuracy of the data analysis. This technology involves using a voltage-sensitive dye that binds to the cell membrane. The fluorescence changes of the dye have a linear relationship to the action potential changes of the cell membrane. These fluorescent changes can then be detected by a photodiode array, a CCD camera or a CMOS camera. This will allow the recording of the action potential in hundreds to thousands of different sites simultaneously. Presented in this chapter are the materials and hardware needed along with step-by-step instructions on setup and techniques used in optical mapping for larger tissue preparations. PMID:20680823

  20. Sources of actual and potential radioactive contamination at the Dnieper River basin with regard to preparation of strategic action plan

    International Nuclear Information System (INIS)

    Full text: The Dnieper River basin is one of the largest drainage areas in Europe. The modern Dnieper is a cascade of large artificial reservoirs (Kiev, Kanev, Kremenchug, Dniprodzerzhinsk, Zaporozhie, Kakhovske) carrying its water to the Black Sea. It is largest water artery of Ukraine where more then 20 million of peoples live, and which water extensively use for water supply, fishery, irrigation and recreation in the region. At the same time the Dnieper basin is the most important industrial, agricultural congested area. About 20 units of Nuclear Reactors are in operation of 6 NPP situated on the territory of Ukraine (4) and Russia (2) as well. This area was also heavy contaminated mainly with long-lived radionuclides such as Cs 137 and Sr 90 and Pu due to Chernobyl releases in 1986. In the central part of Ukraine Uranium mining and uranium ores re-processing industry are developed. At the moment most of these facilities are suspended their activity because economical reason. However the problem of uranium tailing of liquid and solid wastes are remain to be one of the serious sources for the Environmental contamination and uncertainties with its impact to the human health in the region (Zheltie Vodi town and Dnieprodzerzhinsk). The Radiation Risk Assessment of the environmental impacts of these sources ('Hot spots') in the basin and Priorities for potential actions to reduce the ecological Risks of its impacts are considering. The Results of this study are the basis for Strategic Action Plan recommended for three countries (Ukraine, Russia and Belarus) at the Dnieper River Basin obtained using Optimization Procedures and experience of Radiation Protection Practice

  1. Action Learning: Avoiding Conflict or Enabling Action

    Science.gov (United States)

    Corley, Aileen; Thorne, Ann

    2006-01-01

    Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

  2. Assessing the Electrode-Neuron Interface with the Electrically Evoked Compound Action Potential, Electrode Position, and Behavioral Thresholds.

    Science.gov (United States)

    DeVries, Lindsay; Scheperle, Rachel; Bierer, Julie Arenberg

    2016-06-01

    Variability in speech perception scores among cochlear implant listeners may largely reflect the variable efficacy of implant electrodes to convey stimulus information to the auditory nerve. In the present study, three metrics were applied to assess the quality of the electrode-neuron interface of individual cochlear implant channels: the electrically evoked compound action potential (ECAP), the estimation of electrode position using computerized tomography (CT), and behavioral thresholds using focused stimulation. The primary motivation of this approach is to evaluate the ECAP as a site-specific measure of the electrode-neuron interface in the context of two peripheral factors that likely contribute to degraded perception: large electrode-to-modiolus distance and reduced neural density. Ten unilaterally implanted adults with Advanced Bionics HiRes90k devices participated. ECAPs were elicited with monopolar stimulation within a forward-masking paradigm to construct channel interaction functions (CIF), behavioral thresholds were obtained with quadrupolar (sQP) stimulation, and data from imaging provided estimates of electrode-to-modiolus distance and scalar location (scala tympani (ST), intermediate, or scala vestibuli (SV)) for each electrode. The width of the ECAP CIF was positively correlated with electrode-to-modiolus distance; both of these measures were also influenced by scalar position. The ECAP peak amplitude was negatively correlated with behavioral thresholds. Moreover, subjects with low behavioral thresholds and large ECAP amplitudes, averaged across electrodes, tended to have higher speech perception scores. These results suggest a potential clinical role for the ECAP in the objective assessment of individual cochlear implant channels, with the potential to improve speech perception outcomes. PMID:26926152

  3. Effectiveness of elite female basketball players’ technical-tactic actions and ways for their improvement at stage of maximal realization of individual potentials

    Directory of Open Access Journals (Sweden)

    Sushko R.A.

    2015-08-01

    Full Text Available Purpose: study effectiveness of elite female basketball players’ technical-tactic actions and determine the ways for their improvement at stage of maximal realization of individual potentials. Material: the authors analyzed competition functioning’s indicators of female basketball players of national combined team of Ukraine and their age characteristics. Results: effectiveness of technical-tactic actions in structure of national female basketball players’ combined team of Ukraine competition functioning at European championship. The authors present: indicators of team composition; roles in team; won and lost games; quantity of scored and skipped points; technical-tactic actions; age of sportswomen. Age indicators of elite female basketball players at stage of maximal realization have been given. Conclusions: we have composed a list of the most important technical-tactic actions in competition functioning. We also outlined ways for their perfection at stage of maximal realization of individual potentials of elite female basketball players of different game roles.

  4. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical

    International Nuclear Information System (INIS)

    Crotoxin, the main component of Crotalus durissus terrificus snake venom, has been studied since 1938. It is a natural polypeptidic complex with pharmacological potential because of its antitumoral properties which has attracted great interest for diagnosis and therapy of oncological diseases. However, Crotoxin mechanism of action and sites of specific interaction on tumor cells are still misunderstood. Breast cancer is the second most frequent type in the world and the most common cancer in women. About 30 to 60% of mammary tumors overexpress epidermal growth factor receptor (EGFR), a transmembrane protein related to cell proliferation. Since literature has reported that Crotoxin antitumoral effect is more potent on cells with EGFR overexpression the objectives of this work were to evaluate Crotoxin cytotoxic effects on mammary tumor cells human breast carcinoma (MCF-7) and Ehrlich tumor cells (murine ascitics carcinoma), and to investigate the specific molecular interaction of Crotoxin on Ehrlich tumor cells. Initially, Crotoxin was radiolabelled with iodine-125 (125I-Crotoxin) and iodine-131 (131I-Crotoxin). Saturation and competition assay were carried out to characterize Crotoxin in vitro interaction; Crotoxin biodistribution studies and singlephoton emission computed tomography (SPECT) of mice bearing Ehrlich tumor have been evaluated to describe in vivo interaction. Our results showed that Crotoxin presented cytotoxic effect against Ehrlich with DL50 in vitro (concentration of compound which is lethal for 50% of cells) of about one micromolar, but did not present significant effect against MCF-7. Morphological alterations characteristic of apoptosis suggests programmed cell death. 125I-Crotoxin interaction with Ehrlich tumor cells was saturable with approximately 70% specificity, and presented Kd=24.98 nmol/L and Bmax=16,570 sites/cell for low affinity binding sites and Kd=0.06 nmol/L and Bmax=210 sites/cell high affinity binding sites; moreover, the

  5. Prenatal diagnosis of cardiac defects : accuracy and benefit

    NARCIS (Netherlands)

    Clur, S. A.; Van Brussel, P. M.; Ottenkamp, J.; Bilardo, C. M.

    2012-01-01

    Objective The prenatal diagnosis of cardiac defects can potentially reduce postnatal morbidity and mortality. We wanted to evaluate prenatal cardiac diagnosis accuracy in a population referred for echocardiography. Methods Single centre retrospective study of echocardiography referrals between April

  6. Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction: The Link with Cardiac Arrhythmogenesis

    Science.gov (United States)

    Tse, Gary; Yan, Bryan P.; Chan, Yin W. F.; Tian, Xiao Yu; Huang, Yu

    2016-01-01

    Background: Cardiac arrhythmias represent a significant problem globally, leading to cerebrovascular accidents, myocardial infarction, and sudden cardiac death. There is increasing evidence to suggest that increased oxidative stress from reactive oxygen species (ROS), which is elevated in conditions such as diabetes and hypertension, can lead to arrhythmogenesis. Method: A literature review was undertaken to screen for articles that investigated the effects of ROS on cardiac ion channel function, remodeling and arrhythmogenesis. Results: Prolonged endoplasmic reticulum stress is observed in heart failure, leading to increased production of ROS. Mitochondrial ROS, which is elevated in diabetes and hypertension, can stimulate its own production in a positive feedback loop, termed ROS-induced ROS release. Together with activation of mitochondrial inner membrane anion channels, it leads to mitochondrial depolarization. Abnormal function of these organelles can then activate downstream signaling pathways, ultimately culminating in altered function or expression of cardiac ion channels responsible for generating the cardiac action potential (AP). Vascular and cardiac endothelial cells become dysfunctional, leading to altered paracrine signaling to influence the electrophysiology of adjacent cardiomyocytes. All of these changes can in turn produce abnormalities in AP repolarization or conduction, thereby increasing likelihood of triggered activity and reentry. Conclusion: ROS plays a significant role in producing arrhythmic substrate. Therapeutic strategies targeting upstream events include production of a strong reducing environment or the use of pharmacological agents that target organelle-specific proteins and ion channels. These may relieve oxidative stress and in turn prevent arrhythmic complications in patients with diabetes, hypertension, and heart failure. PMID:27536244

  7. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

    DEFF Research Database (Denmark)

    Cotel, Florence; Exley, Richard; Cragg, Stephanie;

    2013-01-01

    Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequat......-HT during motor activity spills over from its release sites to the AIS of motoneurons. Here, activated 5-HT1A receptors inhibit firing and, thereby, muscle contraction. Hence, this is a cellular mechanism for central fatigue......Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle......--as during motor exercise--activated 5-HT1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential...

  8. Anticancer potential and mechanism of action of mango ginger (Curcuma amada Roxb.) supercritical CO₂ extract in human glioblastoma cells.

    Science.gov (United States)

    Ramachandran, Cheppail; Lollett, Ivonne V; Escalon, Enrique; Quirin, Karl-Werner; Melnick, Steven J

    2015-04-01

    Mango ginger (Curcuma amada Roxb.) is among the less-investigated species of Curcuma for anticancer properties. We have investigated the anticancer potential and the mechanism of action of a supercritical CO2 extract of mango ginger (CA) in the U-87MG human glioblastoma cell line. CA demonstrated higher cytotoxicity than temozolomide, etoposide, curcumin, and turmeric force with IC50, IC75, and IC90 values of 4.92 μg/mL, 12.87 μg/mL, and 21.30 μg/mL, respectively. Inhibitory concentration values of CA for normal embryonic mouse hypothalamus cell line (mHypoE-N1) is significantly higher than glioblastoma cell line, indicating the specificity of CA against brain tumor cells. CompuSyn analysis indicates that CA acts synergistically with temozolomide and etoposide for the cytotoxicity with combination index values of <1. CA treatment also induces apoptosis in glioblastoma cells in a dose-dependent manner and downregulates genes associated with apoptosis, cell proliferation, telomerase activity, oncogenesis, and drug resistance in glioblastoma cells.

  9. Electrophysiological evaluation of nerve function in inferior alveolar nerve injury: relationship between nerve action potentials and histomorphometric observations.

    Science.gov (United States)

    Murayama, M; Sasaki, K; Shibahara, T

    2015-12-01

    The objective of this study was to improve the accuracy of diagnosis of inferior alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the sensory nerve action potential (SNAP) and sensory nerve conduction velocity (SCV). Crush and partial and complete nerve amputation injuries were applied to the IAN of rabbits, then SNAPs and histomorphometric observations were recorded at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at 5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an increase at week 10. For partial nerve amputation, small to medium-sized nerve fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10. Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable from week 10, however the SCV was extremely low. This study showed SCV to be an effective factor in the evaluation of nerve injury and regeneration. PMID:26433750

  10. DCT domain feature extraction scheme based on motor unit action potential of EMG signal for neuromuscular disease classification.

    Science.gov (United States)

    Doulah, Abul Barkat Mollah Sayeed Ud; Fattah, Shaikh Anowarul; Zhu, Wei-Ping; Ahmad, M Omair

    2014-01-01

    A feature extraction scheme based on discrete cosine transform (DCT) of electromyography (EMG) signals is proposed for the classification of normal event and a neuromuscular disease, namely the amyotrophic lateral sclerosis. Instead of employing DCT directly on EMG data, it is employed on the motor unit action potentials (MUAPs) extracted from the EMG signal via a template matching-based decomposition technique. Unlike conventional MUAP-based methods, only one MUAP with maximum dynamic range is selected for DCT-based feature extraction. Magnitude and frequency values of a few high-energy DCT coefficients corresponding to the selected MUAP are used as the desired feature which not only reduces computational burden, but also offers better feature quality with high within-class compactness and between-class separation. For the purpose of classification, the K-nearest neighbourhood classifier is employed. Extensive analysis is performed on clinical EMG database and it is found that the proposed method provides a very satisfactory performance in terms of specificity, sensitivity and overall classification accuracy.

  11. Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics.

    Science.gov (United States)

    Djoko, Karrera Y; Goytia, Maira M; Donnelly, Paul S; Schembri, Mark A; Shafer, William M; McEwan, Alastair G

    2015-10-01

    There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria gonorrhoeae showed that Cu(btsc) complexes may act as inhibitors of respiratory dehydrogenases in the electron transport chain. We now show that these complexes are also toxic against pathogens that lack a respiratory chain. Respiration in Escherichia coli was slightly affected by Cu(btsc) complexes, but our results indicate that, in this model bacterium, the complexes act primarily as agents that deliver toxic Cu ions efficiently into the cytoplasm. Although the chemistry of Cu(btsc) complexes may dictate their mechanism of action, their efficacy depends heavily on bacterial physiology. This is linked to the ability of the target bacterium to tolerate Cu and, additionally, the susceptibility of the respiratory chain to direct inhibition by Cu(btsc) complexes. The physiology of N. gonorrhoeae, including multidrug-resistant strains, makes it highly susceptible to damage by Cu ions and Cu(btsc) complexes, highlighting the potential of Cu(btsc) complexes (and Cu-based therapeutics) as a promising treatment against this important bacterial pathogen. PMID:26239980

  12. The Potential Protective Action of Vitamin D in Hepatic Insulin Resistance and Pancreatic Islet Dysfunction in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Leung, Po Sing

    2016-03-01

    Vitamin D deficiency (i.e., hypovitaminosis D) is associated with increased insulin resistance, impaired insulin secretion, and poorly controlled glucose homeostasis, and thus is correlated with the risk of metabolic diseases, including type 2 diabetes mellitus (T2DM). The liver plays key roles in glucose and lipid metabolism, and its dysregulation leads to abnormalities in hepatic glucose output and triglyceride accumulation. Meanwhile, the pancreatic islets are constituted in large part by insulin-secreting β cells. Consequently, islet dysfunction, such as occurs in T2DM, produces hyperglycemia. In this review, we provide a critical appraisal of the modulatory actions of vitamin D in hepatic insulin sensitivity and islet insulin secretion, and we discuss the potential roles of a local vitamin D signaling in regulating hepatic and pancreatic islet functions. This information provides a scientific basis for establishing the benefits of the maintenance, or dietary manipulation, of adequate vitamin D status in the prevention and management of obesity-induced T2DM and non-alcoholic fatty liver disease. PMID:26959059

  13. Effects of Ginkgolide B on action potential and calcium,potassium current in guinea pig ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan QI; Zhi-xiong ZHANG; You-qiu XU

    2004-01-01

    AIM: To investigate the effect of Ginkgolide B (GB) on action potential (AP), delayed rectifier potassium current (IK), and L-type calcium current (ICa-L) in guinea pig ventricular myocytes. METHODS: Single ventricular myocytes were isolated by an enzymatic dissociation method. AP, IK, ICa-L were recorded by whole-cell patch-clamp technique in either current or voltage clamp mode. RESULTS: GB shortened APD in a concentration-dependent manner. GB 0.1, 1, and 10 μmol/L shortened APD50 by 7.9 % (n=5, P>0.05), 18.4 % (n=5, P<0.01), and 28.9 % (n=6, P<0.01), respectively; APD90 by 12.4 % (n=5, P>0.05), 17.6 % (n=5, P<0.01), 26.4 % (n=5, P<0.01),respectively. GB increased IK in a concentration-dependent manner. GB 0.1, 1, and l0 μmol/L increased IK by 20.1% (n=6, P<0.05), 43.1% (n=6, P<0.01), 55.6 % (n=6, P<0.05); increased IKtail by 10.7 % (n=6, P<0.05),25.1% (n=6, P<0.05), and 37.7 % (n=6, P<0.05), respectively at testing potential of +50 mV and shift the I-V curve of Ik upward. But GB had no significant effect on ICa-L at above concentrations. CONCLUSION: GB significantly shortened APD in a concentration-dependent manner which mainly due to increase of IK.

  14. Percutaneous method for single-catheter multiple monophasic action potential recordings during magnetocardiographic mapping in spontaneously breathing rodents

    International Nuclear Information System (INIS)

    To test the feasibility of a novel method to combine magnetocardiographic (MCG) estimate of ventricular repolarization (VR) and multiple monophasic action potential (MultiMAP) recording in spontaneously breathing rodents with percutaneous sub-xyphoid epicardial placement of a MCG-compatible amagnetic catheter (AC), ten Wistar rats (WRs) and ten guinea pigs (GPs) were studied. Under fluoroscopic control, the AC was moved until four stable MAPs were recorded (fixed inter-electrode distance of 1.2 mm). 36-channel DC-SQUID (sensitivity 20 fT Hz–½) were used for MCG mapping. MAPs, differentially amplified (BW: DC-500 Hz), were digitized at 1 kHz. AC pacing provided local ventricular effective refractory period (VERP) estimate. MAP duration (MAPd) was measured at 50% and 90% levels of repolarization. Simultaneous MCG mapping and MultiMAP recording were successful in all animals. Average MAPd50% and MAPd90% were shorter in WRs than in GPs (26.4 ± 2.9 ms versus 110.6 ± 14.3 ms and 60.7 ± 5.4 ms versus 127.7 ± 15.3 ms, respectively). VERP was 51 ± 4.8 ms in WRs and 108.4 ± 12.9 ms in GPs, respectively. The MAP amplitude was 16.9 ± 4.5 in WRs and 16.2 ± 4.2 in GPs. MAP and MCG parameters of VR were in good agreement. All animals survived the procedure. Two also survived a second invasive study; one was followed up until natural death at 52 months. Percutaneous MultiMAP recording is minimally invasive, usually avoids animal sacrifice, is compatible with simultaneous surface MCG mapping and might be used for experimental validation of MCG VR abnormality, to study the arrhythmogenic potential of new drugs and/or animal models of ventricular arrhythmias. (paper)

  15. Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

    Directory of Open Access Journals (Sweden)

    Tianruo Guo

    2013-01-01

    Full Text Available A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation.

  16. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    Energy Technology Data Exchange (ETDEWEB)

    Franzellitti, Silvia, E-mail: silvia.franzellitti@unibo.it [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Buratti, Sara; Capolupo, Marco [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Du, Bowen; Haddad, Samuel P. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Chambliss, C. Kevin [Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798 (United States); Brooks, Bryan W. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy)

    2014-06-01

    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

  17. Finding the rhythm of sudden cardiac death: new opportunities using induced pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Sallam, Karim; Li, Yingxin; Sager, Philip T; Houser, Steven R; Wu, Joseph C

    2015-06-01

    Sudden cardiac death is a common cause of death in patients with structural heart disease, genetic mutations, or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with sudden cardiac death. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology, including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single-ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell-derived cardiomyocytes resemble, but are not identical, adult human cardiomyocytes and provide a new platform for studying arrhythmic disorders leading to sudden cardiac death. A variety of platforms exist to phenotype cellular models, including conventional and automated patch clamp, multielectrode array, and computational modeling. Induced pluripotent stem cell-derived cardiomyocytes have been used to study long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and other hereditary cardiac disorders. Although induced pluripotent stem cell-derived cardiomyocytes are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of sudden cardiac death. PMID:26044252

  18. [Stem cells and cardiac regeneration].

    Science.gov (United States)

    Perez Millan, Maria Ines; Lorenti, Alicia

    2006-01-01

    Stem cells are defined by virtue of their functional attributes: absence of tissue specific differentitated markers, capable of proliferation, able to self-maintain the population, able to produce a large number of differentiated, functional progeny, able to regenerate the tissue after injury. Cell therapy is an alternative for the treatment of several diseases, like cardiac diseases (cell cardiomyoplasty). A variety of stem cells could be used for cardiac repair: from cardiac and extracardiac sources. Each cell type has its own profile of advantages, limitations, and practicability issues in specific clinical settings. Differentiation of bone marrow stem cells to cardiomyocyte-like cells have been observed under different culture conditions. The presence of resident cardiac stem cell population capable of differentiation into cardiomyocyte or vascular lineage suggests that these cells could be used for cardiac tissue repair, and represent a great promise for clinical application. Stem cells mobilization by cytokines may also offer a strategy for cardiac regeneration. The use of stem cells (embryonic and adult) may hold the key to replacing cells lost in many devastating diseases. This potential benefit is a major focus for stem cell research.

  19. Effect of Cerium on Cardiac Muscle of Rat and Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The effect of Ce3+ on cardiac muscle of rat and guinea pig was studied. In vitro, 0.05 mmol.L-1 solution of Ce3+ inhibited the contraction of guinea pig atria. The change of action potential duration(APD) of guinea pig papillary muscle exposed to 0.4 mmol·L-1 Ce3+ was significant, and those exposed to 0.1 and 0.2 mmol·L-1 Ce3+ were not significant. In vivo, compared with the control group, the APD for rat cardiac muscle after long-term feed on Ce3+ was significantly delayed in high dose, and that was not significantly delayed in low dose. The results suggest that Ce3+ with long-term high dose intake might affect the influx of Ca2+, Na+ and outflow of K+ for rat cardiac muscle.

  20. Systemic Inflammatory Response and Potential Prognostic Implications After Out-of-Hospital Cardiac Arrest: A Substudy of the Target Temperature Management Trial

    DEFF Research Database (Denmark)

    Bro-Jeppesen, John; Kjaergaard, Jesper; Wanscher, Michael;

    2015-01-01

    -1β, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-9, interleukin-10, interleukin-12, interleukin-13, tumor necrosis factor-α, interferon-γ, C-reactive protein, and procalcitonin were measured. Mortality at 30 days was evaluated by Cox analysis, and the predictive capability...... of inflammatory markers was evaluated by area under the curve. Level of all inflammatory markers changed significantly within 72 hours after out-of-hospital cardiac arrest (all p values<0.001), but only procalcitonin levels showed overall differences between nonsurvivors and survivors (p=0.0002). At...... baseline, interleukin-6 was independently associated with mortality, whereas both interleukin-6 levels (hazard ratio=1.23 [1.01-1.49]; p=0.04) and procalcitonin levels (hazard ratio=1.20 [1.03-1.39]; p=0.02) 24 hours after out-of-hospital cardiac arrest were associated with 30-day mortality with no...

  1. Combination of CD34-positive cell subsets with infarcted myocardium-like matrix stiffness: a potential solution to cell-based cardiac repair.

    Science.gov (United States)

    Zhang, Shuning; Ma, Xin; Yao, Kang; Zhu, Hong; Huang, Zheyong; Shen, Li; Qian, Juying; Zou, Yunzeng; Sun, Aijun; Ge, Junbo

    2014-06-01

    Detection of the optimal cell transplantation strategy for myocardial infarction (MI) has attracted a great deal of attention. Commitment of engrafted cells to angiogenesis within damaged myocardium is regarded as one of the major targets in cell-based cardiac repair. Bone marrow-derived CD34-positive cells, a well-characterized population of stem cells, might represent highly functional endothelial progenitor cells and result in the formation of new blood vessels. Recently, physical microenvironment (extracellular matrix stiffness) around the engrafted cells was found to exert an essential impact on their fate. Stem cells are able to feel and respond to the tissue-like matrix stiffness to commit to a relevant lineage. Notably, the infarct area after MI experiences a time-dependent stiffness change from flexible to rigid. Our previous observations demonstrated myocardial stiffness-dependent differentiation of the unselected bone marrow-derived mononuclear cells (BMMNCs) along endothelial lineage cells. Myocardial stiffness (~42 kPa) within the optimal time domain of cell engraftment (at week 1 to 2) after MI provided a more favourable physical microenvironment for cell specification and cell-based cardiac repair. However, the difference in tissue stiffness-dependent cell differentiation between the specific cell subsets expressing and no expressing CD34 phenotype remains uncertain. We presumed that CD34-positive cell subsets facilitated angiogenesis and subsequently resulted in cardiac repair under induction of infarcted myocardium-like matrix stiffness compared with CD34-negative cells. If the hypothesis were true, it would contribute greatly to detect the optimal cell subsets for cell therapy and to establish an optimized therapy strategy for cell-based cardiac repair.

  2. Short-term inspiratory muscle training potentiates the benefits of aerobic and resistance training in patients undergoing CABG in phase II cardiac rehabilitation program

    OpenAIRE

    Bárbara Maria Hermes; Dannuey Machado Cardoso; Tiago José Nardi Gomes; Tamires Daros dos Santos; Marília Severo Vicente; Sérgio Nunes Pereira; Viviane Acunha Barbosa; Isabella Martins de Albuquerque

    2015-01-01

    Abstract Objective: To investigate the efficiency of short-term inspiratory muscle training program associated with combined aerobic and resistance exercise on respiratory muscle strength, functional capacity and quality of life in patients who underwent coronary artery bypass and are in the phase II cardiac rehabilitation program. Methods: A prospective, quasi-experimental study with 24 patients who underwent coronary artery bypass and were randomly assigned to two groups in the Phase II c...

  3. Action potential energetics at the organismal level reveal a trade-off in efficiency at high firing rates.

    Science.gov (United States)

    Lewis, John E; Gilmour, Kathleen M; Moorhead, Mayron J; Perry, Steve F; Markham, Michael R

    2014-01-01

    The energetic costs of action potential (AP) production constrain the evolution of neural codes and brain networks. Cellular-level estimates of AP-related costs are typically based on voltage-dependent Na(+) currents that drive active transport by the Na(+)/K(+) ATPase to maintain the Na(+) and K(+) ion concentration gradients necessary for AP production. However, these estimates of AP cost have not been verified at the organismal level. Electric signaling in the weakly electric fish Eigenmannia virescens requires that specialized cells in an electric organ generate APs with large Na(+) currents at high rates (200-600 Hz). We measured these currents using a voltage-clamp protocol and then estimated the energetic cost at the cellular level using standard methods. We then used this energy-intensive signaling behavior to measure changes in whole-animal energetics for small changes in electric discharge rate. At low rates, the whole-animal measure of AP cost was similar to our cellular-level estimates. However, AP cost increased nonlinearly with increasing firing rates. We show, with a biophysical model, that this nonlinearity can arise from the increasing cost of maintaining AP amplitude at high rates. Our results confirm that estimates of energetic costs based on Na(+) influx are appropriate for low baseline firing rates, but that extrapolating to high firing rates may underestimate true costs in cases in which AP amplitude does not decrease. Moreover, the trade-off between energetic cost and firing rate suggests an additional constraint on the evolution of high-frequency signaling in neuronal systems. PMID:24381281

  4. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

    Science.gov (United States)

    Cotel, Florence; Exley, Richard; Cragg, Stephanie J.; Perrier, Jean-François

    2013-01-01

    Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spinal cord of the adult turtle, we found that prolonged stimulation of the raphe-spinal pathway—as during motor exercise—activated 5-HT1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential initiation by modulating a Na+ current. Immunohistochemical staining against 5-HT revealed a high-density innervation of 5-HT terminals on the somatodendritic membrane and a complete absence on the AIS. This observation raised the hypothesis that a 5-HT spillover activates receptors at this latter compartment. We tested it by measuring the level of extracellular 5-HT with cyclic voltammetry and found that prolonged stimulations of the raphe-spinal pathway increased the level of 5-HT to a concentration sufficient to activate 5-HT1A receptors. Together our results demonstrate that prolonged release of 5-HT during motor activity spills over from its release sites to the AIS of motoneurons. Here, activated 5-HT1A receptors inhibit firing and, thereby, muscle contraction. Hence, this is a cellular mechanism for central fatigue. PMID:23487756

  5. Problems, Prescriptions and Potential in Actionable Climate Change Science - A Case Study from California Coastal Marsh Research

    Science.gov (United States)

    MacDonald, G. M.; Ambrose, R. F.; Thorne, K.; Takekawa, J.; Brown, L. N.; Fejtek, S.; Gold, M.; Rosencranz, J.

    2015-12-01

    Frustrations regarding the provision of actionable science extend to both producers and consumers. Scientists decry the lack of application of their research in shaping policy and practices while decision makers bemoan the lack of applicability of scientific research to the specific problems at hand or its narrow focus relative to the plethora of engineering, economic and social considerations that they must also consider. Incorporating climate change adds additional complexity due to uncertainties in estimating many facets of future climate, the inherent variability of climate and the decadal scales over which significant changes will develop. Recently a set of guidelines for successful science-policy interaction was derived from the analysis of transboundary water management. These are; 1 recognizing that science is a crucial but bounded input into the decision-making processes, 2 early establishment of conditions for collaboration and shared commitment among participants, 3 understanding that science-policy interactions are enhanced through greater collaboration and social or group-learning processes, 4 accepting that the collaborative production of knowledge is essential to build legitimate decision-making processes, and 5 engaging boundary organizations and informal networks as well as formal stakeholders. Here we present as a case study research on California coastal marshes, climate change and sea-level that is being conducted by university and USGS scientists under the auspices of the Southwest Climate Science Center. We also present research needs identified by a seperate analysis of best practices for coastal marsh restoration in the face of climate change that was conducted in extensive consultation with planners and managers. The initial communication, scientific research and outreach-dissemination of the marsh scientfic study are outlined and compared to best practices needs identified by planners and the science-policy guidelines outlined above

  6. Evaluation of nystatin containing chitosan hydrogels as potential dual action bio-active restorative materials: in vitro approach.

    Science.gov (United States)

    Perchyonok, V Tamara; Reher, Vanessa; Zhang, Shengmiao; Basson, Nicki; Grobler, Sias

    2014-11-28

    Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into "dual action bioactive restorative materials", capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM), release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.

  7. Evaluation of Nystatin Containing Chitosan Hydrogels as Potential Dual Action Bio-Active Restorative Materials: in Vitro Approach

    Directory of Open Access Journals (Sweden)

    V. Tamara Perchyonok

    2014-11-01

    Full Text Available Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into “dual action bioactive restorative materials”, capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM, release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.

  8. Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.

    Directory of Open Access Journals (Sweden)

    Marino DiFranco

    Full Text Available BACKGROUND: Exercise intolerance in chronic heart failure (HF has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC, but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+ release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers. METHODS AND FINDINGS: Using state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms was markedly (2.6-fold and significantly (p<0.05 smaller than in fibers from healthy volunteers (28±3.3 µM/ms. This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers. CONCLUSIONS: These findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients.

  9. Coagulopathy and hemostatic monitoring in cardiac surgery

    DEFF Research Database (Denmark)

    Johansson, Pär I; Sølbeck, Sacha; Genet, Gustav;

    2012-01-01

    Cardiac surgery with cardiopulmonary bypass (CPB) causes severe derangements in the hemostatic system, which in turn puts the patient at risks of microvascular bleeding. Excessive transfusion and surgical re-exploration after cardiac surgery are potentially associated with a number of adverse...

  10. Stem cell sources for cardiac regeneration

    NARCIS (Netherlands)

    Roccio, M.; Goumans, M. J.; Sluijter, J. P. G.; Doevendans, P. A.

    2008-01-01

    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 cardiomyo

  11. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  12. Using delay differential equations to induce alternans in a model of cardiac electrophysiology.

    Science.gov (United States)

    Eastman, Justin; Sass, Julian; Gomes, Johnny M; Dos Santos, Rodrigo Weber; Cherry, Elizabeth M

    2016-09-01

    Cardiac electrical alternans is a period-2 dynamical behavior with alternating long and short action potential durations (APD) that often precedes dangerous arrhythmias associated with cardiac arrest. Despite the importance of alternans, many current ordinary differential equations models of cardiac electrophysiology do not produce alternans, thereby limiting the use of these models for studying the mechanisms that underlie this condition. Because delay differential equations (DDEs) commonly induce complex dynamics in other biological systems, we investigate whether incorporating DDEs can lead to alternans development in cardiac models by studying the Fox et al. canine ventricular action potential model. After suppressing the alternans in the original model, we show that alternans can be obtained by introducing DDEs in the model gating variables, and we quantitatively compare the DDE-induced alternans with the alternans present in the original model. We analyze the behavior of the voltage, currents, and gating variables of the model to study the effects of the delays and to determine how alternans develops in that setting, and we discuss the mathematical and physiological implications of our findings. In future work, we aim to apply our approach to induce alternans in models that do not naturally exhibit such dynamics. PMID:27302910

  13. Functional cardiac imaging by random access microscopy

    Directory of Open Access Journals (Sweden)

    Claudia eCrocini

    2014-10-01

    Full Text Available Advances in the development of voltage sensitive dyes and Ca2+ sensors in combination with innovative microscopy techniques allowed researchers to perform functional measurements with an unprecedented spatial and temporal resolution. At the moment, one of the shortcomings of available technologies is their incapability of imaging multiple fast phenomena while controlling the biological determinants involved. In the near future, ultrafast deflectors can be used to rapidly scan laser beams across the sample, performing optical measurements of action potential and Ca2+ release from multiple sites within cardiac cells and tissues. The same scanning modality could also be used to control local Ca2+ release and membrane electrical activity by activation of caged compounds and light-gated ion channels. With this approach, local Ca2+ or voltage perturbations could be induced, simulating arrhythmogenic events, and their impact on physiological cell activity could be explored. The development of this optical methodology will provide fundamental insights in cardiac disease, boosting new therapeutic strategies, and, more generally, it will represent a new approach for the investigation of the physiology of excitable cells.

  14. Mechanical communication in cardiac cell synchronized beating

    Science.gov (United States)

    Nitsan, Ido; Drori, Stavit; Lewis, Yair E.; Cohen, Shlomi; Tzlil, Shelly

    2016-05-01

    Cell-cell communication, which enables cells to coordinate their activity and is essential for growth, development and function, is usually ascribed a chemical or electrical origin. However, cells can exert forces and respond to environment elasticity and to mechanical deformations created by their neighbours. The extent to which this mechanosensing ability facilitates intercellular communication remains unclear. Here we demonstrate mechanical communication between cells directly for the first time, providing evidence for a long-range interaction that induces long-lasting alterations in interacting cells. We show that an isolated cardiac cell can be trained to beat at a given frequency by mechanically stimulating the underlying substrate. Deformations are induced using an oscillatory mechanical probe that mimics the deformations generated by a beating neighbouring cardiac cell. Unlike electrical field stimulation, the probe-induced beating rate is maintained by the cell for an hour after the stimulation stops, implying that long-term modifications occur within the cell. These long-term alterations provide a mechanism for cells that communicate mechanically to be less variable in their electromechanical delay. Mechanical coupling between cells therefore ensures that the final outcome of action potential pacing is synchronized beating. We further show that the contractile machinery is essential for mechanical communication.

  15. Dendrite-derived supernumerary axons on adult axotomized motor neurons possess proteins that are essential for the initiation and propagation of action potentials and synaptic vesicle release

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; MacDermid, Victoria E; Montague, Steven J;

    2011-01-01

    on these processes matches the arrangement of these channels that is necessary for the initiation and conduction of action potentials. At terminal bouton-like structures they possess key proteins necessary for the release of synaptic vesicles (SV2 and synaptophysin). Thus, axon-like processes emanating from the tips...

  16. Epicardial Lineages and Cardiac Repair

    Directory of Open Access Journals (Sweden)

    Manvendra K. Singh

    2013-08-01

    Full Text Available The death of cardiac myocytes resulting from myocardial infarction is a major cause of heart failure worldwide. Effective therapies for regenerating lost cardiac myocytes are lacking. Recently, the epicardium has been implicated as a source of inflammatory cytokines, growth factors and progenitor cells that modulate the response to myocardial injury. During embryonic development, epicardially-derived cells have the potential to differentiate into multiple cardiac lineages, including fibroblasts, vascular smooth muscle and potentially other cell types. In the healthy adult heart, epicardial cells are thought to be generally quiescent. However, injury of the adult heart results in reactivation of a developmental gene program in the epicardium, which leads to increased epicardial cell proliferation and differentiation of epicardium-derived cells (EPDCs into various cardiac lineages. Recent work suggests that epicardial reactivation after injury is accompanied by, and contributes to, a robust inflammatory response. In this review, we describe the current status of research related to epicardial biology in cardiac development and regeneration, highlighting important recent discoveries and ongoing controversies.

  17. Health Literacy Predicts Cardiac Knowledge Gains in Cardiac Rehabilitation Participants

    Science.gov (United States)

    Mattson, Colleen C.; Rawson, Katherine; Hughes, Joel W.; Waechter, Donna; Rosneck, James

    2015-01-01

    Objective: Health literacy is increasingly recognised as a potentially important patient characteristic related to patient education efforts. We evaluated whether health literacy would predict gains in knowledge after completion of patient education in cardiac rehabilitation. Method: This was a re-post observational analysis study design based on…

  18. A Comparative Study On The Action Potential Simulation (APS Therapy And The Routine Physiotherapy Protocol In Knee Osteoarthritisin Elderly People

    Directory of Open Access Journals (Sweden)

    Abbas Rahimi

    2012-04-01

    Full Text Available Background and Aim: Knee osteoarthritis is the most common cause for which the elderly people refere to physiotherapy outpatient clinics. This study aimed to investigate the effects of the Action Potential Stimulation (APS Therapy and the routine physiotherapy (PT protocol on relieving pain and swelling as well as the duration of the relief period in patients with knee osteoarthritis. Materials and Methods: 69 patients (62 females & 7 males with knee osteoarthritis were recruited in this study. The subjects were divided into two groups including APS Therapy (n=37, mean age: 55±13 years old and the routine PT protocol (n=32, mean age: 61±14 years old groups. A 10-session treatment period was carried out for each group; and their pain and swelling were measured at the first, fifth and tenth sessions and also one-month after the last session (follow up. The swelling was measured using measuring the circumference of the knee on the patella, 5 Cm above and 5 Cm below the patella. The routine PT protocol consisted of hot pack, ultrasound, TENS and exercise; and the APS therapy protocol included hot pack, APS Therapy and the same exercise. During the follow up, 50 out of 61 subjects were called on the phone and any pain changes were recorded.Results: In terms of swelling, the results showed significant reduction just on the patella only in the APS Therapy group (P<0.05. Visual Analogue Pain Scale (VAPS indicated a significant pain reduction in both groups. However, the APS Therapy group showed significantly pain reduction at the end of sessions five, ten and the follow up session (P<0.05. It was also revealed that while routine PT subjects showed no significant pain changes between the tenth and the follow up session, a gradual pain reduction was seen in the APS therapy group during this period (P<0.05. A gradual dosage reduction was recorded only in the APS therapy group, indicating a slight correlation with pain reduction (r=0.4.Conclusion: The

  19. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  20. A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.

    Directory of Open Access Journals (Sweden)

    Wing-Chiu Tong

    Full Text Available Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C coupling of uterine smooth muscle cells (USMC. Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2+ currents (L- and T-type, Na+ current, an hyperpolarization-activated current, three voltage-gated K+ currents, two Ca2+-activated K+ current, Ca2+-activated Cl current, non-specific cation current, Na+-Ca2+ exchanger, Na+-K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing [Ca2+]i. This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes, the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, [Ca2+]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to

  1. Gene transfer to promote cardiac regeneration.

    Science.gov (United States)

    Collesi, Chiara; Giacca, Mauro

    2016-12-01

    There is an impelling need to develop new therapeutic strategies for patients with myocardial infarction and heart failure. Leading from the large quantity of new information gathered over the last few years on the mechanisms controlling cardiomyocyte proliferation during embryonic and fetal life, it is now possible to devise innovative therapies based on cardiac gene transfer. Different protein-coding genes controlling cell cycle progression or cardiomyocyte specification and differentiation, along with microRNA mimics and inhibitors regulating pre-natal and early post-natal cell proliferation, are amenable to transformation in potential therapeutics for cardiac regeneration. These gene therapy approaches are conceptually revolutionary, since they are aimed at stimulating the intrinsic potential of differentiated cardiac cells to proliferate, rather than relying on the implantation of exogenously expanded cells to achieve tissue regeneration. For efficient and prolonged cardiac gene transfer, vectors based on the Adeno-Associated Virus stand as safe, efficient and reliable tools for cardiac gene therapy applications.

  2. Neuromuscular blockade in cardiac surgery: An update for clinicians

    OpenAIRE

    Hemmerling Thomas; Russo Gianluca; Bracco David

    2008-01-01

    There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary) sufficiently profound neuromuscular blockade during surgery and i...

  3. De novo expression of fetal ED-A(+) fibronectin and B (+) tenascin-C splicing variants in human cardiac allografts: potential impact for targeted therapy of rejection.

    Science.gov (United States)

    Franz, Marcus; Matusiak-Brückner, Monika; Richter, Petra; Grün, Katja; Ziffels, Barbara; Neri, Dario; Maschek, Hansjörg; Schulz, Uwe; Pfeil, Alexander; Jung, Christian; Figulla, Hans R; Gummert, Jan; Berndt, Alexander; Renner, André

    2014-10-01

    Management of acute and especially chronic rejection after human cardiac transplantation is still challenging. Chronic rejection, represented by allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) is known to cause severe long-term complications. Rejection associated tissue-remodelling entails the reoccurrence of fetal variants of Fibronectin (Fn) and Tenascin-C (Tn-C), which are virtually absent in adult human organs. In a rat model, an extensive re-expression could be demonstrated for ED-A(+) Fn with spatial association to CAV and CIF. Thus, it is of great interest to investigate the cardiac tissue expression and distribution in human samples. From 48 heart transplanted patients, 64 tissue specimens derived from right ventricular biopsies were available. Histopathological analysis was performed according to the International Society for Heart and Lung Transplantation (ISHLT) guidelines for the detection of acute rejection. By immunohistochemistry, protein expression of ED-A(+) Fn, B(+) Tn-C, alpha-smooth muscle actin, CD31 and CD45 was assessed and analysed semiquantitatively. Co-localisation studies were performed by means of immunofluorescence double labelling. Histopathological analysis of the 64 samples revealed different ISHLT grades (0R in 36 cases, 1R in 20 cases and 2R in 8 cases). There was a distinct and quantitatively relevant re-occurrence of ED-A(+) Fn and B(+) Tn-C in most samples. Semi-quantitative evaluation did not show any correlation to the acute rejection grade for all markers. Interestingly, significant correlations to the extent of inflammation could be shown for ED-A(+) Fn (r = 0.442, p = 0.000) and B(+) Tn-C (r = 0.408, p = 0.001) as well as between both proteins (r = 0.663, p = 0.000). A spatial association of ED-A(+) Fn and B(+) Tn-C to CAV and CIF could be demonstrated. A relevant re-occurrence of ED-A(+) Fn and B(+) Tn-C following human heart transplantation could be demonstrated with spatial association to

  4. Anti-cancer and potential chemopreventive actions of ginseng by activating Nrf2 (NFE2L2 anti-oxidative stress/anti-inflammatory pathways

    Directory of Open Access Journals (Sweden)

    Wu Qing

    2010-10-01

    Full Text Available Abstract This article reviews recent basic and clinical studies of ginseng, particularly the anti-cancer effects and the potential chemopreventive actions by activating the transcriptional factor, nuclear factor (erythroid-derived 2-like 2 (Nrf2 or NFE2L2-mediated anti-oxidative stress or anti-inflammatory pathways. Nrf2 is a novel target for cancer prevention as it regulates the antioxidant responsive element (ARE, a critical regulatory element in the promoter region of genes encoding cellular phase II detoxifying and anti-oxidative stress enzymes. The studies on the chemopreventive effects of ginseng or its components/products showed that Nrf2 could also be a target for ginseng's actions. A number of papers also demonstrated the anti-inflammatory effects of ginseng. Targeting Nrf2 pathway is a novel approach to the investigation of ginseng's cancer chemopreventive actions, including some oxidative stress and inflammatory conditions responsible for the initiation, promotion and progression of carcinogenesis.

  5. Cardiac perception and cardiac control. A review.

    Science.gov (United States)

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  6. DNA double-strand breaks as potential indicators for the biological effects of ionising radiation exposure from cardiac CT and conventional coronary angiography: a randomised, controlled study

    Energy Technology Data Exchange (ETDEWEB)

    Geisel, Dominik; Zimmermann, Elke; Rief, Matthias; Greupner, Johannes; Hamm, Bernd [Charite Medical School, Department of Radiology, Berlin (Germany); Laule, Michael; Knebel, Fabian [Charite Medical School, Department of Cardiology, Berlin (Germany); Dewey, Marc [Charite Medical School, Department of Radiology, Berlin (Germany); Charite, Institut fuer Radiologie, Berlin (Germany)

    2012-08-15

    To prospectively compare induced DNA double-strand breaks by cardiac computed tomography (CT) and conventional coronary angiography (CCA). 56 patients with suspected coronary artery disease were randomised to undergo either CCA or cardiac CT. DNA double-strand breaks were assessed in fluorescence microscopy of blood lymphocytes as indicators of the biological effects of radiation exposure. Radiation doses were estimated using dose-length product (DLP) and dose-area product (DAP) with conversion factors for CT and CCA, respectively. On average there were 0.12 {+-} 0.06 induced double-strand breaks per lymphocyte for CT and 0.29 {+-} 0.18 for diagnostic CCA (P < 0.001). This relative biological effect of ionising radiation from CCA was 1.9 times higher (P < 0.001) than the effective dose estimated by conversion factors would have suggested. The correlation between the biological effects and the estimated radiation doses was excellent for CT (r = 0.951, P < 0.001) and moderate to good for CCA (r = 0.862, P < 0.001). One day after radiation, a complete repair of double-strand breaks to background levels was found in both groups. Conversion factors may underestimate the relative biological effects of ionising radiation from CCA. DNA double-strand break assessment may provide a strategy for individualised assessments of radiation. (orig.)

  7. DNA double-strand breaks as potential indicators for the biological effects of ionising radiation exposure from cardiac CT and conventional coronary angiography: a randomised, controlled study

    International Nuclear Information System (INIS)

    To prospectively compare induced DNA double-strand breaks by cardiac computed tomography (CT) and conventional coronary angiography (CCA). 56 patients with suspected coronary artery disease were randomised to undergo either CCA or cardiac CT. DNA double-strand breaks were assessed in fluorescence microscopy of blood lymphocytes as indicators of the biological effects of radiation exposure. Radiation doses were estimated using dose-length product (DLP) and dose-area product (DAP) with conversion factors for CT and CCA, respectively. On average there were 0.12 ± 0.06 induced double-strand breaks per lymphocyte for CT and 0.29 ± 0.18 for diagnostic CCA (P < 0.001). This relative biological effect of ionising radiation from CCA was 1.9 times higher (P < 0.001) than the effective dose estimated by conversion factors would have suggested. The correlation between the biological effects and the estimated radiation doses was excellent for CT (r = 0.951, P < 0.001) and moderate to good for CCA (r = 0.862, P < 0.001). One day after radiation, a complete repair of double-strand breaks to background levels was found in both groups. Conversion factors may underestimate the relative biological effects of ionising radiation from CCA. DNA double-strand break assessment may provide a strategy for individualised assessments of radiation. (orig.)

  8. Electrophysiological Cardiac Modeling: A Review.

    Science.gov (United States)

    Beheshti, Mohammadali; Umapathy, Karthikeyan; Krishnan, Sridhar

    2016-01-01

    Cardiac electrophysiological modeling in conjunction with experimental and clinical findings has contributed to better understanding of electrophysiological phenomena in various species. As our knowledge on underlying electrical, mechanical, and chemical processes has improved over time, mathematical models of the cardiac electrophysiology have become more realistic and detailed. These models have provided a testbed for various hypotheses and conditions that may not be easy to implement experimentally. In addition to the limitations in experimentally validating various scenarios implemented by the models, one of the major obstacles for these models is computational complexity. However, the ever-increasing computational power of supercomputers facilitates the clinical application of cardiac electrophysiological models. The potential clinical applications include testing and predicting effects of pharmaceutical agents and performing patient-specific ablation and defibrillation. A review of studies involving these models and their major findings are provided.

  9. Vitamin D and Cardiac Differentiation.

    Science.gov (United States)

    Kim, Irene M; Norris, Keith C; Artaza, Jorge N

    2016-01-01

    Calcitriol (1,25-dihydroxycholecalciferol or 1,25-D3) is the hormonally active metabolite of vitamin D. Experimental studies of vitamin D receptors and 1,25-D3 establish calcitriol to be a critical regulator of the structure and function of the heart. Clinical studies link vitamin D deficiency with cardiovascular disease (CVD). Emerging evidence demonstrates that calcitriol is highly involved in CVD-related signaling pathways, particularly the Wnt signaling pathway. Addition of 1,25-D3 to cardiomyocyte cells and examination of its effects on cardiomyocytes and mainly Wnt11 signaling allowed the specific characterization of the role of calcitriol in cardiac differentiation. 1,25-D3 is demonstrated to: (i) inhibit cell proliferation without promoting apoptosis; (ii) decrease expression of genes related to the regulation of the cell cycle; (iii) promote formation of cardiomyotubes; (iv) induce expression of casein kinase-1-α1, a negative regulator of the canonical Wnt signaling pathway; and (v) increase expression of noncanonical Wnt11, which has been recognized to induce cardiac differentiation during embryonic development and in adult cells. Thus, it appears that vitamin D promotes cardiac differentiation through negative modulation of the canonical Wnt signaling pathway and upregulation of noncanonical Wnt11 expression. Future work to elucidate the role(s) of vitamin D in cardiovascular disorders will hopefully lead to improvement and potentially prevention of CVD, including abnormal cardiac differentiation in settings such as postinfarction cardiac remodeling. PMID:26827957

  10. Chagas cardiomyopathy: The potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogs chronically infected with Trypanosoma cruzi.

    Science.gov (United States)

    Santos, Fabiane M; Mazzeti, Ana L; Caldas, Sérgio; Gonçalves, Karolina R; Lima, Wanderson G; Torres, Rosália M; Bahia, Maria Terezinha

    2016-09-01

    Cardiac involvement represents the main cause of mortality among patients with Chagas disease, and the relevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. In the present study, we used a canine model infected with the benznidazole-sensitive Berenice-78 Trypanosoma cruzi strain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiac muscle tissue damage and left ventricular diastolic dysfunction in the chronic phase of the infection. The effect of the treatment on reducing the parasite load was monitored by blood PCR and blood culture assays, and the effect of the treatment on the outcome of heart tissue damage and on diastolic function was evaluated by histopathology and echo Doppler cardiogram. The benefit of the benznidazole-treatment in reducing the parasite burden was demonstrated by a marked decrease in positive blood culture and PCR assay results until 30days post-treatment. At this time, the PCR and blood culture assays yielded negative results for 82% of the treated animals, compared with only 36% of the untreated dogs. However, a progressive increase in the parasite load could be detected in the peripheral blood for one year post-treatment, as evidenced by a progressive increase in positive results for both the PCR and the blood culture assays at follow-up. The parasite load reduction induced by treatment was compatible with the lower degree of tissue damage among animals euthanized in the first month after treatment and with the increased cardiac damage after this period, reaching levels similar to those in untreated animals at the one-year follow-up. The two infected groups also presented similar, significantly smaller values for early tissue septal velocity (E' SIV) than the non-infected dogs did at this later time. Moreover, in the treated animals, an increase in the E/E' septal tissue filling pressure ratio was observed when compared with basal values as well as with

  11. 乳酸对心肌收缩力和细胞动作电位的影响与运动能力的相关性%The Effect of Lactate on the Contractile Force of Ventricular Papillary Muscle and Cellular Action Potential

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To study the effect of lactate of differentconcentration on the action potential of ventricular papillary muscle cell (n=4) and contractile force (n=10).Method Using intracellular microelectrode technique and microtension depicting method.Result The Result showed the effect of lactated solution of a certain comcentration became obvious. After perfused with lactate solution of 4mmol/L,the vilocity maximum decreased significantly (p<0.05) showed the 4mmol/L lactate solution decreased the rate of depolarization: decreased the efficency of Na + channel; lactate solution decreased the contractile force of cardiac muscle. Conclusion The possible mechanism was: Ca+ influx and Na+ - H+ exchange were inhibited, resulted in the elevation of intracellular H+ concentration; through Na+-Ca2+ exchange, Ca2+ efflux decreased resulted in the intracellular Ca2+ decreased resulted in the intracellular Ca2+ overload.

  12. Role of TGF-β on cardiac structural and electrical remodeling

    Directory of Open Access Journals (Sweden)

    Roberto Ramos-Mondragón

    2008-12-01

    Full Text Available Roberto Ramos-Mondragón, Carlos A Galindo, Guillermo AvilaDepartamento de Bioquímica, Cinvestav-IPN, MéxicoAbstract: The type β transforming growth factors (TGF-βs are involved in a number of human diseases, including heart failure and myocardial arrhythmias. In fact, during the last 20 years numerous studies have demonstrated that TGF-β affects the architecture of the heart under both normal and pathological conditions. Moreover, TGF-β signaling is currently under investigation, with the aim of discovering potential therapeutic roles in human disease. In contrast, only few studies have investigated whether TGF-β affects electrophysiological properties of the heart. This fact is surprising since electrical remodeling represents an important substrate for cardiac disease. This review discusses the potential role of TGF-β on cardiac excitation-contraction (EC coupling, action potentials, and ion channels. We also discuss the effects of TGF-β on cardiac development and disease from structural and electrophysiological points of view.Keywords: transforming growth factor, ion channel, cardiac electrophysiology

  13. The effect of Shen-Fu on gastrointestinal tract injury and its potential mechanism during cardio-pulmonary bypass in patients undergoing cardiac surgery

    Institute of Scientific and Technical Information of China (English)

    夏中元; 詹丽英; 何宇红; 刘先义

    2003-01-01

    Objective: To investigate the effect of Shen-Fu (SF) injection on gastrointestinal tract injury and its potential mechanism. Methods: Thirty-eight patients undergoing elective open heart surgery were assigned to Group C (control group, n=18) and Group SF (n=20) randomly. In Group SF, the patients received intravenous injection of SF (0.5 ml/kg) at the beginning of the surgery followed by a continuous infusion of 100 ml SF (1.0 ml/kg) solution diluted by saline at a rate of 0.004 ml*Kg-1*min-1with a Grasby pump. The control group was injected with normal saline in the same volume. Gastric intramucosal pH (pHi), activity of blood diamine oxidase (DAO), and concentrations of blood LPS and IL-6 were measured before CPB (S0) and 1 h (S1) and 2 h (S2) after aortic declamping, respectively.Results: In Group C, pHi value was significantly lower at S1 and S2 than at S0 ( mean P<0.01) and blood DAO and concentrations of LPS and IL-6 were significantly higher at S1 and S2 than at S0 ( meanP<0.01). In Group SF, pHi was obviously lower at S1 and S2 than at S0 (P<0.05) but LPS and IL-6 levels and DAO were higher at S0 (mean P<0.05). Blood DAO and LPS level demonstrated significant negative correlations with pHi (mean P<0.01) while LPS concentration showed a positive correlation with blood DAO (P<0.01) and IL-6 concentration(P<0.05). At S1 and S2 after aortic declamping, the levels of pHi were higher in Group SF than in Group C (mean P<0.01 ) but DAO and LPS and IL-6 levels were significantly lower in Group SF than in Group C ( P<0.01).Conclusions: SF has a protective effect on gastrointestinal tract and can reduce inflammatory actions.

  14. Allogenic benefit in stem cell therapy: cardiac repair and regeneration.

    Science.gov (United States)

    Al-Daccak, R; Charron, D

    2015-09-01

    Stem cell (SC)-based therapies are a developing mean to repair, restore, maintain, or enhance organ functioning through life span. They are in particular a fast track to restore function in failing heart. Various types of SCs have been used in experimental and clinical studies showing the potential of these cells to revolutionize the treatment of heart diseases. Autologous cells have been privileged to overpass immunological barriers. The field has progressed tremendously and the hurdles, which have been largely overlooked in the excitement over the expected benefit the immunogenicity, have been revealed. Also, manufacturing of patient-specific clinical grade SC product, whether adult stem or reprogrammed induced pluripotent SCs, and the availability of these cells in sufficient amounts and status when needed is questionable. In contrast, adult SCs derived from healthy donors, thus allogeneic, have the advantage to be immediately available as an 'off-the-shelf' therapeutic product. The challenge is to overcome the immunological barriers to their transplantation. Recent research provided new insights into the mode of action and immune behavior of SCs in autologous as well as allogeneic settings. Lessons are learned and immune paradigms are changing: allogenicity, if balanced could be part of the dynamic and durable mechanisms that are critical to sustain cardiac regeneration and repair. We discuss the hurdles, lessons, and advances accomplished in the field through the progressive journey of cardiac-derived stem/progenitor cells toward allogeneic cardiac regenerative/reparative therapy. PMID:26206374

  15. High-order finite element methods for cardiac monodomain simulations

    Directory of Open Access Journals (Sweden)

    Kevin P Vincent

    2015-08-01

    Full Text Available Computational modeling of tissue-scale cardiac electrophysiology requires numerically converged solutions to avoid spurious artifacts. The steep gradients inherent to cardiac action potential propagation necessitate fine spatial scales and therefore a substantial computational burden. The use of high-order interpolation methods has previously been proposed for these simulations due to their theoretical convergence advantage. In this study, we compare the convergence behavior of linear Lagrange, cubic Hermite, and the newly proposed cubic Hermite-style serendipity interpolation methods for finite element simulations of the cardiac monodomain equation. The high-order methods reach converged solutions with fewer degrees of freedom and longer element edge lengths than traditional linear elements. Additionally, we propose a dimensionless number, the cell Thiele modulus, as a more useful metric for determining solution convergence than element size alone. Finally, we use the cell Thiele modulus to examine convergence criteria for obtaining clinically useful activation patterns for applications such as patient-specific modeling where the total activation time is known a priori.

  16. Cardiac Optogenetics: Enhancement by All-trans-Retinal.

    Science.gov (United States)

    Yu, Jinzhu; Chen, Kay; Lucero, Rachel V; Ambrosi, Christina M; Entcheva, Emilia

    2015-11-16

    All-trans-Retinal (ATR) is a photosensitizer, serving as the chromophore for depolarizing and hyperpolarizing light-sensitive ion channels and pumps (opsins), recently employed as fast optical actuators. In mammalian optogenetic applications (in brain and heart), endogenous ATR availability is not considered a limiting factor, yet it is unclear how ATR modulation may affect the response to optical stimulation. We hypothesized that exogenous ATR may improve light responsiveness of cardiac cells modified by Channelrhodopsin2 (ChR2), hence lowering the optical pacing energy. In virally-transduced (Ad-ChR2(H134R)-eYFP) light-sensitive cardiac syncytium in vitro, ATR supplements ≤2 μM improved cardiomyocyte viability and augmented ChR2 membrane expression several-fold, while >4 μM was toxic. Employing integrated optical actuation (470 nm) and optical mapping, we found that 1-2 μM ATR dramatically reduced optical pacing energy (over 30 times) to several μW/mm(2), lowest values reported to date, but also caused action potential prolongation, minor changes in calcium transients and no change in conduction. Theoretical analysis helped explain ATR-caused reduction of optical excitation threshold in cardiomyocytes. We conclude that cardiomyocytes operate at non-saturating retinal levels, and carefully-dosed exogenous ATR can enhance the performance of ChR2 in cardiac cells and yield energy benefits over orders of magnitude for optogenetic stimulation.

  17. Promoting HIV Vaccine Research in African American Communities: Does the Theory of Reasoned Action Explain Potential Outcomes of Involvement?

    OpenAIRE

    Frew, Paula M; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J.

    2007-01-01

    The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration o...

  18. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    Jonas S De Jong

    2010-12-01

    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  19. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    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

  20. Leadless Cardiac Pacemakers: Back to the Future.

    Science.gov (United States)

    Miller, Marc A; Neuzil, Petr; Dukkipati, Srinivas R; Reddy, Vivek Y

    2015-09-01

    Despite significant advances in battery longevity, lead performance, and programming features since the first implanted permanent pacemaker was developed, the basic design of cardiac pacemakers has remained relatively unchanged over the past 50 years. Because of inherent limitations in their design, conventional (transvenous) pacemakers are prone to multiple potential short- and long-term complications. Accordingly, there has been intense interest in a system able to provide the symptomatic and potentially lifesaving therapies of cardiac pacemakers while mitigating many of the risks associated with their weakest link-the transvenous lead. Leadless cardiac pacing represents the future of cardiac pacing systems, similar to the transition that occurred from the use of epicardial pacing systems to the familiar transvenous systems of today. This review summarizes the current evidence and potential benefits of leadless pacing systems, which are either commercially available (in Europe) or under clinical investigation. PMID:26337997

  1. Opposing Actions of Chronic[Deta][superscript 9] Tetrahydrocannabinol and Cannabinoid Antagonists on Hippocampal Long-Term Potentiation

    Science.gov (United States)

    Hoffman, Alexander F.; Oz, Murat; Yang, Ruiqin; Lichtman, Aron H.; Lupica, Carl R.

    2007-01-01

    Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, [Deta][superscript 9]-tetrahydrocannabinol ([Deta][superscript 9]-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation (LTP), a potential substrate for…

  2. [Cardiac potassium channels: molecular structure, physiology, pathophysiology and therapeutic implications].

    Science.gov (United States)

    Mironov, N Iu; Golitsyn, S P

    2013-01-01

    Potassium channels and currents play essential roles in cardiac repolarization. Potassium channel blockade by class III antiarrhythmic drugs prolongs cardiac repolarization and results in termination and prevention of cardiac arrhythmias. Excessive inhomogeneous repolarization prolongation may lead to electrical instability and proarrhythmia (Torsade de Pointes tachycardia). This review focuses on molecular structure, physiology, pathophysiology and therapeutic potential of potassium channels of cardiac conduction system and myocardium providing information on recent findings in pathogenesis of cardiac arrhythmias, including inherited genetic abnormalities, and future perspectives. PMID:24654438

  3. Circadian rhythm of heart rate in the rabbit: prolongation of action potential duration by sustained beta adrenoceptor blockade is not due to associated bradycardia.

    Science.gov (United States)

    Vaughan Williams, E M; Dennis, P D; Garnham, C

    1986-07-01

    Six litters of six young rabbits were injected intraperitoneally, two per litter, with saline, alinidine, or nadolol once or twice daily for two weeks. In four litters successful radiotransmissions of electrocardiograms were recorded once hourly for four days before and during treatment. Alinidine and nadolol produced an overall mean bradycardia in comparison with saline treated animals, the effect of alinidine exceeding that of nadolol. At 48-70 hours after the end of treatment the hearts were used for in vitro electrophysiological study. Nadolol, but not alinidine, induced a prolongation of action potential duration compared with that of saline treated littermates in both atrial and ventricular muscle. An incidental observation was that heart rate in the rabbit followed a circadian rhythm, heart rates being slower in the morning and faster in late afternoon and evening. The circadian rhythm was attenuated but not abolished by alinidine and nadolol. These results suggest that if prolongation of action potential duration by sustained beta blockade in patients after myocardial infarction contributes to protection against sudden death (by a class III antiarrhythmic action) then alinidine would not be expected to provide a comparable prophylaxis.

  4. [Stimulation of gastric mucosa afferents by phenylephrine potentiates anticonvulsive and eliminates sedative action of sodium valproate in the pentylenetetrazol kindling model in rats].

    Science.gov (United States)

    Serdiuk, S E; Gmiro, V E; Veselkina, O S

    2014-01-01

    Sodium valproate after chronic intragastric administration in the high dose of 100-200 mg/kg eliminates generalized clonic-tonic pentylenetetrazol seizures in 100 % of rats, but only in 33-57 % of rats it prevents local clonic kindling seizures. Strong sedation is induced by the specified doses of sodium valproate. The combined oral chronic administration of phenylephrine in threshold, noneffective alone dose of 0.2 mg/kg and sodium valproate in high doses of 100 mg/kg and 200 mg/kg potentiates anticonvulsive action of sodium valproate, because prevents both clonic-tonic kindling. seizures in 100 % of rats and clonic kindling seizures in 86-100 % of rats, and also it increases in 1.7-1.9 times anticonvulsive activity of valproate. The specified combinations of sodium valproate with phenylephrine do not produce the sedative side effect. The basis of the mechanism of potentiation of anticonvulsive action and elimination of sedative action of sodium valproate in high doses is the stimulation of gastric mucosa afferents by phenylephrine.

  5. Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

    Directory of Open Access Journals (Sweden)

    Daniel Minge

    Full Text Available Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP dynamics immediately following status epilepticus (SE in mice. SE was induced by intraperitoneal (i.p. injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV. No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP, was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP-induced Ca(2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+ and K(+ current components.

  6. Dopamine modulates Spike Timing-Dependent Plasticity and action potential properties in CA1 pyramidal neurons of acute rat hippocampal slices

    Directory of Open Access Journals (Sweden)

    Elke eEdelmann

    2011-11-01

    Full Text Available Spike Timing-Dependent Plasticity (STDP is a cellular model of hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15-20, we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent (t-LTP to 171 ± 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10-20 min to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the β-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 ± 6.9% of ACSF values in sucrose prepared slices. These results lead us to suggest that dopamine dependent regulation of action potential properties correlates with the efficiency to elicit STDP in CA1 pyramidal neurons.

  7. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  8. The endothelial function in cardiac surgery.

    Science.gov (United States)

    Ranucci, M

    2006-06-01

    Cardiac operations with cardiopulmonary bypass exerts many different actions which modify the natural function of endothelial cells. The main determinant is the activation of the coagulation system both through the intrinsic and extrinsic pathways, leading to an overwhelming thrombin formation. To counteract the coagulant effects of thrombin, heparin is used in large doses. As a result, the endothelium is asked to promote all its anticoagulant properties, basically through the AT release from the surface, the tissue factor pathway inhibitor release, and the activation of the protein C protein S system. At the end of cardiac operations, all these systems are depleted, and low levels of antithrombin, tissue factor pathway inhibitor, protein C are available for further anticoagulant effects. There is the evidence that levels of antithrombin activity below 50% at the end of cardiac operations with cardiopulmonary bypass are associated to bad outcomes in terms of surgical revision rate, thromboembolic events, and neurological events. Exogenous antithrombin administration has a well defined action in limiting thrombin formation during cardiac operations; however, we are still lacking an evidence-based information about the clinical impact of this and others possible preventive strategies based on exogenous administration of antithrombin before or during cardiac operations. PMID:16682923

  9. Potential effect and mechanism of action of topical chamomile (Matricaria chammomila L.) oil on migraine headache: A medical hypothesis.

    Science.gov (United States)

    Zargaran, Arman; Borhani-Haghighi, Afshin; Faridi, Pouya; Daneshamouz, Saeid; Kordafshari, Gholamreza; Mohagheghzadeh, Abdolali

    2014-11-01

    Migraine is a chronic recurring headache for which no complete treatment has been found yet. Therefore, finding new treatment approaches and medicines is important. In this review, we consider the probable mechanism of action of a traditional and ethnic formulary of chamomile extract in sesame oil as a new topical medication for migraine pain relief. Chamomile oil is prepared in Traditional Persian Medicine by boiling aqueous extract of chamomile in sesame oil. To optimize the procedure, we can use a Clevenger-type apparatus to extract the essential oil and add it to the end product. The preparation includes both essential oils (chamazulene and bisabolol oxide) and polyphenols (a flavonoid such as apigenin and its derivatives). It probably possesses pain relief effects for migraines because of the following properties: (1) chamazulene and apigenin, which inhibit iNOS expression in activated macrophages and can lead to the prohibition of NO release and synthesis; (2) chamomile flavonoids, which have a strong inhibitory effect on endogenous prostaglandin E2 (PGE2) levels in RAW 264.7 macrophages and can play the role of selective COX-2 inhibitor; (3) chamomile polyphenols, which possess anti-inflammatory effects due to the inhibition of pro-inflammatory biomarkers in THP1 macrophages and which can reduce inflammation in neurovascular units (NVU) at the site of migraine pain; (4) chamomile, which has neuroprotective effects because of reduced NO levels; (5) sesamine in sesame oil, which possesses an anti-inflammatory effect. These effects are supported by main pathophysiological theories of migraine such as neural and sensitization theories. Chamomile oil is a traditional formulation still used in Iran as an ethno-medicine. Because of the mentioned mechanisms of action, it can be hypothesized that chamomile oil is a novel medicine for the relief of migraine pain. PMID:25238714

  10. Donnan effect on chloride ion distribution as a determinant of body fluid composition that allows action potentials to spread via fast sodium channels

    Directory of Open Access Journals (Sweden)

    Kurbel Sven

    2011-05-01

    Full Text Available Abstract Proteins in any solution with a pH value that differs from their isoelectric point exert both an electric Donnan effect (DE and colloid osmotic pressure. While the former alters the distribution of ions, the latter forces water diffusion. In cells with highly Cl--permeable membranes, the resting potential is more dependent on the cytoplasmic pH value, which alters the Donnan effect of cell proteins, than on the current action of Na/K pumps. Any weak (positive or negative electric disturbances of their resting potential are quickly corrected by chloride shifts. In many excitable cells, the spreading of action potentials is mediated through fast, voltage-gated sodium channels. Tissue cells share similar concentrations of cytoplasmic proteins and almost the same exposure to the interstitial fluid (IF chloride concentration. The consequence is that similar intra- and extra-cellular chloride concentrations make these cells share the same Nernst value for Cl-. Further extrapolation indicates that cells with the same chloride Nernst value and high chloride permeability should have similar resting membrane potentials, more negative than -80 mV. Fast sodium channels require potassium levels >20 times higher inside the cell than around it, while the concentration of Cl- ions needs to be >20 times higher outside the cell. When osmotic forces, electroneutrality and other ions are all taken into account, the overall osmolarity needs to be near 280 to 300 mosm/L to reach the required resting potential in excitable cells. High plasma protein concentrations keep the IF chloride concentration stable, which is important in keeping the resting membrane potential similar in all chloride-permeable cells. Probable consequences of this concept for neuron excitability, erythrocyte membrane permeability and several features of circulation design are briefly discussed.

  11. Epigenetic mechanisms in cardiac development and disease

    Institute of Scientific and Technical Information of China (English)

    Marcus Vallaster; Caroline Dacwag Vallaster; Sean M. Wu

    2012-01-01

    During mammalian development,cardiac specification and ultimately lineage commitment to a specific cardiac cell type is accomplished by the action of specific transcription factors (TFs) and their meticulous control on an epigenetic level.In this review,we detail how cardiacspecific TFs function in concert with nucleosome remodeling and histone-modifying enzymes to regulate a diverse network of genes required for processes such as cell growth and proliferation,or epithelial to mesenchymal transition (EMT),for instance.We provide examples of how several cardiac TFs,such as Nkx2.5,WHSC1,Tbx5,and Tbx1,which are associated with developmental and congenital heart defects,are required for the recruitment of histone modifiers,such as Jarid2,p300,and Ash21,and components of ATP-dependent remodeling enzymes like Brg1,Baf60c,and Baf180.Binding of these TFs to their respective sites at cardiac genes coincides with a distinct pattern of histone marks,indicating that the precise regulation of cardiac gene networks is orchestrated by interactions between TFs and epigenetic modifiers.Furthermore,we speculate that an epigenetic signature,comprised of TF occupancy,histone modifications,and overall chromatin organization,is an underlying mechanism that governs cardiac morphogenesis and disease.

  12. Short-term cardiac memory and mother rotor fibrillation.

    Science.gov (United States)

    Baher, Ali; Qu, Zhilin; Hayatdavoudi, Ashkan; Lamp, Scott T; Yang, Ming-Jim; Xie, Fagen; Turner, Stephen; Garfinkel, Alan; Weiss, James N

    2007-01-01

    Short-term cardiac memory refers to the effects of pacing history on action potential duration (APD). Although the ionic mechanisms for short-term memory occurring over many heartbeats (also called APD accommodation) are poorly understood, they may have important effects on reentry and fibrillation. To explore this issue, we incorporated a generic memory current into the Phase I Luo and Rudy action potential model, which lacks short-term memory. The properties of this current were matched to simulate quantitatively human ventricular monophasic action potential accommodation. We show that, theoretically, short-term memory can resolve the paradox of how mother rotor fibrillation is initiated in heterogeneous tissue by physiological pacing. In simulated heterogeneous two-dimensional tissue and three-dimensional ventricles containing an inward rectifier K(+) current gradient, short-term memory could spontaneously convert multiple wavelet fibrillation to mother rotor fibrillation or to a mixture of both fibrillation types. This was due to progressive acceleration and stabilization of rotors as accumulation of memory shortened APD and flattened APD restitution slope nonuniformly throughout the tissue. PMID:16891403

  13. Spread of excitation in 3-D models of the anisotropic cardiac tissue. III. Effects of ventricular geometry and fiber structure on the potential distribution.

    Science.gov (United States)

    Colli Franzone, P; Guerri, L; Pennacchio, M; Taccardi, B

    1998-07-01

    In a previous paper we studied the spread of excitation in a simplified model of the left ventricle, affected by fiber structure and obliqueness, curvature of the wall and Purkinje network. In the present paper we investigate the extracellular potential distribution u in the same ventricular model. Given the transmembrane potential v, associated with the spreading excitation, the extracellular potential u is obtained as solution of a linear elliptic equation with the source term related to v. The potential distributions were computed for point stimulations at different intramural depths. The results of the simulations enabled us to identify a number of common features which appears in all the potential patterns irrespective of pacing site. In addition, by splitting the sources into an axial and conormal component, we were able to evaluate the contribution of the classical uniform dipole layer to the total potential field and the role of the superimposed axial component.

  14. Cell and gene therapy for arrhythmias: Repair of cardiac conduction damage

    Institute of Scientific and Technical Information of China (English)

    Yong-Fu Xiao

    2011-01-01

    Action potentials generated in the sinoatrial node(SAN)dominate the rhythm and rate of a healthy human heart.Subsequently,these action potentials propagate to the whole heart via its conduction system .Abnormalities of impulse generation and/or propagation in a heart can cause arrhythmias.For example,SAN dysfunction or conduction block of the atrioventricular node can lead to serious bradycardia which is currently treated with an implanted electronic pacemaker.On the other hand conduction damage may cause reentrant tachyarrhythmias which are primarily treated pharmacologically or by medical device-based therapies,including defibrillation and tissue ablation.However,drug therapies sometimes may not be effective or are associated with serious side effects.Device-based therapies for cardiac arrhythmias,even with well developed technology,still face inadequacies,limitations,hardware complications,and other challenges.Therefore,scientists are actively seeking other alternatives for antiarrhythmic therapy.In particular,cells and genes used for repairing cardiac conduction damage/defect have been investigated in various studies both in vitro and in vivo.Despite the complexities of the excitation and conduction systems of the heart,cell and gene-based strategies provide novel alternatives for treatment or cure of cardiac anhythmias.This review summarizes some highlights of recent research progress in this field.

  15. Green Tea Polyphenols Potentiate the Action of Nerve Growth Factor to Induce Neuritogenesis: Possible Role of Reactive Oxygen Species

    OpenAIRE

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

    2010-01-01

    Exogenously administered nerve growth factor (NGF) repairs injured axons, but it does not cross the blood-brain barrier. Thus, agents that could potentiate the neuritogenic ability of endogenous NGF would be of great utility in treating neurological injuries. Using the PC12 cell model, here we show that unfractionated green tea polyphenols (GTPP) at low concentrations (0.1 μg/ml) potentiate the ability of low concentrations of NGF (2 ng/ml) to induce neuritogenesis at a level comparable to th...

  16. Laparoscopic cholecystectomy in a cardiac transplant recipient

    OpenAIRE

    Pandya, Seema R.; Saloni Paranjape

    2014-01-01

    An increasing number of cardiac transplants are being carried out around the world. With increasing longevity, these patients present a unique challenge to non-transplant anesthesiologists for a variety of transplant related or incidental surgeries. The general considerations related to a cardiac transplant recipient are the physiological and pharmacological problems of allograft denervation, the side-effects of immunosuppression, the risk of infection and the potential for rejection. A thoro...

  17. Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

    Science.gov (United States)

    Martin, Tamara P.; Hortigon-Vinagre, Maria P.; Findlay, Jane E.; Elliott, Christina; Currie, Susan; Baillie, George S.

    2014-01-01

    Phosphorylated heat shock protein 20 (HSP20) is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D) complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling. PMID:25426411

  18. Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

    Directory of Open Access Journals (Sweden)

    Tamara P. Martin

    2014-01-01

    Full Text Available Phosphorylated heat shock protein 20 (HSP20 is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling.

  19. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Westh, Peter; Holm, René

    2015-01-01

    The aggregation number (n), thermodynamic potentials (ΔG, ΔH, ΔS) and critical micelle concentration (CMC) for 6 natural bile salts were determined on the basis of both original and previously published isothermal titration calorimetry (ITC) data. Different procedures to estimate parameters...

  20. Design and application of measuring system of evoked compound action potential%诱发动作电位测量系统的设计与应用

    Institute of Scientific and Technical Information of China (English)

    孟丽; 李平; 訾蕊; 费兴波

    2015-01-01

    目的:为获得电信号刺激神经纤维时的动作电位,本文设计了一种电诱发复合动作电位测量系统,解决了诱发动作电位的精确采集问题,有效去除了本底噪声的影响。方法分析了范围在十几微伏的电诱发复合动作电位到几十毫伏电极电位测量时存在的难点,以及一个测量系统正常工作时需要满足的测量放大器共模容限和差模容限及电流源电压容限问题。基于此,本文提出采用3级运算放大器级联的方式实现诱发动作电位的采集。系统主要由3级级联放大器、自动零点调整环节和基准电压部分组成,实现对弱信号的放大、消除本底噪声和提供过压保护。结果采用本文设计的系统,测量得到11 mV 的蛙类坐骨神经干复合动作电位和17μV 的豚鼠耳蜗电诱发复合动作电位,验证了本系统可有效测量各种诱发电位。结论采用3级放大器级联的方式和自动零点跟踪方式解决了微弱信号的有效放大和精确采集技术,为进一步研究通过电信号直接刺激神经纤维所产生的动作电位的特性提供可靠的测量手段。%Objective When the nerve fiber is stimulated by the electrical pulse,there is an evoked compound action potential which indicates the synchronism property of the nerve fiber. In order to obtain the precise action potential,a measuring system of evoked compound action potential is presented in this paper. The system can collect the compound action potential precisely and eliminate the effect of ground noise. Methods Firstly,we analyzed the difficulty in the measurement of the compound action potential which ranged from μV level to the mV level. Secondly,we discussed the common-mode tolerance,differential mode tolerance and the voltage margin of the electric current which guaranteed the proper functioning of the measuring system. Based on the issues,we proposed a measuring system of compound action

  1. NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure

    DEFF Research Database (Denmark)

    Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T;

    2014-01-01

    AIMS: The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore...... activation. CONCLUSIONS: Downstream effects of a compound acting exclusively on sarcolemmal ion channels are difficult to predict. Remediation of APD to pre-failing state does not ameliorate dysfunction in CaT; however, restoration of notch depth appears to impart modest benefit and a likelihood...

  2. Functiogenesis of cardiac pacemaker activity.

    Science.gov (United States)

    Sakai, Tetsuro; Kamino, Kohtaro

    2016-07-01

    Throughout our investigations on the ontogenesis of the electrophysiological events in early embryonic chick hearts, using optical techniques to record membrane potential probed with voltage-sensitive dyes, we have introduced a novel concept of "functiogenesis" corresponding to "morphogenesis". This article gives an account of the framework of "functiogenesis", focusing on the cardiac pacemaker function and the functional organization of the pacemaking area. PMID:26719289

  3. Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats

    Institute of Scientific and Technical Information of China (English)

    TANG Cheng-chun; MA Gan-shan; CHEN Ji-yuan

    2010-01-01

    Background Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. AIIogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.Methods Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 μmol/L) or control.Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and β-myosin heavy chain (β-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0x106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion.Results By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and β-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the

  4. 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.

  5. [A new ECG electrode concept for the conduction of fetal heart action potentials without penetration of the skin].

    Science.gov (United States)

    Schmidt, S; Langner, K; Rothe, J; Saling, E

    1982-10-01

    Internal cardiotocography is an important method for reliable supervision of the fetus during labor. The main task is the prevention of fetal hypoxia. However, there is a considerable disadvantage as the electrodes used penetrate the fetal skin, creating a possible entry point for organisms. The concept we have developed forms a new way of decreasing the risk of infection during labor by conducting the fetal heart rate potentials without penetrating the skin. The electrode is fixed to the skin of the presenting part by tissue adhesive and electrical contact between the fetal skin and the wire of the electrode is established through using electrolyte fluid.

  6. Sustained Exocytosis after Action Potential-Like Stimulation at Low Frequencies in Mouse Chromaffin Cells Depends on a Dynamin-Dependent Fast Endocytotic Process

    Science.gov (United States)

    Moya-Díaz, José; Álvarez, Yanina D.; Montenegro, Mauricio; Bayonés, Lucas; Belingheri, Ana V.; González-Jamett, Arlek M.; Cárdenas, Ana M.; Marengo, Fernando D.

    2016-01-01

    Under basal conditions the action potential firing rate of adrenal chromaffin cells is lower than 0.5 Hz. The maintenance of the secretory response at such frequencies requires a continuous replenishment of releasable vesicles. However, the mechanism that allows such vesicle replenishment remains unclear. Here, using membrane capacitance measurements on mouse chromaffin cells, we studied the mechanism of replenishment of a group of vesicles released by a single action potential-like stimulus (APls). The exocytosis triggered by APls (ETAP) represents a fraction (40%) of the immediately releasable pool, a group of vesicles highly coupled to voltage dependent calcium channels. ETAP was replenished with a time constant of 0.73 ± 0.11 s, fast enough to maintain synchronous exocytosis at 0.2–0.5 Hz stimulation. Regarding the mechanism involved in rapid ETAP replenishment, we found that it depends on the ready releasable pool; indeed depletion of this vesicle pool significantly delays ETAP replenishment. On the other hand, ETAP replenishment also correlates with a dynamin-dependent fast endocytosis process (τ = 0.53 ± 0.01 s). In this regard, disruption of dynamin function markedly inhibits the fast endocytosis and delays ETAP replenishment, but also significantly decreases the synchronous exocytosis during repetitive APls stimulation at low frequencies (0.2 and 0.5 Hz). Considering these findings, we propose a model in where both the transfer of vesicles from ready releasable pool and fast endocytosis allow rapid ETAP replenishment during low stimulation frequencies. PMID:27507935

  7. A combined method to estimate parameters of the thalamocortical model from a heavily noise-corrupted time series of action potential

    Science.gov (United States)

    Wang, Ruofan; Wang, Jiang; Deng, Bin; Liu, Chen; Wei, Xile; Tsang, K. M.; Chan, W. L.

    2014-03-01

    A combined method composing of the unscented Kalman filter (UKF) and the synchronization-based method is proposed for estimating electrophysiological variables and parameters of a thalamocortical (TC) neuron model, which is commonly used for studying Parkinson's disease for its relay role of connecting the basal ganglia and the cortex. In this work, we take into account the condition when only the time series of action potential with heavy noise are available. Numerical results demonstrate that not only this method can estimate model parameters from the extracted time series of action potential successfully but also the effect of its estimation is much better than the only use of the UKF or synchronization-based method, with a higher accuracy and a better robustness against noise, especially under the severe noise conditions. Considering the rather important role of TC neuron in the normal and pathological brain functions, the exploration of the method to estimate the critical parameters could have important implications for the study of its nonlinear dynamics and further treatment of Parkinson's disease.

  8. SUSTAINED EXOCYTOSIS AFTER ACTION POTENTIAL-LIKE STIMULATION AT LOW FREQUENCIES IN MOUSE CHROMAFFIN CELLS DEPENDS ON A DYNAMIN-DEPENDENT FAST ENDOCYTOTIC PROCESS

    Directory of Open Access Journals (Sweden)

    José Moya-Díaz

    2016-07-01

    Full Text Available Under basal conditions the action potential firing rate of adrenal chromaffin cells is lower than 0.5 Hz. The maintenance of the secretory response at such frequencies requires a continuous replenishment of releasable vesicles. However, the mechanism that allows such vesicle replenishment remains unclear. Here, using membrane capacitance measurements on mouse chromaffin cells, we studied the mechanism of replenishment of a group of vesicles released by a single action potential-like stimulus (APls. The exocytosis triggered by APls (ETAP represents a fraction (40% of the immediately releasable pool, a group of vesicles highly coupled to voltage dependent calcium channels. ETAP was replenished with a time constant of 0.73 +/- 0.11 s, fast enough to maintain synchronous exocytosis at 0.2-0.5 Hz stimulation. Regarding the mechanism involved in rapid ETAP replenishment, we found that it depends on the ready releasable pool; indeed depletion of this vesicle pool significantly delays ETAP replenishment. On the other hand, ETAP replenishment also correlates with a dynamin-dependent fast endocytosis process (τ=0.53±0.01 s. In this regard, disruption of dynamin function markedly inhibits the fast endocytosis and delays ETAP replenishment, but also significantly decreases the synchronous exocytosis during repetitive APls stimulation at low frequencies (0.2 and 0.5 Hz. Considering these findings, we propose a model in where both the transfer of vesicles from ready releasable pool and fast endocytosis allow rapid ETAP replenishment during low stimulation frequencies.

  9. A combined method to estimate parameters of the thalamocortical model from a heavily noise-corrupted time series of action potential

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruofan; Wang, Jiang; Deng, Bin, E-mail: dengbin@tju.edu.cn; Liu, Chen; Wei, Xile [Department of Electrical and Automation Engineering, Tianjin University, Tianjin (China); Tsang, K. M.; Chan, W. L. [Department of Electrical Engineering, The Hong Kong Polytechnic University, Kowloon (Hong Kong)

    2014-03-15

    A combined method composing of the unscented Kalman filter (UKF) and the synchronization-based method is proposed for estimating electrophysiological variables and parameters of a thalamocortical (TC) neuron model, which is commonly used for studying Parkinson's disease for its relay role of connecting the basal ganglia and the cortex. In this work, we take into account the condition when only the time series of action potential with heavy noise are available. Numerical results demonstrate that not only this method can estimate model parameters from the extracted time series of action potential successfully but also the effect of its estimation is much better than the only use of the UKF or synchronization-based method, with a higher accuracy and a better robustness against noise, especially under the severe noise conditions. Considering the rather important role of TC neuron in the normal and pathological brain functions, the exploration of the method to estimate the critical parameters could have important implications for the study of its nonlinear dynamics and further treatment of Parkinson's disease.

  10. Conjugation of cholesterol to HIV-1 fusion inhibitor C34 increases peptide-membrane interactions potentiating its action.

    Directory of Open Access Journals (Sweden)

    Axel Hollmann

    Full Text Available Recently, the covalent binding of a cholesterol moiety to a classical HIV-1 fusion inhibitor peptide, C34, was shown to potentiate its antiviral activity. Our purpose was to evaluate the interaction of cholesterol-conjugated and native C34 with membrane model systems and human blood cells to understand the effects of this derivatization. Lipid vesicles and monolayers with defined compositions were used as model membranes. C34-cholesterol partitions more to fluid phase membranes that mimic biological membranes. Importantly, there is a preference of the conjugate for liquid ordered membranes, rich in cholesterol and/or sphingomyelin, as observed both from partition and surface pressure studies. In human erythrocytes and peripheral blood mononuclear cells (PBMC, C34-cholesterol significantly decreases the membrane dipole potential. In PBMC, the conjugate was 14- and 115-fold more membranotropic than T-1249 and enfuvirtide, respectively. C34 or cholesterol alone did not show significant membrane activity. The enhanced interaction of C34-cholesterol with biological membranes correlates with its higher antiviral potency. Higher partitions for lipid-raft like compositions direct the drug to the receptor-rich domains where membrane fusion is likely to occur. This intermediary membrane binding step may facilitate the drug delivery to gp41 in its pre-fusion state.

  11. Identification of sodium channel isoforms that mediate action potential firing in lamina I/II spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Smith Paula L

    2011-09-01

    Full Text Available Abstract Background Voltage-gated sodium channels play key roles in acute and chronic pain processing. The molecular, biophysical, and pharmacological properties of sodium channel currents have been extensively studied for peripheral nociceptors while the properties of sodium channel currents in dorsal horn spinal cord neurons remain incompletely understood. Thus far, investigations into the roles of sodium channel function in nociceptive signaling have primarily focused on recombinant channels or peripheral nociceptors. Here, we utilize recordings from lamina I/II neurons withdrawn from the surface of spinal cord slices to systematically determine the functional properties of sodium channels expressed within the superficial dorsal horn. Results Sodium channel currents within lamina I/II neurons exhibited relatively hyperpolarized voltage-dependent properties and fast kinetics of both inactivation and recovery from inactivation, enabling small changes in neuronal membrane potentials to have large effects on intrinsic excitability. By combining biophysical and pharmacological channel properties with quantitative real-time PCR results, we demonstrate that functional sodium channel currents within lamina I/II neurons are predominantly composed of the NaV1.2 and NaV1.3 isoforms. Conclusions Overall, lamina I/II neurons express a unique combination of functional sodium channels that are highly divergent from the sodium channel isoforms found within peripheral nociceptors, creating potentially complementary or distinct ion channel targets for future pain therapeutics.

  12. Global Bifurcation Structure and Variability of Pacemaker Rhythm in a Detailed Model of Cardiac Sinoatrial Node Cells

    Science.gov (United States)

    Pan, Zhenxing; Doi, Shinji

    As a cardiac pacemaker, sinoatrial node spontaneously generates periodic electrical signals (action potentials) in its cells. The action potential generation is deeply related to various ion channels in cell membranes, and the abnormalities of ion channels cause sinus arrhythmia. We use the Zhang model of sinoatrial node cells to investigate the relation between pacemaker rhythm (frequency of action potential generation) and ion channels. The Zhang model is described by the Hodgkin-Huxley-type nonlinear ordinary differential equations, and its parameter values vary between periphery and center cells of sinoatrial node. We analyze the bifurcation structure of the Zhang model, and investigate the variability of pacemaker rhythm and its sensitivity on ion channel conductance changes for both periphery and center cells. Moreover, these results are compared with the previous results of another sinoatrial node cell model: Yanagihara-Noma-Irisawa model.

  13. Telocytes in cardiac regeneration and repair.

    Science.gov (United States)

    Bei, Yihua; Zhou, Qiulian; Sun, Qi; Xiao, Junjie

    2016-07-01

    Telocytes (TCs) are a novel type of stromal cells reported by Popescu's group in 2010. The unique feature that distinguishes TCs from other "classical" stromal cells is their extremely long and thin telopodes (Tps). As evidenced by electron microscopy, TCs are widely distributed in almost all tissues and organs. TCs contribute to form a three-dimensional interstitial network and play as active regulators in intercellular communication via homocellular/heterocellular junctions or shed vesicles. Interestingly, increasing evidence suggests the potential role of TCs in regenerative medicine. Although the heart retains some limited endogenous regenerative capacity, cardiac regenerative and repair response is however insufficient to make up the loss of cardiomyocytes upon injury. Developing novel strategies to increase cardiomyocyte renewal and repair is of great importance for the treatment of cardiac diseases. In this review, we focus on the role of TCs in cardiac regeneration and repair. We particularly describe the intercellular communication between TCs and cardiomyocytes, stem/progenitor cells, endothelial cells, and fibroblasts. Also, we discuss the current knowledge about TCs in cardiac repair after myocardial injury, as well as their potential roles in cardiac development and aging. TC-based therapy or TC-derived exosome delivery might be used as novel therapeutic strategies to promote cardiac regeneration and repair. PMID:26826525

  14. Cardiac Function in Patients with Early Cirrhosis during Maximal Beta-Adrenergic Drive

    DEFF Research Database (Denmark)

    Krag, Aleksander; Bendtsen, Flemming; Dahl, Emilie Kristine;

    2014-01-01

    BACKGROUND AND AIM: Cardiac dysfunction in patients with early cirrhosis is debated. We investigated potential cardiac dysfunction by assessing left ventricular systolic performance during a dobutamine stress test in patients with early cirrhosis. PATIENTS AND METHODS: Nineteen patients with Chil...

  15. Healthy universities--time for action: a qualitative research study exploring the potential for a national programme.

    Science.gov (United States)

    Dooris, Mark; Doherty, Sharon

    2010-03-01

    Despite the absence of national or international steers, there is within England growing interest in the Healthy University approach. This article introduces Healthy Universities; reports on a qualitative study exploring the potential for a national programme contributing to health, well-being and sustainable development; and concludes with reflections and recommendations. The study used questionnaires and interviews with key informants from English higher education institutions and national stakeholder organizations. The findings confirmed that higher education offers significant potential to impact positively on the health and well-being of students, staff and wider communities through education, research, knowledge exchange and institutional practice. There was strong support for extending the healthy settings approach beyond schools and further education, through a National Healthy Higher Education Programme that provides a whole system Healthy University Framework. Informants argued that although there are important public health drivers, it will also be necessary to show how a Healthy Universities can help achieve core business objectives and contribute to related agendas such as sustainability. Two models were discussed: an accreditation scheme with externally assessed standardized achievement criteria; and a flexible and light-touch framework focusing on change-related processes and utilizing self-assessment. While highlighting the appeal of league tables, many informants feared that a top-down approach could backfire, generating resistance and resulting in minimal compliance. In contrast, the majority felt that a process-focused aspirational model would be more likely to win hearts and minds and facilitate system-level change. Key recommendations relate to national programme development, research and evaluation and international collaboration and networking. PMID:20167825

  16. Sudden death of cardiac origin and psychotropic drugs

    Directory of Open Access Journals (Sweden)

    Quadiri eTimour

    2012-05-01

    Full Text Available Mortality rate is high in psychiatric patients versus general population. An important cause of this increased mortality is sudden cardiac death (SCD as a major side-effect of psychotropic drugs. These SCDs generally result from arrhythmias occurring when the posology is high and may attain a toxic threshold but also at dosages within therapeutic range, in the presence of risk factors. There are three kinds of risk factors: physiological (e.g.: low cardiac rate of sportsmen, physiopathological (e.g.: hepatic insufficiency, hypothyroidism and "therapeutic" (due to interactions between psychotropic drugs and other medicines. Association of pharmacological agents may increase the likelihood of SCDs either by i a pharmacokinetic mechanism (e.g.: increased torsadogenic potential of a psychotropic drug when its destruction and/or elimination are compromised or ii a pharmacodynamical mechanism (e.g.: mutual potentiation of proarrhythmic properties of two drugs. In addition, some psychotropic drugs may induce sudden death in cases of pre-existing congenital cardiopathies such as i congenital long QT syndrome, predisposing to torsade de pointes that eventually cause syncope and sudden death. ii a Brugada syndrome, that may directly cause ventricular fibrillation due to reduced sodium current through Nav1.5 channels. Moreover, psychotropic drugs may be a direct cause of cardiac lesions also leading to SCD. This is the case, for example, of phenothiazines responsible for ischemic coronaropathies and of clozapine that is involved in the occurrence of myocarditis. The aims of this work are to delineate: i the risk of SCD related to the use of psychotropic drugs; ii mechanisms involved in the occurrence of such SCD; iii preventive actions of psychotropic drugs side effects, on the basis of the knowledge of patient-specific risk factors, documented from clinical history, ionic balance and ECG investigation by the psychiatrist.

  17. Theorems for Testing Local Activity of CNN and Application to Cardiac Equations

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The theorems for testing the local activity in one-port cellular neural/nonlinear network (CNN) cells with four local state variables are presented. Using the theorems computes the bifurcation diagrams of the cardiac Purkinje fiber (CPF) equations which describe the long-lasting action and pace-maker potentials of the Purkinje fiber of the heart. The computer simulation shows that periodic trajectories or convergent trajectories of the CPF Equations can be found if the corresponding cell parameters are located in a positive domain but nearby edge of chaos. In particular, a heart with approximate normal frequency of heartbeat but non-normal electrocardiogram may suddenly stop beating by slightly perturbing the parameters of the corresponding CPF Equations when the parameters are located nearby the edge of chaos in the bifurcation diagrams. This research seems to interpret reasonably the phenomena that patients with cardiac diseases might suddenly die without warning.

  18. The angiogenic effect of dracorhodin perchlorate on human umbilical vein endothelial cells and its potential mechanism of action.

    Science.gov (United States)

    Li, Feng; Jiang, Tao; Liu, Wei; Hu, Quan; Yin, Huinan

    2016-08-01

    Hyperglycemia is the key clinical feature of diabetes, and may induce refractory wound lesions and impaired angiogenesis. Dracorhodin perchlorate (Dra) is the major ingredient of dragon's blood and it has been used as a medicine to treat chronic wounds, such as diabetic foot, since ancient times in many cultures. The current study aimed to investigate the effect of Dra on human umbilical vein endothelial cells (HUVECs) under high‑glucose (HG) stimulation and its potential mechanism. Dra was observed to increase the multiplication capacity of HUVECs both under low glucose (LG) and HG concentrations. Additionally, migration and tube formation in HUVECs was facilitated by Dra. The expression levels of Ras, mitogen‑activated protein kinase (MAPK) and vascular endothelial growth factor, which are key components of the Ras/MAPK pathway, were upregulated following Dra treatment. The present study is the first report, to the best of our knowledge, of the effects of Dra on wound healing, and the association with the Ras/MAPK signaling pathway. PMID:27357516

  19. Recent actions taken on methyl bromide under the Montreal Protocol: Their potential economic implications on international trade

    International Nuclear Information System (INIS)

    Methyl bromide (MB) produced and used by man is a versatile, highly effective, fastacting fumigant employed in a number of important ways to kill organisms destructive to plants. A wide spectrum of commodities is treated with MB. The compound is unique in that it provides a wide range of pest control, may be applied to a broad spectrum of both food and non-food commodities, can be used for fumigation of large and small quantities of materials, and, when applied properly, leaves no residues of toxicological significance. Recently, this compound has come under scientific scrutiny and has been identified as a potentially potent ozone depleting chemical. As a result, countries operating under the Montreal Protocol will be restricting its use, and, in some cases, eliminating its use altogether. To date there are no alternative chemical fumigants to replace methyl bromide. Non-chemical treatments such as irradiation, hot and cold treatments, modified atmosphere, etc., are the most promising. The paper focuses on the magnitude of the economic consequences on international trade and the necessity to have available alternative treatments that are highly effective, fast-acting, and practical. 8 refs, 12 tabs

  20. Effects of dexmedetomidine on the monophasic action potential duration and transmural dispersion of re-polarization during ischemia-reperfusion in isolated rabbit hearts%右美托咪定对家兔离体心脏缺血-再灌注时心肌单相动作电位及跨室壁复极离散度的影响

    Institute of Scientific and Technical Information of China (English)

    张凯强; 高鸿; 刘军; 刘艳秋; 龙娟; 李惠

    2016-01-01

    Objective To study the effects of dexmedetomidine on the monophasic action po-tential duration and the transmural dispersion of repolarization during ischemia-reperfusion of isolated rabbit hearts and thus explore its effect on myocardial ischemia-reperfusion electrophysiological char-acteristics.Methods Eighteen healthy adult rabbits,weighing (2.0±0.5)kg,were randomly divided into 3 groups after successful preparation of Langendorff isolated heart perfusion model and 1 5 min perfusion and balance of K-H fluid.In the control group (group C),37 ℃ K-H fluid was continuously perfused and balanced for 1 50 min.In the ischemia/reperfusion group (group IR),K-H fluid was stopped after continuous perfusion and balance for 1 5 min and cardiac arrest was induced for 60 min with the injection of Thomas solution (4 ℃,10 ml/kg)while the heart was protected by the low tem-perature Thomas solution (4 ℃)around it.Reperfusion of Thomas solution (4 ℃,5 ml/kg)was performed for 30 min and the heart was resuscitated by the perfusion of K-H fluid for 60 min.In dexmedetomidine group (group DEX),dexmedetomidine (25 ng/ml)was added in the K-H fluid and the Thomas solution.Other procedures were same as in group IR.Heart rate(HR),monophasic ac-tion potential amplitude (MAPA)of the three layers of heart [endocardium (Endo),myocardium (Mid)and epicardium (Epi)],0 phase maximal increase rate (Vmax),90% monophasic action po-tential duration (MAPD90 )and transmural dispersion of repolarization (TDR)were recorded at the time of continuous balance perfusion 1 5 min(T0 ),continuous perfusion 1 5 min/balance 30 min(T1 ), reperfusion 30 min/balance 120 min(T2 )and reperfusion 60 min/balance 1 50 min(T3 ).Cardiac ar-rhythmia and resuscitation time at cardiac reperfusion were observed,without using drugs to restore normal cardiac rhythm.Results In group DEX,cardiac resuscitation time was significantly shorter (1 6.67±3.78)s than that in group IR (46.33±7.29)s (P <0.05);At T2 ,in group IR

  1. Molecular mechanisms of action and potential biomarkers of growth inhibition of dasatinib (BMS-354825) on hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    Molecular targeted therapy has emerged as a promising treatment of Hepatocellular carcinoma (HCC). One potential target is the Src family Kinase (SFK). C-Src, a non-receptor tyrosine kinase is a critical link of multiple signal pathways that regulate proliferation, invasion, survival, metastasis, and angiogenesis. In this study, we evaluated the effects of a novel SFK inhibitor, dasatinib (BMS-354825), on SFK/FAK/p130CAS, PI3K/PTEN/Akt/mTOR, Ras/Raf/MAPK and Stats pathways in 9 HCC cell lines. Growth inhibition was assessed by MTS assay. EGFR, Src and downstream proteins FAK, Akt, MAPK42/44, Stat3 expressions were measured by western blot. Cell adhesion, migration and invasion were performed with and without dasatinib treatment. The IC50 of 9 cell lines ranged from 0.7 μM ~ 14.2 μM. In general the growth inhibition by dasatinib was related to total Src (t-Src) and the ratio of activated Src (p-Src) to t-Src. There was good correlation of the sensitivity to dasatinib and the inhibition level of p-Src, p-FAK576/577 and p-Akt. No inhibition was found on Stat3 and MAPK42/44 in all cell lines. The inhibition of cell adhesion, migration and invasion were correlated with p-FAK inhibition. Dasatinib inhibits the proliferation, adhesion, migration and invasion of HCC cells in vitro via inhibiting of Src tyrosine kinase and affecting SFK/FAK and PI3K/PTEN/Akt, but not Ras/Raf/MEK/ERK and JAK/Stat pathways. T-Src and p-Src/t-Src may be useful biomarkers to select HCC patients for dasatinib treatment

  2. Addictive evaluation of cholic acid-verticinone ester, a potential cough therapeutic agent with agonist action of opioid receptor

    Institute of Scientific and Technical Information of China (English)

    Jiu-liang ZHANG; Hui WANG; Chang CHEN; Hui-fang PI; Han-li RUAN; Peng ZHANG; Ji-zhou WU

    2009-01-01

    Aim: The purpose of this work was to search for potential drugs with potent antitussive and expectorant activities as well as a low toxicity, but without addictive properties. Cholic acid-verticinone ester (CA-Ver) was synthesized based on the clearly elucidated antitussive and expectorant activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. In our previous study, CA-Vet showed a much more potent activity than codeine phosphate. This study was carried out to investigate the central antitussive mechanism and the addictive evaluation of CA-Ver.Methods: Testing on a capsaicin-induced cough model of mice pretreated with naloxone, a non-selective opioid receptor antagonist, was performed for the observation of CA-Ver's central antitussive mechanism. We then took naloxone-induced withdrawal tests of mice for the judgment of CA-Ver's addiction. Lastly, we determined the opioid dependence of CA-Ver in the guinea pig ileum. Results: The test on the capsaicin-induced cough model showed that naloxone could block the antitussive effect of CA-Ver,suggesting the antitussive mechanism of CA-Ver was related to the central opioid receptors. The naloxone-urged withdrawal tests of the mice showed that CA-Ver was not addictive, and the test of the opioid dependence in the guinea pig ileum showed that CA-Ver had no withdrawal response.Conclusion: These findings suggested that CA-Ver deserved attention for its potent antitussive effects related to the central opioid receptors, but without addiction, and had a good development perspective.

  3. 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...

  4. 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 ...

  5. Mesenchymal stem cell delivery strategies to promote cardiac regeneration following ischemic injury.

    Science.gov (United States)

    Russo, Valerio; Young, Stuart; Hamilton, Andrew; Amsden, Brian G; Flynn, Lauren E

    2014-04-01

    Myocardial infarction (MI) is one of the leading causes of mortality worldwide and is associated with irreversible cardiomyocyte death and pathological remodeling of cardiac tissue. In the past 15 years, several animal models have been developed for pre-clinical testing to assess the potential of stem cells for functional tissue regeneration and the attenuation of left ventricular remodeling. The promising results obtained in terms of improved cardiac function, neo-angiogenesis and reduction in infarct size have motivated the initiation of clinical trials in humans. Despite the potential, the results of these studies have highlighted that the effective delivery and retention of viable cells within the heart remain significant challenges that have limited the therapeutic efficacy of cell-based therapies for treating the ischemic myocardium. In this review, we discuss key elements for designing clinically translatable cell-delivery approaches to promote myocardial regeneration. Key topics addressed include cell selection, with a focus on mesenchymal stem cells derived from the bone marrow (bMSCs) and adipose tissue (ASCs), including a discussion of their potential mechanisms of action. Natural and synthetic biomaterials that have been investigated as injectable cell delivery vehicles for cardiac applications are critically reviewed, including an analysis of the role of the biomaterials themselves in the therapeutic scheme. PMID:24560461

  6. A vertical approach to cardiac arrhythmias.

    Science.gov (United States)

    Vaughan Williams, E M

    1987-10-01

    Study of cardiac arrhythmia may be pursued vertically, as up the rungs of a ladder, from symptom to ECG, to EPS, to local lesion, to intracellular metabolism and to alterations of the latter and their effects on charge-transfer by ions across the cell membrane. Raised intracellular cAMP and calcium concentrations are responses to normal physiological controls, and highly abnormal ECGs occur in normal people under stress without progressing to life threatening arrhythmias, yet do so in susceptible individuals. Conversely, appropriate stimulation can precipitate ventricular fibrillation in normal myocardium. Selective stimulation of different types of adrenoceptor has differing electrophysiological effects. Beta 1-adrenoceptors increase contraction and calcium current, and shorten action potential duration (APD) by increasing potassium conductance. Beta 2-adrenoceptors do not increase calcium entry, but shorten APD by stimulating electrogenic Na/K pumping, alpha-adrenoceptors prolong contractions and lengthen APD. It is suggested that the tachycardia, extrasystoles and shortening of APD occurring in response to adrenergic stimuli and hypoxia, are accessory factors, not primary causes, in the development of arrhythmias, and constitute a danger when there is an appropriate anatomical substrate for re-entry. Serious arrhythmias are of multifactorial origin, of which "calcium overload" is but one, not proven to be a frequent one.

  7. Prehospital behaviour of patients admitted with acute coronary syndrome or witnessed cardiac arrest

    DEFF Research Database (Denmark)

    Ottesen, Michael Mundt; Dixen, Ulrik; Torp-Pedersen, Christian;

    2003-01-01

    OBJECTIVE: To study prehospital behaviour of patients admitted with acute coronary syndrome or witnessed cardiac arrest. DESIGN: Structured interview of 250 consecutive patients with acute coronary syndrome and relatives of 48 patients with witnessed cardiac arrest. The following courses of action......-four per cent of the patients admitted with cardiac arrest expressed no prior symptoms. Two-thirds of patients with typical symptoms interpreted it as cardiac-still only half took action within 20 min. Fifty per cent of patients who called a physician were delayed by wrong advice or misinterpretation. One...

  8. A time dependent anatomically detailed model of cardiac conduction

    Science.gov (United States)

    Saxberg, B. E.; Grumbach, M. P.; Cohen, R. J.

    1985-01-01

    In order to understand the determinants of transitions in cardiac electrical activity from normal patterns to dysrhythmias such as ventricular fibrillation, we are constructing an anatomically and physiologically detailed finite element simulation of myocardial electrical propagation. A healthy human heart embedded in paraffin was sectioned to provide a detailed anatomical substrate for model calculations. The simulation of propagation includes anisotropy in conduction velocity due to fiber orientation as well as gradients in conduction velocities, absolute and relative refractory periods, action potential duration and electrotonic influence of nearest neighbors. The model also includes changes in the behaviour of myocardial tissue as a function of the past local activity. With this model, we can examine the significance of fiber orientation and time dependence of local propagation parameters on dysrhythmogenesis.

  9. Bifurcations, chaos, and sensitivity to parameter variations in the Sato cardiac cell model

    Science.gov (United States)

    Otte, Stefan; Berg, Sebastian; Luther, Stefan; Parlitz, Ulrich

    2016-08-01

    The dynamics of a detailed ionic cardiac cell model proposed by Sato et al. (2009) is investigated in terms of periodic and chaotic action potentials, bifurcation scenarios, and coexistence of attractors. Starting from the model's standard parameter values bifurcation diagrams are computed to evaluate the model's robustness with respect to (small) parameter changes. While for some parameters the dynamics turns out to be practically independent from their values, even minor changes of other parameters have a very strong impact and cause qualitative changes due to bifurcations or transitions to coexisting attractors. Implications of this lack of robustness are discussed.

  10. Biophysical characterization of inwardly rectifying potassium currents (I(K1) I(K,ACh), I(K,Ca)) using sinus rhythm or atrial fibrillation action potential waveforms

    DEFF Research Database (Denmark)

    Tang, Chuyi; Skibsbye, Lasse; Yuan, Lei;

    2015-01-01

    remain unclear. Both I(K1) and I(K,ACh) are implicated in atrial fibrillation (AF), and recently also I(K,Ca) has been speculated to be linked with the genesis and sustainability of AF. All these three currents have been shown to be involved in the electrical remodeling in the atria of patients suffering...... to voltage protocols adapted from atrial action potentials recorded in human tissue at 1 and 3 Hz. The current recordings were performed in the HEK-293 heterologous cell system expressing either I(K1), I(K,ACh) or I(K,Ca) to establish the individual contribution of each of these currents during the voltage...

  11. [Cardiac evaluation before non-cardiac surgery].

    Science.gov (United States)

    Menzenbach, Jan; Boehm, Olaf

    2016-07-01

    Before non-cardiac surgery, evaluation of cardiac function is no frequent part of surgical treatment. European societies of anesthesiology and cardiology published consensus-guidelines in 2014 to present a reasonable approach for preoperative evaluation. This paper intends to differentiate the composite of perioperative risk and to display the guidelines methodical approach to handle it. Features to identify patients at risk from an ageing population with comorbidities, are the classification of surgical risk, functional capacity and risk indices. Application of diagnostic means, should be used adjusted to this risk estimation. Cardiac biomarkers are useful to discover risk of complications or mortality, that cannot be assessed by clinical signs. After preoperative optimization and perioperative cardiac protection, the observation of the postoperative period remains, to prohibit complications or even death. In consideration of limited resources of intensive care department, postoperative ward rounds beyond intensive care units are considered to be an appropriate instrument to avoid or recognize complications early to reduce postoperative mortality. PMID:27479258

  12. Menthol-induced action potentials in Conocephalum conicum as a result of unspecific interactions between menthol and the lipid phase of the plasma membrane.

    Science.gov (United States)

    Kupisz, Kamila; Trebacz, Kazimierz; Gruszecki, Wiesław I

    2015-07-01

    Our previous study has shown that the liverwort Conocephalum conicum generates action potentials (APs) in response to both temperature drop and menthol, which are also activators of the TRPM8 (transient receptor potential melastatin 8) receptor in animals. Not only similarities but also differences between electrical reactions to menthol and cooling observed in the liverwort aroused our interest in the action of menthol at the molecular level. Patch-clamp investigations have shown that menthol causes a reduction of current flowing through slow vacuolar (SV) channels to 29 ± 10% of the initial value (n = 9); simultaneously, it does not influence magnitudes of currents passing through a single SV channel. This may point to an unspecific interaction between menthol and the lipid phase of the membrane. An influence of menthol on lipid organization in membranes was investigated in two-component monomolecular layers formed with menthol and dipalmitoylphosphatidylcholine (DPPC) at the argon-water interface. Analyses of the mean molecular area parameters vs the molar fraction of the menthol component have shown over-additivity (approximately 20 Å(2) ) in the region of high molar fractions of menthol. Infrared absorption spectroscopy studies have shown that menthol, most probably, induces breaking of a hydrogen bond network formed by ester carbonyl groups and water bridges in the lipid membrane and binds to the polar head group region of DPPC. We conclude that the disruption in the lipid phase of the membrane influences ion channels and/or pumps and subsequently causes generation of APs in excitable plants such as C. conicum.

  13. ERK 1/2 and PI-3 kinase pathways as a potential mechanism of ghrelin action on cell proliferation and apoptosis in the porcine ovarian follicular cells.

    Science.gov (United States)

    Rak-Mardyla, A; Gregoraszczuk, E L

    2010-08-01

    Recently, we reported the stimulatory effect of ghrelin on ovarian cell proliferation in parallel with the inhibitory action of ghrelin on cell apoptosis. The aim of the presented data propose local activation of extracellular signal-regulated protein kinase 1 and 2 (ERK 1/2) and phosphoinositide-3 (PI-3) kinase pathways as a mechanism of ghrelin effect in the porcine ovary. To test this hypothesis, action of ghrelin on levels of ERK 1/2 with PI-3 kinase activity and protein expression using ELISA and western blot analysis, respectively, was examined. Additionally, to determine which pathways (ERK 1/2 or PI-3 kinase) are the potential signals of ghrelin-mediated cell proliferation and apoptosis in ovarian cells, we used PD098059 (50 microM) and wortmannin (200 microM), well-known inhibitors of these kinases. Treatment of ovarian coculture cells with ghrelin (100, 250, 500 and 1000 pg/ml) showed stimulation of phospho-ERK 1/2 levels and PI-3 kinase activity, with the maximum effect observed after 15 min of cell incubation. Additionally, western blot analysis indicated that ghrelin increased expression of both kinases. Moreover, ghrelin used in combination with PD098059 or wortmannin significantly decreased cell proliferation, which was measured by the Alamar Blue assay and increased apoptosis, which was measured by caspase - 3 activity and DNA fragmentation. In conclusion, these results suggest that the ERK 1/2 and PI-3 kinase pathways may be potential signals of ghrelin mediate the cell proliferation and apoptosis of ovary cells.

  14. Stem cell sources for cardiac regeneration.

    Science.gov (United States)

    Roccio, M; Goumans, M J; Sluijter, J P G; Doevendans, P A

    2008-03-01

    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 cardiomyocytes to ameliorate the injured myocardium, compensate for the loss of ventricular mass and contractility and eventually restore cardiac function. An array of cell types has been explored in this respect, including skeletal muscle, bone marrow derived stem cells, embryonic stem cells (ESC) and more recently cardiac progenitor cells. The best-studied cell types are mouse and human ESC cells, which have undisputedly been demonstrated to differentiate into cardiomyocyte and vascular lineages and have been of great help to understand the differentiation process of pluripotent cells. However, due to their immunogenicity, risk of tumor development and the ethical challenge arising from their embryonic origin, they do not provide a suitable cell source for a regenerative therapy approach. A better option, overcoming ethical and allogenicity problems, seems to be provided by bone marrow derived cells and by the recently identified cardiac precursors. This report will overview current knowledge on these different cell types and their application in cardiac regeneration and address issues like implementation of delivery methods, including tissue engineering approaches that need to be developed alongside.

  15. Stem cells for cardiac repair: an introduction

    Institute of Scientific and Technical Information of China (English)

    Bastiaan C du Pr(e); Pieter A Doevendans; Linda W van Laake

    2013-01-01

    Cardiovascular disease is a major cause of morbidity and mortality throughout the world. Most cardiovascular diseases, such as ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes. Unfortunately, the heart has a limited regenerative capacity and is not able to replace these cardiomyocytes once lost. In recent years, stem cells have been put forward as a potential source for cardiac regeneration. Pre-clinical studies that use stem cell-derived cardiac cells show promising results. The mechanisms, though, are not well understood, results have been variable, sometimes transient in the long term, and often without a mechanistic explanation. There are still several major hurdles to be taken. Stem cell-derived cardiac cells should resemble original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Finally, stem cell therapy needs to be safe, reproducible, and affordable. In this review, we will give an introduction to the principles of stem cell based cardiac repair.

  16. A modified FitzHugh-Nagumo model for cardiac instabilities: The replacement of a conductance variable with Ca current as a slow variable

    Science.gov (United States)

    Osaka, Motohisa

    2013-02-01

    The FitzHugh-Nagumo model of nerve conduction is also used as a model of cardiac excitability. We propose the replacement of a gating variable of the conductance of K+ current with Ca2+ current as a slow variable of the model, in which plays a key role in the cardiac action potential. Since ion currents conduct transversely as well as longitudinally through gap junctions between myocytes, particularly in ischemia, a respective diffusion term is involved to both equations of a fast variable and a slow variable. We show that only a small increase of a coefficient of the diffusion term of Ca2+ current may cause cardiac instabilities, which are presumed to cause breakup of conduction and finally a lethal arrhythmia, ventricular fibrillation. Particularly, these instabilities do not occur without the diffusion term of Ca2+ current.

  17. Action potential initial dynamical control and analysis of a minimum neuron model%最小神经元模型放电起始动态控制与分析

    Institute of Scientific and Technical Information of China (English)

    金淇涛; 王江; 魏熙乐; 邓斌; 车艳秋

    2011-01-01

    本文采用最小神经元模型,从生理学角度设计wash-out滤波器,实现了不同放电起始动态机理之间的转换,并证明wash-out滤波器控制通过影响阈下电流的竞争结果改变了神经元的放电起始动态机理.%Neuron is a basic unit of information transmission in the nervous system . Neuron encodes the information input from the dendrites by generating action potential sequences of different firing patterns. The different firing patterns result from different action potential initial dynamic mechanisms for neurons to generate spikes. The result of competition between neuron ion currents with different dynamic features in the sub threshold potential determines the action potential initial dynamic mechanism. In this paper, we adopt a minimum neuron model to design the wash-out filter from a physiological view for achieving the transition between different action potential initial dynamic mechanisms and for verifying that the wash-out filter control changes the action potential initial dynamic mechanism of neuron by affecting the result of competition between currents with different dynamic features in the sub-threshold potential.

  18. Model digital signal cardiac processing in developed Matlab

    Directory of Open Access Journals (Sweden)

    Kervin Benito Rojas Ochoa

    2013-09-01

    Full Text Available ABSTRACTThe present research aimed to design a model of digital cardiac signal processing developed in MatLab. This is because they wanted to use the potentialities of the computer tool, to emulate a digital processing environment. The design is not experimental, transactional since this model does not directly manipulates the cardiac patient information, but uses the theoretical characteristics of the variable in study. In addition, research is documentary, driven by the precepts of a feasible project, whose methodology consisted of four key stages: characterization of cardiac signal, establishment of the requirements for filtering of cardiac wave, sampling and coding of the signal, and representation of the model in MatLab, as a result, achieved the model of digital processing of cardiac signals using the MatLab tool and corroborating their applicability.Keywords: Model, Process, Cardiac Signals, MatLab.

  19. 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.

  20. Cardiac rehabilitation services in Denmark: still room for expansion

    DEFF Research Database (Denmark)

    Zwisler, Ann-Dorthe O; Traeden, Ulla I; Videbaek, Jørgen;

    2005-01-01

    AIM: European cardiologists agree that cardiac rehabilitation (CR) should be offered as an integrated part of cardiac care, and CR guidelines have been published. The authors aimed to ascertain the potential for expanding CR coverage at hospitals in Denmark. METHOD: A cross-sectional questionnair...