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Sample records for human circadian pacemaker

  1. Physiological effects of light on the human circadian pacemaker

    Science.gov (United States)

    Shanahan, T. L.; Czeisler, C. A.

    2000-01-01

    The physiology of the human circadian pacemaker and its influence and on the daily organization of sleep, endocrine and behavioral processes is an emerging interest in science and medicine. Understanding the development, organization and fundamental properties underlying the circadian timing system may provide insight for the application of circadian principles to the practice of clinical medicine, both diagnostically (interpretation of certain clinical tests are dependent on time of day) and therapeutically (certain pharmacological responses vary with the time of day). The light-dark cycle is the most powerful external influence acting upon the human circadian pacemaker. It has been shown that timed exposure to light can both synchronize and reset the phase of the circadian pacemaker in a predictable manner. The emergence of detectable circadian rhythmicity in the neonatal period is under investigation (as described elsewhere in this issue). Therefore, the pattern of light exposure provided in the neonatal intensive care setting has implications. One recent study identified differences in both amount of sleep time and weight gain in infants maintained in a neonatal intensive care environment that controlled the light-dark cycle. Unfortunately, neither circadian phase nor the time of day has been considered in most clinical investigations. Further studies with knowledge of principles characterizing the human circadian timing system, which governs a wide array of physiological processes, are required to integrate these findings with the practice of clinical medicine.

  2. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

    Science.gov (United States)

    Zeitzer, J. M.; Dijk, D. J.; Kronauer, R.; Brown, E.; Czeisler, C.

    2000-01-01

    Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

  3. Circadian Pacemaker – Temperature Compensation

    NARCIS (Netherlands)

    Gerkema, Menno P.; Binder, Marc D.; Hirokawa, Nobutaka; Windhorst, Uwe

    2009-01-01

    One of the defining characteristics of circadian pacemakers and indicates the independence of the speed of circadian clock processes of environmental temperature. Mechanisms involved, so far not elucidated in full detail, entail at least two processes that are similarly affected by temperature

  4. The Drosophila melanogaster circadian pacemaker circuit

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Keywords. circadian rhythm; neuronal network; ion channel; behaviour; neurotransmitter; electrophysiology; Drosophila. Abstract. As an experimental model system, the fruit fly Drosophila melanogaster has been seminal in shaping our understanding of the circadian clockwork. The wealth of genetic tools ...

  5. A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents. IV. Entrainment : Pacemaker as Clock

    NARCIS (Netherlands)

    Pittendrigh, Colin S.; Daan, Serge

    1976-01-01

    1. In the first part of the paper, the model of non-parametric entrainment of circadian pacemakers is tested for the case of nocturnal rodents. The model makes use of the available data on freerunning period (τ) in constant darkness and on phase response curves (PRC) for short light pulses. It is

  6. Circadian rhythms in healthy aging--effects downstream from the pacemaker

    Science.gov (United States)

    Monk, T. H.; Kupfer, D. J.

    2000-01-01

    Using both previously published findings and entirely new data, we present evidence in support of the argument that the circadian dysfunction of advancing age in the healthy human is primarily one of failing to transduce the circadian signal from the circadian timing system (CTS) to rhythms "downstream" from the pacemaker rather than one of failing to generate the circadian signal itself. Two downstream rhythms are considered: subjective alertness and objective performance. For subjective alertness, we show that in both normal nychthemeral (24 h routine, sleeping at night) and unmasking (36 h of constant wakeful bed rest) conditions, advancing age, especially in men, leads to flattening of subjective alertness rhythms, even when circadian temperature rhythms are relatively robust. For objective performance, an unmasking experiment involving manual dexterity, visual search, and visual vigilance tasks was used to demonstrate that the relationship between temperature and performance is strong in the young, but not in older subjects (and especially not in older men).

  7. Circadian locomotor rhythms in the cricket, Gryllodes sigillatus. II. Interactions between bilaterally paired circadian pacemakers.

    Science.gov (United States)

    Ushirogawa, H; Abe, Y; Tomioka, K

    1997-10-01

    The optic lobe is essential for circadian locomotor rhythms in the cricket, Gryllodes sigillatus. We examined potential interactions between the bilaterally paired optic lobes in circadian rhythm generation. When one optic lobe was removed, the free-running period of the locomotor rhythm slightly but significantly lengthened. When exposed to light-dark cycles (LD) with 26 hr period, intact and sham operated animals were clearly entrained to the light cycle, but a large number of animals receiving unilateral optic nerve severance showed rhythm dissociation. In the dissociation, two rhythmic components appeared; one was readily entrained to the given LD and the other free-ran with a period shorter than 24 hr, and activity was expressed only when they were inphase. The period of the free-running component was significantly longer than that of the animals with a single blinded pacemaker kept in LD13:13, suggesting that the pacemaker on the intact side had some influence on the blinded pacemaker even in the dissociated state. The ratio of animals with rhythm dissociation was greater with the lower light intensity of the LD. The results suggest that the bilaterally distributed pacemakers are only weakly coupled to one another but strongly suppress the activity driven by the partner pacemaker during their subjective day. The strong suppression of activity would be advantageous to keep a stable nocturnality for this cricket living indoors.

  8. Circadian pacemaking in cells and circuits of the suprachiasmatic nucleus.

    Science.gov (United States)

    Hastings, M H; Brancaccio, M; Maywood, E S

    2014-01-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian pacemaker of the brain. It co-ordinates the daily rhythms of sleep and wakefulness, as well as physiology and behaviour, that set the tempo to our lives. Disturbance of this daily pattern, most acutely with jet-lag but more insidiously with rotational shift-work, can have severely deleterious effects for mental function and long-term health. The present review considers recent developments in our understanding of the properties of the SCN that make it a robust circadian time-keeper. It first focuses on the intracellular transcriptional/ translational feedback loops (TTFL) that constitute the cellular clockwork of the SCN neurone. Daily timing by these loops pivots around the negative regulation of the Period (Per) and Cryptochrome (Cry) genes by their protein products. The period of the circadian cycle is set by the relative stability of Per and Cry proteins, and this can be controlled by both genetic and pharmacological interventions. It then considers the function of these feedback loops in the context of cytosolic signalling by cAMP and intracellular calcium ([Ca(2+) ]i ), which are both outputs from, and inputs to, the TTFL, as well as the critical role of vasoactive intestinal peptide (VIP) signalling in synchronising cellular clocks across the SCN. Synchronisation by VIP in the SCN is paracrine, operating over an unconventionally long time frame (i.e. 24 h) and wide spatial domain, mediated via the cytosolic pathways upstream of the TTFL. Finally, we show how intersectional pharmacogenetics can be used to control G-protein-coupled signalling in individual SCN neurones, and how manipulation of Gq/[Ca(2+) ]i -signalling in VIP neurones can re-programme the circuit-level encoding of circadian time. Circadian pacemaking in the SCN therefore provides an unrivalled context in which to understand how a complex, adaptive behaviour can be organised by the dynamic activity of a relatively

  9. A forced desynchrony study of circadian pacemaker characteristics in seasonal affective disorder

    NARCIS (Netherlands)

    Koorengevel, Kathelijne M.; Beersma, Domien G.M.; den Boer, Johan; Hoofdakker, Rutger H. van den

    2002-01-01

    The circadian pacemaker is an endogenous clock that regulates oscillations in most physiological and psychological processes with a near 24-h period. In many species, this pacemaker triggers seasonal changes in behavior. The seasonality of symptoms and the efficacy of light therapy suggest

  10. Circadian Activators Are Expressed Days before They Initiate Clock Function in Late Pacemaker Neurons from Drosophila.

    Science.gov (United States)

    Liu, Tianxin; Mahesh, Guruswamy; Houl, Jerry H; Hardin, Paul E

    2015-06-03

    Circadian pacemaker neurons in the Drosophila brain control daily rhythms in locomotor activity. These pacemaker neurons can be subdivided into early or late groups depending on whether rhythms in period (per) and timeless (tim) expression are initiated at the first instar (L1) larval stage or during metamorphosis, respectively. Because CLOCK-CYCLE (CLK-CYC) heterodimers initiate circadian oscillator function by activating per and tim transcription, a Clk-GFP transgene was used to mark when late pacemaker neurons begin to develop. We were surprised to see that CLK-GFP was already expressed in four of five clusters of late pacemaker neurons during the third instar (L3) larval stage. CLK-GFP is only detected in postmitotic neurons from L3 larvae, suggesting that these four late pacemaker neuron clusters are formed before the L3 larval stage. A GFP-cyc transgene was used to show that CYC, like CLK, is also expressed exclusively in pacemaker neurons from L3 larval brains, demonstrating that CLK-CYC is not sufficient to activate per and tim in late pacemaker neurons at the L3 larval stage. These results suggest that most late pacemaker neurons develop days before novel factors activate circadian oscillator function during metamorphosis. Copyright © 2015 the authors 0270-6474/15/358662-10$15.00/0.

  11. The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus

    Science.gov (United States)

    Albers, H. Elliott; Walton, James C.; Gamble, Karen L.; McNeill, John K.; Hummer, Daniel L.

    2016-01-01

    Virtually every neuron within the suprachiasmatic nucleus (SCN) communicates via GABAergic signaling. The extracellular levels of GABA within the SCN are determined by a complex interaction of synthesis and transport, as well as synaptic and non-synaptic release. The response to GABA is mediated by GABAA receptors that respond to both phasic and tonic GABA release and that can produce excitatory as well as inhibitory cellular responses. GABA also influences circadian control through the exclusively inhibitory effects of GABAB receptors. Both GABA and neuropeptide signaling occur within the SCN, although the functional consequences of the interactions of these signals are not well understood. This review considers the role of GABA in the circadian pacemaker, in the mechanisms responsible for the generation of circadian rhythms, in the ability of non-photic stimuli to reset the phase of the pacemaker, and in the ability of the day-night cycle to entrain the pacemaker. PMID:27894927

  12. Generation of activity-rest patterns by dual circadian pacemaker systems : a model

    NARCIS (Netherlands)

    Beersma, Domien G.M.; Daan, Serge

    1992-01-01

    Activity-rest patterns displayed by an animal under various circumstances are suggested to result from the combined influences of two virtually identical circadian pacemaker components. Increased output of each component proportionally increases the probability of activity of the animal. Such a dual

  13. Plasticity of the intrinsic period of the human circadian timing system.

    Directory of Open Access Journals (Sweden)

    Frank A J L Scheer

    2007-08-01

    Full Text Available Human expeditions to Mars will require adaptation to the 24.65-h Martian solar day-night cycle (sol, which is outside the range of entrainment of the human circadian pacemaker under lighting intensities to which astronauts are typically exposed. Failure to entrain the circadian time-keeping system to the desired rest-activity cycle disturbs sleep and impairs cognitive function. Furthermore, differences between the intrinsic circadian period and Earth's 24-h light-dark cycle underlie human circadian rhythm sleep disorders, such as advanced sleep phase disorder and non-24-hour sleep-wake disorders. Therefore, first, we tested whether exposure to a model-based lighting regimen would entrain the human circadian pacemaker at a normal phase angle to the 24.65-h Martian sol and to the 23.5-h day length often required of astronauts during short duration space exploration. Second, we tested here whether such prior entrainment to non-24-h light-dark cycles would lead to subsequent modification of the intrinsic period of the human circadian timing system. Here we show that exposure to moderately bright light ( approximately 450 lux; approximately 1.2 W/m(2 for the second or first half of the scheduled wake episode is effective for entraining individuals to the 24.65-h Martian sol and a 23.5-h day length, respectively. Estimations of the circadian periods of plasma melatonin, plasma cortisol, and core body temperature rhythms collected under forced desynchrony protocols revealed that the intrinsic circadian period of the human circadian pacemaker was significantly longer following entrainment to the Martian sol as compared to following entrainment to the 23.5-h day. The latter finding of after-effects of entrainment reveals for the first time plasticity of the period of the human circadian timing system. Both findings have important implications for the treatment of circadian rhythm sleep disorders and human space exploration.

  14. Stress-induced changes in circadian rhythms of body temperature and activity in rats are not caused by pacemaker changes

    NARCIS (Netherlands)

    Meerlo, P; vandenHoofdakker, RH; Koolhaas, JM; Daan, S

    1997-01-01

    Previous work has shown that social stress in rats (i.e., defeat by an aggressive male conspecific) causes a variety of behavioral and physiological changes including alterations in the daily rhythms of body temperature and activity. To study the role of the circadian pacemaker in these

  15. Reentrainment of the circadian pacemaker during jet lag: East-west asymmetry and the effects of north-south travel.

    Science.gov (United States)

    Diekman, Casey O; Bose, Amitabha

    2018-01-21

    The normal alignment of circadian rhythms with the 24-h light-dark cycle is disrupted after rapid travel between home and destination time zones, leading to sleep problems, indigestion, and other symptoms collectively known as jet lag. Using mathematical and computational analysis, we study the process of reentrainment to the light-dark cycle of the destination time zone in a model of the human circadian pacemaker. We calculate the reentrainment time for travel between any two points on the globe at any time of the day and year. We construct one-dimensional entrainment maps to explain several properties of jet lag, such as why most people experience worse jet lag after traveling east than west. We show that this east-west asymmetry depends on the endogenous period of the traveler's circadian clock as well as daylength. Thus the critical factor is not simply whether the endogenous period is greater than or less than 24 h as is commonly assumed. We show that the unstable fixed point of an entrainment map determines whether a traveler reentrains through phase advances or phase delays, providing an understanding of the threshold that separates orthodromic and antidromic modes of reentrainment. Contrary to the conventional wisdom that jet lag only occurs after east-west travel across multiple time zones, we predict that the change in daylength encountered during north-south travel can cause jet lag even when no time zones are crossed. Our techniques could be used to provide advice to travelers on how to minimize jet lag on trips involving multiple destinations and a combination of transmeridian and translatitudinal travel. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Pacemaker

    Science.gov (United States)

    ... close to a security system metal detector. Notify security staff if you have a pacemaker. Also, stay at least 2 feet away from industrial welders and electrical generators. Some medical procedures can ...

  17. Putative pacemakers in the eyestalk and brain of the crayfish Procambarus clarkii show circadian oscillations in levels of mRNA for crustacean hyperglycemic hormone.

    Directory of Open Access Journals (Sweden)

    Janikua Nelson-Mora

    Full Text Available Crustacean hyperglycemic hormone (CHH synthesizing cells in the optic lobe, one of the pacemakers of the circadian system, have been shown to be present in crayfish. However, the presence of CHH in the central brain, another putative pacemaker of the multi-oscillatory circadian system, of this decapod and its circadian transcription in the optic lobe and brain have yet to be explored. Therefore, using qualitative and quantitative PCR, we isolated and cloned a CHH mRNA fragment from two putative pacemakers of the multi-oscillatory circadian system of Procambarus clarkii, the optic lobe and the central brain. This CHH transcript synchronized to daily light-dark cycles and oscillated under dark, constant conditions demonstrating statistically significant daily and circadian rhythms in both structures. Furthermore, to investigate the presence of the peptide in the central brain of this decapod, we used immunohistochemical methods. Confocal microscopy revealed the presence of CHH-IR in fibers and cells of the protocerebral and tritocerebal clusters and neuropiles, particularly in some neurons located in clusters 6, 14, 15 and 17. The presence of CHH positive neurons in structures of P. clarkii where clock proteins have been reported suggests a relationship between the circadian clockwork and CHH. This work provides new insights into the circadian regulation of CHH, a pleiotropic hormone that regulates many physiological processes such as glucose metabolism and osmoregulatory responses to stress.

  18. A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents. V. Pacemaker Structure : A Clock for All Seasons

    NARCIS (Netherlands)

    Pittendrigh, Colin S.; Daan, Serge

    1976-01-01

    1. This paper is an attempt to integrate in a general model the major findings reported earlier in this series on: lability and history dependence of circadian period, τ; dependence of τ and α on light intensity as described in Aschoffs Rule; the interrelationships between τ and phase response

  19. Heart pacemaker

    Science.gov (United States)

    Cardiac pacemaker implantation; Artificial pacemaker; Permanent pacemaker; Internal pacemaker; Cardiac resynchronization therapy; CRT; Biventricular pacemaker; Arrhythmia - pacemaker; Abnormal heart ...

  20. Circadian Rhythms, Sleep Deprivation, and Human Performance

    Science.gov (United States)

    Goel, Namni; Basner, Mathias; Rao, Hengyi; Dinges, David F.

    2014-01-01

    Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep–wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using special laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Individual differences in circadian rhythms and genetic and other components underlying such differences also influence waking neurobehavioral functions. Both acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Recent evidence indicating a high degree of stability in neurobehavioral responses to sleep loss suggests that these trait-like individual differences are phenotypic and likely involve genetic components, including circadian genes. Recent experiments have revealed both sleep homeostatic and circadian effects on brain metabolism and neural activation. Investigation of the neural and genetic mechanisms underlying the dynamically complex interaction between sleep homeostasis and circadian systems is beginning. A key goal of this work is to identify biomarkers that accurately predict human performance in situations in which the circadian and sleep homeostatic systems are perturbed. PMID:23899598

  1. Serotonin regulates the phase of the rat suprachiasmatic circadian pacemaker in vitro only during the subjective day.

    Science.gov (United States)

    Medanic, M; Gillette, M U

    1992-05-01

    1. The suprachiasmatic nucleus (SCN) of the hypothalamus is the primary pacemaker for circadian rhythms in mammals. The 24 h pacemaker is endogenous to the SCN and persists for multiple cycles in the suprachiasmatic brain slice. 2. While serotonin is not endogenous to the SCN, a major midbrain hypothalamic afferent pathway is serotonergic. Within this tract the dorsal raphe nucleus sends direct projections to the ventrolateral portions of the SCN. We investigated a possible regulatory role for serotonin in the mammalian circadian system by examining its effect, when applied at projection sites, on the circadian rhythm of neuronal activity in rat SCN in vitro. 3. Eight-week-old male rats from our inbred colony, housed on a 12 h light: 12 h dark schedule, were used. Hypothalamic brain slices containing the paired SCN were prepared in the day and maintained in glucose and bicarbonate-supplemented balanced salt solution for up to 53 h. 4. A 10(-11) ml drop of 10(-6) M-serotonin (5-hydroxytryptamine (5-HT) creatinine sulphate complex) in medium was applied to the ventrolateral portion of one of the SCN for 5 min on the first day in vitro. The effect of the treatment at each of seven time points across the circadian cycle was examined. The rhythm of spontaneous neuronal activity was recorded extracellularly on the second and third days in vitro. Phase shifts were determined by comparing the time-of-peak of neuronal activity in serotonin- vs. media-treated slices. 5. Application of serotonin during the subjective day induced significant advances in the phase of the electrical activity rhythm (n = 11). The most sensitive time of treatment was CT 7 (circadian time 7 is 7 h after 'lights on' in the animal colony), when a 7.0 +/- 0.1 h phase advance was observed (n = 3). This phase advance was perpetuated on day 3 in vitro without decrement. Serotonin treatment during the subjective night had no effect on the timing of the electrical activity rhythm (n = 9). 6. The

  2. Clinical Trial of the Effect of Exercise on Resetting of the Endogenous Circadian Pacemaker

    National Research Council Canada - National Science Library

    Czeisler, Charles

    2000-01-01

    ...: test the hypothesis that multiple nightly bouts of exercise will induce significant delays in the endogenous circadian rhythms of core body temperature, plasma - melatonin, reaction time, alertness...

  3. Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function.

    Directory of Open Access Journals (Sweden)

    Alexandra Vaccaro

    2017-01-01

    Full Text Available Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0 and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1 clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila.

  4. Reciprocal cholinergic and GABAergic modulation of the small ventrolateral pacemaker neurons of Drosophila's circadian clock neuron network.

    Science.gov (United States)

    Lelito, Katherine R; Shafer, Orie T

    2012-04-01

    The relatively simple clock neuron network of Drosophila is a valuable model system for the neuronal basis of circadian timekeeping. Unfortunately, many key neuronal classes of this network are inaccessible to electrophysiological analysis. We have therefore adopted the use of genetically encoded sensors to address the physiology of the fly's circadian clock network. Using genetically encoded Ca(2+) and cAMP sensors, we have investigated the physiological responses of two specific classes of clock neuron, the large and small ventrolateral neurons (l- and s-LN(v)s), to two neurotransmitters implicated in their modulation: acetylcholine (ACh) and γ-aminobutyric acid (GABA). Live imaging of l-LN(v) cAMP and Ca(2+) dynamics in response to cholinergic agonist and GABA application were well aligned with published electrophysiological data, indicating that our sensors were capable of faithfully reporting acute physiological responses to these transmitters within single adult clock neuron soma. We extended these live imaging methods to s-LN(v)s, critical neuronal pacemakers whose physiological properties in the adult brain are largely unknown. Our s-LN(v) experiments revealed the predicted excitatory responses to bath-applied cholinergic agonists and the predicted inhibitory effects of GABA and established that the antagonism of ACh and GABA extends to their effects on cAMP signaling. These data support recently published but physiologically untested models of s-LN(v) modulation and lead to the prediction that cholinergic and GABAergic inputs to s-LN(v)s will have opposing effects on the phase and/or period of the molecular clock within these critical pacemaker neurons.

  5. Emergence of noise-induced oscillations in the central circadian pacemaker.

    Directory of Open Access Journals (Sweden)

    Caroline H Ko

    2010-10-01

    Full Text Available Bmal1 is an essential transcriptional activator within the mammalian circadian clock. We report here that the suprachiasmatic nucleus (SCN of Bmal1-null mutant mice, unexpectedly, generates stochastic oscillations with periods that overlap the circadian range. Dissociated SCN neurons expressed fluctuating levels of PER2 detected by bioluminescence imaging but could not generate circadian oscillations intrinsically. Inhibition of intercellular communication or cyclic-AMP signaling in SCN slices, which provide a positive feed-forward signal to drive the intracellular negative feedback loop, abolished the stochastic oscillations. Propagation of this feed-forward signal between SCN neurons then promotes quasi-circadian oscillations that arise as an emergent property of the SCN network. Experimental analysis and mathematical modeling argue that both intercellular coupling and molecular noise are required for the stochastic rhythms, providing a novel biological example of noise-induced oscillations. The emergence of stochastic circadian oscillations from the SCN network in the absence of cell-autonomous circadian oscillatory function highlights a previously unrecognized level of circadian organization.

  6. Two Coupled Oscillators : Simulations of the Circadian Pacemaker in Mammalian Activity Rhythms

    NARCIS (Netherlands)

    Daan, Serge; Berde, Charles

    1978-01-01

    In the activity rhythms of captive small mammals a variety of features, most notably “splitting”, sugges that two coupled oscillators may constitute the pacemaker system which underlies the rhythms. A proposed phenomenological model is developed and expanded here using an explicit quantitative

  7. Light and the human circadian clock.

    Science.gov (United States)

    Roenneberg, Till; Kantermann, Thomas; Juda, Myriam; Vetter, Céline; Allebrandt, Karla V

    2013-01-01

    The circadian clock can only reliably fulfil its function if it is stably entrained. Most clocks use the light-dark cycle as environmental signal (zeitgeber) for this active synchronisation. How we think about clock function and entrainment has been strongly influenced by the early concepts of the field's pioneers, and the astonishing finding that circadian rhythms continue a self-sustained oscillation in constant conditions has become central to our understanding of entrainment.Here, we argue that we have to rethink these initial circadian dogmas to fully understand the circadian programme and how it entrains. Light is also the prominent zeitgeber for the human clock, as has been shown experimentally in the laboratory and in large-scale epidemiological studies in real life, and we hypothesise that social zeitgebers act through light entrainment via behavioural feedback loops (zeitnehmer). We show that human entrainment can be investigated in detail outside of the laboratory, by using the many 'experimental' conditions provided by the real world, such as daylight savings time, the 'forced synchrony' imposed by the introduction of time zones, or the fact that humans increasingly create their own light environment. The conditions of human entrainment have changed drastically over the past 100 years and have led to an increasing discrepancy between biological and social time (social jetlag). The increasing evidence that social jetlag has detrimental consequences for health suggests that shift-work is only an extreme form of circadian misalignment, and that the majority of the population in the industrialised world suffers from a similarly 'forced synchrony'.

  8. Circadian locomotor rhythms in the cricket, Gryllodes sigillatus. I. Localization of the pacemaker and the photoreceptor.

    Science.gov (United States)

    Abe, Y; Ushirogawa, H; Tomioka, K

    1997-10-01

    Circadian locomotor rhythm and its underlying mechanism were investigated in the cricket, Gryllodes sigillatus. Adult male crickets showed a nocturnal locomotor rhythm peaking early in the dark phase of a light to dark cycle. This rhythm persisted under constant darkness (DD) with a free-running period averaging 23.1 +/- 0.3 hr. Although constant bright light made most animals arrhythmic, about 40% of the animals showed free-running rhythms with a period longer than 24 hr under constant dim light condition. On transfer to DD, all arrhythmic animals restored the locomotor rhythm. Bilateral optic nerve severance resulted in free-running of the rhythm even under light-dark cycles. The free-running period of the optic nerve severed animals was significantly longer than sham operated crickets in DD, suggesting that the compound eye plays some role in determining the free-running period. Removal of bilateral lamina-medulla portion of the optic lobe abolished the rhythm under DD. These results demonstrate that the photoreceptor for entrainment is the compound eye and the optic lobe is indispensable for persistence of the rhythm. However, 75% and 54% of the optic lobeless animals showed aberrant rhythms with a period very close to 24 hr under light and temperature cycles, respectively, suggesting that there are neural and/or humoral mechanisms for the aberrant rhythms outside of the optic lobe. Since ocelli removal did not affect the photoperiodically induced rhythm, it is likely that the photoreception for the rhythm is performed through an extraretinal photoreceptor.

  9. Calcium Transient and Sodium-Calcium Exchange Current in Human versus Rabbit Sinoatrial Node Pacemaker Cells

    Directory of Open Access Journals (Sweden)

    Arie O. Verkerk

    2013-01-01

    Full Text Available There is an ongoing debate on the mechanism underlying the pacemaker activity of sinoatrial node (SAN cells, focusing on the relative importance of the “membrane clock” and the “Ca2+ clock” in the generation of the small net membrane current that depolarizes the cell towards the action potential threshold. Specifically, the debate centers around the question whether the membrane clock-driven hyperpolarization-activated current, If, which is also known as the “funny current” or “pacemaker current,” or the Ca2+ clock-driven sodium-calcium exchange current, INaCa, is the main contributor to diastolic depolarization. In our contribution to this journal’s “Special Issue on Cardiac Electrophysiology,” we present a numerical reconstruction of If and INaCa in isolated rabbit and human SAN pacemaker cells based on experimental data on action potentials, If, and intracellular calcium concentration ([Ca2+]i that we have acquired from these cells. The human SAN pacemaker cells have a smaller If, a weaker [Ca2+]i transient, and a smaller INaCa than the rabbit cells. However, when compared to the diastolic net membrane current, INaCa is of similar size in human and rabbit SAN pacemaker cells, whereas If is smaller in human than in rabbit cells.

  10. Light and the human circadian clock

    NARCIS (Netherlands)

    Roenneberg, Till; Kantermann, Thomas; Juda, Myriam; Vetter, Céline; Allebrandt, Karla V

    2013-01-01

    The circadian clock can only reliably fulfil its function if it is stably entrained. Most clocks use the light-dark cycle as environmental signal (zeitgeber) for this active synchronisation. How we think about clock function and entrainment has been strongly influenced by the early concepts of the

  11. Circadian rhythm and its role in malignancy

    Directory of Open Access Journals (Sweden)

    Mahmood Saqib

    2010-03-01

    Full Text Available Abstract Circadian rhythms are daily oscillations of multiple biological processes directed by endogenous clocks. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN of the hypothalamus. Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs including various cell cycle genes. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. This may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder. The genetic or functional disruption of the molecular circadian clock has been found in various cancers including breast, ovarian, endometrial, prostate and hematological cancers. The acquisition of current data in circadian clock mechanism may help chronotherapy, which takes into consideration the biological time to improve treatments by devising new therapeutic approaches for treating circadian-related disorders, especially cancer.

  12. Neurobiology of circadian systems.

    Science.gov (United States)

    Schulz, Pierre; Steimer, Thierry

    2009-01-01

    Time is a dimension tightly associated with the biology of living species. There are cycles of varied lengths in biological activities, from very short (ultradian) rhythms to rhythms with a period of approximately one day (circadian) and rhythms with longer cycles, of a week, a month, a season, or even longer. These rhythms are generated by endogenous biological clocks, i.e. time-keeping structures, rather than being passive reactions to external fluctuations. In mammals, the suprachiasmatic nucleus (SCN) is the major pacemaker. The pineal gland, which secretes melatonin, is the major pacemaker in other phyla. There also exist biological clocks generating circadian rhythms in peripheral tissues, for example the liver. A series of clock genes generates the rhythm through positive and negative feedback effect of proteins on their own synthesis, and this system oscillates with a circadian period. External factors serve as indicators of the astronomical (solar) time and are called zeitgebers, literally time-givers. Light is the major zeitgeber, which resets daily the SCN circadian clock. In the absence of zeitgebers, the circadian rhythm is said to be free running; it has a period that differs from 24 hours. The SCN, together with peripheral clocks, enables a time-related homeostasis, which can become disorganized in its regulation by external factors (light, social activities, food intake), in the coordination and relative phase position of rhythms, or in other ways. Disturbances of rhythms are found in everyday life (jet lag, shift work), in sleep disorders, and in several psychiatric disorders including affective disorders. As almost all physiological and behavioural functions in humans occur on a rhythmic basis, the possibility that advances, delays or desynchronization of circadian rhythms might participate in neurological and psychiatric disorders has been a theme of research. In affective disorders, a decreased circadian amplitude of several rhythms as well as a

  13. A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents. III. Heavy Water and Constant Light : Homeostasis of Frequency?

    NARCIS (Netherlands)

    Daan, Serge; Pittendrigh, Colin S.

    1976-01-01

    1. In a preceding paper differences in the lability of the freerunning circadian period (τ) in constant darkness (DD) were described among four species of rodents. This lability (i) is strongly correlated with the responses of τ to (ii) D2O-administration and to (iii) constant light (LL) of various

  14. Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

    Science.gov (United States)

    Wilking, Melissa; Ndiaye, Mary; Mukhtar, Hasan

    2013-01-01

    Abstract Significance: Oxygen and circadian rhythmicity are essential in a myriad of physiological processes to maintain homeostasis, from blood pressure and sleep/wake cycles, down to cellular signaling pathways that play critical roles in health and disease. If the human body or cells experience significant stress, their ability to regulate internal systems, including redox levels and circadian rhythms, may become impaired. At cellular as well as organismal levels, impairment in redox regulation and circadian rhythms may lead to a number of adverse effects, including the manifestation of a variety of diseases such as heart diseases, neurodegenerative conditions, and cancer. Recent Advances: Researchers have come to an understanding as to the basics of the circadian rhythm mechanism, as well as the importance of the numerous species of oxidative stress components. The effects of oxidative stress and dysregulated circadian rhythms have been a subject of intense investigations since they were first discovered, and recent investigations into the molecular mechanisms linking the two have started to elucidate the bases of their connection. Critical Issues: While much is known about the mechanics and importance of oxidative stress systems and circadian rhythms, the front where they interact has had very little research focused on it. This review discusses the idea that these two systems are together intricately involved in the healthy body, as well as in disease. Future Directions: We believe that for a more efficacious management of diseases that have both circadian rhythm and oxidative stress components in their pathogenesis, targeting both systems in tandem would be far more successful. Antioxid. Redox Signal. 19, 192–208 PMID:23198849

  15. New methods to assess circadian clocks in humans

    Czech Academy of Sciences Publication Activity Database

    Nováková, Marta; Sumová, Alena

    2014-01-01

    Roč. 52, č. 5 (2014), s. 404-412 ISSN 0019-5189 R&D Projects: GA MZd(CZ) NT11474 Grant - others:Univerzita Karlova(CZ) 22810 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : circadian * clock gene * melatonin * human Subject RIV: ED - Physiology Impact factor: 0.835, year: 2014

  16. Heart pacemaker - discharge

    Science.gov (United States)

    Cardiac pacemaker implantation - discharge; Artificial pacemaker - discharge; Permanent pacemaker - discharge; Internal pacemaker - discharge; Cardiac resynchronization therapy - discharge; CRT - discharge; ...

  17. Circadian control of the sleep-wake cycle

    NARCIS (Netherlands)

    Beersma, Domien G. M.; Gordijn, Marijke C. M.

    2007-01-01

    It is beyond doubt that the timing of sleep is under control of the circadian pacemaker. Humans are a diurnal species; they sleep mostly at night, and they do so at approximately 24-h intervals. If they do not adhere to this general pattern, for instance when working night shifts or when travelling

  18. Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice.

    Science.gov (United States)

    Zhao, Yue; Liu, Min; Chan, Xue Ying; Tan, Sue Yee; Subramaniam, Sharrada; Fan, Yong; Loh, Eva; Chang, Kenneth Tou En; Tan, Thiam Chye; Chen, Qingfeng

    2017-11-02

    Many immune parameters show circadian rhythms during the 24-hour day in mammals. The most striking circadian oscillation is the number of circulating immune cells that display an opposite rhythm between humans and mice. The physiological roles and mechanisms of circadian variations in mouse leukocytes are well studied, whereas for humans they remain unclear because of the lack of a proper model. In this study, we found that consistent with their natural host species, mouse and human circulating leukocytes exhibited opposite circadian oscillations in humanized mice. This cyclic pattern of trafficking correlated well with the diurnal expression levels of C-X-C chemokine receptor 4, which were controlled by the intracellular hypoxia-inducible factor 1α/aryl hydrocarbon receptor nuclear translocator-like heterodimer. Furthermore, we also discovered that p38 mitogen-activated protein kinases/mitogen-activated 2 had opposite effects between mice and humans in generating intracellular reactive oxygen species, which subsequently regulated HIF-1α expression. In conclusion, we propose humanized mice as a robust model for human circadian studies and reveal insights on a novel molecular clock network in the human circadian rhythm. © 2017 by The American Society of Hematology.

  19. Does calcium influx regulate melatonin production through the circadian pacemaker in chick pineal cells? Effects of nitrendipine, Bay K 8644, Co2+, Mn2+, and low external Ca2+.

    Science.gov (United States)

    Zatz, M; Mullen, D A

    1988-11-01

    We have recently described a system, using dispersed chick pineal cells in static culture, which displays a persistent, photosensitive, circadian rhythm of melatonin production and release. Here, we describe the effects of nitrendipine (NTR) (a dihydropyridine 'antagonist' of L-type calcium channels), Bay K 8644 (BK) (a dihydropyridine calcium channel 'agonist'), cobalt and manganese ions (both inorganic calcium channel blockers), and low external calcium concentrations, on the melatonin rhythm. NTR inhibited and BK stimulated melatonin output; they were potent and effective. Co2+, Mn2+, and low external Ca2+ markedly inhibited melatonin output. These results support a role for calcium influx through voltage-dependent calcium channels (L-type) in the regulation of melatonin production. Four or 8 h pulses of white light or darkness, in otherwise constant red light, cause, in addition to acute effects, phase-dependent phase shifts of the melatonin rhythm in subsequent cycles. Such phase shifts indicate an effect on (proximal to) the pacemaker generating the rhythm. Four or 8 h pulses of NTR, BK, Co2+, or low Ca2+, however, did not appreciably alter the phase of subsequent melatonin cycles. Neither did BK interfere with phase shifts induced by light pulses. Mn2+ pulses did induce phase-dependent phase shifts, but, unlike those evoked by light or dark pulses, these were all delays. Such effects of Mn2+ in other systems have been attributed to, and are characteristic of, 'metabolic inhibitors'. On balance, the results fail to support a prominent role for calcium influx in regulating the pacemaker underlying the circadian rhythm in chick pineal cells. Rather, calcium influx appears to regulate melatonin production primarily by acting on the melatonin-synthesizing apparatus, distal to the pacemaker.

  20. The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.

    Directory of Open Access Journals (Sweden)

    Frank A J L Scheer

    Full Text Available Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM, potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1 platelet function and (2 platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise.We studied 12 healthy adults (6 female who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01. These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM. The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors.These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous

  1. Nutrigenetics and Nutrimiromics of the Circadian System: The Time for Human Health.

    Science.gov (United States)

    Micó, Víctor; Díez-Ricote, Laura; Daimiel, Lidia

    2016-02-26

    Even though the rhythmic oscillations of life have long been known, the precise molecular mechanisms of the biological clock are only recently being explored. Circadian rhythms are found in virtually all organisms and affect our lives. Thus, it is not surprising that the correct running of this clock is essential for cellular functions and health. The circadian system is composed of an intricate network of genes interwined in an intrincated transcriptional/translational feedback loop. The precise oscillation of this clock is controlled by the circadian genes that, in turn, regulate the circadian oscillations of many cellular pathways. Consequently, variations in these genes have been associated with human diseases and metabolic disorders. From a nutrigenetics point of view, some of these variations modify the individual response to the diet and interact with nutrients to modulate such response. This circadian feedback loop is also epigenetically modulated. Among the epigenetic mechanisms that control circadian rhythms, microRNAs are the least studied ones. In this paper, we review the variants of circadian-related genes associated to human disease and nutritional response and discuss the current knowledge about circadian microRNAs. Accumulated evidence on the genetics and epigenetics of the circadian system points to important implications of chronotherapy in the clinical practice, not only in terms of pharmacotherapy, but also for dietary interventions. However, interventional studies (especially nutritional trials) that include chronotherapy are scarce. Given the importance of chronobiology in human health such studies are warranted in the near future.

  2. Pacemaker (image)

    Science.gov (United States)

    A pacemaker is a small, battery-operated electronic device which is inserted under the skin to help the heart beat regularly and at an appropriate rate. The pacemaker has leads that travel through a large vein ...

  3. Human circadian phase estimation from signals collected in ambulatory conditions using an autoregressive model

    NARCIS (Netherlands)

    Gil, Enrique A; Aubert, Xavier L; Møst, Els I S; Beersma, Domien G M

    Phase estimation of the human circadian rhythm is a topic that has been explored using various modeling approaches. The current models range from physiological to mathematical, all attempting to estimate the circadian phase from different physiological or behavioral signals. Here, we have focused on

  4. Cardiac Pacemakers

    International Nuclear Information System (INIS)

    Fiandra, O.; Espasandin, W.; Fiandra, H.

    1984-01-01

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control

  5. An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism

    Science.gov (United States)

    Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT in...

  6. Circadian rhythms, metabolism, and chrononutrition in rodents and humans

    Science.gov (United States)

    Chrononutrition is an emerging discipline that builds on the intimate relation between endogenous circadian (24-h) rhythms and metabolism. Circadian regulation of metabolic function can be observed from the level of intracellular biochemistry to whole-organism physiology and even postprandial respon...

  7. Circadian light

    Directory of Open Access Journals (Sweden)

    Bierman Andrew

    2010-02-01

    Full Text Available Abstract The present paper reflects a work in progress toward a definition of circadian light, one that should be informed by the thoughtful, century-old evolution of our present definition of light as a stimulus for the human visual system. This work in progress is based upon the functional relationship between optical radiation and its effects on nocturnal melatonin suppression, in large part because the basic data are available in the literature. Discussed here are the fundamental differences between responses by the visual and circadian systems to optical radiation. Brief reviews of photometry, colorimetry, and brightness perception are presented as a foundation for the discussion of circadian light. Finally, circadian light (CLA and circadian stimulus (CS calculation procedures based on a published mathematical model of human circadian phototransduction are presented with an example.

  8. Interaction between circadian rhythms and stress

    Directory of Open Access Journals (Sweden)

    C.E. Koch

    2017-02-01

    Full Text Available Life on earth has adapted to the day-night cycle by evolution of internal, so-called circadian clocks that adjust behavior and physiology to the recurring changes in environmental conditions. In mammals, a master pacemaker located in the suprachiasmatic nucleus (SCN of the hypothalamus receives environmental light information and synchronizes peripheral tissues and central non-SCN clocks to geophysical time. Regulatory systems such as the hypothalamus-pituitary-adrenal (HPA axis and the autonomic nervous system (ANS, both being important for the regulation of stress responses, receive strong circadian input. In this review, we summarize the interaction of circadian and stress systems and the resulting physiological and pathophysiological consequences. Finally, we critically discuss the relevance of rodent stress studies for humans, addressing complications of translational approaches and offering strategies to optimize animal studies from a chronobiological perspective.

  9. Entrainment of the circadian clock in humans: mechanism and implications for sleep disorders.

    Directory of Open Access Journals (Sweden)

    David Metcalfe

    2007-01-01

    Full Text Available Humans exhibit behaviour and physiology controlled by a circadian clock. The circadian period is genetically determined and administered by a series of interlocked autoregulatory feedback loops largely in the suprachiasmatic nuclei of the hypothalamus. The phase of the clock is, however, synchronised by a number of external environmental cues such as light. A failure or change in any one of the requisite clock components may result in the onset of a long-term sleep disorder. This review discusses the mechanism regulating circadian physiology in humans and explores how disturbances of this mechanism may result in sleep pathologies.

  10. Combination of light and melatonin time cues for phase advancing the human circadian clock.

    Science.gov (United States)

    Burke, Tina M; Markwald, Rachel R; Chinoy, Evan D; Snider, Jesse A; Bessman, Sara C; Jung, Christopher M; Wright, Kenneth P

    2013-11-01

    Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure. Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time. Sleep and chronobiology laboratory environment free of time cues. Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD). Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances. Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.

  11. Evolution of circadian rhythms: from bacteria to human.

    Science.gov (United States)

    Bhadra, Utpal; Thakkar, Nirav; Das, Paromita; Pal Bhadra, Manika

    2017-07-01

    The human body persists in its rhythm as per its initial time zone, and transition always occur according to solar movements around the earth over 24 h. While traveling across different latitudes and longitudes, at the pace exceeding the earth's movement, the changes in the external cues exceed the level of toleration of the body's biological clock. This poses an alteration in our physiological activities of sleep-wake pattern, mental alertness, organ movement, and eating habits, causing them to temporarily lose the track of time. This is further re-synchronized with the physiological cues of the destination over time. The mechanism of resetting of the clocks with varying time zones and cues occur in organisms from bacteria to humans. It is the result of the evolution of different pathways and molecular mechanisms over the time. There has been evolution of numerous comprehensive mechanisms using various research tools to get a deeper insight into the rapid turnover of molecular mechanisms in various species. This review reports insights into the evolution of the circadian mechanism and its evolutionary shift which is vital and plays a major role in assisting different organisms to adapt in different zones and controls their internal biological clocks with changing external cues. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Evidence for widespread dysregulation of circadian clock progression in human cancer

    Directory of Open Access Journals (Sweden)

    Jarrod Shilts

    2018-01-01

    Full Text Available The ubiquitous daily rhythms in mammalian physiology are guided by progression of the circadian clock. In mice, systemic disruption of the clock can promote tumor growth. In vitro, multiple oncogenes can disrupt the clock. However, due to the difficulties of studying circadian rhythms in solid tissues in humans, whether the clock is disrupted within human tumors has remained unknown. We sought to determine the state of the circadian clock in human cancer using publicly available transcriptome data. We developed a method, called the clock correlation distance (CCD, to infer circadian clock progression in a group of samples based on the co-expression of 12 clock genes. Our method can be applied to modestly sized datasets in which samples are not labeled with time of day and coverage of the circadian cycle is incomplete. We used the method to define a signature of clock gene co-expression in healthy mouse organs, then validated the signature in healthy human tissues. By then comparing human tumor and non-tumor samples from twenty datasets of a range of cancer types, we discovered that clock gene co-expression in tumors is consistently perturbed. Subsequent analysis of data from clock gene knockouts in mice suggested that perturbed clock gene co-expression in human cancer is not caused solely by the inactivation of clock genes. Furthermore, focusing on lung cancer, we found that human lung tumors showed systematic changes in expression in a large set of genes previously inferred to be rhythmic in healthy lung. Our findings suggest that clock progression is dysregulated in many solid human cancers and that this dysregulation could have broad effects on circadian physiology within tumors. In addition, our approach opens the door to using publicly available data to infer circadian clock progression in a multitude of human phenotypes.

  13. Numerical study of entrainment of the human circadian system and recovery by light treatment.

    Science.gov (United States)

    Kim, Soon Ho; Goh, Segun; Han, Kyungreem; Kim, Jong Won; Choi, MooYoung

    2018-05-09

    While the effects of light as a zeitgeber are well known, the way the effects are modulated by features of the sleep-wake system still remains to be studied in detail. A mathematical model for disturbance and recovery of the human circadian system is presented. The model combines a circadian oscillator and a sleep-wake switch that includes the effects of orexin. By means of simulations, we characterize the period-locking zone of the model, where a stable 24-hour circadian rhythm exists, and the occurrence of circadian disruption due to both insufficient light and imbalance in orexin. We also investigate how daily bright light treatments of short duration can recover the normal circadian rhythm. It is found that the system exhibits continuous phase advance/delay at lower/higher orexin levels. Bright light treatment simulations disclose two optimal time windows, corresponding to morning and evening light treatments. Among the two, the morning light treatment is found effective in a wider range of parameter values, with shorter recovery time. This approach offers a systematic way to determine the conditions under which circadian disruption occurs, and to evaluate the effects of light treatment. In particular, it could potentially offer a way to optimize light treatments for patients with circadian disruption, e.g., sleep and mood disorders, in clinical settings.

  14. Rapid Adjustment of Circadian Clocks to Simulated Travel to Time Zones across the Globe.

    Science.gov (United States)

    Harrison, Elizabeth M; Gorman, Michael R

    2015-12-01

    Daily rhythms in mammalian physiology and behavior are generated by a central pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN), the timing of which is set by light from the environment. When the ambient light-dark cycle is shifted, as occurs with travel across time zones, the SCN and its output rhythms must reset or re-entrain their phases to match the new schedule-a sluggish process requiring about 1 day per hour shift. Using a global assay of circadian resetting to 6 equidistant time-zone meridians, we document this characteristically slow and distance-dependent resetting of Syrian hamsters under typical laboratory lighting conditions, which mimic summer day lengths. The circadian pacemaker, however, is additionally entrainable with respect to its waveform (i.e., the shape of the 24-h oscillation) allowing for tracking of seasonally varying day lengths. We here demonstrate an unprecedented, light exposure-based acceleration in phase resetting following 2 manipulations of circadian waveform. Adaptation of circadian waveforms to long winter nights (8 h light, 16 h dark) doubled the shift response in the first 3 days after the shift. Moreover, a bifurcated waveform induced by exposure to a novel 24-h light-dark-light-dark cycle permitted nearly instant resetting to phase shifts from 4 to 12 h in magnitude, representing a 71% reduction in the mismatch between the activity rhythm and the new photocycle. Thus, a marked enhancement of phase shifting can be induced via nonpharmacological, noninvasive manipulation of the circadian pacemaker waveform in a model species for mammalian circadian rhythmicity. Given the evidence of conserved flexibility in the human pacemaker waveform, these findings raise the promise of flexible resetting applicable to circadian disruption in shift workers, frequent time-zone travelers, and any individual forced to adjust to challenging schedules. © 2015 The Author(s).

  15. Response of the human circadian system to millisecond flashes of light.

    Directory of Open Access Journals (Sweden)

    Jamie M Zeitzer

    Full Text Available Ocular light sensitivity is the primary mechanism by which the central circadian clock, located in the suprachiasmatic nucleus (SCN, remains synchronized with the external geophysical day. This process is dependent on both the intensity and timing of the light exposure. Little is known about the impact of the duration of light exposure on the synchronization process in humans. In vitro and behavioral data, however, indicate the circadian clock in rodents can respond to sequences of millisecond light flashes. In a cross-over design, we tested the capacity of humans (n = 7 to respond to a sequence of 60 2-msec pulses of moderately bright light (473 lux given over an hour during the night. Compared to a control dark exposure, after which there was a 3.5±7.3 min circadian phase delay, the millisecond light flashes delayed the circadian clock by 45±13 min (p<0.01. These light flashes also concomitantly increased subjective and objective alertness while suppressing delta and sigma activity (p<0.05 in the electroencephalogram (EEG. Our data indicate that phase shifting of the human circadian clock and immediate alerting effects can be observed in response to brief flashes of light. These data are consistent with the hypothesis that the circadian system can temporally integrate extraordinarily brief light exposures.

  16. Advanced Pacemaker

    Science.gov (United States)

    1990-01-01

    Synchrony, developed by St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.) is an advanced state-of-the-art implantable pacemaker that closely matches the natural rhythm of the heart. The companion element of the Synchrony Pacemaker System is the Programmer Analyzer APS-II which allows a doctor to reprogram and fine tune the pacemaker to each user's special requirements without surgery. The two-way communications capability that allows the physician to instruct and query the pacemaker is accomplished by bidirectional telemetry. APS-II features 28 pacing functions and thousands of programming combinations to accommodate diverse lifestyles. Microprocessor unit also records and stores pertinent patient data up to a year.

  17. A pacemaker powered by an implantable biofuel cell operating under conditions mimicking the human blood circulatory system--battery not included.

    Science.gov (United States)

    Southcott, Mark; MacVittie, Kevin; Halámek, Jan; Halámková, Lenka; Jemison, William D; Lobel, Robert; Katz, Evgeny

    2013-05-07

    Biocatalytic electrodes made of buckypaper were modified with PQQ-dependent glucose dehydrogenase on the anode and with laccase on the cathode and were assembled in a flow biofuel cell filled with serum solution mimicking the human blood circulatory system. The biofuel cell generated an open circuitry voltage, Voc, of ca. 470 mV and a short circuitry current, Isc, of ca. 5 mA (a current density of 0.83 mA cm(-2)). The power generated by the implantable biofuel cell was used to activate a pacemaker connected to the cell via a charge pump and a DC-DC converter interface circuit to adjust the voltage produced by the biofuel cell to the value required by the pacemaker. The voltage-current dependencies were analyzed for the biofuel cell connected to an Ohmic load and to the electronic loads composed of the interface circuit, or the power converter, and the pacemaker to study their operation. The correct pacemaker operation was confirmed using a medical device - an implantable loop recorder. Sustainable operation of the pacemaker was achieved with the system closely mimicking human physiological conditions using a single biofuel cell. This first demonstration of the pacemaker activated by the physiologically produced electrical energy shows promise for future electronic implantable medical devices powered by electricity harvested from the human body.

  18. l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.

    Science.gov (United States)

    Yasuo, Shinobu; Iwamoto, Ayaka; Lee, Sang-Il; Ochiai, Shotaro; Hitachi, Rina; Shibata, Satomi; Uotsu, Nobuo; Tarumizu, Chie; Matsuoka, Sayuri; Furuse, Mitsuhiro; Higuchi, Shigekazu

    2017-12-01

    Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 l-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before l-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of l-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: l-Serine administration enhanced light-induced phase shifts in mice (1.86-fold; P light-dark cycle by 6 h, l-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, l-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-l-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances. © 2017 American Society for Nutrition.

  19. The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts.

    Directory of Open Access Journals (Sweden)

    Lucia Pagani

    Full Text Available BACKGROUND: Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls", clock properties measured in human fibroblasts correlated with extreme diurnal behavior. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have measured circadian period in human primary fibroblasts taken from normal individuals and, for the first time, compared it directly with physiological period measured in vivo in the same subjects. Human physiological period length was estimated via the secretion pattern of the hormone melatonin in two different groups of sighted subjects and one group of totally blind subjects, each using different methods. Fibroblast period length was measured via cyclical expression of a lentivirally delivered circadian reporter. Within each group, a positive linear correlation was observed between circadian period length in physiology and in fibroblast gene expression. Interestingly, although blind individuals showed on average the same fibroblast clock properties as sighted ones, their physiological periods were significantly longer. CONCLUSIONS/SIGNIFICANCE: We conclude that the period of human circadian behaviour is mostly driven by cellular clock properties in normal individuals and can be approximated by measurement in peripheral cells such as fibroblasts. Based upon differences among sighted and blind subjects, we also speculate that period can be modified by prolonged unusual conditions such as the total light deprivation of blindness.

  20. Programmable Pacemaker

    Science.gov (United States)

    1996-01-01

    Released in 1995, the Trilogy cardiac pacemaker is the fourth generation of a unit developed in the 1970s by NASA, Johns Hopkins Applied Physics Laboratory and St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.). The new system incorporates the company's PDx diagnostic and programming software and a powerful microprocessor that allows more functions to be fully automatic and gives more detailed information on the patient's health and the performance of the pacing systems. The pacemaker incorporates bidirectional telemetry used for space communications for noninvasive communication with the implanted pacemaker, smaller implantable pulse generators from space microminiaturization, and longer-life batteries from technology for spacecraft electrical power systems.

  1. Pacemaker wires

    International Nuclear Information System (INIS)

    Fransson, S.G.

    1993-01-01

    Evaluation of pacemaker wires were performed by comparing Advanced Multiple Beam Equalization Radiography (AMBER) with conventional chest radiography. The scanning equalization technique of the AMBER unit makes it superior to conventional technique in the depiction of different structures in the mediastinum or in the pleural sinuses. So far motion artifacts have not been considered clinically important. The longer exposure time, however, may impair the assessment of pacemaker wires. The motion artifact described may not only make adequate evaluation impossible but may even give a false impression of a lead fracture. The difference between the two systems was significant. (orig.)

  2. Software tools for data modelling and processing of human body temperature circadian dynamics.

    Science.gov (United States)

    Petrova, Elena S; Afanasova, Anastasia I

    2015-01-01

    This paper is presenting a software development for simulating and processing thermometry data. The motivation of this research is the miniaturization of actuators attached to human body which allow frequent temperature measurements and improve the medical diagnosis procedures related to circadian dynamics.

  3. The Progression of Circadian Phase during Light Exposure in Animals and Humans

    NARCIS (Netherlands)

    Beersma, Domien G. M.; Comas, Marian; Hut, Roelof A.; Gordijn, Marijke C. M.; Rueger, Melanie; Daan, Serge

    Studies in humans and mice revealed that circadian phase shifting effects of light are larger at the beginning of a light exposure interval than during subsequent exposure. Little is known about the dynamics of this response reduction phenomenon. Here the authors propose a method to obtain

  4. Acute and phase-shifting effects of ocular and extraocular light in human circadian physiology

    NARCIS (Netherlands)

    Rüger, Melanie; Gordijn, Marijke C.M.; Beersma, Domien G.M.; de Vries, Bonnie; Daan, Serge

    2003-01-01

    Light can influence physiology and performance of humans in two distinct ways. It can acutely change the level of physiological and behavioral parameters, and it can induce a phase shift in the circadian oscillators underlying variations in these levels. Until recently, both effects were thought to

  5. Hierarchical organization of the circadian timing system

    NARCIS (Netherlands)

    Steensel, Mariska van

    2006-01-01

    In order to cope with and to predict 24-hour rhythms in the environment, most, if not all, organisms have a circadian timing system. The most important mammalian circadian pacemaker is located in the suprachiasmatic nucleus at the base of the hypothalamus in the brain. Over the years, it has become

  6. Circadian phase assessment by ambulatory monitoring in humans: correlation with dim light melatonin onset.

    Science.gov (United States)

    Bonmati-Carrion, M A; Middleton, B; Revell, V; Skene, D J; Rol, M A; Madrid, J A

    2014-02-01

    The increased prevalence of circadian disruptions due to abnormal coupling between internal and external time makes the detection of circadian phase in humans by ambulatory recordings a compelling need. Here, we propose an accurate practical procedure to estimate circadian phase with the least possible burden for the subject, that is, without the restraints of a constant routine protocol or laboratory techniques such as melatonin quantification, both of which are standard procedures. In this validation study, subjects (N = 13) wore ambulatory monitoring devices, kept daily sleep diaries and went about their daily routine for 10 days. The devices measured skin temperature at wrist level (WT), motor activity and body position on the arm, and light exposure by means of a sensor placed on the chest. Dim light melatonin onset (DLMO) was used to compare and evaluate the accuracy of the ambulatory variables in assessing circadian phase. An evening increase in WT: WTOnset (WTOn) and "WT increase onset" (WTiO) was found to anticipate the evening increase in melatonin, while decreases in motor activity (Activity Offset or AcOff), body position (Position Offset (POff)), integrative TAP (a combination of WT, activity and body position) (TAPOffset or TAPOff) and an increase in declared sleep propensity were phase delayed with respect to DLMO. The phase markers obtained from subjective sleep (R = 0.811), WT (R = 0.756) and the composite variable TAP (R = 0.720) were highly and significantly correlated with DLMO. The findings strongly support a new method to calculate circadian phase based on WT (WTiO) that accurately predicts and shows a temporal association with DLMO. WTiO is especially recommended due to its simplicity and applicability to clinical use under conditions where knowing endogenous circadian phase is important, such as in cancer chronotherapy and light therapy.

  7. The effects of gender on circadian rhythm of human physiological indexes in high temperature environment

    Science.gov (United States)

    Zheng, G. Z.; Li, K.; Bu, W. T.; Lu, Y. Z.; Wang, Y. J.

    2018-03-01

    In the context of frequent high temperature weather in recent years, peoples’ physical health is seriously threatened by the indoor high temperature. The physiological activities of human body show a certain changes of circadian rhythm. In this paper, the circadian rhythms of the physiological indexes in indoor high temperature environment were quantified and compared between the male subjects and female subjects. Ten subjects (five males and five females) were selected. The temperature conditions were set at 28°C, 32°C, 36°C and 38°C, respectively. The blood pressure, heart rate, rectal temperature, eardrum temperature, forehead temperature and mean skin temperature were measured for 24 hours continuously. The medians, amplitudes and acrophases of the circadian rhythms were obtained by the cosinor analysis method. Then the effects of gender on the circadian rhythm of the human body in high temperature environment were analyzed. The results indicate that, compared with the female subjects, the male medians of the systolic pressure and diastolic pressure were higher, and the male medians of heart rate and rectal temperature were lower, however, no significant differences were found between eardrum temperature, forehead temperature and mean skin temperature. This study can provide scientific basis for the health protection of the indoor relevant personnel.

  8. Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

    Science.gov (United States)

    Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

    2018-05-01

    Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

  9. Human seasonal and circadian studies in Antarctica (Halley, 75°S).

    Science.gov (United States)

    Arendt, Josephine; Middleton, Benita

    2018-03-01

    Living for extended periods in Antarctica exposes base personnel to extremes of daylength (photoperiod) and temperature. At the British Antarctic Survey base of Halley, 75°S, the sun does not rise for 110 d in the winter and does not set for 100 d in summer. Photoperiod is the major time cue governing the timing of seasonal events such as reproduction in many species. The neuroendocrine signal providing photoperiodic information to body physiology is the duration of melatonin secretion which reflects the length of the night: longer in the short days of winter and shorter in summer. Light of sufficient intensity and spectral composition serves to suppress production of melatonin and to set the circadian timing and the duration of the rhythm. In humans early observations suggested that bright (>2000 lux) white light was needed to suppress melatonin completely. Shortly thereafter winter depression (Seasonal Affective Disorder or SAD) was described, and its successful treatment by an artificial summer photoperiod of bright white light, sufficient to shorten melatonin production. At Halley dim artificial light intensity during winter was measured, until 2003, at a maximum of approximately 500 lux in winter. Thus a strong seasonal and circadian time cue was absent. It seemed likely that winter depression would be common in the extended period of winter darkness and could be treated with an artificial summer photoperiod. These observations, and predictions, inspired a long series of studies regarding human seasonal and circadian status, and the effects of light treatment, in a small overwintering, isolated community, living in the same conditions for many months at Halley. We found little evidence of SAD, or change in duration of melatonin production with season. However the timing of the melatonin rhythm itself, and/or that of its metabolite 6-sulphatoxymelatonin (aMT6s), was used as a primary marker of seasonal, circadian and treatment changes. A substantial phase

  10. Maternal exercise, season and sex modify the human fetal circadian rhythm.

    Science.gov (United States)

    Sletten, Julie; Cornelissen, Germaine; Assmus, Jørg; Kiserud, Torvid; Albrechtsen, Susanne; Kessler, Jörg

    2018-05-13

    The knowledge on circadian rhythmicity is rapidly expanding. We aimed to define the longitudinal development of the circadian heart rate rhythm in the human fetus in an unrestricted, out-of-hospital setting, and to examine the effects of maternal physical activity, season and fetal sex. We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Circadian rhythmicity in fetal heart rate and fetal heart rate variation was detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. For the fetal heart rate and fetal heart rate variation, a significant circadian rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings, respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (prhythm diversity was found in male fetuses, during higher maternal physical activity and during the summer season. The dynamic development of the fetal circadian heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Circadian variation of EEG power spectra in NREM and REM sleep in humans: dissociation from body temperature

    Science.gov (United States)

    Dijk, D. J.

    1999-01-01

    In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.

  12. Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome.

    Science.gov (United States)

    Kervezee, Laura; Cuesta, Marc; Cermakian, Nicolas; Boivin, Diane B

    2018-05-22

    Misalignment of the endogenous circadian timing system leads to disruption of physiological rhythms and may contribute to the development of the deleterious health effects associated with night shift work. However, the molecular underpinnings remain to be elucidated. Here, we investigated the effect of a 4-day simulated night shift work protocol on the circadian regulation of the human transcriptome. Repeated blood samples were collected over two 24-hour measurement periods from eight healthy subjects under highly controlled laboratory conditions before and 4 days after a 10-hour delay of their habitual sleep period. RNA was extracted from peripheral blood mononuclear cells to obtain transcriptomic data. Cosinor analysis revealed a marked reduction of significantly rhythmic transcripts in the night shift condition compared with baseline at group and individual levels. Subsequent analysis using a mixed-effects model selection approach indicated that this decrease is mainly due to dampened rhythms rather than to a complete loss of rhythmicity: 73% of transcripts rhythmically expressed at baseline remained rhythmic during the night shift condition with a similar phase relative to habitual bedtimes, but with lower amplitudes. Functional analysis revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways. These results show that 4 days of simulated night shifts leads to a loss in temporal coordination between the human circadian transcriptome and the external environment and impacts biological processes related to the adverse health effects associated to night shift work.

  13. An agent-based model of cellular dynamics and circadian variability in human endotoxemia.

    Directory of Open Access Journals (Sweden)

    Tung T Nguyen

    Full Text Available As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications.

  14. Aging and Circadian Rhythms

    Science.gov (United States)

    Duffy, Jeanne F.; Zitting, Kirsi-Marja; Chinoy, Evan D.

    2015-01-01

    Aging is associated with numerous changes, including changes in sleep timing, duration, and quality. The circadian timing system interacts with a sleep-wake homeostatic system to regulate human sleep, including sleep timing and structure. Here, we review key features of the human circadian timing system, age-related changes in the circadian timing system, and how those changes may contribute to the observed alterations in sleep. PMID:26568120

  15. Cardiac pacemaker

    International Nuclear Information System (INIS)

    Kolenik, S.A.

    1976-01-01

    The construction of a cardiac pacemaker is described which is characterized by particularly small dimensions, small weight and long life duration. The weight is under 100g, the specific weight under 1.7. Mass inertia forces which occur through acceleration and retardation processes, thus remain below the threshold values, above which one would have to reckon with considerable damaging of the surrounding body tissue. The maintaining of small size and slight weight is achieved by using an oscillator on COSMOS basis, where by considerably lower energy consumption, amongst others the lifetimes of the batteries used - a lithium anode with thionyl chloride electrolyte - is extended to over 5 years. The reliability can be increased by the use of 2 or more batteries. The designed dimension are 20x60x60 mm 3 . (ORU/LH) [de

  16. 21 CFR 870.3610 - Implantable pacemaker pulse generator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implantable pacemaker pulse generator. 870.3610 Section 870.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has...

  17. 21 CFR 870.1750 - External programmable pacemaker pulse generator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External programmable pacemaker pulse generator. 870.1750 Section 870.1750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker...

  18. Identification of human circadian genes based on time course gene expression profiles by using a deep learning method.

    Science.gov (United States)

    Cui, Peng; Zhong, Tingyan; Wang, Zhuo; Wang, Tao; Zhao, Hongyu; Liu, Chenglin; Lu, Hui

    2018-06-01

    Circadian genes express periodically in an approximate 24-h period and the identification and study of these genes can provide deep understanding of the circadian control which plays significant roles in human health. Although many circadian gene identification algorithms have been developed, large numbers of false positives and low coverage are still major problems in this field. In this study we constructed a novel computational framework for circadian gene identification using deep neural networks (DNN) - a deep learning algorithm which can represent the raw form of data patterns without imposing assumptions on the expression distribution. Firstly, we transformed time-course gene expression data into categorical-state data to denote the changing trend of gene expression. Two distinct expression patterns emerged after clustering of the state data for circadian genes from our manually created learning dataset. DNN was then applied to discriminate the aperiodic genes and the two subtypes of periodic genes. In order to assess the performance of DNN, four commonly used machine learning methods including k-nearest neighbors, logistic regression, naïve Bayes, and support vector machines were used for comparison. The results show that the DNN model achieves the best balanced precision and recall. Next, we conducted large scale circadian gene detection using the trained DNN model for the remaining transcription profiles. Comparing with JTK_CYCLE and a study performed by Möller-Levet et al. (doi: https://doi.org/10.1073/pnas.1217154110), we identified 1132 novel periodic genes. Through the functional analysis of these novel circadian genes, we found that the GTPase superfamily exhibits distinct circadian expression patterns and may provide a molecular switch of circadian control of the functioning of the immune system in human blood. Our study provides novel insights into both the circadian gene identification field and the study of complex circadian-driven biological

  19. Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood.

    Science.gov (United States)

    Lech, Karolina; Ackermann, Katrin; Revell, Victoria L; Lao, Oscar; Skene, Debra J; Kayser, Manfred

    2016-02-01

    The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study. Statistically significant rhythms in expression were observed for STAT3, SREBF1, TRIB1, and THRA1 in samples from both the S/SD and the CR studies, indicating that their rhythmicity is driven by the endogenous clock. The MKNK2 gene was significantly rhythmic in the S/SD but not the CR study, which implies its exogenously driven rhythmic expression. In addition, we confirmed the circadian expression of PER1, PER3, and REV-ERBα in the CR study samples, while BMAL1 and HSPA1B were not significantly rhythmic in the CR samples; all 5 genes previously showed significant expression in the S/SD study samples. Overall, our results demonstrate that rhythmic expression patterns of clock and selected clock-controlled genes in human blood cells are in part determined by exogenous factors (sleep and fasting state) and in part by the endogenous circadian timing system. Knowledge of the exogenous and endogenous regulation of gene expression rhythms is needed prior to the selection of potential candidate marker genes for future applications in medical and forensic settings. © 2015 The Author(s).

  20. The Drosophila melanogaster circadian pacemaker circuit

    Indian Academy of Sciences (India)

    2008-12-07

    Dec 7, 2008 ... jority of the DN1 project towards the dorsal fusion commissure (red) and do not cross the ... 1998). The four pairs of s-LNv send out projections (that are thought to ..... oscillation, with bursts of action potentials riding the crest.

  1. In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells.

    Science.gov (United States)

    Fang, Mingzhu; Kang, Hwan-Goo; Park, Youngil; Estrella, Brian; Zarbl, Helmut

    2017-09-28

    The circadian rhythm is a fundamental physiological process present in all organisms that regulates biological processes ranging from gene expression to sleep behavior. In vertebrates, circadian rhythm is controlled by a molecular oscillator that functions in both the suprachiasmatic nucleus (SCN; central pacemaker) and individual cells comprising most peripheral tissues. More importantly, disruption of circadian rhythm by exposure to light-at-night, environmental stressors and/or toxicants is associated with increased risk of chronic diseases and aging. The ability to identify agents that can disrupt central and/or peripheral biological clocks, and agents that can prevent or mitigate the effects of circadian disruption, has significant implications for prevention of chronic diseases. Although rodent models can be used to identify exposures and agents that induce or prevent/mitigate circadian disruption, these experiments require large numbers of animals. In vivo studies also require significant resources and infrastructure, and require researchers to work all night. Thus, there is an urgent need for a cell-type appropriate in vitro system to screen for environmental circadian disruptors and enhancers in cell types from different organs and disease states. We constructed a vector that drives transcription of the destabilized luciferase in eukaryotic cells under the control of the human PERIOD 2 gene promoter. This circadian reporter construct was stably transfected into human mammary epithelial cells, and circadian responsive reporter cells were selected to develop the in vitro bioluminescence assay. Here, we present a detailed protocol to establish and validate the assay. We further provide details for proof of concept experiments demonstrating the ability of our in vitro assay to recapitulate the in vivo effects of various chemicals on the cellular biological clock. The results indicate that the assay can be adapted to a variety of cell types to screen for both

  2. Chronic ethanol intake alters circadian phase shifting and free-running period in mice.

    Science.gov (United States)

    Seggio, Joseph A; Fixaris, Michael C; Reed, Jeffrey D; Logan, Ryan W; Rosenwasser, Alan M

    2009-08-01

    Chronic alcohol intake is associated with widespread disruptions in sleep and circadian rhythms in both human alcoholics and in experimental animals. Recent studies have demonstrated that chronic and acute ethanol treatments alter fundamental properties of the circadian pacemaker--including free-running period and responsiveness to photic and nonphotic phase-shifting stimuli--in rats and hamsters. In the present work, the authors extend these observations to the C57BL/6J mouse, an inbred strain characterized by very high levels of voluntary ethanol intake and by reliable and stable free-running circadian activity rhythms. Mice were housed individually in running-wheel cages under conditions of either voluntary or forced ethanol intake, whereas controls were maintained on plain water. Forced ethanol intake significantly attenuated photic phase delays (but not phase advances) and shortened free-running period in constant darkness, but voluntary ethanol intake failed to affect either of these parameters. Thus, high levels of chronic ethanol intake, beyond those normally achieved under voluntary drinking conditions, are required to alter fundamental circadian pacemaker properties in C57BL/6J mice. These observations may be related to the relative ethanol insensitivity displayed by this strain in several other phenotypic domains, including ethanol-induced sedation, ataxia, and withdrawal. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes.

  3. Circadian variations of interferon-induced enhancement of human natural killer (NK) cell activity.

    Science.gov (United States)

    Gatti, G; Cavallo, R; Sartori, M L; Carignola, R; Masera, R; Delponte, D; Salvadori, A; Angeli, A

    1988-01-01

    We searched for circadian changes in the enhancement of the NK activity after exposure to IFN-gamma of peripheral blood mononuclear (PBM) cells obtained serially throughout the 24-h cycle. In August-October 1986, blood was drawn from 7 healthy, diurnally active and nocturnally resting male volunteers (22-34 yr) at 4-h intervals for 24 h starting at 08:00. PBM cells were immediately separated and assayed for NK cell activity, using K 562 cultured cells as a target in a 4-h 51Cr release assay after prior incubation for 20 h with buffer or 300 IU rIFN-gamma. Circadian variations of the spontaneous NK cell cytotoxicity were apparent; the activity was at its maximum at the end of the night or in the early morning and then declined in the afternoon. The 24-h rhythmic pattern was validated with statistical significance by the Cosinor method (p less than 0.02; acrophase 04:22). Maximum enhancement by IFN-gamma was attained in the second part of the night or in the early morning, i.e. in phase with the peak of the spontaneous NK cell activity. A significant circadian rhythm of the percent increase above control levels was validated by the Cosinor method (p less than 0.01; acrophase 04:03). Our findings may be of relevance to a better understanding of the mechanisms of control of human NK activity and warrant consideration as an approach to improve the effectiveness of time-qualified immunotherapy.

  4. Circadian and ultradian components of hunger in human non-homeostatic meal-to-meal eating.

    Science.gov (United States)

    Wuorinen, Elizabeth C; Borer, Katarina T

    2013-10-02

    A unifying physiological explanation of the urge to initiate eating is still not available as human hunger in meal-to-meal eating may not be under homeostatic control. We hypothesized that a central circadian and a gastrointestinal ultradian timing mechanism coordinate non-deprivation meal-to-meal eating. We examined hunger as a function of time of day, inter-meal (IM) energy expenditure (EE), and concentrations of proposed hunger-controlling hormones ghrelin, leptin, and insulin. In two crossover studies, 10 postmenopausal women, BMI 23-26 kg/m(2) engaged in exercise (EX) and sedentary (SED) trials. Weight maintenance meals were provided at 6h intervals with an ad libitum meal at 13 h in study 1 and 21 h snack in study 2. EE during IM intervals was measured by indirect calorimetry and included EX EE of 801 kcal in study 1, and 766-1,051 kcal in study 2. Hunger was assessed with a visual analog scale and blood was collected for hormonal determination. Hunger displayed a circadian variation with acrophase at 13 and 19 h and was unrelated to preceding EE. Hunger was suppressed by EX between 10 and 16 h and bore no relationship to either EE during preceding IM intervals or changes in leptin, insulin, and ghrelin; however leptin reflected IM energy changes and ghrelin and insulin, prandial events. During non-deprivation meal-to-meal eating, hunger appears to be under non-homeostatic central circadian control as it is unrelated to EE preceding meals or concentrations of proposed appetite-controlling hormones. Gastrointestinal meal processing appears to intermittently suppress this control and entrain an ultradian hunger pattern. © 2013 Elsevier Inc. All rights reserved.

  5. Circadian Macronutrients Variations over the First 7 Weeks of Human Milk Feeding of Preterm Infants.

    Science.gov (United States)

    Moran-Lev, Hadar; Mimouni, Francis B; Ovental, Amit; Mangel, Laurence; Mandel, Dror; Lubetzky, Ronit

    2015-09-01

    Little is known about circadian variations of macronutrients content of expressed preterm human milk (HM). This study evaluated diurnal variations of macronutrients and energy content of preterm HM over the first 7 weeks of lactation and tested the hypothesis that values obtained during a morning sample are predictive of those obtained from an evening sample. Expressed HM was obtained from 32 mothers of preterm infants (26-33 weeks in gestational age), who routinely expressed all their milk every 3 hours from the beginning of the second to the seventh week after delivery. One aliquot was obtained from the first morning expression and the second from the evening expression. Energy and macronutrients contents were measured using an HM analyzer. Mean fat and energy contents of all samples obtained during the whole period were significantly higher in evening samples (p < 0.0001). There were no significant differences between morning and evening carbohydrates and protein contents. Concentrations of protein, carbohydrates, and fat from morning samples were predictive of evening concentrations to different extents (R(2) = 0.720, R(2) = 0.663, and R(2) = 0.20, respectively; p < 0.02). The predictability of evening values by morning values was not influenced by the week of lactation at sampling or by individual patients. In repeated-measures analysis of variance performed on 11 patients who completed the whole 7-week period, over time, there was a significant decrease in fat, energy, and protein contents, whereas carbohydrates content remained unchanged. Day-night differences remained significant only for fat content. Circadian variations in fat and energy concentrations of HM are consistent over the first 7 weeks of lactation. There are no consistent circadian variations in HM protein and carbohydrates. Over a given day, there are little variations in protein and carbohydrates content, but fat concentrations are more variable, and evening values are less well predicted by

  6. Cardiac Pacemakers; Marcapasos Cardiacos

    Energy Technology Data Exchange (ETDEWEB)

    Fiandra, O [Universidad de la Republica, Facultad de Maedicina, Departamento de Cardiologia, Montevideo(Uruguay); Espasandin, W [Universidad de la Republica, Facultad de Medicina, Departamento de Cirugia Cardiaca, Montevideo (Uruguay); Fiandra, H [Instituto Nacional de Cirugia Cardiaca, Departamento de Hemodinamia y Marcapasos, Montevideo (Uruguay); and others

    1984-07-01

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control.

  7. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    Science.gov (United States)

    Ho Mien, Ivan; Chua, Eric Chern-Pin; Lau, Pauline; Tan, Luuan-Chin; Lee, Ivan Tian-Guang; Yeo, Sing-Chen; Tan, Sara Shuhui; Gooley, Joshua J

    2014-01-01

    Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

  8. Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

    Directory of Open Access Journals (Sweden)

    Ivan Ho Mien

    Full Text Available Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2 s(-1, intermittent red light (1 min on/off, or bright white light (2,500 lux near the onset of nocturnal melatonin secretion (n = 8 in each group. Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69, with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

  9. An Approximation to the Temporal Order in Endogenous Circadian Rhythms of Genes Implicated in Human Adipose Tissue Metabolism

    Science.gov (United States)

    GARAULET, MARTA; ORDOVÁS, JOSÉ M.; GÓMEZ-ABELLÁN, PURIFICACIÓN; MARTÍNEZ, JOSE A.; MADRID, JUAN A.

    2015-01-01

    Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT including genes implicated in metabolic processes such as energy intake and expenditure, insulin resistance, adipocyte differentiation, dyslipidemia, and body fat distribution. Visceral and subcutaneous abdominal AT biopsies (n = 6) were obtained from morbid obese women (BMI ≥ 40 kg/m2). To investigate rhythmic expression pattern, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h using quantitative real-time PCR. Clock genes, glucocorticoid metabolism-related genes, leptin, adiponectin and their receptors were studied. Significant differences were found both in achrophases and relative-amplitude among genes (P 30%). When interpreting the phase map of gene expression in both depots, data indicated that circadian rhythmicity of the genes studied followed a predictable physiological pattern, particularly for subcutaneous AT. Interesting are the relationships between adiponectin, leptin, and glucocorticoid metabolism-related genes circadian profiles. Their metabolic significance is discussed. Visceral AT behaved in a different way than subcutaneous for most of the genes studied. For every gene, protein mRNA levels fluctuated during the day in synchrony with its receptors. We have provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue. PMID:21520059

  10. Application of an ex vivo cellular model of circadian variation for bipolar disorder research: a proof of concept study.

    Science.gov (United States)

    Bamne, Mikhil N; Ponder, Christine A; Wood, Joel A; Mansour, Hader; Frank, Ellen; Kupfer, David J; Young, Michael W; Nimgaonkar, Vishwajit L

    2013-09-01

    Disruption of circadian function has been observed in several human disorders, including bipolar disorder (BD). Research into these disorders can be facilitated by human cellular models that evaluate external factors (zeitgebers) that impact circadian pacemaker activity. Incorporating a firefly luciferase reporter system into human fibroblasts provides a facile, bioluminescent readout that estimates circadian phase, while leaving the cells intact. We evaluated whether this system can be adapted to clinical BD research and whether it can incorporate zeitgeber challenge paradigms. Fibroblasts from patients with bipolar I disorder (BD-I) (n = 13) and controls (n = 12) were infected ex vivo with a lentiviral reporter incorporating the promoter sequences for Bmal1, a circadian gene to drive expression of the firefly luciferase gene. Following synchronization, the bioluminescence was used to estimate period length. Phase response curves (PRCs) were also generated following forskolin challenge and the phase response patterns were characterized. Period length and PRCs could be estimated reliably from the constructs. There were no significant case-control differences in period length, with a nonsignificant trend for differences in PRCs following the phase-setting experiments. An ex vivo cellular fibroblast-based model can be used to investigate circadian function in BD-I. It can be generated from specific individuals and this could usefully complement ongoing circadian clinical research. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Short wavelength light filtering by the natural human lens and IOLs -- implications for entrainment of circadian rhythm

    DEFF Research Database (Denmark)

    Brøndsted, Adam Elias; Lundeman, Jesper Holm; Kessel, Line

    2013-01-01

    Photoentrainment of circadian rhythm begins with the stimulation of melanopsin containing retinal ganglion cells that respond directly to blue light. With age, the human lens becomes a strong colour filter attenuating transmission of short wavelengths. The purpose of the study was to examine the ...

  12. IgE-dependent activation of human mast cells and fMLP-mediated activation of human eosinophils is controlled by the circadian clock.

    Science.gov (United States)

    Baumann, Anja; Feilhauer, Katharina; Bischoff, Stephan C; Froy, Oren; Lorentz, Axel

    2015-03-01

    Symptoms of allergic attacks frequently exhibit diurnal variations. Accordingly, we could recently demonstrate that mast cells and eosinophils - known as major effector cells of allergic diseases - showed an intact circadian clock. Here, we analyzed the role of the circadian clock in the functionality of mast cells and eosinophils. Human intestinal mast cells (hiMC) were isolated from intestinal mucosa; human eosinophils were isolated from peripheral blood. HiMC and eosinophils were synchronized by dexamethasone before stimulation every 4h around the circadian cycle by FcɛRI crosslinking or fMLP, respectively. Signaling molecule activation was examined using Western blot, mRNA expression by real-time RT-PCR, and mediator release by multiplex analysis. CXCL8 and CCL2 were expressed and released in a circadian manner by both hiMC and eosinophils in response to activation. Moreover, phosphorylation of ERK1/2, known to be involved in activation of hiMC and eosinophils, showed circadian rhythms in both cell types. Interestingly, all clock genes hPer1, hPer2, hCry1, hBmal1, and hClock were expressed in a similar circadian pattern in activated and unstimulated cells indicating that the local clock controls hiMC and eosinophils and subsequently allergic reactions but not vice versa. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health

    Science.gov (United States)

    Ribas-Latre, Aleix; Eckel-Mahan, Kristin

    2016-01-01

    , can destroy synchrony between peripheral clocks and the central pacemaker in the brain as well as between peripheral clocks themselves. In addition, we review several studies looking at clock gene SNPs in humans and the metabolic phenotypes or tendencies associated with particular clock gene mutations. Major conclusions Targeted use of specific nutrients based on chronotype has the potential for immense clinical utility in the future. Macronutrients and micronutrients have the ability to function as zeitgebers for the clock by activating or modulating specific clock proteins or accessory proteins (such as nuclear receptors). Circadian clock control by nutrients can be tissue-specific. With a better understanding of the mechanisms that support nutrient-induced circadian control in specific tissues, human chronotype and SNP information might eventually be used to tailor nutritional regimens for metabolic disease treatment and thus be an important part of personalized medicine's future. PMID:26977390

  14. A train of blue light pulses delivered through closed eyelids suppresses melatonin and phase shifts the human circadian system

    Directory of Open Access Journals (Sweden)

    Figueiro MG

    2013-10-01

    Full Text Available Mariana G Figueiro, Andrew Bierman, Mark S ReaLighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USAAbstract: A model of circadian phototransduction was published in 2005 to predict the spectral sensitivity of the human circadian system to narrow-band and polychromatic light sources by combining responses to light from the spectral-opponent “blue” versus “yellow” cone bipolar pathway with direct responses to light by the intrinsically photosensitive retinal ganglion cells. In the model, depolarizing “blue” responses, but not hyperpolarizing “yellow” responses, from the “blue” versus “yellow” pathway are combined with the intrinsically photosensitive retinal ganglion cell responses. Intrinsically photosensitive retinal ganglion cell neurons are known to be much slower to respond to light than the cone pathway, so an implication of the model is that periodic flashes of “blue” light, but not “yellow” light, would be effective for stimulating the circadian system. A within-subjects study was designed to test the implications of the model regarding retinal exposures to brief flashes of light. The study was also aimed at broadening the foundation for clinical treatment of circadian sleep disorders by delivering flashing light through closed eyelids while people were asleep. In addition to a dark control night, the eyelids of 16 subjects were exposed to three light-stimulus conditions in the phase delay portion of the phase response curve while they were asleep: (1 2-second flashes of 111 W/m2 of blue (λmax ≈ 480 nm light once every minute for 1 hour, (2 131 W/m2 of green (λmax ≈ 527 nm light, continuously on for 1 hour, and (3 2-second flashes of the same green light once every minute for 1 hour. Inferential statistics showed that the blue flash light-stimulus condition significantly delayed circadian phase and significantly suppressed nocturnal melatonin. The results of this study further our

  15. Circadian changes in urinary Na + /K + ratio in humans: is there a ...

    African Journals Online (AJOL)

    Background: There are indications that the renal excretion of Na+ and K+ is affected by the body's circadian rhythm. Aldosterone is known to be the major determinant of urinary Na+/K+ ratio. However, recent reports suggest that the circadian rhythm of K+ excretion does not depend on endogenous aldosterone.

  16. Sex differences in the circadian regulation of sleep and waking cognition in humans.

    Science.gov (United States)

    Santhi, Nayantara; Lazar, Alpar S; McCabe, Patrick J; Lo, June C; Groeger, John A; Dijk, Derk-Jan

    2016-05-10

    The sleep-wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep-wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging.

  17. Sex differences in the circadian regulation of sleep and waking cognition in humans

    Science.gov (United States)

    Santhi, Nayantara; Lazar, Alpar S.; McCabe, Patrick J.; Lo, June C.; Groeger, John A.; Dijk, Derk-Jan

    2016-01-01

    The sleep–wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep–wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging. PMID:27091961

  18. Effects of (± 3,4-Methylenedioxymethamphetamine (MDMA on Sleep and Circadian Rhythms

    Directory of Open Access Journals (Sweden)

    Una D. McCann

    2007-01-01

    Full Text Available Abuse of stimulant drugs invariably leads to a disruption in sleep-wake patterns by virtue of the arousing and sleep-preventing effects of these drugs. Certain stimulants, such as 3,4-methylenedioxymethamphetamine (MDMA, may also have the potential to produce persistent alterations in circadian regulation and sleep because they can be neurotoxic toward brain monoaminergic neurons involved in normal sleep regulation. In particular, MDMA has been found to damage brain serotonin (5-HT neurons in a variety of animal species, including nonhuman primates, with growing evidence that humans are also susceptible to MDMA-induced brain 5-HT neurotoxicity. 5-HT is an important modulator of sleep and circadian rhythms and, therefore, individuals who sustain MDMA-induced 5-HT neurotoxicity may be at risk for developing chronic abnormalities in sleep and circadian patterns. In turn, such abnormalities could play a significant role in other alterations reported in abstinent in MDMA users (e.g., memory disturbance. This paper will review preclinical and clinical studies that have explored the effects of prior MDMA exposure on sleep, circadian activity, and the circadian pacemaker, and will highlight current gaps in knowledge and suggest areas for future research.

  19. Accuracy of circadian entrainment under fluctuating light conditions : Contributions of phase and period responses

    NARCIS (Netherlands)

    Beersma, DGM; Daan, S; Hut, RA

    The accuracy with which a circadian pacemaker can entrain to an environmental 24-h zeitgeber signal depends on (a) characteristics of the entraining signal and (b) response characteristics and intrinsic stability of the pacemaker itself. Position of the sun, weather conditions, shades, and

  20. What Is a Pacemaker?

    Science.gov (United States)

    ... your pacemaker. • If you work around industrial microwaves, electricity, cars or other large motors, ask your doctor about possible effects. Can I use a cell phone or microwave oven if I have a pacemaker? Microwave ovens, electric blankets, remote controls for TV and other common ...

  1. Circadian rhythms of women with fibromyalgia

    Science.gov (United States)

    Klerman, E. B.; Goldenberg, D. L.; Brown, E. N.; Maliszewski, A. M.; Adler, G. K.

    2001-01-01

    Fibromyalgia syndrome is a chronic and debilitating disorder characterized by widespread nonarticular musculoskeletal pain whose etiology is unknown. Many of the symptoms of this syndrome, including difficulty sleeping, fatigue, malaise, myalgias, gastrointestinal complaints, and decreased cognitive function, are similar to those observed in individuals whose circadian pacemaker is abnormally aligned with their sleep-wake schedule or with local environmental time. Abnormalities in melatonin and cortisol, two hormones whose secretion is strongly influenced by the circadian pacemaker, have been reported in women with fibromyalgia. We studied the circadian rhythms of 10 women with fibromyalgia and 12 control healthy women. The protocol controlled factors known to affect markers of the circadian system, including light levels, posture, sleep-wake state, meals, and activity. The timing of the events in the protocol were calculated relative to the habitual sleep-wake schedule of each individual subject. Under these conditions, we found no significant difference between the women with fibromyalgia and control women in the circadian amplitude or phase of rhythms of melatonin, cortisol, and core body temperature. The average circadian phases expressed in hours posthabitual bedtime for women with and without fibromyalgia were 3:43 +/- 0:19 and 3:46 +/- 0:13, respectively, for melatonin; 10:13 +/- 0:23 and 10:32 +/- 0:20, respectively for cortisol; and 5:19 +/- 0:19 and 4:57 +/- 0:33, respectively, for core body temperature phases. Both groups of women had similar circadian rhythms in self-reported alertness. Although pain and stiffness were significantly increased in women with fibromyalgia compared with healthy women, there were no circadian rhythms in either parameter. We suggest that abnormalities in circadian rhythmicity are not a primary cause of fibromyalgia or its symptoms.

  2. Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.

    Science.gov (United States)

    Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

    2016-09-26

    As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. [Analysis of pacemaker ECGs].

    Science.gov (United States)

    Israel, Carsten W; Ekosso-Ejangue, Lucy; Sheta, Mohamed-Karim

    2015-09-01

    The key to a successful analysis of a pacemaker electrocardiogram (ECG) is the application of the systematic approach used for any other ECG without a pacemaker: analysis of (1) basic rhythm and rate, (2) QRS axis, (3) PQ, QRS and QT intervals, (4) morphology of P waves, QRS, ST segments and T(U) waves and (5) the presence of arrhythmias. If only the most obvious abnormality of a pacemaker ECG is considered, wrong conclusions can easily be drawn. If a systematic approach is skipped it may be overlooked that e.g. atrial pacing is ineffective, the left ventricle is paced instead of the right ventricle, pacing competes with intrinsic conduction or that the atrioventricular (AV) conduction time is programmed too long. Apart from this analysis, a pacemaker ECG which is not clear should be checked for the presence of arrhythmias (e.g. atrial fibrillation, atrial flutter, junctional escape rhythm and endless loop tachycardia), pacemaker malfunction (e.g. atrial or ventricular undersensing or oversensing, atrial or ventricular loss of capture) and activity of specific pacing algorithms, such as automatic mode switching, rate adaptation, AV delay modifying algorithms, reaction to premature ventricular contractions (PVC), safety window pacing, hysteresis and noise mode. A systematic analysis of the pacemaker ECG almost always allows a probable diagnosis of arrhythmias and malfunctions to be made, which can be confirmed by pacemaker control and can often be corrected at the touch of the right button to the patient's benefit.

  4. Short-Wavelength Countermeasures for Circadian Desynchrony

    National Research Council Canada - National Science Library

    Heller, H. C; Smith, Mark

    2008-01-01

    .... Exposure of humans to bright light for an hour or more at the right phase of the circadian cycle produces significant phase shifts of circadian rhythms speeding recovery from jet-lag, and optimizing...

  5. Effect of age, gender and exercise on salivary dehydroepiandrosterone circadian rhythm profile in human volunteers.

    Science.gov (United States)

    Al-Turk, Walid; Al-Dujaili, Emad A S

    2016-02-01

    There has been a lot of effort by scientists to elucidate the multi functions of the naturally occurring hormone, dehydroepiandrosterone (DHEA). However, to plan research experiments optimally, it is important first to characterize the diurnal rhythm in healthy individuals. The aim of this research was to investigate the daily circadian rhythms of DHEA among the 2 genders, and the effect of age and exercise on salivary DHEA circadian rhythms. Volunteers (20-39 and 40-60 years) were recruited for 2 studies investigating the salivary DHEA circadian rhythm. The first study looked at the effect of gender and age on DHEA levels on 2 non-consecutive days, and the second study explored the effect of exercise on DHEA circadian rhythm in males. DHEA levels were estimated by a sensitive and specific ELISA method. The results showed a clear daily circadian rhythm in salivary DHEA in all participants groups, however the profile was flatter in the older female group. There was a significant difference between age and gender groups particularly at 8.00 h. In young males DHEA reduced from 541.1 ± 101.3 (mean ± sd) at 8.00 h to 198.9 ± 90.7 pg/mL at 18.00 h; pcircadian rhythm in salivary DHEA in all participants was observed, but the profile was flatter in the older groups. Copyright © 2016. Published by Elsevier Inc.

  6. Endogenous Circadian Regulation of Pro-inflammatory Cytokines and Chemokines in the Presence of Bacterial Lipopolysaccharide in Humans

    Science.gov (United States)

    Rahman, Shadab A.; Castanon-Cervantes, Oscar; Scheer, Frank A.J.L.; Shea, Steven A.; Czeisler, Charles A.; Davidson, Alec J.; Lockley, Steven W.

    2015-01-01

    Various aspects of immune response exhibit 24-hour variations suggesting that infection susceptibility and treatment efficacy may vary by time of day. Whether these 24-hour variations are endogenous or evoked by changes in environmental or behavioral conditions is not known. We assessed the endogenous circadian control and environmental and behavioral influences on ex-vivo lipopolysaccharide stimulation of whole blood in thirteen healthy participants under 48 hours of baseline conditions with standard sleep-wake schedules and 40–50 hours of constant environmental and behavioral (constant routine; CR) conditions. Significant 24-hour rhythms were observed under baseline conditions in Monocyte Chemotactic Protein, Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin 8 but not Tumor Necrosis Factor alpha whereas significant 24-hour rhythms were observed in all four immune factors under CR conditions. The rhythm amplitudes, expressed as a percentage of mean, were comparable between immune factors and across conditions. In contrast, the acrophase time (time of the fitted peak) was different between immune factors, and included daytime and nighttime peaks and changes across behavioral conditions. These results suggest that the endogenous circadian system underpins the temporal organization of immune responses in humans with additional effects of external environmental and behavioral cycles. These findings have implications for understanding the adverse effects of recurrent circadian disruption and sleep curtailment on immune function. PMID:25452149

  7. Relevance of Electrical Remodeling in Human Atrial Fibrillation Results of the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial Mechanisms of Atrial Fibrillation Study

    NARCIS (Netherlands)

    Healey, Jeff S.; Israel, Carsten W.; Connolly, Stuart J.; Hohnloser, Stefan H.; Nair, Girish M.; Divakaramenon, Syamkumar; Capucci, Alessandro; Van Gelder, Isabelle C.; Lau, Chu-Pak; Gold, Michael R.; Carlson, Mark; Themeles, Ellison; Morillo, Carlos A.

    Background-In animal models of atrial fibrillation (AF), changes in atrial electrophysiological properties are associated with the development of AF. Their relevance to human AF is unclear. Methods and Results-The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the

  8. Molecular Mechanisms of Circadian Regulation During Spaceflight

    Science.gov (United States)

    Zanello, S. B.; Boyle, R.

    2012-01-01

    The physiology of both vertebrates and invertebrates follows internal rhythms coordinated in phase with the 24-hour daily light cycle. This circadian clock is governed by a central pacemaker, the suprachiasmatic nucleus (SCN) in the brain. However, peripheral circadian clocks or oscillators have been identified in most tissues. How the central and peripheral oscillators are synchronized is still being elucidated. Light is the main environmental cue that entrains the circadian clock. Under the absence of a light stimulus, the clock continues its oscillation in a free-running condition. In general, three functional compartments of the circadian clock are defined. The vertebrate retina contains endogenous clocks that control many aspects of retinal physiology, including retinal sensitivity to light, neurohormone synthesis (melatonin and dopamine), rod disk shedding, signalling pathways and gene expression. Neurons with putative local circadian rhythm generation are found among all the major neuron populations in the mammalian retina. In the mouse, clock genes and function are more localized to the inner retinal and ganglion cell layers. The photoreceptor, however, secrete melatonin which may still serve a an important circadian signal. The reception and transmission of the non-visual photic stimulus resides in a small subpopulation (1-3%) or retinal ganglion cells (RGC) that express the pigment melanopsin (Opn4) and are called intrisically photoreceptive RGC (ipRGC). Melanopsin peak absorption is at 420 nm and all the axons of the ipRGC reach the SCN. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate the risk of fatigue and health and performance decrement due to circadian rhythm disruption. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. We hypothesize that spaceflight may affect ip

  9. Physiological links of circadian clock and biological clock of aging.

    Science.gov (United States)

    Liu, Fang; Chang, Hung-Chun

    2017-07-01

    Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self-sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurodegenerative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resembled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.

  10. Human responses to bright light of different durations.

    Science.gov (United States)

    Chang, Anne-Marie; Santhi, Nayantara; St Hilaire, Melissa; Gronfier, Claude; Bradstreet, Dayna S; Duffy, Jeanne F; Lockley, Steven W; Kronauer, Richard E; Czeisler, Charles A

    2012-07-01

    Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

  11. Day-night contrast as source of health for the human circadian system.

    Science.gov (United States)

    Martinez-Nicolas, Antonio; Madrid, Juan Antonio; Rol, Maria Angeles

    2014-04-01

    Modern societies are characterized by a 24/7 lifestyle (LS) with no environmental differences between day and night, resulting in weak zeitgebers (weak day light, absence of darkness during night, constant environmental temperature, sedentary LS and frequent snacking), and as a consequence, in an impaired circadian system (CS) through a process known as chronodisruption. Both weak zeitgebers and CS impairment are related to human pathologies (certain cancers, metabolic syndrome and affective and cognitive disorders), but little is known about how to chronoenhance the CS. The aim of this work is to propose practical strategies for chronoenhancement, based on accentuating the day/night contrast. For this, 131 young subjects were recruited, and their wrist temperature (WT), activity, body position, light exposure, environmental temperature and sleep were recorded under free-living conditions for 1 week. Subjects with high contrast (HC) and low contrast (LC) for each variable were selected to analyze the HC effect in activity, body position, environmental temperature, light exposure and sleep would have on WT. We found that HC showed better rhythms than LC for every variable except sleep. Subjects with HC and LC for WT also demonstrated differences in LS, where HC subjects had a slightly advanced night phase onset and a general increase in day/night contrast. In addition, theoretical high day/night contrast calculated using mathematical models suggests an improvement by means of LS contrast. Finally, some individuals classified as belonging to the HC group in terms of WT when they are exposed to the LS characteristic of the LC group, while others exhibit WT arrhythmicity despite their good LS habits, revealing two different WT components: an exogenous component modified by LS and another endogenous component that is refractory to it. Therefore, intensifying day/night contrast in subject's LS has proven to be a feasible measure to chronoenhance the CS.

  12. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

    OpenAIRE

    Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

    2017-01-01

    Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Droso...

  13. Insights into the role of the habenular circadian clock in addiction

    Directory of Open Access Journals (Sweden)

    Nora L Salaberry

    2016-01-01

    Full Text Available Drug addiction is a brain disease involving alterations in anatomy and functional neural communication. Drug intake and toxicity show daily rhythms in both humans and rodents. Evidence concerning the role of clock genes in drug intake has been previously reported. However, the implication of a timekeeping brain locus is much less known. The epithalamic lateral habenula (LHb is now emerging as a key nucleus in drug intake and addiction. This brain structure modulates the activity of dopaminergic neurons from the ventral tegmental area, a central part of the reward system. Moreover, the LHb has circadian properties: LHb cellular activity (i.e., firing rate and clock genes expression oscillates in a 24h range, and the nucleus is affected by photic stimulation and has anatomical connections with the main circadian pacemaker, the suprachiasmatic nucleus. Here, we describe the current insights on the role of the LHb as a circadian oscillator and its possible implications on the rhythmic regulation of the dopaminergic activity and drug intake. This data could inspire new strategies to treat drug addiction, considering circadian timing as a principal factor.

  14. Circadian rhythms and reproduction.

    Science.gov (United States)

    Boden, Michael J; Kennaway, David J

    2006-09-01

    There is a growing recognition that the circadian timing system, in particular recently discovered clock genes, plays a major role in a wide range of physiological systems. Microarray studies, for example, have shown that the expression of hundreds of genes changes many fold in the suprachiasmatic nucleus, liver heart and kidney. In this review, we discuss the role of circadian rhythmicity in the control of reproductive function in animals and humans. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance, but there are sufficient redundancies in their function that many of the knockout mice produced do not show overt reproductive failure. Furthermore, important strain differences have emerged from the studies especially between the various Clock (Circadian Locomotor Output Cycle Kaput) mutant strains. Nevertheless, there is emerging evidence that the primary clock genes, Clock and Bmal1 (Brain and Muscle ARNT-like protein 1, also known as Mop3), strongly influence reproductive competency. The extent to which the circadian timing system affects human reproductive performance is not known, in part, because many of the appropriate studies have not been done. With the role of Clock and Bmal1 in fertility becoming clearer, it may be time to pursue the effect of polymorphisms in these genes in relation to the various types of infertility in humans.

  15. Circadian Rhythms in Diet-Induced Obesity.

    Science.gov (United States)

    Engin, Atilla

    2017-01-01

    The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronizes these with daily cycles, feeding patterns also regulates circadian clocks. The clock genes and adipocytokines show circadian rhythmicity. Dysfunction of these genes are involved in the alteration of these adipokines during the development of obesity. Food availability promotes the stimuli associated with food intake which is a circadian oscillator outside of the suprachiasmatic nucleus (SCN). Its circadian rhythm is arranged with the predictable daily mealtimes. Food anticipatory activity is mediated by a self-sustained circadian timing and its principal component is food entrained oscillator. However, the hypothalamus has a crucial role in the regulation of energy balance rather than food intake. Fatty acids or their metabolites can modulate neuronal activity by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. The timing of three-meal schedules indicates close association with the plasma levels of insulin and preceding food availability. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition can lead to uncoupling of peripheral clocks from the central pacemaker and to the development of metabolic disorders. Metabolic dysfunction is associated with circadian disturbances at both central and peripheral levels and, eventual disruption of circadian clock functioning can lead to obesity. While CLOCK expression levels are increased with high fat diet-induced obesity, peroxisome proliferator-activated receptor (PPAR) alpha increases the transcriptional level of brain and muscle ARNT-like 1 (BMAL1) in obese subjects. Consequently, disruption of clock genes results in dyslipidemia, insulin resistance and obesity. Modifying the time of feeding alone can greatly affect body weight. Changes in the circadian clock are associated with temporal alterations in

  16. Radiation effect on implanted pacemakers

    International Nuclear Information System (INIS)

    Pourhamidi, A.H.

    1983-01-01

    It was previously thought that diagnostic or therapeutic ionizing radiation did not have an adverse effect on the function of cardiac pacemakers. Recently, however, some authors have reported damaging effect of therapeutic radiation on cardiac pulse generators. An analysis of a recently-extracted pacemaker documented the effect of radiation on the pacemaker pulse generator

  17. Circadian rhythms and metabolic syndrome: from experimental genetics to human disease.

    Science.gov (United States)

    Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

    2010-02-19

    The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal clock system, and sleep, constitute risk factors for disorders including obesity, diabetes mellitus, cardiovascular disease, thrombosis and even inflammation. An exciting aspect of the field has been the integration of behavioral and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics.

  18. A novel algorithm for detecting human circadian rhythms using a thoracic temperature sensor

    Directory of Open Access Journals (Sweden)

    Aly Chkeir

    2017-07-01

    Full Text Available Circadian rhythms undergo high perturbations due to cancer progression and worsening of metabolic diseases. This paper proposes an original method for detecting such perturbations using a novel thoracic temperature sensor. Such an infrared sensor records the skin temperature every five minutes, although some data might be missing. In this pilot study, five control subjects were evaluated over four days of recordings. In order to overcome the problem of missing data, first four different interpolation methods were compared. Using interpolation helps covering the gaps and extending the recordings frequency, subsequently prolonging sensor battery life. Afterwards, a Cosinor model was proposed to characterize circadian rhythms, and extract relevant parameters, with their confidence limits. A divergence study is then performed to detect changes in these parameters. The results are promising, supporting the enlargement of the sample size and warranting further assessment in cancer patients.

  19. Circadian rhythms and metabolic syndrome: from experimental genetics to human disease

    OpenAIRE

    Maury, Eleonore; Ramsey, Kathryn Moynihan; Bass, Joseph

    2010-01-01

    The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal ...

  20. Relationships between the circadian system and Alzheimer's disease-like symptoms in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dani M Long

    Full Text Available Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer's disease (AD, are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-β (Aβ peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing Aβ peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per01. No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived Aβ peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic Aβ peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of Aβ peptides causes rhythm degradation downstream from the central clock mechanism.

  1. Waiting for a pacemaker

    DEFF Research Database (Denmark)

    Risgaard, Bjarke; Elming, Hanne; Jensen, Gunnar

    2012-01-01

    AIMS: To determine waiting period-related morbidity, mortality, and adverse events in acute patients waiting for a permanent pacemaker (PPM).METHODS AND RESULTS: A retrospective chart review of all PPM implantations in Region Zealand, Denmark, in 2009 was conducted. Patients were excluded...... at least one adverse event during the waiting period. The present study indicates that a waiting period is dangerous as it is associated with an increased risk of adverse events. Acute PPMs should be implanted with a 24-h pacemaker implantation service capacity....

  2. Atrioventricular Pacemaker Lead Reversal

    Directory of Open Access Journals (Sweden)

    Mehmet K Aktas, MD

    2007-01-01

    Full Text Available During cardiac surgery temporary epicardial atrial and ventricular leads are placed in case cardiac pacing is required postoperatively. We present the first reported series of patients with reversal of atrioventricular electrodes in the temporary pacemaker without any consequent deleterious hemodynamic effect. We review the electrocardiographic findings and discuss the findings that lead to the discovery of atrioventricular lead reversal.

  3. Circadian disorganization alters intestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Robin M Voigt

    Full Text Available Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.

  4. A longitudinal assessment of sleep timing, circadian phase, and phase angle of entrainment across human adolescence.

    Directory of Open Access Journals (Sweden)

    Stephanie J Crowley

    Full Text Available The aim of this descriptive analysis was to examine sleep timing, circadian phase, and phase angle of entrainment across adolescence in a longitudinal study design. Ninety-four adolescents participated; 38 (21 boys were 9-10 years ("younger cohort" and 56 (30 boys were 15-16 years ("older cohort" at the baseline assessment. Participants completed a baseline and then follow-up assessments approximately every six months for 2.5 years. At each assessment, participants wore a wrist actigraph for at least one week at home to measure self-selected sleep timing before salivary dim light melatonin onset (DLMO phase - a marker of the circadian timing system - was measured in the laboratory. Weekday and weekend sleep onset and offset and weekend-weekday differences were derived from actigraphy. Phase angles were the time durations from DLMO to weekday sleep onset and offset times. Each cohort showed later sleep onset (weekend and weekday, later weekend sleep offset, and later DLMO with age. Weekday sleep offset shifted earlier with age in the younger cohort and later in the older cohort after age 17. Weekend-weekday sleep offset differences increased with age in the younger cohort and decreased in the older cohort after age 17. DLMO to sleep offset phase angle narrowed with age in the younger cohort and became broader in the older cohort. The older cohort had a wider sleep onset phase angle compared to the younger cohort; however, an age-related phase angle increase was seen in the younger cohort only. Individual differences were seen in these developmental trajectories. This descriptive study indicated that circadian phase and self-selected sleep delayed across adolescence, though school-day sleep offset advanced until no longer in high school, whereupon offset was later. Phase angle changes are described as an interaction of developmental changes in sleep regulation interacting with psychosocial factors (e.g., bedtime autonomy.

  5. Device orientation of a leadless pacemaker and subcutaneous implantable cardioverter-defibrillator in canine and human subjects and the effect on intrabody communication

    NARCIS (Netherlands)

    Quast, Anne-Floor B. E.; Tjong, Fleur V. Y.; Koop, Brendan E.; Wilde, Arthur A. M.; Knops, Reinoud E.; Burke, Martin C.

    2018-01-01

    The development of communicating modular cardiac rhythm management systems relies on effective intrabody communication between a subcutaneous implantable cardioverter-defibrillator (S-ICD) and a leadless pacemaker (LP), using conducted communication. Communication success is affected by the LP and

  6. Pacemakers charging using body energy

    Directory of Open Access Journals (Sweden)

    Dinesh Bhatia

    2010-01-01

    Full Text Available Life-saving medical implants like pacemakers and defibrillators face a big drawback that their batteries eventually run out and patients require frequent surgery to have these batteries replaced. With the advent of technology, alternatives can be provided for such surgeries. To power these devices, body energy harvesting techniques may be employed. Some of the power sources are patient′s heartbeat, blood flow inside the vessels, movement of the body parts, and the body temperature (heat. Different types of sensors are employed, such as for sensing the energy from the heartbeat the piezoelectric and semiconducting coupled nanowires are used that convert the mechanical energy into electricity. Similarly, for sensing the blood flow energy, nanogenerators driven by ultrasonic waves are used that have the ability to directly convert the hydraulic energy in human body to electrical energy. Another consideration is to use body heat employing biothermal battery to generate electricity using multiple arrays of thermoelectric generators built into an implantable chip. These generators exploit the well-known thermocouple effect. For the biothermal device to work, it needs a 2°C temperature difference across it. But there are many parts of the body where a temperature difference of 5°C exists - typically in the few millimeters just below the skin, where it is planned to place this device. This study focuses on using body heat as an alternative energy source to recharge pacemaker batteries and other medical devices and prevent the possibility of life-risk during repeated surgery.

  7. Pacemakers charging using body energy

    Science.gov (United States)

    Bhatia, Dinesh; Bairagi, Sweeti; Goel, Sanat; Jangra, Manoj

    2010-01-01

    Life-saving medical implants like pacemakers and defibrillators face a big drawback that their batteries eventually run out and patients require frequent surgery to have these batteries replaced. With the advent of technology, alternatives can be provided for such surgeries. To power these devices, body energy harvesting techniques may be employed. Some of the power sources are patient's heartbeat, blood flow inside the vessels, movement of the body parts, and the body temperature (heat). Different types of sensors are employed, such as for sensing the energy from the heartbeat the piezoelectric and semiconducting coupled nanowires are used that convert the mechanical energy into electricity. Similarly, for sensing the blood flow energy, nanogenerators driven by ultrasonic waves are used that have the ability to directly convert the hydraulic energy in human body to electrical energy. Another consideration is to use body heat employing biothermal battery to generate electricity using multiple arrays of thermoelectric generators built into an implantable chip. These generators exploit the well-known thermocouple effect. For the biothermal device to work, it needs a 2°C temperature difference across it. But there are many parts of the body where a temperature difference of 5°C exists – typically in the few millimeters just below the skin, where it is planned to place this device. This study focuses on using body heat as an alternative energy source to recharge pacemaker batteries and other medical devices and prevent the possibility of life-risk during repeated surgery. PMID:21814432

  8. Device orientation of a leadless pacemaker and subcutaneous implantable cardioverter-defibrillator in canine and human subjects and the effect on intrabody communication.

    Science.gov (United States)

    Quast, Anne-Floor B E; Tjong, Fleur V Y; Koop, Brendan E; Wilde, Arthur A M; Knops, Reinoud E; Burke, Martin C

    2018-02-14

    The development of communicating modular cardiac rhythm management systems relies on effective intrabody communication between a subcutaneous implantable cardioverter-defibrillator (S-ICD) and a leadless pacemaker (LP), using conducted communication. Communication success is affected by the LP and S-ICD orientation. This study is designed to evaluate the orientation of the LP and S-ICD in canine subjects and measure success and threshold of intrabody communication. To gain more human insights, we will explore device orientation in LP and S-ICD patients. Canine subjects implanted with a prototype S-ICD and LP (both Boston Scientific, MA, USA) with anterior-posterior fluoroscopy images were included in this analysis. For comparison, a retrospective analysis of human S-ICD and LP patients was performed. The angle of the long axis of the LP towards the vertical axis of 0°, and distance between the coil and LP were measured. Twenty-three canine subjects were analysed. Median angle of the LP was 29° and median distance of the S-ICD coil to LP was 0.8 cm. All canine subjects had successful communication. The median communicating threshold was 2.5 V. In the human retrospective analysis, 72 LP patients and 100 S-ICD patients were included. The mean angle of the LP was 56° and the median distance between the S-ICD coil and LP was 4.6 cm. Despite the less favourable LP orientation in canine subjects, all communication attempts were successful. In the human subjects, we observed a greater and in theory more favourable LP angle towards the communication vector. These data suggests suitability of human anatomy for conductive intrabody communication.

  9. Ischemic stroke destabilizes circadian rhythms

    Directory of Open Access Journals (Sweden)

    Borjigin Jimo

    2008-10-01

    Full Text Available Abstract Background The central circadian pacemaker is a remarkably robust regulator of daily rhythmic variations of cardiovascular, endocrine, and neural physiology. Environmental lighting conditions are powerful modulators of circadian rhythms, but regulation of circadian rhythms by disease states is less clear. Here, we examine the effect of ischemic stroke on circadian rhythms in rats using high-resolution pineal microdialysis. Methods Rats were housed in LD 12:12 h conditions and monitored by pineal microdialysis to determine baseline melatonin timing profiles. After demonstration that the circadian expression of melatonin was at steady state, rats were subjected to experimental stroke using two-hour intralumenal filament occlusion of the middle cerebral artery. The animals were returned to their cages, and melatonin monitoring was resumed. The timing of onset, offset, and duration of melatonin secretion were calculated before and after stroke to determine changes in circadian rhythms of melatonin secretion. At the end of the monitoring period, brains were analyzed to determine infarct volume. Results Rats demonstrated immediate shifts in melatonin timing after stroke. We observed a broad range of perturbations in melatonin timing in subsequent days, with rats exhibiting onset/offset patterns which included: advance/advance, advance/delay, delay/advance, and delay/delay. Melatonin rhythms displayed prolonged instability several days after stroke, with a majority of rats showing a day-to-day alternation between advance and delay in melatonin onset and duration. Duration of melatonin secretion changed in response to stroke, and this change was strongly determined by the shift in melatonin onset time. There was no correlation between infarct size and the direction or amplitude of melatonin phase shifting. Conclusion This is the first demonstration that stroke induces immediate changes in the timing of pineal melatonin secretion, indicating

  10. Circadian Rhythms

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 11. Circadian Rhythms ... M Vaze1 Vijay Kumar Sharma1. Chronobiology Laboratory Evolutionary and Organismal Biology Unit, Jawaharlal Nehru Centre for Advanced Scientific Research Jakkur, PO Box 6436, Bangalore 560 064, India.

  11. Circadian Rhythms

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 2. Circadian Rhythms: Why do ... Nikhil Vijay Kumar Sharma1. Chronobiology Laboratory Evolutionary and Organismal Biology Unit Jawaharlal Nehru Centre for Advanced Scientific Research Jakkur, PO Box 6436, Bangalore 560 064, India.

  12. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    and clocks driving such rhythms have been studied for a long time now, our ... passage of time using near 24 h oscillation as a reference process, and (iii) Output .... Bünning's work on circadian rhythms across model systems ranging from ..... E Bünning, The Physiological Clock, Revised 3rd Edition, The English. Universities ...

  13. Circadian Rhythms

    Indian Academy of Sciences (India)

    IAS Admin

    Early studies on circadian rhythms focussed on unravelling the fundamental .... careful analysis revealed that deaths of most arrhythmic indi- viduals were due to .... is no more a sci-fi movie script and is achievable through a technique called ...

  14. Circadian Control of the Estrogenic Circuits Regulating GnRH Secretion and the Preovulatory Luteinizing Hormone Surge

    Directory of Open Access Journals (Sweden)

    Lance J Kriegsfeld

    2012-05-01

    Full Text Available Female reproduction requires the precise temporal organization of interacting, estradiol-sensitive neural circuits that converge to optimally drive hypothalamo-pituitary-gonadal (HPG axis functioning. In mammals, the master circadian pacemaker in the suprachaismatic nucleus (SCN of the anterior hypothalamus coordinates reproductively-relevant neuroendocrine events necessary to maximize reproductive success. Likewise, in species where periods of fertility are brief, circadian oversight of reproductive function ensures that estradiol-dependent increases in sexual motivation coincide with ovulation. Across species, including humans, disruptions to circadian timing (e.g., through rotating shift work, night shift work, poor sleep hygiene lead to pronounced deficits in ovulation and fecundity. Despite the well-established roles for the circadian system in female reproductive functioning, the specific neural circuits and neurochemical mediators underlying these interactions are not fully understood. Most work to date has focused on the direct and indirect communication from the SCN to the GnRH system in control of the preovulatory LH surge. However, the same clock genes underlying circadian rhythms at the cellular level in SCN cells are also common to target cell populations of the SCN, including the GnRH neuronal network. Exploring the means by which the master clock synergizes with subordinate clocks in GnRH cells and its upstream modulatory systems represents an exciting opportunity to further understand the role of endogenous timing systems in female reproduction. Herein we provide an overview of the state of knowledge regarding interactions between the circadian timing system and estradiol-sensitive neural circuits driving GnRH secretion and the preovulatory LH surge.

  15. [Sport for pacemaker patients].

    Science.gov (United States)

    Israel, C W

    2012-06-01

    Sport activity is an important issue in many patients with a pacemaker either because they performed sport activities before pacemaker implantation to reduce the cardiovascular risk or to improve the course of an underlying cardiovascular disease (e.g. coronary artery disease, heart failure) by sports. Compared to patients with an implantable cardioverter defibrillator (ICD) the risks from underlying cardiovascular disease (e.g. ischemia, heart failure), arrhythmia, lead dysfunction or inappropriate therapy are less important or absent. Sport is contraindicated in dyspnea at rest, acute heart failure, new complex arrhythmia, acute myocarditis and acute myocardial infarction, valvular disease with indications for intervention and surgery and comorbidities which prevent physical activity. Patients with underlying cardiovascular disease (including hypertension) should preferably perform types and levels of physical activity that are aerobic (with dynamic exercise) such as running, swimming, cycling instead of sport with high anaerobic demands and high muscular workload. In heart failure, studies demonstrated advantages of isometric sport that increases the amount of muscle, thereby preventing cardiac cachexia. Sport with a risk of blows to the chest or physical contact (e.g. boxing, rugby, martial arts) should be avoided. Implantation, programming and follow-up should respect specific precautions to allow optimal physical activity with a pacemaker including implantation of bipolar leads on the side contralateral to the dominant hand, individual programming of the upper sensor and tracking rate and regular exercise testing.

  16. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators

    Science.gov (United States)

    Saini, Camille; Morf, Jörg; Stratmann, Markus; Gos, Pascal; Schibler, Ueli

    2012-01-01

    The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles. PMID:22379191

  17. Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators.

    Science.gov (United States)

    Saini, Camille; Morf, Jörg; Stratmann, Markus; Gos, Pascal; Schibler, Ueli

    2012-03-15

    The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles.

  18. CIRCADIAN REGULATION METABOLIC SIGNALING MECHANISMS OF HUMAN BREAST CANCER GROWTH BY THE NOCTURNAL MELATONIN SIGNAL AND THE CONSEQUENCES OF ITS DISRUPTION BY LIGHT AT NIGHT

    Science.gov (United States)

    Blask, David E.; Hill, Steven M.; Dauchy, Robert T.; Xiang, Shulin; Yuan, Lin; Duplessis, Tamika; Mao, Lulu; Dauchy, Erin; Sauer, Leonard A.

    2011-01-01

    This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular, dietary and metabolic signaling mechanisms involved in human breast cancer growth and the consequences of circadian disruption by exposure to light-at-night (LAN). The antiproliferative effects of the circadian melatonin signal are mediated through a major mechanism involving the activation of MT1 melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor (ERα+) human breast cancer cells, melatonin suppresses both ERα mRNA expression and estrogen-induced transcriptional activity of the ERα via MT1-induced activation of Gαi2 signaling and reduction of cAMP levels. Melatonin also regulates the transactivation of additional members of the steroid hormone/nuclear receptor super-family, enzymes involved in estrogen metabolism, expression/activation of telomerase and the expression of core clock and clock-related genes. The anti-invasive/anti-metastatic actions of melatonin involve the blockade of p38 phosphorylation and the expression of matrix metalloproteinases. Melatonin also inhibits the growth of human breast cancer xenografts via another critical pathway involving MT1-mediated suppression of cAMP leading to blockade of linoleic acid (LA) uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Down-regulation of 13-HODE reduces the activation of growth factor pathways supporting cell proliferation and survival. Experimental evidence in rats and humans indicating that LAN-induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism and signaling provides the strongest mechanistic support, thus far, for population and ecological studies demonstrating elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN. PMID:21605163

  19. Trends in Cardiac Pacemaker Batteries

    Directory of Open Access Journals (Sweden)

    Venkateswara Sarma Mallela

    2004-10-01

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

  20. Metabolic Compensation and Circadian Resilience in Prokaryotic Cyanobacteria

    Science.gov (United States)

    Johnson, Carl Hirschie; Egli, Martin

    2014-01-01

    For a biological oscillator to function as a circadian pacemaker that confers a fitness advantage, its timing functions must be stable in response to environmental and metabolic fluctuations. One such stability enhancer, temperature compensation, has long been a defining characteristic of these timekeepers. However, an accurate biological timekeeper must also resist changes in metabolism, and this review suggests that temperature compensation is actually a subset of a larger phenomenon, namely metabolic compensation, which maintains the frequency of circadian oscillators in response to a host of factors that impinge on metabolism and would otherwise destabilize these clocks. The circadian system of prokaryotic cyanobacteria is an illustrative model because it is composed of transcriptional and nontranscriptional oscillators that are coupled to promote resilience. Moreover, the cyanobacterial circadian program regulates gene activity and metabolic pathways, and it can be manipulated to improve the expression of bioproducts that have practical value. PMID:24905782

  1. Introduction: circadian rhythm and its disruption: impact on reproductive function.

    Science.gov (United States)

    Casper, Robert F; Gladanac, Bojana

    2014-08-01

    Almost all forms of life have predictable daily or circadian rhythms in molecular, endocrine, and behavioral functions. In mammals, a central pacemaker located in the suprachiasmatic nuclei coordinates the timing of these rhythms. Daily light exposure that affects the retina of the eye directly influences this area, which is required to align endogenous processes to the appropriate time of day. The present "Views and Reviews" articles discuss the influence of circadian rhythms, especially nightly secretion of melatonin, on reproductive function and parturition. In addition, an examination is made of problems that arise from recurrent circadian rhythm disruption associated with changes in light exposure patterns common to modern day society. Finally, a possible solution to prevent disruptions in circadian phase markers by filtering out short wavelengths from nocturnal light is reviewed. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Pacemaker Use Following Heart Transplantation

    Science.gov (United States)

    Mallidi, Hari R.; Bates, Michael

    2017-01-01

    Background: The incidence of permanent pacemaker implantation after orthotopic heart transplantation has been reported to be 2%-24%. Transplanted hearts usually exhibit sinus rhythm in the operating room following reperfusion, and most patients do not exhibit significant arrhythmias during the postoperative period. However, among the patients who do exhibit abnormalities, pacemakers may be implanted for early sinus node dysfunction but are rarely used after 6 months. Permanent pacing is often required for atrioventricular block. A different cohort of transplant patients presents later with bradycardia requiring pacemaker implantation, reported to occur in approximately 1.5% of patients. The objectives of this study were to investigate the indications for pacemaker implantation, compare the need for pacemakers following bicaval vs biatrial anastomosis, and examine the long-term outcomes of heart transplant patients who received pacemakers. Methods: For this retrospective, case-cohort, single-institution study, patients were identified from clinical research and administrative transplant databases. Information was supplemented with review of the medical records. Standard statistical techniques were used, with chi-square testing for categorical variables and the 2-tailed t test for continuous variables. Survival was compared with the use of log-rank methods. Results: Between January 1968 and February 2008, 1,450 heart transplants were performed at Stanford University. Eighty-four patients (5.8%) were identified as having had a pacemaker implanted. Of these patients, 65.5% (55) had the device implanted within 30 days of transplantation, and 34.5% (29) had late implantation. The mean survival of patients who had an early pacemaker implant was 6.4 years compared to 7.7 years for those with a late pacemaker implant (Ppacemaker implantation. Starting in 1997, a bicaval technique was used for implantation. The incidence of pacemaker implantation by technique was 2.0% for

  3. [Effect of Earth magnetic field on circadian rhythm of total antioxidant capacity of human saliva in the North].

    Science.gov (United States)

    Borisenkov, M F

    2007-01-01

    In the inhabitants of the North during increase of geomagnetic activity and during magnetic calm the decrease of amplitude of circadian rhythm of total antioxidant capacity of saliva is observed. The most favorable conditions to display the circadian rhythm are observed at Kp from 0,5 up to 2. The long residing in the North is connected to influence of irregularly varying geomagnetic activity causing disturbance of function of circadian and antioxidant systems that, probably, is one of the reasons of acceleration of process of aging at northerner and of higher risk of occurrence in them the age associated diseases.

  4. Neurogenetics of Drosophila circadian clock: expect the unexpected.

    Science.gov (United States)

    Jarabo, Patricia; Martin, Francisco A

    2017-12-01

    Daily biological rhythms (i.e. circadian) are a fundamental part of animal behavior. Numerous reports have shown disruptions of the biological clock in neurodegenerative disorders and cancer. In the latter case, only recently we have gained insight into the molecular mechanisms. After 45 years of intense study of the circadian rhtythms, we find surprising similarities among species on the molecular clock that governs biological rhythms. Indeed, Drosophila is one of the most widely used models in the study of chronobiology. Recent studies in the fruit fly have revealed unpredicted roles for the clock machinery in different aspects of behavior and physiology. Not only the central pacemaker cells do have non-classical circadian functions but also circadian genes work in other cells and tissues different from central clock neurons. In this review, we summarize these new evidences. We also recapitulate the most basic features of Drosophila circadian clock, including recent data about the inputs and outputs that connect the central pacemaker with other regions of the brain. Finally, we discuss the advantages and drawbacks of using natural versus laboratory conditions.

  5. A Screening of UNF Targets Identifies Rnb, a Novel Regulator of Drosophila Circadian Rhythms.

    Science.gov (United States)

    Kozlov, Anatoly; Jaumouillé, Edouard; Machado Almeida, Pedro; Koch, Rafael; Rodriguez, Joseph; Abruzzi, Katharine C; Nagoshi, Emi

    2017-07-12

    Behavioral circadian rhythms are controlled by multioscillator networks comprising functionally different subgroups of clock neurons. Studies have demonstrated that molecular clocks in the fruit fly Drosophila melanogaster are regulated differently in clock neuron subclasses to support their specific functions (Lee et al., 2016; Top et al., 2016). The nuclear receptor unfulfilled ( unf ) represents a regulatory node that provides the small ventral lateral neurons (s-LNvs) unique characteristics as the master pacemaker (Beuchle et al., 2012). We previously showed that UNF interacts with the s-LNv molecular clocks by regulating transcription of the core clock gene period ( per ) (Jaumouillé et al., 2015). To gain more insight into the mechanisms by which UNF contributes to the functioning of the circadian master pacemaker, we identified UNF target genes using chromatin immunoprecipitation. Our data demonstrate that a previously uncharacterized gene CG7837 , which we termed R and B ( Rnb ), acts downstream of UNF to regulate the function of the s-LNvs as the master circadian pacemaker. Mutations and LNv-targeted adult-restricted knockdown of Rnb impair locomotor rhythms. RNB localizes to the nucleus, and its loss-of-function blunts the molecular rhythms and output rhythms of the s-LNvs, particularly the circadian rhythms in PDF accumulation and axonal arbor remodeling. These results establish a second pathway by which UNF interacts with the molecular clocks in the s-LNvs and highlight the mechanistic differences in the molecular clockwork within the pacemaker circuit. SIGNIFICANCE STATEMENT Circadian behavior is generated by a pacemaker circuit comprising diverse classes of pacemaker neurons, each of which contains a molecular clock. In addition to the anatomical and functional diversity, recent studies have shown the mechanistic differences in the molecular clockwork among the pacemaker neurons in Drosophila Here, we identified the molecular characteristics

  6. Regulation of reproduction by the circadian rhythms.

    Science.gov (United States)

    Zhang, Wen-Xiang; Chen, Si-Yu; Liu, Chang

    2016-12-25

    Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. Circadian rhythm is controlled by the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and the peripheral clocks in various tissues. More importantly, the central clock can integrate photic/nonphotic signals to generate rhythmic outputs, and then drive the slave oscillators in peripheral tissues through neuroendocrine and behavioral signals. Human reproductive activities, as some other physiological functions, are controlled by the biological clocks. Accumulating lines of epidemiological and genetic evidence indicate that disruption of circadian clock can be directly involved in multiple pathological processes, including infertility. In this review, we mainly discuss the presence of a circadian clock in reproductive tissues and its roles in follicles development, ovulation, spermatogenesis, fertilization and embryo implantation, etc. As the increased shift work and assisted reproductive technologies possibly disrupt circadian rhythmicity to impact reproduction, the importance of circadian rhythms should be highlighted in the regulation of reproductive process.

  7. 1978 Pacemaker Newspaper Awards: What Makes a Pacemaker?

    Science.gov (United States)

    Brasler, Wayne

    1979-01-01

    Lists the nine high school and college newspapers, and the one newsmagazine, that won Pacemaker Awards in 1978; discusses characteristics that make each of them outstanding, and provides reproductions of a front page from each publication. (GT)

  8. Circadian timekeeping : from basic clock function to implications for health

    NARCIS (Netherlands)

    Lucassen, Eliane Alinda

    2016-01-01

    In modern society, circadian rhythms and sleep are often disturbed, which may negatively affect health. This thesis examines these associations and focuses on the basic functioning of sleep and the circadian system in mice and in humans. Circadian rhythms are orchestrated by ~20,000 neurons in the

  9. A New Perspective for Parkinson's Disease: Circadian Rhythm.

    Science.gov (United States)

    Li, Siyue; Wang, Yali; Wang, Fen; Hu, Li-Fang; Liu, Chun-Feng

    2017-02-01

    Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative consequences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

  10. Pacemaker lead perforation of the right ventricle associated with Moraxella phenylpyruvica infection in a dog.

    Science.gov (United States)

    Ciavarella, A; Nimmo, J; Hambrook, L

    2016-04-01

    A 13-year-old neutered male Border Collie was presented with acute onset syncope, weakness and anorexia 10 months after transvenous pacemaker implantation. The patient was laterally recumbent, bradycardic (36 beats/min) and febrile (40.7°C) on presentation. An electrocardiogram (ECG) revealed recurrence of third-degree atrioventricular block with a ventricular escape rhythm. Fluoroscopy identified migration of the pacemaker tip through the apex of the right ventricle. Echocardiography failed to reveal any evidence of pericardial effusion or cardiac tamponade. Full postmortem was performed after euthanasia. The pacemaker lead had perforated the apex of the right ventricle and lodged in the right pleural space. Culture of blood (taken antemortem), pericardial sac, right ventricular wall (surrounding pacemaker lead), pacemaker lead tip and pericardial fluid revealed a pure growth of Moraxella phenylpyruvica. Bacteraemia associated with M. phenylpyruvica has never been reported in the dog, but sporadic cases are reported in humans. Infection could have resulted from either pre-existing myocarditis or opportunistic infection and bacteraemia post pacemaker implantation. Evaluation of the pacemaker function at regular intervals would allow early detection of poor pacemaker-to-myocardium contact, which would prompt further investigation of pacemaker lead abnormalities such as perforation. © 2016 Australian Veterinary Association.

  11. Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology.

    Science.gov (United States)

    Reiter, Russel J; Tan, Dun Xian; Korkmaz, Ahmet; Rosales-Corral, Sergio A

    2014-01-01

    Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on the peripheral reproductive organs. Likewise, numerous investigations have documented that stable circadian rhythms are also helpful in maintaining reproductive health. The relationship of melatonin and circadian rhythmicity to maternal and fetal health is summarized in this review. Databases were searched for the related published English literature up to 15 May 2013. The search terms used in various combinations included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress and free radicals. The results of the studies uncovered are summarized herein. Both melatonin and circadian rhythms impact reproduction, especially during pregnancy. Melatonin is a multifaceted molecule with direct free radical scavenging and indirect antioxidant activities. Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress. The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction. This may contribute to pre-eclampsia and other disorders which often complicate pregnancy. Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals. Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei. Optimal circadian rhythmicity in the mother is important since her

  12. Lab mice in the field : Unorthodox daily activity and effects of a dysfunctional circadian clock allele

    NARCIS (Netherlands)

    Daan, Serge; Spoelstra, Kamiel; Albrecht, Urs; Schmutz, Isabelle; Daan, Moritz; Daan, Berte; Rienks, Froukje; Poletaeva, Inga; Dell'Omo, Giacomo; Vyssotski, Alexei; Lipp, Hans-Peter; Omo, Giacomo Dell’

    Daily patterns of animal behavior are potentially of vast functional importance. Fitness benefits have been identified in nature by the association between individual timing and survival or by the fate of individuals after experimental deletion of their circadian pacemaker. The recent advances in

  13. Lab mice in the field: unorthodox daily activity and effects of a dysfunctional circadian clock allele

    NARCIS (Netherlands)

    Daan, S.; Spoelstra, K.; Albrecht, U.; Schmutz, I.; Daan, M.; Daan, B.; Rienks, F.; Poletaeva, I.; Dell'Omo, G.; Vyssotski, A.; Lipp, H.P.

    2011-01-01

    Daily patterns of animal behavior are potentially of vast functional importance. Fitness benefits have been identified in nature by the association between individual timing and survival or by the fate of individuals after experimental deletion of their circadian pacemaker. The recent advances in

  14. Extraocular light via the ear canal does not acutely affect human circadian physiology, alertness and psychomotor vigilance performance.

    Science.gov (United States)

    Bromundt, Vivien; Frey, Sylvia; Odermatt, Jonas; Cajochen, Christian

    2014-04-01

    We aimed at testing potential effects of extraocular bright light via the ear canals on human evening melatonin levels, sleepiness and psychomotor vigilance performance. Twenty healthy young men and women (10/10) kept a regular sleep-wake cycle during the 2-week study. The volunteers reported to the laboratory on three evenings, 2 h 15 min before usual bedtime, on average at 21:45 h. They were exposed to three different light conditions, each lasting for 12 min: extraocular bright light via the ear canal, ocular bright light as an active control condition and a control condition (extraocular light therapy device with completely blacked out LEDs). The timing of exposure was on average from 22:48 to 23:00 h. During the 2-h protocol, saliva samples were collected in 15-min intervals for melatonin assays along with subjective sleepiness ratings, and the volunteers performed a 10-min visual psychomotor vigilance task (PVT) prior to and after each light condition. The evening melatonin rise was significantly attenuated after the 12-min ocular bright light exposure while no significant changes were observed after the extraocular bright light and sham light condition. Subjective sleepiness decreased immediately over a short period only after ocular light exposure. No significant differences were observed for mean reaction times and the number of lapses for the PVT between the three light conditions. We conclude that extraocular transcranial light exposure in the late evening does not suppress melatonin, reduce subjective sleepiness or improve performance, and therefore, does not acutely influence the human circadian timing system.

  15. Development of the cardiac pacemaker

    Science.gov (United States)

    Liang, Xingqun; Evans, Sylvia M.

    2017-01-01

    The sinoatrial node (SAN) is the dominant pacemaker of the heart. Abnormalities in SAN formation and function can cause sinus arrhythmia, including sick sinus syndrome and sudden death. A better understanding of genes and signaling pathways that regulate SAN development and function is essential to develop more effective treatment to sinus arrhythmia, including biological pacemakers. In this review, we briefly summarize the key processes of SAN morphogenesis during development, and focus on the transcriptional network that drives SAN development. PMID:27770149

  16. Modeling the dual pacemaker system of the tau mutant hamster.

    Science.gov (United States)

    Oda, G A; Menaker, M; Friesen, W O

    2000-06-01

    Circadian pacemakers in many animals are compound. In rodents, a two-oscillator model of the pacemaker composed of an evening (E) and a morning (M) oscillator has been proposed based on the phenomenon of "splitting" and bimodal activity peaks. The authors describe computer simulations of the pacemaker in tau mutant hamsters viewed as a system of mutually coupled E and M oscillators. These mutant animals exhibit normal type 1 PRCs when released into DD but make a transition to a type 0 PRC when held for many weeks in DD. The two-oscillator model describes particularly well some recent behavioral experiments on these hamsters. The authors sought to determine the relationships between oscillator amplitude, period, PRC, and activity duration through computer simulations. Two complementary approaches proved useful for analyzing weakly coupled oscillator systems. The authors adopted a "distinct oscillators" view when considering the component E and M oscillators and a "system" view when considering the system as a whole. For strongly coupled systems, only the system view is appropriate. The simulations lead the authors to two primary conjectures: (1) the total amplitude of the pacemaker system in tau mutant hamsters is less than in the wild-type animals, and (2) the coupling between the unit E and M oscillators is weakened during continuous exposure of hamsters to DD. As coupling strength decreases, activity duration (alpha) increases due to a greater phase difference between E and M. At the same time, the total amplitude of the system decreases, causing an increase in observable PRC amplitudes. Reduced coupling also increases the relative autonomy of the unit oscillators. The relatively autonomous phase shifts of E and M oscillators can account for both immediate compression and expansion of activity bands in tau mutant and wild-type hamsters subjected to light pulses.

  17. The effect of lens aging and cataract surgery on circadian rhythm.

    Science.gov (United States)

    Yan, Shen-Shen; Wang, Wei

    2016-01-01

    Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment. Suprachiasmatic nucleus (SCN) is the central pacemaker of circadian rhythm, and its activity is entrained to the external light-dark cycle. The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway. Light, especially short-wavelength blue light, is the most potent environmental time cue in circadian photoentrainment. Recently, the discovery of a novel type of retinal photoreceptors, intrinsically photosensitive retinal ganglion cells, sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system. With age, light transmittance is significantly decreased due to the aging of crystalline lens, thus possibly resulting in progressive loss of circadian photoreception. In the current review, we summarize the circadian physiology, highlight the important role of light in circadian rhythm regulation, discuss about the correlation between age-related cataract and sleep disorders, and compare the effect of blue light- filtering intraocular lenses (IOLs) and ultraviolet only filtering IOLs on circadian rhythm.

  18. Circadian analysis of large human populations: inferences from the power grid.

    Science.gov (United States)

    Stowie, Adam C; Amicarelli, Mario J; Crosier, Caitlin J; Mymko, Ryan; Glass, J David

    2015-03-01

    Few, if any studies have focused on the daily rhythmic nature of modern industrialized populations. The present study utilized real-time load data from the U.S. Pacific Northwest electrical power grid as a reflection of human operative household activity. This approach involved actigraphic analyses of continuously streaming internet data (provided in 5 min bins) from a human subject pool of approximately 43 million primarily residential users. Rhythm analyses reveal striking seasonal and intra-week differences in human activity patterns, largely devoid of manufacturing and automated load interference. Length of the diurnal activity period (alpha) is longer during the spring than the summer (16.64 h versus 15.98 h, respectively; p job-related or other weekday morning arousal cues, substantiating a preference or need to sleep longer on weekends. Finally, a shift in onset time can be seen during the transition to Day Light Saving Time, but not the transition back to Standard Time. The use of grid power load as a means for human actimetry assessment thus offers new insights into the collective diurnal activity patterns of large human populations.

  19. Circadian remodeling of neuronal circuits involved in rhythmic behavior.

    Directory of Open Access Journals (Sweden)

    María Paz Fernández

    2008-03-01

    Full Text Available Clock output pathways are central to convey timing information from the circadian clock to a diversity of physiological systems, ranging from cell-autonomous processes to behavior. While the molecular mechanisms that generate and sustain rhythmicity at the cellular level are well understood, it is unclear how this information is further structured to control specific behavioral outputs. Rhythmic release of pigment dispersing factor (PDF has been proposed to propagate the time of day information from core pacemaker cells to downstream targets underlying rhythmic locomotor activity. Indeed, such circadian changes in PDF intensity represent the only known mechanism through which the PDF circuit could communicate with its output. Here we describe a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit, which display higher complexity during the day and significantly lower complexity at nighttime, both under daily cycles and constant conditions. In support to its circadian nature, cycling is lost in bona fide clockless mutants. We propose this clock-controlled structural plasticity as a candidate mechanism contributing to the transmission of the information downstream of pacemaker cells.

  20. Rhythms of mammalian body temperature can sustain peripheral circadian clocks.

    Science.gov (United States)

    Brown, Steven A; Zumbrunn, Gottlieb; Fleury-Olela, Fabienne; Preitner, Nicolas; Schibler, Ueli

    2002-09-17

    Low-amplitude temperature oscillations can entrain the phase of circadian rhythms in several unicellular and multicellular organisms, including Neurospora and Drosophila. Because mammalian body temperature is subject to circadian variations of 1 degrees C-4 degrees C, we wished to determine whether these temperature cycles could serve as a Zeitgeber for circadian gene expression in peripheral cell types. In RAT1 fibroblasts cultured in vitro, circadian gene expression could be established by a square wave temperature rhythm with a (Delta)T of 4 degrees C (12 hr 37 degrees C/12 hr 33 degrees C). To examine whether natural body temperature rhythms can also affect circadian gene expression, we first measured core body temperature cycles in the peritoneal cavities of mice by radiotelemetry. We then reproduced these rhythms with high precision in the liquid medium of cultured fibroblasts for several days by means of a homemade computer-driven incubator. While these "in vivo" temperature rhythms were incapable of establishing circadian gene expression de novo, they could maintain previously induced rhythms for multiple days; by contrast, the rhythms of control cells kept at constant temperature rapidly dampened. Moreover, circadian oscillations of environmental temperature could reentrain circadian clocks in the livers of mice, probably via the changes they imposed upon both body temperature and feeding behavior. Interestingly, these changes in ambient temperature did not affect the phase of the central circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. We postulate that both endogenous and environmental temperature cycles can participate in the synchronization of peripheral clocks in mammals.

  1. Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers

    NARCIS (Netherlands)

    Jacobs, Bart A W; Deenen, Maarten J; Pluim, Dick; van Hasselt, J G Coen; Krähenbühl, Martin D; van Geel, Robin M J M; de Vries, Niels; Rosing, Hilde; Meulendijks, Didier; Burylo, Artur M; Cats, Annemieke; Beijnen, Jos H; Huitema, Alwin D R; Schellens, Jan H M

    AIMS: The enzymatic activity of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important for the tolerability and efficacy of the fluoropyrimidine drugs. In the present study, we explored between-subject variability (BSV) and circadian rhythmicity in DPD and TS activity in

  2. Dynamical Analysis of bantam-Regulated Drosophila Circadian Rhythm Model

    Science.gov (United States)

    Li, Ying; Liu, Zengrong

    MicroRNAs (miRNAs) interact with 3‧untranslated region (UTR) elements of target genes to regulate mRNA stability or translation, and play a crucial role in regulating many different biological processes. bantam, a conserved miRNA, is involved in several functions, such as regulating Drosophila growth and circadian rhythm. Recently, it has been discovered that bantam plays a crucial role in the core circadian pacemaker. In this paper, based on experimental observations, a detailed dynamical model of bantam-regulated circadian clock system is developed to show the post-transcriptional behaviors in the modulation of Drosophila circadian rhythm, in which the regulation of bantam is incorporated into a classical model. The dynamical behaviors of the model are consistent with the experimental observations, which shows that bantam is an important regulator of Drosophila circadian rhythm. The sensitivity analysis of parameters demonstrates that with the regulation of bantam the system is more sensitive to perturbations, indicating that bantam regulation makes it easier for the organism to modulate its period against the environmental perturbations. The effectiveness in rescuing locomotor activity rhythms of mutated flies shows that bantam is necessary for strong and sustained rhythms. In addition, the biological mechanisms of bantam regulation are analyzed, which may help us more clearly understand Drosophila circadian rhythm regulated by other miRNAs.

  3. Wireless power transfer for a pacemaker application.

    Science.gov (United States)

    Vulfin, Vladimir; Sayfan-Altman, Shai; Ianconescu, Reuven

    2017-05-01

    An artificial pacemaker is a small medical device that uses electrical impulses, delivered by electrodes contracting the heart muscles, to regulate the beating of the heart. The pacemaker is implanted under the skin, and uses for many years regular non-rechargeable batteries. However, the demand for rechargeable batteries in pacemakers increased, and the aim of this work is to design an efficient charging system for pacemakers.

  4. Circadian adaptations to meal timing: Neuroendocrine mechanisms

    Directory of Open Access Journals (Sweden)

    Danica F Patton

    2013-10-01

    Full Text Available Circadian rhythms of behavior and physiology are generated by central and peripheral circadian oscillators entrained by periodic environmental or physiological stimuli. A master circadian pacemaker in the hypothalamic suprachiasmatic nucleus is directly entrained by daily light-dark cycles, and coordinates the timing of other oscillators by direct and indirect neural, hormonal and behavioral outputs. The daily rhythm of food intake provides stimuli that entrain most peripheral and central oscillators, some of which can drive a daily rhythm of food anticipatory activity if food is restricted to one daily mealtime. The location of food-entrainable oscillators (FEOs that drive food anticipatory rhythms, and the food-related stimuli that entrain these oscillators, remain to be clarified. Here, we critically examine the role of peripheral metabolic hormones as potential internal entrainment stimuli or outputs for FEOs controlling food anticipatory rhythms in rats and mice. Hormones for which data are available include corticosterone, ghrelin, leptin, insulin, glucagon, and glucagon-like peptide 1. All of these hormones exhibit daily rhythms of synthesis and secretion that are synchronized by meal timing. There is some evidence that ghrelin and leptin modulate the expression of food anticipatory rhythms, but none of the hormones examined so far are necessary for entrainment. Ghrelin and leptin likely modulate food-entrained rhythms by actions in hypothalamic circuits utilizing melanocortin and orexin signaling, although again food-entrained behavioral rhythms can persist in lesion and gene knockout models in which these systems are disabled. Actions of these hormones on circadian oscillators in central reward circuits remain to be evaluated. Food-entrained activity rhythms are likely mediated by a distributed system of circadian oscillators sensitive to multiple feeding related inputs. Metabolic hormones appear to play a modulatory role within this

  5. Cell-permeable Circadian Clock Proteins

    National Research Council Canada - National Science Library

    Johnson, Carl

    2002-01-01

    .... These 'biological clocks' are important to human physiology. For example, psychiatric and medical studies have shown that circadian rhythmicity is involved in some forms of depressive illness, 'jet lag', drug tolerance/efficacy, memory, and insomnia...

  6. Radioisotope-powered cardiac pacemaker program. Clinical studies of the nuclear pacemaker model NU-5. Final report

    International Nuclear Information System (INIS)

    1980-06-01

    Beginning in February, 1970, the Nuclear Materials and Equipment Corporation (NUMEC) undertook a program to design, develop and manufacture a radioisotope powered cardiac pacemaker system. The scope of technical work was specified to be: establish system, component, and process cost reduction goals using the prototype Radioisotope Powered Cardiac Pacemaker (RCP) design and develop production techniques to achieve these cost reduction objectives; fabricate radioisotope powered fueled prototype cardiac pacemakers (RCP's) on a pilot production basis; conduct liaison with a Government-designated fueling facility for purposes of defining fueling requirements, fabrication and encapsulation procedures, safety design criteria and quality control and inspection requirements; develop and implement Quality Assurance and Reliability Programs; conduct performance, acceptance, lifetime and reliability tests of fueled RCP's in the laboratory; conduct liaison with the National Institutes of Health and with Government specified medical research institutions selected for the purpose of undertaking clinical evaluation of the RCP in humans; monitor and evaluate, on a continuing basis, all test data; and perform necessary safety analyses and tests. Pacemaker designs were developed and quality assurance and manufacturing procedures established. Prototype pacemakers were fabricated. A total of 126 radioisotope powered units were implanted and have been followed clinically for approximately seven years. Four (4) of these units have failed. Eighty-three (83) units remain implanted and satisfactorily operational. An overall failure rate of less than the target 0.15% per month has been achieved

  7. 21 CFR 870.3670 - Pacemaker charger.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker charger. 870.3670 Section 870.3670 Food... DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a) Identification. A pacemaker charger is a device used transcutaneously to recharge the batteries of a rechargeable...

  8. 21 CFR 870.3700 - Pacemaker programmers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker programmers. 870.3700 Section 870.3700...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3700 Pacemaker programmers. (a) Identification. A pacemaker programmer is a device used to change noninvasively one or more of...

  9. Influencing programmable pacemakers by radiation therapy

    International Nuclear Information System (INIS)

    Wilm, M.; Kronholz, H.L.; Schuetz, J.; Koch, T.

    1994-01-01

    More than 300,000 pacemakers are implanted worldwide. During radiation therapy a damage of the pacemaker elektronic is possible. Twenty pacemakers have been irradiated with photons or electrons experimentally in three different situations: a) pacemaker and pacemaker electrode outside of the irradiation field; b) pacemaker outside, pacemaker electrode inside the irradiation field; c) all things inside the irradiation field. The voltage in the pacemaker electrode produced by the electric field of the accelerator did not exceed 0.8 mV if the electrode was outside the irradiation field. Induced voltage was up to 1.2 mV during irradiation with electrons (18 MeV) and the electrode being inside the treatment field with more than two thirds of its length. After delivering of not more than 10 Gy (photons) to the pacemaker, a decreasing amplitude of the pacemaker pulse occurred. The pulse frequency did not show any deviation. This seems to signal a severe early irreversible damage of the pacemaker that may cause sudden breakdown days or weeks after radiation. Two pacemakers showed a complete breakdown after irradiation with not more than 10 Gy. The others had a complete breakdown beyond doses of 50 Gy. (orig./MG) [de

  10. Influence of photoperiod and running wheel access on the entrainment of split circadian rhythms in hamsters

    Directory of Open Access Journals (Sweden)

    Elliott Jeffrey A

    2005-06-01

    Full Text Available Abstract Background In the laboratory, behavioral and physiological states of nocturnal rodents alternate, with a period near 24 h, between those appropriate for the night (e.g., elevated wheel-running activity and high melatonin secretion and for the day (e.g., rest and low melatonin secretion. Under appropriate 24 h light:dark:light:dark conditions, however, rodents may be readily induced to express bimodal rest/activity cycles that reflect a global temporal reorganization of the central neural pacemaker in the hypothalamus. We examine here how the relative length of the light and dark phases of the environmental cycle influences this rhythm splitting and the necessity of a running wheel for expression of this entrainment condition. Results Rhythm splitting was observed in wheel-running and general locomotion of Siberian and Syrian hamsters. The latter also manifest split rhythms in body temperature. Access to a running wheel was necessary neither for the induction nor maintenance of this entrainment pattern. While rhythms were only transiently split in many animals with two 5 h nights, the incidence of splitting was greater with twice daily nights of shorter duration. Removal of running wheels altered the body temperature rhythm but did not eliminate its clear bimodality. Conclusion The expression of entrained, split circadian rhythms exhibits no strict dependence on access to a running wheel, but can be facilitated by manipulation of ambient lighting conditions. These circadian entrainment patterns may be of therapeutic value to human shift-workers and others facing chronobiological challenges.

  11. Does high-power computed tomography scanning equipment affect the operation of pacemakers?

    International Nuclear Information System (INIS)

    Yamaji, Satoshi; Imai, Shinobu; Saito, Fumio; Yagi, Hiroshi; Kushiro, Toshio; Uchiyama, Takahisa

    2006-01-01

    Computed tomography (CT) is widely used in clinical practice, but there has not been a detailed report of its effect on the functioning of pacemakers. During CT, ECGs were recorded in 11 patients with pacemakers and the electromagnetic field in the CT room was also measured. The effect of CT on a pacemaker was also investigated in a human body model with and without shielding by rubber or lead. Transient malfunctions of pacemakers during CT occurred in 6 of 11 patients. The model showed that malfunctioning of the pacemaker was induced by CT scanning and this was prevented by lead but not by rubber. The alternating electrical field was 150 V/m on the CT scanning line, which was lower than the level influencing pacemaker functions. The alternating magnetic field was 15μT on the CT scanning line, which was also lower than the level influencing pacemaker functions. Malfunctions of the pacemaker during CT may be caused by diagnostic radiant rays and although they are transient, the possibility of lethal arrhythmia cannot be ignored. (author)

  12. Fifty years of pacemaker advancements.

    Science.gov (United States)

    Steinhaus, David

    2008-12-01

    A 1957 power blackout in Minnesota prompted C. Walton Lillehei, MD, a pioneer in open heart surgery, to ask Earl Bakken, the co-founder of Medtronic, Inc., to create a battery-operated pacemaker for pediatric patients. That conversation led to the development of the first external battery-operated pacemaker. That first bulky device is far removed from the tiny implantable computers available to heart patients today. Now, the size of two silver dollars stacked on top of one another, a pacemaker is prescribed for a person whose heart beats too slowly or pauses irregularly. Slightly larger devices have more recently evolved from pacing and regulating the heartbeat to being able to provide therapeutic high voltage shocks when needed to stop runaway fast heart rates, recording heart activity, and other physiologic functions, even resynchronizing the heart's chambers-all while providing information on the patient's condition and device performance to the doctor remotely or in the office.

  13. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2015-02-01

    Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright light duration?

    Science.gov (United States)

    Crowley, Stephanie J.; Eastman, Charmane I.

    2015-01-01

    OBJECTIVE Efficient treatments to phase advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. METHODS Fifty adults (27 males) aged 25.9±5.1 years participated. Sleep/dark was advanced 1 hour/day for 3 treatment days. Participants took 0.5 mg melatonin 5 hours before baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright light (~5000 lux) patterns upon waking each morning: four 30-minute exposures separated by 30 minutes of room light (2 h group); four 15-minute exposures separated by 45 minutes of room light (1 h group), and one 30-minute exposure (0.5 h group). Dim light melatonin onsets (DLMOs) before and after treatment determined the phase advance. RESULTS Compared to the 2 h group (phase shift=2.4±0.8 h), smaller phase advance shifts were seen in the 1 h (1.7±0.7 h) and 0.5 h (1.8±0.8 h) groups. The 2-hour pattern produced the largest phase advance; however, the single 30-minute bright light exposure was as effective as 1 hour of bright light spread over 3.25 h, and produced 75% of the phase shift observed with 2 hours of bright light. CONCLUSIONS A 30-minute morning bright light exposure with afternoon melatonin is an efficient treatment to phase advance human circadian rhythms. PMID:25620199

  15. Runaway pacemaker: a forgotten phenomenon?

    Science.gov (United States)

    Ortega, Daniel F; Sammartino, M Victoria; Pellegrino, Graciela M M; Barja, Luis D; Albina, Gaston; Segura, Eliseo V; Balado, Roberto; Laiño, Ruben; Giniger, Alberto G

    2005-11-01

    Runaway is an uncommon pacemaker dysfunction, characterized by fast and erratic spikes at non-physiological rates. This infrequent but potentially lethal failure mode may be related to low battery voltage. Four single chamber pacemaker patients were analyzed (Medtronic Minix ST 8330, Minneapolis, MN, had been implanted in two patients and two CPI Triumph VR 1124, St Paul, MN, in the other two). They had been admitted because of presyncopal episodes. Typical high rate stimuli at 2000 ppm alternating with pacing at 60-65 ppm were recorded in all ECGs. Lead system tests were normal. The pulse generators had to be replaced.

  16. Psychosocial responses of children to cardiac pacemakers.

    Science.gov (United States)

    Alpern, D; Uzark, K; Dick, M

    1989-03-01

    To examine the psychosocial responses of children and adolescents with a cardiac pacemaker and compare their responses to those of their peers, we evaluated 30 pediatric pacemaker patients, aged 7 to 19 years, and two age- and sex-matched comparison groups, including 30 patients with similar heart disease but without pacemakers and 30 physically healthy children, using standardized psychometric tests and a specific interview format. We postulated that children with pacemakers would experience greater stress in psychosocial adaptation. No significant differences on standardized measures of trait anxiety, self-competence, or self-esteem were found between the pacemaker group and the comparison groups. In contrast, pacemaker subjects were significantly (p less than 0.05) more external in their locus-of-control orientation than were healthy subjects, suggesting a diminished sense of personal control and less autonomy. Pacemaker subjects, particularly the older ones, had significantly (p less than 0.05) greater knowledge of pacemaker systems than did subjects in the other two groups, facilitating the use of intellectualization as a coping mechanism. The pacemaker patients were likely to be as fearful of social rejection as of potential pacemaker failure. All three groups identified potential negative peer reactions toward an individual with a pacemaker. The patients with cardiac disease but without pacemakers and the healthy subjects perceived significant (p less than 0.05) social and emotional differences between patients with pacemakers and their peers, but the pacemaker patients did not view themselves as different from their peers. This study demonstrates healthy psychosocial adaptation of children with cardiac pacemakers. Although these children appear to cope effectively with the stress of their life situation through the use of denial and intellectualization, they may experience problems both in the development of autonomy and in social isolation and rejection.

  17. Application of RI power sources to cardiac pacemakers and aftercare in its implantation

    International Nuclear Information System (INIS)

    Hori, Motokazu

    1974-01-01

    RI power sources have long life when they are implanted into human bodies together with cardiac pacemakers, as compared with e.g. mercury batteries. Therefore, the frequency of their replacement can be by far less. However, there are the problems of radiation protection, high cost, availability, etc. The following matters are described: The cardiac pacemaker and its power supply, implantation into human body, problems with patients and conventional power sources; the current state of RI power sources for cardiac pacemakers, including plutonium-238 RTG and 147 Pm and 3 H batteries; and problems with the RI power sources. (Mori, K.)

  18. [Wide QRS tachycardia preceded by pacemaker spikes].

    Science.gov (United States)

    Romero, M; Aranda, A; Gómez, F J; Jurado, A

    2014-04-01

    The differential diagnosis and therapeutic management of wide QRS tachycardia preceded by pacemaker spike is presented. The pacemaker-mediated tachycardia, tachycardia fibrillo-flutter in patients with pacemakers, and runaway pacemakers, have a similar surface electrocardiogram, but respond to different therapeutic measures. The tachycardia response to the application of a magnet over the pacemaker could help in the differential diagnosis, and in some cases will be therapeutic, as in the case of a tachycardia-mediated pacemaker. Although these conditions are diagnosed and treated in hospitals with catheterization laboratories using the application programmer over the pacemaker, patients presenting in primary care clinic and emergency forced us to make a diagnosis and treat the haemodynamically unstable patient prior to referral. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  19. First Degree Pacemaker Exit Block

    Directory of Open Access Journals (Sweden)

    Johnson Francis

    2016-10-01

    Full Text Available Usually atrial and ventricular depolarizations follow soon after the pacemaker stimulus (spike on the ECG. But there can be an exit block due to fibrosis at the electrode - tissue interface at the lead tip. This can increase the delay between the spike and atrial or ventricular depolarization.

  20. Impact of behavior on central and peripheral circadian clocks in the common vole Microtus arvalis, a mammal with ultradian rhythms

    NARCIS (Netherlands)

    van der Veen, DR; Le Minh, N; Gos, P; Arneric, M; Gerkema, MP; Schibler, U; Takahashi, Joseph S.

    2006-01-01

    In most mammals, daily rhythms in physiology are driven by a circadian timing system composed of a master pacemaker in the suprachiasmatic nucleus (SCN) and peripheral oscillators in most body cells. The SCN clock, which is phase-entrained by light-dark cycles, is thought to synchronize subsidiary

  1. Pacemakers and Implantable Defibrillators: MedlinePlus Health Topic

    Science.gov (United States)

    ... ClinicalTrials.gov: Pacemaker, Artificial (National Institutes of Health) Journal Articles References and abstracts from MEDLINE/PubMed (National ... Leadless Cardiac Pacemakers: The Next Evolution in Pacemaker Technology. ... on Pacemakers and Implantable Defibrillators is the National Heart, Lung, and Blood Institute Other Languages Find health information in languages other than English on Pacemakers and ...

  2. Disruption of Circadian Rhythms by Light During Day and Night.

    Science.gov (United States)

    Figueiro, Mariana G

    2017-06-01

    This study aims to discuss possible reasons why research to date has not forged direct links between light at night, acute melatonin suppression or circadian disruption, and risks for disease. Data suggest that irregular light-dark patterns or light exposures at the wrong circadian time can lead to circadian disruption and disease risks. However, there remains an urgent need to: (1) specify light stimulus in terms of circadian rather than visual response; (2) when translating research from animals to humans, consider species-specific spectral and absolute sensitivities to light; (3) relate the characteristics of photometric measurement of light at night to the operational characteristics of the circadian system; and (4) examine how humans may be experiencing too little daytime light, not just too much light at night. To understand the health effects of light-induced circadian disruption, we need to measure and control light stimulus during the day and at night.

  3. Circadian Metabolomics in Time and Space

    Directory of Open Access Journals (Sweden)

    Kenneth A. Dyar

    2017-07-01

    Full Text Available Circadian rhythms are widely known to govern human health and disease, but specific pathogenic mechanisms linking circadian disruption to metabolic diseases are just beginning to come to light. This is thanks in part to the development and application of various “omics”-based tools in biology and medicine. Current high-throughput technologies allow for the simultaneous monitoring of multiple dynamic cellular events over time, ranging from gene expression to metabolite abundance and sub-cellular localization. These fundamental temporal and spatial perspectives have allowed for a more comprehensive understanding of how various dynamic cellular events and biochemical processes are related in health and disease. With advances in technology, metabolomics has become a more routine “omics” approach for studying metabolism, and “circadian metabolomics” (i.e., studying the 24-h metabolome has recently been undertaken by several groups. To date, circadian metabolomes have been reported for human serum, saliva, breath, and urine, as well as tissues from several species under specific disease or mutagenesis conditions. Importantly, these studies have consistently revealed that 24-h rhythms are prevalent in almost every tissue and metabolic pathway. Furthermore, these circadian rhythms in tissue metabolism are ultimately linked to and directed by internal 24-h biological clocks. In this review, we will attempt to put these data-rich circadian metabolomics experiments into perspective to find out what they can tell us about metabolic health and disease, and what additional biomarker potential they may reveal.

  4. Runaway pacemaker: a still existing complication and therapeutic guidelines

    DEFF Research Database (Denmark)

    Mickley, H; Andersen, C; Nielsen, L H

    1989-01-01

    Runaway pacemaker is a rare, but still existing potential lethal complication in permanent pacemakers. Within 4 1/2 years, we saw two cases of runaway pacemaker in patients with multiprogrammable, VVI pacemakers (Siemens-Elema, Model 668). In both cases a pacemaker-induced ventricular tachycardia...... pacemaker may be connected to the permanent pacing lead. Thereafter, the lead can be safely cut. As an alternative, a temporary transvenous pacing lead may be established prior to disconnecting the permanent pacing lead....

  5. On the Evolution of the Cardiac Pacemaker

    Directory of Open Access Journals (Sweden)

    Silja Burkhard

    2017-04-01

    Full Text Available The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells. Understanding the evolutionary origin and development of cardiac pacemaker cells will help us outline the important pathways and factors involved. Key patterning factors, such as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM-homeodomain transcription factor Islet-1, components of the T-box (Tbx, and bone morphogenic protein (Bmp families are well conserved. Here we compare the dominant pacemaking systems in various organisms with respect to the underlying molecular regulation. Comparative analysis of the pathways involved in patterning the pacemaker domain in an evolutionary context might help us outline a common fundamental pacemaker cell gene programme. Special focus is given to pacemaker development in zebrafish, an extensively used model for vertebrate development. Finally, we conclude with a summary of highly conserved key factors in pacemaker cell development and function.

  6. Epithermal neutron beam interference with cardiac pacemakers

    International Nuclear Information System (INIS)

    Koivunoro, H.; Serén, T.; Hyvönen, H.; Kotiluoto, P.; Iivonen, P.; Auterinen, I.; Seppälä, T.; Kankaanranta, L.; Pakarinen, S.; Tenhunen, M.; Savolainen, S.

    2011-01-01

    In this paper, a phantom study was performed to evaluate the effect of an epithermal neutron beam irradiation on the cardiac pacemaker function. Severe malfunction occurred in the pacemakers after substantially lower dose from epithermal neutron irradiation than reported in the fast neutron or photon beams at the same dose rate level. In addition the pacemakers got activated, resulting in nuclides with half-lives from 25 min to 115 d. We suggest that BNCT should be administrated only after removal of the pacemaker from the vicinity of the tumor.

  7. On the Evolution of the Cardiac Pacemaker

    Science.gov (United States)

    Burkhard, Silja; van Eif, Vincent; Garric, Laurence; Christoffels, Vincent M.; Bakkers, Jeroen

    2017-01-01

    The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells. Understanding the evolutionary origin and development of cardiac pacemaker cells will help us outline the important pathways and factors involved. Key patterning factors, such as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM-homeodomain transcription factor Islet-1, components of the T-box (Tbx), and bone morphogenic protein (Bmp) families are well conserved. Here we compare the dominant pacemaking systems in various organisms with respect to the underlying molecular regulation. Comparative analysis of the pathways involved in patterning the pacemaker domain in an evolutionary context might help us outline a common fundamental pacemaker cell gene programme. Special focus is given to pacemaker development in zebrafish, an extensively used model for vertebrate development. Finally, we conclude with a summary of highly conserved key factors in pacemaker cell development and function. PMID:29367536

  8. Epithermal neutron beam interference with cardiac pacemakers

    Energy Technology Data Exchange (ETDEWEB)

    Koivunoro, H., E-mail: hanna.koivunoro@helsinki.fi [Department of Physics, P.O.B. 64, FI-00014 University of Helsinki (Finland)] [Department of Oncology, Helsinki University Central Hospital, P.O.B. 180, FIN-00029 HUS (Finland)] [Boneca Corporation, Finland, Filnland (Finland); Seren, T. [VTT Technical Research Centre of Finland (Finland); Hyvoenen, H. [Boneca Corporation, Finland, Filnland (Finland); Kotiluoto, P. [VTT Technical Research Centre of Finland (Finland); Iivonen, P. [St. Jude Medical (Finland); Auterinen, I. [VTT Technical Research Centre of Finland (Finland); Seppaelae, T.; Kankaanranta, L. [Department of Oncology, Helsinki University Central Hospital, P.O.B. 180, FIN-00029 HUS (Finland); Pakarinen, S. [Department of Cardiology, Helsinki University Central Hospital (Finland); Tenhunen, M. [Department of Oncology, Helsinki University Central Hospital, P.O.B. 180, FIN-00029 HUS (Finland); Savolainen, S. [HUS Helsinki Medical Imaging Center, Helsinki University Central Hospital (Finland)

    2011-12-15

    In this paper, a phantom study was performed to evaluate the effect of an epithermal neutron beam irradiation on the cardiac pacemaker function. Severe malfunction occurred in the pacemakers after substantially lower dose from epithermal neutron irradiation than reported in the fast neutron or photon beams at the same dose rate level. In addition the pacemakers got activated, resulting in nuclides with half-lives from 25 min to 115 d. We suggest that BNCT should be administrated only after removal of the pacemaker from the vicinity of the tumor.

  9. The nuclear pacemaker: Is renewed interest warranted

    International Nuclear Information System (INIS)

    Parsonnet, V.; Berstein, A.D.; Perry, G.Y.

    1990-01-01

    From 1973 through 1987, 155 radioisotope-powered nuclear pacemakers were implanted in 132 patients at the Newark Beth Israel Medical Center. The longevity of the first 15 devices, all of which were fixed-rate (VOO) pacemakers, was significantly better than that of 15 lithium-chemistry demand (VVI) pacemakers used as control devices (p = 0.0002). Of the entire cohort of 155 nuclear pacemakers, 136 were VVI devices and 19 were VOO units. The patients with VOO pacemakers needed reoperations more often than did those with VVI pacemakers, chiefly for mode change (p less than 0.001). Power-source failure was observed in only 1 case, but 47 nuclear pacemakers were removed for other reasons, including component malfunction (15 units), mode change (12 units), high pacing thresholds (8 units) and lead or connector problems (5 units). The actuarial survival at 15 years was 99% for power sources and 82% for the entire pacing systems (pulse generators plus leads). The frequency of malignancy was similar to that of the population at large and primary tumor sites were randomly distributed. Deaths most commonly were due to cardiac causes (68%). Thus, nuclear pacemakers are safe and reliable and their greater initial cost appears to be offset by their longevity and the resulting decrease in the frequency of reoperations. It is reasonable to suggest that further use be made of long-lasting nuclear power sources for modern pacemakers and other implantable rhythm-management devices

  10. Ionizing radiation effects on implanted pacemakers

    International Nuclear Information System (INIS)

    Holzer, J.; Aiginger, H.; Binder, W.

    1998-01-01

    Fourteen multi-programmable pacemakers and 2 intercardial defibrillators were exposed to 60 Co radiation, to 9 MeV electrons and to 6 MV and 10 MV photon radiation. The pacemakers were placed into a water phantom. The following parameters were examined: telemetry, battery, pulse frequency, pulse amplitude, and period at accumulated doses from 2 Gy to 100 Gy. It is concluded that pacemakers in CMOS/Bipolar technology and in 8μ CMOS technology should not be exposed to an absorbed dose exceeding 5 Gy, the latest generation of pacemakers in the 3μm technology will perform satisfactorily up to 70 Gy. (P.A.)

  11. Quantitative analysis of circadian single cell oscillations in response to temperature.

    Science.gov (United States)

    Abraham, Ute; Schlichting, Julia Katharina; Kramer, Achim; Herzel, Hanspeter

    2018-01-01

    Body temperature rhythms synchronize circadian oscillations in different tissues, depending on the degree of cellular coupling: the responsiveness to temperature is higher when single circadian oscillators are uncoupled. So far, the role of coupling in temperature responsiveness has only been studied in organotypic tissue slices of the central circadian pacemaker, because it has been assumed that peripheral target organs behave like uncoupled multicellular oscillators. Since recent studies indicate that some peripheral tissues may exhibit cellular coupling as well, we asked whether peripheral network dynamics also influence temperature responsiveness. Using a novel technique for long-term, high-resolution bioluminescence imaging of primary cultured cells, exposed to repeated temperature cycles, we were able to quantitatively measure period, phase, and amplitude of central (suprachiasmatic nuclei neuron dispersals) and peripheral (mouse ear fibroblasts) single cell oscillations in response to temperature. Employing temperature cycles of different lengths, and different cell densities, we found that some circadian characteristics appear cell-autonomous, e.g. period responses, while others seem to depend on the quality/degree of cellular communication, e.g. phase relationships, robustness of the oscillation, and amplitude. Overall, our findings indicate a strong dependence on the cell's ability for intercellular communication, which is not only true for neuronal pacemakers, but, importantly, also for cells in peripheral tissues. Hence, they stress the importance of comparative studies that evaluate the degree of coupling in a given tissue, before it may be used effectively as a target for meaningful circadian manipulation.

  12. Circadian Rhythm Sleep Disorders

    Directory of Open Access Journals (Sweden)

    Erhan Akinci

    2016-06-01

    Full Text Available The circadian rhythm sleep disorders define the clinical conditions where sleep and ndash;wake rhythm is disrupted despite optimum environmental and social conditions. They occur as a result of the changes in endogenous circadian hours or non-compatibility of environmental factors or social life with endogenous circadian rhythm. The sleep and ndash;wake rhythm is disrupted continuously or in repeating phases depending on lack of balance between internal and external cycles. This condition leads to functional impairments which cause insomnia, excessive sleepiness or both in people. Application of detailed sleep anamnesis and sleep diary with actigraphy record, if possible, will be sufficient for diagnosis. The treatment aims to align endogenous circadian rhythm with environmental conditions. The purpose of this article is to review pathology, clinical characteristics, diagnosis and treatment of circadian rhythm disorder. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 178-189

  13. Circadian-Time Sickness: Time-of-Day Cue-Conflicts Directly Affect Health.

    Science.gov (United States)

    van Ee, Raymond; Van de Cruys, Sander; Schlangen, Luc J M; Vlaskamp, Björn N S

    2016-11-01

    A daily rhythm that is not in synchrony with the environmental light-dark cycle (as in jetlag and shift work) is known to affect mood and health through an as yet unresolved neural mechanism. Here, we combine Bayesian probabilistic 'cue-conflict' theory with known physiology of the biological clock of the brain, entailing the insight that, for a functional pacemaker, it is sufficient to have two interacting units (reflecting environmental and internal time-of-day cues), without the need for an extra homuncular directing unit. Unnatural light-dark cycles cause a time-of-day cue-conflict that is reflected by a desynchronization between the ventral (environmental) and dorsal (internal) pacemaking signals of the pacemaker. We argue that this desynchronization, in-and-of-itself, produces health issues that we designate as 'circadian-time sickness', analogous to 'motion sickness'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Ambulatory assessment of human circadian phase and related sleep disorders from heart rate variability and other non-invasive physiological measurements

    NARCIS (Netherlands)

    Gil Ponce, Enrique

    2017-01-01

    The circadian system plays a key role in our well-being and its effects can be seen in many aspects of our lives. Our master circadian clock, located deep in our brain, influences various physiological processes such as heart rate, body temperature, energy metabolism, hormones, and sleep, to name a

  15. Validation of the Netherlands pacemaker patient registry

    NARCIS (Netherlands)

    Dijk, WA; Kingma, T; Hooijschuur, CAM; Dassen, WRM; Hoorntje, JCA; van Gelder, LM

    1997-01-01

    This paper deals with the validation of the information stored in the Netherlands central pacemaker patient database. At this moment the registry database contains information on more than 70500 patients, 85000 pacemakers and 90000 leads. The validation procedures consisted of an internal

  16. On the Evolution of the Cardiac Pacemaker

    NARCIS (Netherlands)

    Burkhard, Silja; van Eif, Vincent; Garric, Laurence; Christoffels, Vincent M.; Bakkers, Jeroen

    2017-01-01

    The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not

  17. Feasibility of pacemaker therapy after dynamic cardiomyoplasty

    NARCIS (Netherlands)

    Van den Berg, MP; Nagelkerke, D; Brouwer, RMHJ; Mulder, H; De Boer, H; Crijns, HJGM

    1999-01-01

    A 54-year-old man presented with total atrioventricular (AV) block 3 months after dynamic cardiomyoplasty was performed because of heart failure due to idiopathic dilated cardiomyopathy. Though the cardiomyostimulator acted as a back-up pacemaker, a DDDR pacemaker was implanted to optimize

  18. NPAS2 Compensates for Loss of CLOCK in Peripheral Circadian Oscillators.

    Directory of Open Access Journals (Sweden)

    Dominic Landgraf

    2016-02-01

    Full Text Available Heterodimers of CLOCK and BMAL1 are the major transcriptional activators of the mammalian circadian clock. Because the paralog NPAS2 can substitute for CLOCK in the suprachiasmatic nucleus (SCN, the master circadian pacemaker, CLOCK-deficient mice maintain circadian rhythms in behavior and in tissues in vivo. However, when isolated from the SCN, CLOCK-deficient peripheral tissues are reportedly arrhythmic, suggesting a fundamental difference in circadian clock function between SCN and peripheral tissues. Surprisingly, however, using luminometry and single-cell bioluminescence imaging of PER2 expression, we now find that CLOCK-deficient dispersed SCN neurons and peripheral cells exhibit similarly stable, autonomous circadian rhythms in vitro. In CLOCK-deficient fibroblasts, knockdown of Npas2 leads to arrhythmicity, suggesting that NPAS2 can compensate for loss of CLOCK in peripheral cells as well as in SCN. Our data overturn the notion of an SCN-specific role for NPAS2 in the molecular circadian clock, and instead indicate that, at the cellular level, the core loops of SCN neuron and peripheral cell circadian clocks are fundamentally similar.

  19. Biofilm on artificial pacemaker: fiction or reality?

    Science.gov (United States)

    Santos, Ana Paula Azevedo; Watanabe, Evandro; Andrade, Denise de

    2011-11-01

    Cardiac pacing through cardiac pacemaker is one of the most promising alternatives in the treatment of arrhythmias, but it can cause reactions natural or complex reactions, either early or late. This study aimed to describe the scientific evidence on the risk of infection and biofilm formation associated with cardiac pacemaker. This is a study of integrative literature review. It included 14 publications classified into three thematic categories: diagnosis (microbiological and/or clinical), complications and therapy of infections. Staphylococcus epidermidis and Staphylococcus aureus were the microorganisms most frequently isolated. It was not possible to determine the incidence of infection associated with pacemakers, since the studies were generally of prevalence. In terms of therapy, the complete removal of pacemakers stood out, especially in cases of suspected biofilm. Still controversial is the use of systemic antibiotic prophylaxis in reducing the incidence of infection associated with implantation of a pacemaker.

  20. Isotopic cardiac pacemaker during pregnancy. Three cases

    International Nuclear Information System (INIS)

    Laurens, P.; Gavelle, P.; Maurice, P.; Haiat, R.; Chiche, P.

    1976-01-01

    Three cases of full term pregnancies, without complications, in women with isotopic pacemakers are reported. The newborn infants were normal. In one case, pregnancy occurred in a patient who already had a pacemaker. In two cases, the pacemaker was inserted during pregnancy (at 1 and 1/2 and 5 months respectively), in the treatment of syncopal attacks due to paroxysmal atrioventricular block. This type of pacemaker using a radioactive source (plutonium 238) is, by virtue of the low degree of radiation, harmless and may be used in women of childbearing age. Under the least favourable conditions (pacemaker box in abdominal situation), the dose delivered during pregnancy (57 mrem) is approximately 20 times less than the authorized dose (1125 mrem) [fr

  1. Organization of Circadian Behavior Relies on Glycinergic Transmission.

    Science.gov (United States)

    Frenkel, Lia; Muraro, Nara I; Beltrán González, Andrea N; Marcora, María S; Bernabó, Guillermo; Hermann-Luibl, Christiane; Romero, Juan I; Helfrich-Förster, Charlotte; Castaño, Eduardo M; Marino-Busjle, Cristina; Calvo, Daniel J; Ceriani, M Fernanda

    2017-04-04

    The small ventral lateral neurons (sLNvs) constitute a central circadian pacemaker in the Drosophila brain. They organize daily locomotor activity, partly through the release of the neuropeptide pigment-dispersing factor (PDF), coordinating the action of the remaining clusters required for network synchronization. Despite extensive efforts, the basic principles underlying communication among circadian clusters remain obscure. We identified classical neurotransmitters released by sLNvs through disruption of specific transporters. Adult-specific RNAi-mediated downregulation of the glycine transporter or impairment of glycine synthesis in LNv neurons increased period length by nearly an hour without affecting rhythmicity of locomotor activity. Electrophysiological recordings showed that glycine reduces spiking frequency in circadian neurons. Interestingly, downregulation of glycine receptor subunits in specific sLNv targets impaired rhythmicity, revealing involvement of glycine in information processing within the network. These data identify glycinergic inhibition of specific targets as a cue that contributes to the synchronization of the circadian network. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Multicellular models of intercellular synchronization in circadian neural networks

    International Nuclear Information System (INIS)

    Henson, Michael A.

    2013-01-01

    The circadian clock generates 24 h rhythms that drive physiological and behavioral processes in a diverse range of organisms including microbes, plants, insects, and mammals. Recent experimental advances have produced improved understanding of the molecular mechanisms involved in circadian rhythm generation at the single cell level. However, the intercellular mechanisms that allow large populations of coupled pacemaker cells to synchronize and coordinate their rhythms remain poorly understood. The purpose of this article is to review recent progress in dynamic modeling of the circadian clock with a focus on multicellular models required to describe cell population synchronization. Mammalian systems are emphasized to illustrate the highly heterogeneous structure and rich dynamical behavior of multicellular circadian systems. Available multicellular models are characterized with respect to their single cell descriptions, intercellular coupling mechanisms, and network topologies. Examples drawn from our own research are used to demonstrate the advantages associated with integrating detailed single cell models within realistic multicellular networks for prediction of mammalian system dynamics. Mathematical modeling is shown to represent a powerful tool for understanding the intracellular and intercellular mechanisms utilized to robustly synchronize large populations of highly heterogeneous and sparsely coupled single cell oscillators. The article concludes with some possible directions for future research

  3. Radiotherapy for breast cancer and pacemaker

    International Nuclear Information System (INIS)

    Menard, J.; Campana, F.; Bollet, M.A.; Dendale, R.; Fournier-Bidoz, N.; Marchand, V.; Mazal, A.; Fourquet, A.; Kirova, Y.M.; Kirov, K.M.; Esteve, M.

    2011-01-01

    Purpose. - Patients with permanent cardiac pacemakers occasionally require radiotherapy. Therapeutic Irradiation may cause pacemakers to malfunction due to the effects of ionizing radiation or electromagnetic interference. We studied the breast cancer patients who needed breast and/or chest wall and lymph node irradiation to assess the feasibility and tolerance in this population of patients. Patients and methods. - From November 2008 to December 2009, more than 900 patients received radiotherapy for their breast cancer in our department using megavoltage linear accelerator (X 4-6 MV and electrons). Among them, seven patients were with permanent pacemaker. All patients have been treated to the breast and chest wall and/or lymph nodes. Total dose to breast and/or chest wall was 50 Gy/25 fractions and 46 Gy/23 fractions to lymph nodes. Patients who underwent conserving surgery followed by breast irradiation were boosted when indicated to tumour bed with 16 Gy/8 fractions. All patients were monitored everyday in presence of radiation oncologist to follow the function of their pacemaker. All pacemakers were controlled before and after radiotherapy by the patients' cardiologist. Results. - Seven patients were referred in our department for postoperative breast cancer radiotherapy. Among them, only one patient was declined for radiotherapy and underwent mastectomy without radiotherapy. In four cases the pacemaker was repositioned before the beginning of radiotherapy. Six patients, aged between 48 and 84 years underwent irradiation for their breast cancer. Four patients were treated with conserving surgery followed by breast radiotherapy and two with mastectomy followed by chest wall and internal mammary chain, supra- and infra-clavicular lymph node irradiation. The dose to the pacemaker generator was kept below 2 Gy. There was no pacemaker dysfunction observed during the radiotherapy. Conclusion. - The multidisciplinary work with position change of the pacemaker before

  4. Later endogenous circadian temperature nadir relative to an earlier wake time in older people

    Science.gov (United States)

    Duffy, J. F.; Dijk, D. J.; Klerman, E. B.; Czeisler, C. A.

    1998-01-01

    The contribution of the circadian timing system to the age-related advance of sleep-wake timing was investigated in two experiments. In a constant routine protocol, we found that the average wake time and endogenous circadian phase of 44 older subjects were earlier than that of 101 young men. However, the earlier circadian phase of the older subjects actually occurred later relative to their habitual wake time than it did in young men. These results indicate that an age-related advance of circadian phase cannot fully account for the high prevalence of early morning awakening in healthy older people. In a second study, 13 older subjects and 10 young men were scheduled to a 28-h day, such that they were scheduled to sleep at many circadian phases. Self-reported awakening from scheduled sleep episodes and cognitive throughput during the second half of the wake episode varied markedly as a function of circadian phase in both groups. The rising phase of both rhythms was advanced in the older subjects, suggesting an age-related change in the circadian regulation of sleep-wake propensity. We hypothesize that under entrained conditions, these age-related changes in the relationship between circadian phase and wake time are likely associated with self-selected light exposure at an earlier circadian phase. This earlier exposure to light could account for the earlier clock hour to which the endogenous circadian pacemaker is entrained in older people and thereby further increase their propensity to awaken at an even earlier time.

  5. 21 CFR 870.3600 - External pacemaker pulse generator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External pacemaker pulse generator. 870.3600... pacemaker pulse generator. (a) Identification. An external pacemaker pulse generator is a device that has a... intrinsic pacing sytem until a permanent pacemaker can be implanted, or to control irregular heartbeats in...

  6. 21 CFR 870.3620 - Pacemaker lead adaptor.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a pacemaker lead so that it...

  7. 21 CFR 870.3640 - Indirect pacemaker generator function analyzer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Indirect pacemaker generator function analyzer... Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an electrically powered device that is used to determine pacemaker function or...

  8. Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording

    NARCIS (Netherlands)

    Schaap, J.; Bos, N. P.; de Jeu, M. T.; Geurtsen, A. M.; Meijer, J. H.; Pennartz, C. M.

    1999-01-01

    The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological

  9. Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects

    Science.gov (United States)

    Klerman, E. B.; Zeitzer, J. M.; Duffy, J. F.; Khalsa, S. B.; Czeisler, C. A.

    2001-01-01

    The daily rhythm of melatonin influences multiple physiological measures, including sleep tendency, circadian rhythms, and reproductive function in seasonally breeding mammals. The biological signal for photoperiodic changes in seasonally breeding mammals is a change in the duration of melatonin secretion, which in a natural environment reflects the different durations of daylight across the year, with longer nights leading to a longer duration of melatonin secretion. These seasonal changes in the duration of melatonin secretion do not simply reflect the known acute suppression of melatonin secretion by ocular light exposure, but also represent long-term changes in the endogenous nocturnal melatonin episode that persist in constant conditions. As the eyes of totally blind individuals do not transmit ocular light information, we hypothesized that the duration of the melatonin secretory episode in blind subjects would be longer than those in sighted individuals, who are exposed to light for all their waking hours in an urban environment. We assessed the melatonin secretory profile during constant posture, dim light conditions in 17 blind and 157 sighted adults, all of whom were healthy and using no prescription or nonprescription medications. The duration of melatonin secretion was not significantly different between blind and sighted individuals. Healthy blind individuals after years without ocular light exposure do not have a longer duration of melatonin secretion than healthy sighted individuals.

  10. The oral cavity is not a primary source for implantable pacemaker or cardioverter defibrillator infections

    Science.gov (United States)

    2013-01-01

    Background To test the hypothesis that the oral cavity is a potential source for implantable pacemaker and cardioverter defibrillators infections, the bacterial diversity on explanted rhythm heart management devices was investigated and compared to the oral microbiome. Methods A metagenomic approach was used to analyze the bacterial diversity on the surfaces of non-infected and infected pacemakers. The DNA from surfaces swaps of 24 non-infected and 23 infected pacemaker were isolated and subjected to bacterial-specific DNA amplification, single strand conformation polymorphism- (SSCP) and sequencing analysis. Species-specific primer sets were used to analyze for any correlation between bacterial diversity on pacemakers and in the oral cavity. Results DNA of bacterial origin was detected in 21 cases on infected pacemakers and assigned to the bacterial phylotypes Staphylococcus epidermidis, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus schleiferi and Stapyhlococcus. In 17 cases bacterial DNA was found on pacemakers with no clinical signs of infections. On the basis of the obtained sequence data, the phylotypes Propionibacterium acnes, Staphylococcus and an uncultured bacterium were identified. Propionibacterium acnes and Staphylococcus epidermidis were the only bacteria detected in pacemeaker (n = 25) and oral samples (n = 11). Conclusions The frequency of the coincidental detection of bacteria on infected devices and in the oral cavity is low and the detected bacteria are highly abundant colonizers of non-oral human niches. The transmission of oral bacteria to the lead or device of implantable pacemaker or cardioverter defibrillators is unlikely relevant for the pathogenesis of pacemaker or cardioverter defibrillators infections. PMID:23575037

  11. Damaging effect of therapeutic radiation on programmable pacemakers

    International Nuclear Information System (INIS)

    Adamec, R.; Haefliger, J.M.; Killisch, J.P.; Niederer, J.; Jaquet, P.

    1982-01-01

    Two series of present-day pacemakers were tested in vitro with pulsed x-ray radiation. The first series of 12 pacemakers consisted of 10 different types and models of demand pacemakers (VVI). The second series of 13 pacemakers had 9 different types and models of programmable pacemakers. Unlike the first series which showed only mild changes in frequency and pulse width, all but four of the programmable pacemakers presented sudden complete failure after different radiation doses. We conclude that direct pulse radiation at therapeutic levels of programmable pacemakers should be avoided

  12. Universal pacemaker of genome evolution.

    Science.gov (United States)

    Snir, Sagi; Wolf, Yuri I; Koonin, Eugene V

    2012-01-01

    A fundamental observation of comparative genomics is that the distribution of evolution rates across the complete sets of orthologous genes in pairs of related genomes remains virtually unchanged throughout the evolution of life, from bacteria to mammals. The most straightforward explanation for the conservation of this distribution appears to be that the relative evolution rates of all genes remain nearly constant, or in other words, that evolutionary rates of different genes are strongly correlated within each evolving genome. This correlation could be explained by a model that we denoted Universal PaceMaker (UPM) of genome evolution. The UPM model posits that the rate of evolution changes synchronously across genome-wide sets of genes in all evolving lineages. Alternatively, however, the correlation between the evolutionary rates of genes could be a simple consequence of molecular clock (MC). We sought to differentiate between the MC and UPM models by fitting thousands of phylogenetic trees for bacterial and archaeal genes to supertrees that reflect the dominant trend of vertical descent in the evolution of archaea and bacteria and that were constrained according to the two models. The goodness of fit for the UPM model was better than the fit for the MC model, with overwhelming statistical significance, although similarly to the MC, the UPM is strongly overdispersed. Thus, the results of this analysis reveal a universal, genome-wide pacemaker of evolution that could have been in operation throughout the history of life.

  13. Identification of circadian clock modulators from existing drugs.

    Science.gov (United States)

    Tamai, T Katherine; Nakane, Yusuke; Ota, Wataru; Kobayashi, Akane; Ishiguro, Masateru; Kadofusa, Naoya; Ikegami, Keisuke; Yagita, Kazuhiro; Shigeyoshi, Yasufumi; Sudo, Masaki; Nishiwaki-Ohkawa, Taeko; Sato, Ayato; Yoshimura, Takashi

    2018-04-17

    Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is costly and hugely time-consuming. We therefore performed a high-throughput chemical screen of existing drugs for circadian clock modulators in human U2OS cells, with the aim of repurposing known bioactive compounds. Approximately 5% of the drugs screened altered circadian period, including the period-shortening compound dehydroepiandrosterone (DHEA; also known as prasterone). DHEA is one of the most abundant circulating steroid hormones in humans and is available as a dietary supplement in the USA Dietary administration of DHEA to mice shortened free-running circadian period and accelerated re-entrainment to advanced light-dark (LD) cycles, thereby reducing jet-lag. Our drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and the BCR serine/threonine kinase in regulating circadian period. Thus, drug repurposing is a useful approach to identify new circadian clock modulators and potential therapies for circadian disorders. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  14. Radiation protection for pacemakers with radionuclide batteries

    International Nuclear Information System (INIS)

    Stieve, F.E.

    1976-01-01

    Radionuclide batteries ( 147 Pm, 238 Pu) in pacemakers bring risks for the patient and the environment, if the radioactive material cannot be secured for subsequent application or for safe end storage. This is why the expenditure connected with pacemakers is very high. So the application of such pacemakers is only indicated when the patient's expectation of life is presumably higher than 5-10 years, when there are no other diseases besides cardiac dysrhytmia, and when the securing of the radionuclide batteries is guaranteed. (orig.) [de

  15. Epigenetic and Posttranslational Modifications in Light Signal Transduction and the Circadian Clock in Neurospora crassa

    Directory of Open Access Journals (Sweden)

    Marco Proietto

    2015-07-01

    Full Text Available Blue light, a key abiotic signal, regulates a wide variety of physiological processes in many organisms. One of these phenomena is the circadian rhythm presents in organisms sensitive to the phase-setting effects of blue light and under control of the daily alternation of light and dark. Circadian clocks consist of autoregulatory alternating negative and positive feedback loops intimately connected with the cellular metabolism and biochemical processes. Neurospora crassa provides an excellent model for studying the molecular mechanisms involved in these phenomena. The White Collar Complex (WCC, a blue-light receptor and transcription factor of the circadian oscillator, and Frequency (FRQ, the circadian clock pacemaker, are at the core of the Neurospora circadian system. The eukaryotic circadian clock relies on transcriptional/translational feedback loops: some proteins rhythmically repress their own synthesis by inhibiting the activity of their transcriptional factors, generating self-sustained oscillations over a period of about 24 h. One of the basic mechanisms that perpetuate self-sustained oscillations is post translation modification (PTM. The acronym PTM generically indicates the addition of acetyl, methyl, sumoyl, or phosphoric groups to various types of proteins. The protein can be regulatory or enzymatic or a component of the chromatin. PTMs influence protein stability, interaction, localization, activity, and chromatin packaging. Chromatin modification and PTMs have been implicated in regulating circadian clock function in Neurospora. Research into the epigenetic control of transcription factors such as WCC has yielded new insights into the temporal modulation of light-dependent gene transcription. Here we report on epigenetic and protein PTMs in the regulation of the Neurospora crassa circadian clock. We also present a model that illustrates the molecular mechanisms at the basis of the blue light control of the circadian clock.

  16. Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment

    DEFF Research Database (Denmark)

    Kessel, Line; Lundeman, Jesper Holm; Herbst, Kristina

    2010-01-01

    To characterize age-related changes in the transmission of light through noncataractous human lenses.......To characterize age-related changes in the transmission of light through noncataractous human lenses....

  17. Vitamin concentrations in human milk vary with time within feed, circadian rhythm, and single-dose supplementation

    Science.gov (United States)

    Importance: Human milk is the subject of many nutrition studies but methods for representative sample collection are not established. Our recently improved, validated methods for analyzing micronutrients in human milk now enable systematic study of factors affecting their concentration. Objective...

  18. Devices That May Interfere with Pacemakers

    Science.gov (United States)

    ... Communications Commission (FCC) makes new frequencies available. Newer cellphones using these new frequencies might make pacemakers less reliable. A group of cellphone companies is studying that possibility. Bluetooth® headsets do ...

  19. Circadian variation in sports performance.

    Science.gov (United States)

    Atkinson, G; Reilly, T

    1996-04-01

    Chronobiology is the science concerned with investigations of time-dependent changes in physiological variables. Circadian rhythms refer to variations that recur every 24 hours. Many physiological circadian rhythms at rest are endogenously controlled, and persist when an individual is isolated from environmental fluctuations. Unlike physiological variables, human performance cannot be monitored continuously in order to describe circadian rhythmicity. Experimental studies of the effect of circadian rhythms on performance need to be carefully designed in order to control for serial fatigue effects and to minimise disturbances in sleep. The detection of rhythmicity in performance variables is also highly influenced by the degree of test-retest repeatability of the measuring equipment. The majority of components of sports performance, e.g. flexibility, muscle strength, short term high power output, vary with time of day in a sinusoidal manner and peak in the early evening close to the daily maximum in body temperature. Psychological tests of short term memory, heart rate-based tests of physical fitness, and prolonged submaximal exercise performance carried out in hot conditions show peak times in the morning. Heart rate-based tests of work capacity appear to peak in the morning because the heart rate responses to exercise are minimal at this time of day. Post-lunch declines are evident with performance variables such as muscle strength, especially if measured frequently enough and sequentially within a 24-hour period to cause fatigue in individuals. More research work is needed to ascertain whether performance in tasks demanding fine motor control varies with time of day. Metabolic and respiratory rhythms are flattened when exercise becomes strenuous whilst the body temperature rhythm persists during maximal exercise. Higher work-rates are selected spontaneously in the early evening. At present, it is not known whether time of day influences the responses of a set

  20. Regulation of circadian blood pressure: from mice to astronauts.

    Science.gov (United States)

    Agarwal, Rajiv

    2010-01-01

    Circadian variation is commonly seen in healthy people; aberration in these biological rhythms is an early sign of disease. Impaired circadian variation of blood pressure (BP) has been shown to be associated with greater target organ damage and with an elevated risk of cardiovascular events independent of the BP load. The purpose of this review is to examine the physiology of circadian BP variation and propose a tripartite model that explains the regulation of circadian BP. The time-keeper in mammals resides centrally in the suprachiasmatic nucleus. Apart from this central clock, molecular clocks exist in most peripheral tissues including vascular tissue and the kidney. These molecular clocks regulate sodium balance, sympathetic function and vascular tone. A physiological model is proposed that integrates our understanding of molecular clocks in mice with the circadian BP variation among humans. The master regulator in this proposed model is the sleep-activity cycle. The equivalents of peripheral clocks are endothelial and adrenergic functions. Thus, in the proposed model, the variation in circadian BP is dependent upon three major factors: physical activity, autonomic function, and sodium sensitivity. The integrated consideration of physical activity, autonomic function, and sodium sensitivity appears to explain the physiology of circadian BP variation and the pathophysiology of disrupted BP rhythms in various conditions and disease states. Our understanding of molecular clocks in mice may help to explain the provenance of blunted circadian BP variation even among astronauts.

  1. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Uduak S. Udoh

    2015-10-01

    Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

  2. The circadian response of intrinsically photosensitive retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Andrew J Zele

    Full Text Available Intrinsically photosensitive retinal ganglion cells (ipRGC signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central or intrinsic (retinal network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18-30 years with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC and outer retina (cone photoreceptors was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux. Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin retinal ganglion cells mediate this circadian variation.

  3. Nuclear-powered pacemaker fuel cladding study

    International Nuclear Information System (INIS)

    Shoup, R.L.

    1976-01-01

    The composite of metals and alloys used in the fabrication of 238 Pu cardiac pacemaker fuel capsules resists the effects of high temperatures, high mechanical forces, and chemical corrosives and provides more than adequate protection to the fuel pellet even from deliberate attempts to dissolve the cladding in inorganic acids. This does not imply that opening a pacemaker fuel capsule by inorganic acids is impossible but that it would not be a wise choice

  4. Mathematical Models of Cardiac Pacemaking Function

    Science.gov (United States)

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

    2013-10-01

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

  5. Mathematical Models of Cardiac Pacemaking Function

    Directory of Open Access Journals (Sweden)

    Pan eLi

    2013-10-01

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

  6. Circadian physiology of metabolism.

    Science.gov (United States)

    Panda, Satchidananda

    2016-11-25

    A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

  7. Circadian Rhythms in Cyanobacteria

    Science.gov (United States)

    Golden, Susan S.

    2015-01-01

    SUMMARY Life on earth is subject to daily and predictable fluctuations in light intensity, temperature, and humidity created by rotation of the earth. Circadian rhythms, generated by a circadian clock, control temporal programs of cellular physiology to facilitate adaptation to daily environmental changes. Circadian rhythms are nearly ubiquitous and are found in both prokaryotic and eukaryotic organisms. Here we introduce the molecular mechanism of the circadian clock in the model cyanobacterium Synechococcus elongatus PCC 7942. We review the current understanding of the cyanobacterial clock, emphasizing recent work that has generated a more comprehensive understanding of how the circadian oscillator becomes synchronized with the external environment and how information from the oscillator is transmitted to generate rhythms of biological activity. These results have changed how we think about the clock, shifting away from a linear model to one in which the clock is viewed as an interactive network of multifunctional components that are integrated into the context of the cell in order to pace and reset the oscillator. We conclude with a discussion of how this basic timekeeping mechanism differs in other cyanobacterial species and how information gleaned from work in cyanobacteria can be translated to understanding rhythmic phenomena in other prokaryotic systems. PMID:26335718

  8. Pacemaker diagnostics in atrial fibrillation: limited usefulness for therapy initiation in a pacemaker practice.

    Science.gov (United States)

    Yedlapati, Neeraja; Fisher, John D

    2014-09-01

    We aimed to determine the practical value of pacemaker diagnostics for atrial fibrillation (AF) in an unselected general pacemaker practice, specifically workflow and initiation of anticoagulation or antiarrhythmic drug (AAD) therapy. We prospectively followed consecutive pacemaker interrogations over a period of 1 year to identify patients with AF (burden from 1% to 99%). We contacted referring physicians with AF details, and then determined whether the information resulted in therapeutic changes. Of the 1,100 pacemakers interrogated, 728 were dual chamber (DDDs) with AF diagnostic capability. AF was recorded in 73 (10%) but seven had limited information, leaving 66 patients; of these, 42 (63%) patients were already anticoagulated and in five (7%) patients, anticoagulation had been stopped because of complications. Initial diagnosis of AF was made by the pacemaker in 17 patients (26% of 66; 2% of 728); four (6% of 66) patients were newly initiated on anticoagulation. Of the 66 patients, 17 patients were already on AADs; 49 (74%) had satisfactory rate control or had other issues; only two (3% of 66; 0.3% of 728) received new AADs. Of 728 patients with DDD pacemakers, only 17 were newly discovered to have AF, and six (0.8%) had changes in medications based on the pacemaker data. Adding pacemaker-derived data to existing clinical information had little therapeutic impact, due to a combination of cumbersome workflow, and because AF was usually known to practitioners. Developments in automated monitoring systems may provide more accessible and therapeutically useful information. ©2014 Wiley Periodicals, Inc.

  9. Impaired clock output by altered connectivity in the circadian network.

    Science.gov (United States)

    Fernández, María de la Paz; Chu, Jessie; Villella, Adriana; Atkinson, Nigel; Kay, Steve A; Ceriani, María Fernanda

    2007-03-27

    Substantial progress has been made in elucidating the molecular processes that impart a temporal control to physiology and behavior in most eukaryotes. In Drosophila, dorsal and ventral neuronal networks act in concert to convey rhythmicity. Recently, the hierarchical organization among the different circadian clusters has been addressed, but how molecular oscillations translate into rhythmic behavior remains unclear. The small ventral lateral neurons can synchronize certain dorsal oscillators likely through the release of pigment dispersing factor (PDF), a neuropeptide central to the control of rhythmic rest-activity cycles. In the present study, we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the potassium channel slowpoke (slo) to examine the relevance of specific neuronal populations involved in the circadian control of behavior. We show that altered neuronal function associated with the null mutation specifically impaired PDF accumulation in the dorsal protocerebrum and, in turn, desynchronized molecular oscillations in the dorsal clusters. However, molecular oscillations in the small ventral lateral neurons are properly running in the null mutant, indicating that slo is acting downstream of these core pacemaker cells, most likely in the output pathway. Surprisingly, disrupted PDF signaling by slo dysfunction directly affects the structure of the underlying circuit. Our observations demonstrate that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity.

  10. Aggregatibacter aphrophilus pacemaker endocarditis: a case report.

    Science.gov (United States)

    Patel, Sahil R; Patel, Nishi H; Borah, Amit; Saltzman, Heath

    2014-12-08

    Aggregatibacter bacteria are a rare cause of endocarditis in adults. They are part of a group of organisms known as HACEK--Haemophilus, Aggregatibacter, Cardiobacter, Eikenella, and Kingella. Among these organisms, several Haemophilus species have been reclassified under the genus Aggregatibacter. Very few cases of Aggregatibacter endocarditis in patients with pacemaker devices have been reported. We present here what we believe to be the first case of Aggregatibacter aphrophilus pacemaker endocarditis. A 62-year-old African American male with a medical history significant for dual-chamber pacemaker placement in 1996 for complete heart block with subsequent lead manipulation in 2007, presented to his primary care doctor with fever, chills, night sweats, fatigue, and ten-pound weight loss over a four-month period. Physical examination revealed a new murmur and jugular venous distension which prompted initiation of antibiotics for suspicion of endocarditis. Both sets of initial blood cultures were positive for A. aphrophilus. Transesophageal echocardiogram revealed vegetations on the tricuspid valve and the right ventricular pacemaker lead (Figure 1). This case highlights the importance of identifying rare causes of endocarditis and recognizing that treatment may not differ from the standard treatment for typical presentations. The patient received intravenous ceftriaxone for his endocarditis for a total of six weeks. Upon device removal, temporary jugular venous pacing wires were placed. After two weeks of antibiotic treatment and no clinical deterioration, a new permanent pacemaker was placed and the patient was discharged home. This is the first case of A. aphrophilus endocarditis in a patient with a permanent pacemaker. Our patient had no obvious risk factors other than poor dentition and a history of repeated pacemaker lead manipulation. This suggests that valvulopathies secondary to repeated lead manipulation can be clinically significant factors in morbidity

  11. An autonomous circadian clock in the inner mouse retina regulated by dopamine and GABA.

    Directory of Open Access Journals (Sweden)

    Guo-Xiang Ruan

    2008-10-01

    Full Text Available The influence of the mammalian retinal circadian clock on retinal physiology and function is widely recognized, yet the cellular elements and neural regulation of retinal circadian pacemaking remain unclear due to the challenge of long-term culture of adult mammalian retina and the lack of an ideal experimental measure of the retinal circadian clock. In the current study, we developed a protocol for long-term culture of intact mouse retinas, which allows retinal circadian rhythms to be monitored in real time as luminescence rhythms from a PERIOD2::LUCIFERASE (PER2::LUC clock gene reporter. With this in vitro assay, we studied the characteristics and location within the retina of circadian PER2::LUC rhythms, the influence of major retinal neurotransmitters, and the resetting of the retinal circadian clock by light. Retinal PER2::LUC rhythms were routinely measured from whole-mount retinal explants for 10 d and for up to 30 d. Imaging of vertical retinal slices demonstrated that the rhythmic luminescence signals were concentrated in the inner nuclear layer. Interruption of cell communication via the major neurotransmitter systems of photoreceptors and ganglion cells (melatonin and glutamate and the inner nuclear layer (dopamine, acetylcholine, GABA, glycine, and glutamate did not disrupt generation of retinal circadian PER2::LUC rhythms, nor did interruption of intercellular communication through sodium-dependent action potentials or connexin 36 (cx36-containing gap junctions, indicating that PER2::LUC rhythms generation in the inner nuclear layer is likely cell autonomous. However, dopamine, acting through D1 receptors, and GABA, acting through membrane hyperpolarization and casein kinase, set the phase and amplitude of retinal PER2::LUC rhythms, respectively. Light pulses reset the phase of the in vitro retinal oscillator and dopamine D1 receptor antagonists attenuated these phase shifts. Thus, dopamine and GABA act at the molecular level of PER

  12. Biological Clocks & Circadian Rhythms

    Science.gov (United States)

    Robertson, Laura; Jones, M. Gail

    2009-01-01

    The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian…

  13. Circadian rhythms regulate amelogenesis.

    Science.gov (United States)

    Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

    2013-07-01

    Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Pacemaker patients’ perspective and experiences in a pacemaker outpatient clinic in relation to test intervals of the pacemaker

    DEFF Research Database (Denmark)

    Lauberg, Astrid; Hansen, Tina; Pedersen, Trine Pernille Dahl

    an evident decline in quality of life regarding psychological and social aspects 6 month after the implantation in terms of cognitive function, work ability, and sexual activity. Mlynarski et al (2009) have found correlations between pacemaker implantation and anxiety and depression. Aim The aim...... the pacemaker and psychological reactions. Patients with pacemakers older than 3 months lacked communication with fellowmen. Conclusion The patients express receiving competent and professional treatment when visiting the outpatient clinic, there seems to be a discrepancy between the long test intervals...... and the critical period in which anxiety and depression may occur. Minor problems and questions may grow into fatal conditions if the patients are not offered an opportunity to discuss this with experts. Patients are not informed that it is possible to discuss problems that imply psychological topics and they do...

  15. Synchronization of Coupled Neurons Controlled by a Pacemaker

    International Nuclear Information System (INIS)

    Li Mei-Sheng; Zhang Hong-Hui; Zhao Yong; Shi Xia

    2011-01-01

    We investigate synchronization of Hindmarsh—Rose neurons with gap junctions under the control of a pacemaker. In a ring Hindmarsh—Rose neuronal network, the coupled neurons with the pacemaker can occur in synchronization more easily than those without the pacemaker. Furthermore, the pacemaker can induce phase synchronization or nearly-complete synchronization of nonidentical neurons. This synchronization can occur more easily when time delay is considered. Theses results can be helpful to understand the activities of the real neuronal system. (general)

  16. 21 CFR 870.3730 - Pacemaker service tools.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker service tools. 870.3730 Section 870.3730...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3730 Pacemaker service tools. (a) Identification. Pacemaker service tools are devices such as screwdrivers and Allen wrenches...

  17. 21 CFR 870.5550 - External transcutaneous cardiac pacemaker (noninvasive).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External transcutaneous cardiac pacemaker... § 870.5550 External transcutaneous cardiac pacemaker (noninvasive). (a) Identification. An external transcutaneous cardiac pacemaker (noninvasive) is a device used to supply a periodic electrical pulse intended to...

  18. 21 CFR 870.3720 - Pacemaker electrode function tester.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker electrode function tester. 870.3720... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3720 Pacemaker electrode function tester. (a) Identification. A pacemaker electrode function tester is a device which is...

  19. 21 CFR 870.3650 - Pacemaker polymeric mesh bag.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker polymeric mesh bag. 870.3650 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. (a) Identification. A pacemaker polymeric mesh bag is an implanted device used to hold a...

  20. 21 CFR 870.3630 - Pacemaker generator function analyzer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker generator function analyzer. 870.3630... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device that is...

  1. 21 CFR 870.3710 - Pacemaker repair or replacement material.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

  2. Analysis of a five year experience of permanent pacemaker ...

    African Journals Online (AJOL)

    Introduction: Permanent pacemaker implantation is available in Nigeria. There is however no national registry or framework for pacemaker data collection. A pacemaker database has been developed in our institution and the results are analyzed in this study. Methods: The study period was between January 2008 and ...

  3. Wenckebach upper rate response in single chamber pacemaker.

    Science.gov (United States)

    Barold, S S

    2000-07-01

    The Medtronic Minix pacemaker during normal function in the VVT mode was found to exhibit a Wenckenbach upper rate response similar to that of dual chamber devices. This behavior occurred only when the upper rate interval was longer than the pacemaker refractory period. In a single chamber device this response may simulate pacemaker malfunction.

  4. 21 CFR 870.3690 - Pacemaker test magnet.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker test magnet. 870.3690 Section 870.3690...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet. (a) Identification. A pacemaker test magnet is a device used to test an inhibited or triggered type...

  5. Uniform pacemaker and ICD information system in the Netherlands

    NARCIS (Netherlands)

    Cam, H; Wa, D; Callaos, N; Farsi, D; EshaghianWilner, M; Hanratty, T; Rishe, N

    2003-01-01

    The Central Pacemaker Patient Registry (CPPR) in the Netherlands (founded in 1977) collects information of pacemaker patients from all 110 Dutch hospitals. It contains data of over 98.000 patients, 118.500 pacemakers, 1.950 ICD's and 131.000 leads. Initially data was entered manually. As local

  6. The pacemaker-twiddler's syndrome: an infrequent cause of pacemaker failure.

    Science.gov (United States)

    Salahuddin, Mohammad; Cader, Fathima Aaysha; Nasrin, Sahela; Chowdhury, Mashhud Zia

    2016-01-20

    The pacemaker-twiddler's syndrome is an uncommon cause of pacemaker malfunction. It occurs due to unintentional or deliberate manipulation of the pacemaker pulse generator within its skin pocket by the patient. This causes coiling of the lead and its dislodgement, resulting in failure of ventricular pacing. More commonly reported among elderly females with impaired cognition, the phenomenon usually occurs in the first year following pacemaker implantation. Treatment involves repositioning of the dislodged leads and suture fixation of the lead and pulse generator within its pocket. An 87 year old Bangladeshi lady who underwent a single chamber ventricular pacemaker (VVI mode: i.e. ventricle paced, ventricle sensed, inhibitory mode) implantation with the indication of complete heart block, and presented to us again 7 weeks later, with syncopal attacks. She admitted to repeatedly manipulating the pacemaker generator in her left pectoral region. Physical examination revealed a heart rate of 42 beats/minute, blood pressure 140/80 mmHg and bilateral crackles on lung auscultation. She had no cognitive deficit. An immediate electrocardiogram showed complete heart block with pacemaker spikes and failure to capture. Chest X-ray showed coiled and retracted right ventricular lead and rotated pulse generator. An emergent temporary pace maker was set at a rate of 60 beats per minute. Subsequently, she underwent successful lead repositioning with strong counselling to avoid further twiddling. Twiddler's syndrome should be considered as a cause of pacemaker failure in elderly patients presenting with bradyarrythmias following pacemaker implantation. Chest X-ray and electrocardiograms are simple and easily-available first line investigations for its diagnosis. Lead repositioning is required, however proper patient education and counselling against further manipulation is paramount to long-term management.

  7. Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures.

    Science.gov (United States)

    Potter, Gregory D M; Skene, Debra J; Arendt, Josephine; Cade, Janet E; Grant, Peter J; Hardie, Laura J

    2016-12-01

    Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.

  8. Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures

    Science.gov (United States)

    Skene, Debra J.; Arendt, Josephine; Cade, Janet E.; Grant, Peter J.; Hardie, Laura J.

    2016-01-01

    Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important. PMID:27763782

  9. Neural Mechanisms of Circadian Regulation of Natural and Drug Reward

    Directory of Open Access Journals (Sweden)

    Lauren M. DePoy

    2017-01-01

    Full Text Available Circadian rhythms are endogenously generated near 24-hour variations of physiological and behavioral functions. In humans, disruptions to the circadian system are associated with negative health outcomes, including metabolic, immune, and psychiatric diseases, such as addiction. Animal models suggest bidirectional relationships between the circadian system and drugs of abuse, whereby desynchrony, misalignment, or disruption may promote vulnerability to drug use and the transition to addiction, while exposure to drugs of abuse may entrain, disrupt, or perturb the circadian timing system. Recent evidence suggests natural (i.e., food and drug rewards may influence overlapping neural circuitry, and the circadian system may modulate the physiological and behavioral responses to these stimuli. Environmental disruptions, such as shifting schedules or shorter/longer days, influence food and drug intake, and certain mutations of circadian genes that control cellular rhythms are associated with altered behavioral reward. We highlight the more recent findings associating circadian rhythms to reward function, linking environmental and genetic evidence to natural and drug reward and related neural circuitry.

  10. Electromagnetic and radiation environments: effects on pacemakers

    International Nuclear Information System (INIS)

    Mouton, J.; Trochet, R.; Vicrey, J.; Sauvage, M.; Chauvenet, B.; Ostrovski, A.; Leroy, E.; Haug, R.; Dodinot, B.; Joffre, F.

    1999-01-01

    Nowadays, medical care development allows many people to share the benefits of implanted pacemakers (PM). PM can be perturbed and even fall in complete breakdowns in an electromagnetic and radiation environment. A stimuli-dependent patient can thus be seriously in danger. This article presents the effect of ionizing radiation from either a cobalt-60 source or from a linear accelerator (Saturne 43) on 12 pacemakers. It seems that technological progress make electronic circuits more sensitive to the cumulated dose of radiation. This survey shows that pacemakers have great difficulties to sustain ionizing radiation doses that are commonly delivered to patients during therapies. Usually perturbed functioning appears suddenly and means a strong shift of stimuli that might lead to heart failure

  11. Does bipolar pacemaker current activate blood platelets?

    DEFF Research Database (Denmark)

    Gjesdal, Grunde; Hansen, Annebirthe Bo; Brandes, Axel

    2009-01-01

    OBJECTIVE: The aim of this study was to investigate whether bipolar pacemaker current lead can activate blood platelets. The null hypothesis was that 1 minute of electrical stimulation of platelets would not influence their subsequent reactivity to adenosine diphosphate (ADP). BACKGROUND: Both...... platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets......, to the depolarizing current. Platelet activation may ensue, resulting in aggregation, release reaction, and contraction. In contrast, a unipolar pacemaker system will not depolarize blood, but transmit current directly into the myocardium, and the current afterward passes through other tissues before returning...

  12. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock

    OpenAIRE

    David M. Virshup; Rajesh Narasimamurthy

    2017-01-01

    An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep–wake cycle, feeding–fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entr...

  13. Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels.

    Science.gov (United States)

    Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

    2016-01-01

    The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca(2+)-activated K(+) channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

  14. Pineal photoreceptor cells are required for maintaining the circadian rhythms of behavioral visual sensitivity in zebrafish.

    Directory of Open Access Journals (Sweden)

    Xinle Li

    Full Text Available In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity.

  15. Adrenal clocks and the role of adrenal hormones in the regulation of circadian physiology.

    Science.gov (United States)

    Leliavski, Alexei; Dumbell, Rebecca; Ott, Volker; Oster, Henrik

    2015-02-01

    The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders. © 2014 The Author(s).

  16. Pigment-Dispersing Factor-expressing neurons convey circadian information in the honey bee brain

    Science.gov (United States)

    Beer, Katharina; Kolbe, Esther; Kahana, Noa B.; Yayon, Nadav; Weiss, Ron; Menegazzi, Pamela; Bloch, Guy

    2018-01-01

    Pigment-Dispersing Factor (PDF) is an important neuropeptide in the brain circadian network of Drosophila and other insects, but its role in bees in which the circadian clock influences complex behaviour is not well understood. We combined high-resolution neuroanatomical characterizations, quantification of PDF levels over the day and brain injections of synthetic PDF peptide to study the role of PDF in the honey bee Apis mellifera. We show that PDF co-localizes with the clock protein Period (PER) in a cluster of laterally located neurons and that the widespread arborizations of these PER/PDF neurons are in close vicinity to other PER-positive cells (neurons and glia). PDF-immunostaining intensity oscillates in a diurnal and circadian manner with possible influences for age or worker task on synchrony of oscillations in different brain areas. Finally, PDF injection into the area between optic lobes and the central brain at the end of the subjective day produced a consistent trend of phase-delayed circadian rhythms in locomotor activity. Altogether, these results are consistent with the hypothesis that PDF is a neuromodulator that conveys circadian information from pacemaker cells to brain centres involved in diverse functions including locomotion, time memory and sun-compass orientation. PMID:29321240

  17. Circadian rhythms of Per2::Luc in individual primary mouse hepatocytes and cultures.

    Directory of Open Access Journals (Sweden)

    Casey J Guenthner

    Full Text Available BACKGROUND: Hepatocytes, the parenchymal cells of the liver, express core clock genes, such as Period2 and Cryptochrome2, which are involved in the transcriptional/translational feedback loop of the circadian clock. Whether or not the liver is capable of sustaining rhythms independent of a central pacemaker is controversial. Whether and how circadian information may be shared among cells in the liver in order to sustain oscillations is currently unknown. RESULTS: In this study we isolated primary hepatocytes from transgenic Per2(Luc mice and used bioluminescence as a read-out of the state of the circadian clock. Hepatocytes cultured in a collagen gel sandwich configuration exhibited persistent circadian rhythms for several weeks. The amplitude of the rhythms damped, but medium changes consistently reset the phase and amplitude of the cultures. Cry2(-/- Per2(Luc cells oscillated robustly and expressed a longer period. Co-culturing with wildtype cells did not significantly shorten the period, indicating that coupling among hepatocytes is insufficient to synchronize cells with significantly differing periods. However, spatial patterns revealed by cellular imaging of wildtype cultures provided evidence of weak local coupling among the hepatocytes. CONCLUSIONS: Our results with primary hepatocyte cultures demonstrate that cultured hepatocytes are weakly coupled. While this coupling is not sufficient to sustain global synchrony, it does increase local synchrony, which may stabilize the circadian rhythms of peripheral oscillators, such as the liver, against noise in the entraining signals.

  18. Modified-release hydrocortisone to provide circadian cortisol profiles.

    Science.gov (United States)

    Debono, Miguel; Ghobadi, Cyrus; Rostami-Hodjegan, Amin; Huatan, Hiep; Campbell, Michael J; Newell-Price, John; Darzy, Ken; Merke, Deborah P; Arlt, Wiebke; Ross, Richard J

    2009-05-01

    Cortisol has a distinct circadian rhythm regulated by the brain's central pacemaker. Loss of this rhythm is associated with metabolic abnormalities, fatigue, and poor quality of life. Conventional glucocorticoid replacement cannot replicate this rhythm. Our objectives were to define key variables of physiological cortisol rhythm, and by pharmacokinetic modeling test whether modified-release hydrocortisone (MR-HC) can provide circadian cortisol profiles. The study was performed at a Clinical Research Facility. Using data from a cross-sectional study in healthy reference subjects (n = 33), we defined parameters for the cortisol rhythm. We then tested MR-HC against immediate-release hydrocortisone in healthy volunteers (n = 28) in an open-label, randomized, single-dose, cross-over study. We compared profiles with physiological cortisol levels, and modeled an optimal treatment regimen. The key variables in the physiological cortisol profile included: peak 15.5 microg/dl (95% reference range 11.7-20.6), acrophase 0832 h (95% confidence interval 0759-0905), nadir less than 2 microg/dl (95% reference range 1.5-2.5), time of nadir 0018 h (95% confidence interval 2339-0058), and quiescent phase (below the mesor) 1943-0531 h. MR-HC 15 mg demonstrated delayed and sustained release with a mean (sem) maximum observed concentration of 16.6 (1.4) microg/dl at 7.41 (0.57) h after drug. Bioavailability of MR-HC 5, 10, and 15 mg was 100, 79, and 86% that of immediate-release hydrocortisone. Modeling suggested that MR-HC 15-20 mg at 2300 h and 10 mg at 0700 h could reproduce physiological cortisol levels. By defining circadian rhythms and using modern formulation technology, it is possible to allow a more physiological circadian replacement of cortisol.

  19. Nuclear-powered pacemaker fuel cladding study

    International Nuclear Information System (INIS)

    Shoup, R.L.

    1976-07-01

    The fabrication of fuel capsules with refractory metal and alloy clads used in nuclear-powered cardiac pacemakers precludes the expedient dissolution of the clad in inorganic acid solutions. An experiment to measure penetration rates of acids on commonly used fuel pellet clads indicated that it is not impossible, but that it would be very difficult to dissolve the multiple cladding. This work was performed because of a suggestion that a 238 PuO 2 -powered pacemaker could be transformed into a terrorism weapon

  20. Human phase response curve to a 1 h pulse of bright white light

    Science.gov (United States)

    St Hilaire, Melissa A; Gooley, Joshua J; Khalsa, Sat Bir S; Kronauer, Richard E; Czeisler, Charles A; Lockley, Steven W

    2012-01-01

    The phase resetting response of the human circadian pacemaker to light depends on the timing of exposure and is described by a phase response curve (PRC). The current study aimed to construct a PRC for a 1 h exposure to bright white light (∼8000 lux) and to compare this PRC to a dim background light PRC. These data were also compared to a previously completed 6.7 h bright white light PRC and a dim background light PRC constructed under similar conditions. Participants were randomized for exposure to 1 h of either bright white light (n= 18) or dim background light (n= 18) scheduled at 1 of 18 circadian phases. Participants completed constant routine (CR) procedures in dim light (light exposure to assess circadian phase. Phase shifts were calculated as the difference in timing of dim light melatonin onset (DLMO) during pre- and post-stimulus CRs. Exposure to 1 h of bright white light induced a Type 1 PRC with a fitted peak-to-trough amplitude of 2.20 h. No discernible PRC was observed in the dim background light PRC. The fitted peak-to-trough amplitude of the 1 h bright light PRC was ∼40% of that for the 6.7 h PRC despite representing only 15% of the light exposure duration, consistent with previous studies showing a non-linear duration–response function for the effects of light on circadian resetting. PMID:22547633

  1. The influence of radiation therapy on cardiac pacemakers

    International Nuclear Information System (INIS)

    Coles, J.R.; Ciddor, G.S.

    1980-01-01

    The results of an investigation to determine the influence on pacemaking of ionizing radiation and electromagnetic radiation from a number of radiotherapy machines are reported. In vitro tests were carried out on unipolar cardiac pacemakers of the ventricular inhibited type. The pacemakers were largely unaffected by the environment of clinical radiotherapy machines. Ionizing radiation had no detrimental effect on the pacemakers and electromagnetic interference caused only temporary single-beat inhibition at most. With the betatron used, malfunction of the pacemakers regularly occurred whilst in their inhibited made of operation. The demand function became disabled allowing competitive asynchronous pulses to be produced

  2. Leadless Pacemakers: State of the Art and Future Perspectives.

    Science.gov (United States)

    Della Rocca, Domenico G; Gianni, Carola; Di Biase, Luigi; Natale, Andrea; Al-Ahmad, Amin

    2018-03-01

    Leadless pacemaker therapy is a new technology that aims at avoiding lead- and pocket-related complications of conventional transvenous and epicardial pacing. To date, 2 self-contained leadless pacemakers for right ventricular pacing have been clinically available: the Nanostim Leadless Pacemaker System and the Micra Transcatheter Pacing System. Additionally, a new multicomponent leadless pacemaker for endocardial left ventricular pacing has been proposed as an alternative choice for cardiac resynchronization therapy. In this review, we describe the state of the art of leadless pacing and compare the currently available devices with traditional transvenous leadless pacemakers. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The Development of the circadian heart rate rhytm (CDR) in Asian infants

    OpenAIRE

    Stanislaus Sandarupa, Drs., M.A., Ph.D.

    2011-01-01

    Although the human fetus can follow the maternal circadian thythm, the enterained expression of the circadian clock, based in the suprachiasmatic nucleus (SCN) of the hypothalamus awaits postnatal maturation of the retinal hypothalamic tract, and melatonin neurotransmission. Objective: To test the hypothesis that term-born Asian Infants, at reduced risk to die of Sudden Infant Death Syndrome (SIDS) exhibit a circadian heat rate thythm (CHR) at a later age than non-Asian term infants.

  4. Circadian dysregulation in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Aleksandar Videnovic

    2017-01-01

    Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disorder that affects over one million individuals in the US alone. PD is characterized by a plethora of motor and non-motor manifestations, resulting from a progressive degeneration of dopaminergic neurons and disbalance of several other neurotransmitters. A growing body of evidence points to significant alterations of the circadian system in PD. This is not surprising given the pivotal role that dopamine plays in circadian regulation as well as the role of circadian influences in dopamine metabolism. In this review we present basic and clinical investigations that examined the function of the circadian system in PD.

  5. Redox regulation and pro-oxidant reactions in the physiology of circadian systems.

    Science.gov (United States)

    Méndez, Isabel; Vázquez-Martínez, Olivia; Hernández-Muñoz, Rolando; Valente-Godínez, Héctor; Díaz-Muñoz, Mauricio

    2016-05-01

    Rhythms of approximately 24 h are pervasive in most organisms and are known as circadian. There is a molecular circadian clock in each cell sustained by a feedback system of interconnected "clock" genes and transcription factors. In mammals, the timing system is formed by a central pacemaker, the suprachiasmatic nucleus, in coordination with a collection of peripheral oscillators. Recently, an extensive interconnection has been recognized between the molecular circadian clock and the set of biochemical pathways that underlie the bioenergetics of the cell. A principle regulator of metabolic networks is the flow of electrons between electron donors and acceptors. The concomitant reduction and oxidation (redox) reactions directly influence the balance between anabolic and catabolic processes. This review summarizes and discusses recent findings concerning the mutual and dynamic interactions between the molecular circadian clock, redox reactions, and redox signaling. The scope includes the regulatory role played by redox coenzymes (NAD(P)+/NAD(P)H, GSH/GSSG), reactive oxygen species (superoxide anion, hydrogen peroxide), antioxidants (melatonin), and physiological events that modulate the redox state (feeding condition, circadian rhythms) in determining the timing capacity of the molecular circadian clock. In addition, we discuss a purely metabolic circadian clock, which is based on the redox enzymes known as peroxiredoxins and is present in mammalian red blood cells and in other biological systems. Both the timing system and the metabolic network are key to a better understanding of widespread pathological conditions such as the metabolic syndrome, obesity, and diabetes. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  6. A dual-color luciferase assay system reveals circadian resetting of cultured fibroblasts by co-cultured adrenal glands.

    Directory of Open Access Journals (Sweden)

    Takako Noguchi

    Full Text Available In mammals, circadian rhythms of various organs and tissues are synchronized by pacemaker neurons in the suprachiasmatic nucleus (SCN of the hypothalamus. Glucocorticoids released from the adrenal glands can synchronize circadian rhythms in other tissues. Many hormones show circadian rhythms in their plasma concentrations; however, whether organs outside the SCN can serve as master synchronizers to entrain circadian rhythms in target tissues is not well understood. To further delineate the function of the adrenal glands and the interactions of circadian rhythms in putative master synchronizing organs and their target tissues, here we report a simple co-culture system using a dual-color luciferase assay to monitor circadian rhythms separately in various explanted tissues and fibroblasts. In this system, circadian rhythms of organs and target cells were simultaneously tracked by the green-emitting beetle luciferase from Pyrearinus termitilluminans (ELuc and the red-emitting beetle luciferase from Phrixothrix hirtus (SLR, respectively. We obtained tissues from the adrenal glands, thyroid glands, and lungs of transgenic mice that expressed ELuc under control of the promoter from a canonical clock gene, mBmal1. The tissues were co-cultured with Rat-1 fibroblasts as representative target cells expressing SLR under control of the mBmal1 promoter. Amplitudes of the circadian rhythms of Rat-1 fibroblasts were potentiated when the fibroblasts were co-cultured with adrenal gland tissue, but not when co-cultured with thyroid gland or lung tissue. The phases of Rat-1 fibroblasts were reset by application of adrenal gland tissue, whereas the phases of adrenal gland tissue were not influenced by Rat-1 fibroblasts. Furthermore, the effect of the adrenal gland tissue on the fibroblasts was blocked by application of a glucocorticoid receptor (GR antagonist. These results demonstrate that glucocorticoids are strong circadian synchronizers for fibroblasts and that

  7. Circadian rhythms in cognitive performance: implications for neuropsychological assessment

    Directory of Open Access Journals (Sweden)

    Valdez P

    2012-12-01

    Full Text Available Pablo Valdez, Candelaria Ramírez, Aída GarcíaLaboratory of Psychophysiology, School of Psychology, University of Nuevo León, Monterrey, Nuevo León, MéxicoAbstract: Circadian variations have been found in human performance, including the efficiency to execute many tasks, such as sensory, motor, reaction time, time estimation, memory, verbal, arithmetic calculations, and simulated driving tasks. Performance increases during the day and decreases during the night. Circadian rhythms have been found in three basic neuropsychological processes (attention, working memory, and executive functions, which may explain oscillations in the performance of many tasks. The time course of circadian rhythms in cognitive performance may be modified significantly in patients with brain disorders, due to chronotype, age, alterations of the circadian rhythm, sleep deprivation, type of disorder, and medication. This review analyzes the recent results on circadian rhythms in cognitive performance, as well as the implications of these rhythms for the neuropsychological assessment of patients with brain disorders such as traumatic head injury, stroke, dementia, developmental disorders, and psychiatric disorders.Keywords: human circadian rhythms, cognitive performance, neuropsychological assessment, attention, working memory, executive functions

  8. Biventricular pacemaker implantation with the BV Pulsera

    Energy Technology Data Exchange (ETDEWEB)

    Wright, J.D.W.; Todd, D.; Waktare, J.E.P.; Hughes, S.; Abell, C. [The Cardiothoracic Centre, Liverpool (United Kingdom)

    2005-07-01

    The BV Pulsera mobile X-ray system is used for biventricular pacemaker implantation in a surgical environment. It provides high-quality images of the moving structures, including the fine coronary leads, and can be used for long fluoroscopy runs without overheating. (orig.)

  9. Biventricular pacemaker implantation with the BV Pulsera

    International Nuclear Information System (INIS)

    Wright, J.D.W.; Todd, D.; Waktare, J.E.P.; Hughes, S.; Abell, C.

    2005-01-01

    The BV Pulsera mobile X-ray system is used for biventricular pacemaker implantation in a surgical environment. It provides high-quality images of the moving structures, including the fine coronary leads, and can be used for long fluoroscopy runs without overheating. (orig.)

  10. Keeping the Rhythm : Cardiac Pacemaker Cell Development

    NARCIS (Netherlands)

    Burkhard, S.B.

    2017-01-01

    The heart is the first organ to form and function in the developing vertebrate embryo. Its proper morphogenesis and function is crucial for survival. Here we focus on the development and characterization of a highly specialized subset of cardiac cells, the pacemaker cells. In the mammalian heart,

  11. Quality assessment of pacemaker implantations in Denmark

    DEFF Research Database (Denmark)

    Møller, M; Arnsbo, P; Asklund, Mogens

    2002-01-01

    AIMS: Quality assessment of therapeutic procedures is essential to insure a cost-effective health care system. Pacemaker implantation is a common procedure with more than 500,000 implantations world-wide per year, but the general complication rate is not well described. We studied procedure relat...

  12. Metabolic effects of bariatric surgery in mouse models of circadian disruption.

    Science.gov (United States)

    Arble, D M; Sandoval, D A; Turek, F W; Woods, S C; Seeley, R J

    2015-08-01

    Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (for example, night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared with the non-disrupted population. However, it is unclear whether the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity. Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in mouse models of genetic and environmental circadian disruption. VSG led to a reduction in body weight and fat mass in both Clock(Δ19) mutant and constant-light mouse models (Pdisruption. Interestingly, the decrease in body weight occurred without altering diurnal feeding or activity patterns (P>0.05). Within circadian-disrupted models, VSG also led to improved glucose tolerance and lipid handling (Pdisruption, and that the potent effects of bariatric surgery are orthogonal to circadian biology. However, as the effects of bariatric surgery are independent of circadian disruption, VSG cannot be considered a cure for circadian disruption. These data have important implications for circadian-disrupted obese patients. Moreover, these results reveal new information about the metabolic pathways governing the effects of bariatric surgery as well as of circadian disruption.

  13. Measuring pacemaker dose: A clinical perspective

    Energy Technology Data Exchange (ETDEWEB)

    Studenski, Matthew T., E-mail: matthew.studenski@jeffersonhospital.org [Department of Radiation Oncology at the Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Xiao Ying; Harrison, Amy S. [Department of Radiation Oncology at the Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

    2012-07-01

    Recently in our clinic, we have seen an increased number of patients presenting with pacemakers and defibrillators. Precautions are taken to develop a treatment plan that minimizes the dose to the pacemaker because of the adverse effects of radiation on the electronics. Here we analyze different dosimeters to determine which is the most accurate in measuring pacemaker or defibrillator dose while at the same time not requiring a significant investment in time to maintain an efficient workflow in the clinic. The dosimeters analyzed here were ion chambers, diodes, metal-oxide-semiconductor field effect transistor (MOSFETs), and optically stimulated luminescence (OSL) dosimeters. A simple phantom was used to quantify the angular and energy dependence of each dosimeter. Next, 8 patients plans were delivered to a Rando phantom with all the dosimeters located where the pacemaker would be, and the measurements were compared with the predicted dose. A cone beam computed tomography (CBCT) image was obtained to determine the dosimeter response in the kilovoltage energy range. In terms of the angular and energy dependence of the dosimeters, the ion chamber and diode were the most stable. For the clinical cases, all the dosimeters match relatively well with the predicted dose, although the ideal dosimeter to use is case dependent. The dosimeters, especially the MOSFETS, tend to be less accurate for the plans, with many lateral beams. Because of their efficiency, we recommend using a MOSFET or a diode to measure the dose. If a discrepancy is observed between the measured and expected dose (especially when the pacemaker to field edge is <10 cm), we recommend analyzing the treatment plan to see whether there are many lateral beams. Follow-up with another dosimeter rather than repeating multiple times with the same type of dosimeter. All dosimeters should be placed after the CBCT has been acquired.

  14. Precise Estimation of Cellular Radio Electromagnetic Field in Elevators and EMI Impact on Implantable Cardiac Pacemakers

    Science.gov (United States)

    Harris, Louis-Ray; Hikage, Takashi; Nojima, Toshio

    The purpose of this paper is to investigate the possible impact of cellular phones' signals on implantable cardiac pacemakers in elevators. This is achieved by carrying out precise numerical simulations based on the Finite-Difference-Time-Domain method to examine the electromagnetic fields in elevator models. In order to examine the realistic and complicated situations where humans are present in the elevator, we apply the realistic homogeneous human phantom and cellular radios operating in the frequency bands 800MHz, 1.5GHz and 2GHz. These computed results of field strength inside the elevator are compared with a certain reference level determined from the experimentally obtained maximum interference distance of implantable cardiac pacemakers. This enables us to carry out a quantitative evaluation of the EMI risk to pacemakers by cellular radio transmission. The results show that for the case when up to 5 mobile radio users are present in the elevator model used, there is no likelihood of pacemaker malfunction for the frequency bands 800MHz, 1.5GHz and 2GHz.

  15. Alteration of circadian rhythm during epileptogenesis: implications for the suprachiasmatic nucleus circuits.

    Science.gov (United States)

    Xiang, Yan; Li, Zhi-Xiao; Zhang, Ding-Yu; He, Zhi-Gang; Hu, Ji; Xiang, Hong-Bing

    2017-01-01

    It is important to realize that characterization of the circadian rhythm patterns of seizure occurrence can implicate in diagnosis and treatment of selected types of epilepsy. Evidence suggests a role for the suprachiasmatic nucleus (SCN) circuits in overall circadian rhythm and seizure susceptibility both in animals and humans. Thus, we conclude that SCN circuits may exert modifying effects on circadian rhythmicity and neuronal excitability during epileptogenesis. SCN circuits will be studied in our brain centre and collaborating centres to explore further the interaction between the circadian rhythm and epileptic seizures. More and thorough research is warranted to provide insight into epileptic seizures with circadian disruption comorbidities such as disorders of cardiovascular parameters and core body temperature circadian rhythms.

  16. Phase delaying the human circadian clock with a single light pulse and moderate delay of the sleep/dark episode: no influence of iris color.

    Science.gov (United States)

    Canton, Jillian L; Smith, Mark R; Choi, Ho-Sun; Eastman, Charmane I

    2009-07-17

    Light exposure in the late evening and nighttime and a delay of the sleep/dark episode can phase delay the circadian clock. This study assessed the size of the phase delay produced by a single light pulse combined with a moderate delay of the sleep/dark episode for one day. Because iris color or race has been reported to influence light-induced melatonin suppression, and we have recently reported racial differences in free-running circadian period and circadian phase shifting in response to light pulses, we also tested for differences in the magnitude of the phase delay in subjects with blue and brown irises. Subjects (blue-eyed n = 7; brown eyed n = 6) maintained a regular sleep schedule for 1 week before coming to the laboratory for a baseline phase assessment, during which saliva was collected every 30 minutes to determine the time of the dim light melatonin onset (DLMO). Immediately following the baseline phase assessment, which ended 2 hours after baseline bedtime, subjects received a 2-hour bright light pulse (~4,000 lux). An 8-hour sleep episode followed the light pulse (i.e. was delayed 4 hours from baseline). A final phase assessment was conducted the subsequent night to determine the phase shift of the DLMO from the baseline to final phase assessment.Phase delays of the DLMO were compared in subjects with blue and brown irises. Iris color was also quantified from photographs using the three dimensions of red-green-blue color axes, as well as a lightness scale. These variables were correlated with phase shift of the DLMO, with the hypothesis that subjects with lighter irises would have larger phase delays. The average phase delay of the DLMO was -1.3 +/- 0.6 h, with a maximum delay of ~2 hours, and was similar for subjects with blue and brown irises. There were no significant correlations between any of the iris color variables and the magnitude of the phase delay. A single 2-hour bright light pulse combined with a moderate delay of the sleep/dark episode

  17. Phase delaying the human circadian clock with a single light pulse and moderate delay of the sleep/dark episode: no influence of iris color

    Directory of Open Access Journals (Sweden)

    Choi Ho-Sun

    2009-07-01

    Full Text Available Abstract Background Light exposure in the late evening and nighttime and a delay of the sleep/dark episode can phase delay the circadian clock. This study assessed the size of the phase delay produced by a single light pulse combined with a moderate delay of the sleep/dark episode for one day. Because iris color or race has been reported to influence light-induced melatonin suppression, and we have recently reported racial differences in free-running circadian period and circadian phase shifting in response to light pulses, we also tested for differences in the magnitude of the phase delay in subjects with blue and brown irises. Methods Subjects (blue-eyed n = 7; brown eyed n = 6 maintained a regular sleep schedule for 1 week before coming to the laboratory for a baseline phase assessment, during which saliva was collected every 30 minutes to determine the time of the dim light melatonin onset (DLMO. Immediately following the baseline phase assessment, which ended 2 hours after baseline bedtime, subjects received a 2-hour bright light pulse (~4,000 lux. An 8-hour sleep episode followed the light pulse (i.e. was delayed 4 hours from baseline. A final phase assessment was conducted the subsequent night to determine the phase shift of the DLMO from the baseline to final phase assessment. Phase delays of the DLMO were compared in subjects with blue and brown irises. Iris color was also quantified from photographs using the three dimensions of red-green-blue color axes, as well as a lightness scale. These variables were correlated with phase shift of the DLMO, with the hypothesis that subjects with lighter irises would have larger phase delays. Results The average phase delay of the DLMO was -1.3 ± 0.6 h, with a maximum delay of ~2 hours, and was similar for subjects with blue and brown irises. There were no significant correlations between any of the iris color variables and the magnitude of the phase delay. Conclusion A single 2-hour bright light

  18. Circadian Rhythms in Human Memory.

    Science.gov (United States)

    Folkard, Simon; Monk, Timothy H.

    1980-01-01

    Two experiments are described that examined the influence of time-of-day of presentation on immediate and delayed retention and its potential effects on retrieval from long-term memory. Time of presentation was found to influence both immediate and delayed (28 day) retention, but not retrieval from long-term memory. (Author/SJL)

  19. Circadian disruption and health: Shift work as a harbinger of the toll taken by electric lighting.

    Science.gov (United States)

    Stevens, Richard G

    Electric light is one of the signature inventions of human beings. A problem, however, is that electric light can confuse our endogenous circadian rhythmicity. It has now become apparent that circadian biology is fundamental to the functioning and adaptation of almost all life forms. In the modern world, everyone is exposed to electric light during the day and night, and thereby can experience some level of circadian disruption. Perhaps as a canary in the coal mine, study of people whose work hours include nighttime (shift workers) is beginning to yield insights on the adverse health effects of circadian disruption from electric light.

  20. Pacemakers and implantable cardioverter defibrillators - general and anesthetic considerations

    Directory of Open Access Journals (Sweden)

    Amy G. Rapsang

    2014-06-01

    Full Text Available A pacemaking system consists of an impulse generator and lead or leads to carry the electrical impulse to the patient's heart. Pacemaker and implantable cardioverter defibrillator codes were made to describe the type of pacemaker or implantable cardioverter defibrillator implanted. Indications for pacing and implantable cardioverter defibrillator implantation were given by the American College of Cardiologists. Certain pacemakers have magnet-operated reed switches incorporated; however, magnet application can have serious adverse effects; hence, devices should be considered programmable unless known otherwise. When a device patient undergoes any procedure (with or without anesthesia, special precautions have to be observed including a focused history/physical examination, interrogation of pacemaker before and after the procedure, emergency drugs/temporary pacing and defibrillation, reprogramming of pacemaker and disabling certain pacemaker functions if required, monitoring of electrolyte and metabolic disturbance and avoiding certain drugs and equipments that can interfere with pacemaker function. If unanticipated device interactions are found, consider discontinuation of the procedure until the source of interference can be eliminated or managed and all corrective measures should be taken to ensure proper pacemaker function should be done. Post procedure, the cardiac rate and rhythm should be monitored continuously and emergency drugs and equipments should be kept ready and consultation with a cardiologist or a pacemaker-implantable cardioverter defibrillator service may be necessary.

  1. Preliminary evidences of circadian fan activity rhythm in Sabella spallanzanii (Gmelin, 1791 (Polychaeta: Sabellidae

    Directory of Open Access Journals (Sweden)

    Jacopo Aguzzi

    2006-12-01

    Full Text Available The fan activity rhythm of Sabella spallanzanii (Gmelin, 1791 and its entrainment capability to light were studied. Animals were tested under constant darkness (DD followed by two consecutive 24 h light-darkness regimes: a first 11 h light period (LD and a second 9 h light period, with its phase inverted (DL. An infrared analogical video-camera took shots each 30 s. A number of pictures with open fan were counted every 15 min. In DD a weak free-running periodicity in the circadian range was found, thus reinforcing the matching of the 24 h period under study in both photoperiod regimes. A nocturnal activity was characterised with a consistent anticipation to lightOFF (i.e. entrainment. Moreover, this phase of entrainment differed between DL and LD. The presence of endogenous activity rhythm with a variable phase angle of entrainment is a distinctive feature of circadian pacemakers.

  2. The effects of chronic marijuana use on circadian entrainment.

    Science.gov (United States)

    Whitehurst, Lauren N; Fogler, Kethera; Hall, Kate; Hartmann, Matthew; Dyche, Jeff

    2015-05-01

    Animal literature suggests a connection between marijuana use and altered circadian rhythms. However, the effect has not yet been demonstrated in humans. The present study examined the effect of chronic marijuana use on human circadian function. Participants consisted of current users who reported smoking marijuana daily for at least a year and non-marijuana user controls. Participants took a neurocognitive assessment, wore actigraphs and maintained sleep diaries for three weeks. While no significant cognitive changes were found between groups, data revealed that chronic marijuana use may act as an additional zeitgeber and lead to increased entrainment in human users.

  3. Troponin T elevation after permanent pacemaker implantation.

    Science.gov (United States)

    Chen, Xueying; Yu, Ziqing; Bai, Jin; Hu, Shulan; Wang, Wei; Qin, Shengmei; Wang, Jingfeng; Sun, Zhe; Su, Yangang; Ge, Junbo

    2017-08-01

    The objective of the study is to study the incidence, significance, and factors associated with cardiac troponin T (CTNT) elevation after pacemaker implantation. Three hundred seventy-four patients (104 single-chamber pacemakers or ICD, 243 dual-chamber pacemakers, and 27 cardiac resynchronization therapy/cardiac resynchronization therapy defibrillator) who had normal levels of CTNT at baseline and underwent implantation of a permanent pacemaker system were included in this study. Serum levels of CTNT were measured at baseline, 6 and 24 h after the implantation procedure. The median of CTNT levels increased from 0.012 ng/mL at baseline to 0.032 and 0.019 ng/mL at 6 and 24 h after the procedure, respectively (all p 0.09 ng/mL). After 1-year follow-up, the incidence of complications including dislodgement of the lead, pocket infection, pneumothorax, hemothorax, and vein thrombus and cardiac outcomes including hospitalization of heart failure, coronary artery disease, arrhythmia, and cardiovascular mortality was not significantly different between the normal and elevated CTNT groups at 6 h after the procedure. By logistic regression analysis, gender, N-terminal pro-B type natriuretic peptide (NT-pro-BNP) at baseline, left ventricular ejection fractions (LVEF), estimated glomerular filtration rate (eGFR), and fluoroscopy time were independently associated with CTNT elevation after adjusted for age, pacemaker types, right ventricle lead location (RVA or RVOT), heart function, and left ventricular end systolic dimension. Pacemaker implantation was found to be accompanied with CTNT elevation in 55.6% of the patients at 6 h after the procedure, and its kinetics were fast, which might not be related to the complications and adverse cardiac outcomes within 1 year of follow-up. Moreover, gender, NT-pro-BNP at baseline, LVEF, eGFR, and fluoroscopy time were found to be independent predictors of CTNT elevation.

  4. Sex and ancestry determine the free-running circadian period.

    Science.gov (United States)

    Eastman, Charmane I; Tomaka, Victoria A; Crowley, Stephanie J

    2017-10-01

    The endogenous, free-running circadian period (τ) determines the phase relationship that an organism assumes when entrained to the 24-h day. We found a shorter circadian period in African Americans compared to non-Hispanic European Americans (24.07 versus 24.33 h). We speculate that a short circadian period, closer to 24 h, was advantageous to humans living around the equator, but when humans migrated North out of Africa, where the photoperiod changes with seasons, natural selection favoured people with longer circadian periods. Recently, in evolutionary terms, immigrants came from Europe and Africa to America ('the New World'). The Europeans were descendents of people who had lived in Europe for thousands of years with changing photoperiods (and presumably longer periods), whereas Africans had ancestors who had always lived around the equator (with shorter periods). It may have been advantageous to have a longer circadian period while living in Europe early in the evolution of humans. In our modern world, however, it is better to have a shorter period, because it helps make our circadian rhythms earlier, which is adaptive in our early-bird-dominated society. European American women had a shorter circadian period than men (24.24 versus 24.41), but there was no sex difference in African Americans (24.07 for both men and women). We speculate that selection pressures in Europe made men develop a slightly longer period than women to help them track dawn which could be useful for hunters, but less important for women as gatherers. © 2017 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

  5. Gremlin-2 is a BMP antagonist that is regulated by the circadian clock

    DEFF Research Database (Denmark)

    Yeung, Ching-Yan Chloé; Gossan, Nicole; Lu, Yinhui

    2014-01-01

    knowledge of tendon gene regulation is essential for a complete understanding of FCT biology. Here we show autonomous circadian rhythms in mouse tendon and primary human tenocytes, controlled by an intrinsic molecular circadian clock. Time-series microarrays identified the first circadian transcriptome...... of murine tendon, revealing that 4.6% of the transcripts (745 genes) are expressed in a circadian manner. One of these genes was Grem2, which oscillated in antiphase to BMP signaling. Moreover, recombinant human Gremlin-2 blocked BMP2-induced phosphorylation of Smad1/5 and osteogenic differentiation...... of human tenocytes in vitro. We observed dampened Grem2 expression, deregulated BMP signaling, and spontaneously calcifying tendons in young CLOCKΔ19 arrhythmic mice and aged wild-type mice. Thus, disruption of circadian control, through mutations or aging, of Grem2/BMP signaling becomes a new focus...

  6. 76 FR 64223 - Cardiovascular Devices; Reclassification of External Pacemaker Pulse Generator Devices

    Science.gov (United States)

    2011-10-17

    ... Drug Administration 21 CFR Part 870 Cardiovascular Devices; Reclassification of External Pacemaker... Special Controls Guidance Document: External Pacemaker Pulse Generator; Availability; Proposed Rule and... [Docket No. FDA-2011-N-0650] Cardiovascular Devices; Reclassification of External Pacemaker Pulse...

  7. Neutron absorbed dose in a pacemaker CMOS

    International Nuclear Information System (INIS)

    Borja H, C. G.; Guzman G, K. A.; Valero L, C.; Banuelos F, A.; Hernandez D, V. M.; Vega C, H. R.; Paredes G, L.

    2012-01-01

    The neutron spectrum and the absorbed dose in a Complementary Metal Oxide Semiconductor (CMOS), has been estimated using Monte Carlo methods. Eventually a person with a pacemaker becomes an oncology patient that must be treated in a linear accelerator. Pacemaker has integrated circuits as CMOS that are sensitive to intense and pulsed radiation fields. Above 7 MV therapeutic beam is contaminated with photoneutrons that could damage the CMOS. Here, the neutron spectrum and the absorbed dose in a CMOS cell was calculated, also the spectra were calculated in two point-like detectors in the room. Neutron spectrum in the CMOS cell shows a small peak between 0.1 to 1 MeV and a larger peak in the thermal region, joined by epithermal neutrons, same features were observed in the point-like detectors. The absorbed dose in the CMOS was 1.522 x 10 -17 Gy per neutron emitted by the source. (Author)

  8. Neutron absorbed dose in a pacemaker CMOS

    Energy Technology Data Exchange (ETDEWEB)

    Borja H, C. G.; Guzman G, K. A.; Valero L, C.; Banuelos F, A.; Hernandez D, V. M.; Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico); Paredes G, L., E-mail: fermineutron@yahoo.com [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2012-06-15

    The neutron spectrum and the absorbed dose in a Complementary Metal Oxide Semiconductor (CMOS), has been estimated using Monte Carlo methods. Eventually a person with a pacemaker becomes an oncology patient that must be treated in a linear accelerator. Pacemaker has integrated circuits as CMOS that are sensitive to intense and pulsed radiation fields. Above 7 MV therapeutic beam is contaminated with photoneutrons that could damage the CMOS. Here, the neutron spectrum and the absorbed dose in a CMOS cell was calculated, also the spectra were calculated in two point-like detectors in the room. Neutron spectrum in the CMOS cell shows a small peak between 0.1 to 1 MeV and a larger peak in the thermal region, joined by epithermal neutrons, same features were observed in the point-like detectors. The absorbed dose in the CMOS was 1.522 x 10{sup -17} Gy per neutron emitted by the source. (Author)

  9. Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice

    Science.gov (United States)

    Landgraf, Dominic; Long, Jaimie E.; Proulx, Christophe D.; Barandas, Rita; Malinow, Roberto; Welsh, David K.

    2016-01-01

    Background Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. Methods We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). Results In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Conclusions Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. PMID:27113500

  10. Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice.

    Science.gov (United States)

    Landgraf, Dominic; Long, Jaimie E; Proulx, Christophe D; Barandas, Rita; Malinow, Roberto; Welsh, David K

    2016-12-01

    Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

  11. Cardiac pacemaker dysfunction in children after thoracic drainage catheter manipulation.

    Science.gov (United States)

    Lobdell, K W; Walters, H L; Hudson, C; Hakimi, M

    1997-05-01

    Two children underwent placement of permanent, epicardial-lead, dual-chamber, unipolar pacemaker systems for complete heart block. Postoperatively, both patients demonstrated subcutaneous emphysema-in the area of their pulse generators-temporally related to thoracic catheter manipulation. Acutely, each situation was managed with manual compression of the pulse generator, ascertaining appropriate pacemaker sensing and pacing. Maintenance of compression with pressure dressings, vigilant observation/monitoring, and education of the care givers resulted in satisfactory pacemaker function without invasive intervention.

  12. Pacemaker lead erosion simulating "Loch Ness Monster": conservative management.

    Science.gov (United States)

    Garg, Naveen; Moorthy, Nagaraja

    2012-12-01

    The majority of pacemaker pocket or lead erosions are due to either mechanical erosion by the bulky pulse generator or secondary to pacemaker pocket infection. We describe an unusual case of delayed pacemaker lead erosion causing extrusion of a portion of the pacing lead, with separate entry and exit points, with the gap filled with new skin formation, simulating the "Loch Ness Monster", which was successfully managed conservatively by surgical reinsertion.

  13. Cardiac pacemaker and its production methods

    International Nuclear Information System (INIS)

    Purdy, D.L.; Speicher, V.; Shipko, F.J.; Johnson, W.L.

    1977-01-01

    The construction method of the cardiac pacemakers proposes to arrange the impulse machine and the battery between two container halves, to weld the container halves with the help of a laser beam under a protective atmosphere and finally to inject polyurethane foam through an orifice into the form. There is also the possibility to embed the impulse machine and the battery first into the polyurethane foam and afterwards to close both container halves. Titanium is a suitable material for the container. (DG) [de

  14. Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus

    Directory of Open Access Journals (Sweden)

    Jinmi Koo

    2015-09-01

    Full Text Available BackgroundIn mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN. Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions.MethodsWe examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2 gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC knock-in mice using a real-time bioluminescence measurement system.ResultsAdministration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms.ConclusionThese findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

  15. Circadian clocks, epigenetics, and cancer

    KAUST Repository

    Masri, Selma; Kinouchi, Kenichiro; Sassone-Corsi, Paolo

    2015-01-01

    The interplay between circadian rhythm and cancer has been suggested for more than a decade based on the observations that shift work and cancer incidence are linked. Accumulating evidence implicates the circadian clock in cancer survival and proliferation pathways. At the molecular level, multiple control mechanisms have been proposed to link circadian transcription and cell-cycle control to tumorigenesis.The circadian gating of the cell cycle and subsequent control of cell proliferation is an area of active investigation. Moreover, the circadian clock is a transcriptional system that is intricately regulated at the epigenetic level. Interestingly, the epigenetic landscape at the level of histone modifications, DNA methylation, and small regulatory RNAs are differentially controlled in cancer cells. This concept raises the possibility that epigenetic control is a common thread linking the clock with cancer, though little scientific evidence is known to date.This review focuses on the link between circadian clock and cancer, and speculates on the possible connections at the epigenetic level that could further link the circadian clock to tumor initiation or progression.

  16. The Optic Lobes Regulate Circadian Rhythms of Olfactory Learning and Memory in the Cockroach.

    Science.gov (United States)

    Lubinski, Alexander J; Page, Terry L

    2016-04-01

    The cockroach, Leucophaea maderae, can be trained in an associative olfactory memory task by either classical or operant conditioning. When trained by classical conditioning, memory formation is regulated by a circadian clock, but once the memory is formed, it can be recalled at any circadian time. In contrast, when trained via operant conditioning, animals can learn the task at any circadian phase, but the ability to recall the long-term memory is tied to the phase of training. The optic lobes of the cockroach contain a circadian clock that drives circadian rhythms of locomotor activity, mating behavior, sensitivity of the compound eye to light, and the sensitivity of olfactory receptors in the antennae. To evaluate the role of the optic lobes in regulating learning and memory processes, the authors examined the effects of surgical ablation of the optic lobes on memory formation in classical conditioning and memory recall following operant conditioning. The effect of optic lobe ablation was to "rescue" the deficit in memory acquisition at a time the animals normally cannot learn and "rescue" the animal's ability to recall a memory formed by operant conditioning at a phase where memory was not normally expressed. The results suggested that the optic lobe pacemaker regulates these processes through inhibition at "inappropriate" times of day. As a pharmacological test of this hypothesis, the authors showed that injections of fipronil, an antagonist of GABA and glutamate-activated chloride channels, had the same effects as optic lobe ablation on memory formation and recall. The data suggest that the optic lobes contain the circadian clock(s) that regulate learning and memory processes via inhibition of neural processes in the brain. © 2015 The Author(s).

  17. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture.

    Science.gov (United States)

    Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

    2017-01-01

    Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC)-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER) protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF), which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the intact circadian

  18. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

    Directory of Open Access Journals (Sweden)

    Virginie Sabado

    2017-10-01

    Full Text Available Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF, which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the

  19. Leadless cardiac pacemakers: present and the future.

    Science.gov (United States)

    Chew, Derek S; Kuriachan, Vikas

    2018-01-01

    Pacing technology for many decades has been composed of a generator attached to leads that are usually transvenous. Recently, leadless pacemakers have been studied in clinical settings and now available for use in many countries. This includes the single-component Nanostim Leadless Cardiac Pacemaker and Micra Transcatheter Pacing System, as well as the multicomponent Wireless Stimulation Endocardial system. Clinical studies in single-component leadless pacing technology has shown that they can be successfully implanted with minimal complications. The follow-up studies also seem to confirm the findings from the initial clinical trials. These systems offer some advantages over a traditional pacing system comprised of a subcutaneous generator and transvenous leads. In many ways, these leadless systems are disruptive technologies that are changing the traditional pacemaker concept and preferred for some patients. Ongoing research is needed to better assess their long-term function, safety, and end-of-life strategies. In the future, multichamber leadless pacing is expected to be developed and perhaps obviating the need for transvenous leads and their associated complications.

  20. Pacemaker therapy in low-birth-weight infants.

    Science.gov (United States)

    Fuchigami, Tai; Nishioka, Masahiko; Akashige, Toru; Shimabukuro, Atsuya; Nagata, Nobuhiro

    2018-02-01

    Infants born with complete atrioventricular block (CAVB) and fetal bradycardia are frequently born with low birth weight. Three low-birth-weight CAVB infants underwent temporary pacemaker implantation, followed by permanent single-chamber pacemaker implantation at median body weights of 1.7 and 3.2 kg, respectively. All infants caught up with their growth curves and had >3 years of estimated residual battery life. This two-stage strategy was successful in facilitating permanent pacemaker implantation in low-birth-weight babies. Placement of single-chamber pacemaker on the apex of the left ventricle appears to be associated with longer battery lifespan. © 2018 Wiley Periodicals, Inc.

  1. Links between circadian rhythms and psychiatric disease

    Directory of Open Access Journals (Sweden)

    Ilia N Karatsoreos

    2014-05-01

    Full Text Available Determining the cause of psychiatric disorders is a goal of modern neuroscience, and will hopefully lead to the discovery of treatments to either prevent or alleviate the suffering caused by these diseases. One roadblock to attaining this goal is the realization that neuropsychiatric diseases are rarely due to a single gene polymorphism, environmental exposure, or developmental insult. Rather, it is a complex interaction between these various influences that likely leads to the development of clinically relevant syndromes. Our lab is exploring the links between environmental exposures and neurobehavioral function by investigating how disruption of the circadian (daily clock alters the structure and function of neural circuits, with the hypothesis that disrupting this crucial homeostatic system can directly contribute to altered vulnerability of the organism to other factors that interact to produce psychiatric illness. This review explores some historical and more recent findings that link disrupted circadian clocks to neuropsychiatric disorders, particularly depression, mania, and schizophrenia. We take a comparative approach by exploring the effects observed in human populations, as well as some experimental models used in the laboratory to unravel mechanistic and causal relationships between disruption of the circadian clock and behavioral abnormalities. This is a rich area of research that we predict will contribute greatly to our understanding of how genes, environment, and development interact to modulate an individual’s vulnerability to psychiatric disorders.

  2. Nocturia: The circadian voiding disorder

    Directory of Open Access Journals (Sweden)

    Jin Wook Kim

    2016-05-01

    Full Text Available Nocturia is a prevalent condition of waking to void during the night. The concept of nocturia has evolved from being a symptomatic aspect of disease associated with the prostate or bladder to a form of lower urinary tract disorder. However, recent advances in circadian biology and sleep science suggest that it might be important to consider nocturia as a form of circadian dysfunction. In the current review, nocturia is reexamined with an introduction to sleep disorders and recent findings in circadian biology in an attempt to highlight the importance of rediscovering nocturia as a problem of chronobiology.

  3. 76 FR 53851 - Effective Date of Requirement for Premarket Approval for Cardiovascular Permanent Pacemaker...

    Science.gov (United States)

    2011-08-30

    ... Pacemaker Electrode; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Proposed rule; correction... preamendments device: Cardiovascular permanent pacemaker electrode. The document was published with an incorrect...

  4. Protection of pacemaker wearers: effects on magnetic fields on the operation of implanted cardiac pacemakers

    International Nuclear Information System (INIS)

    Souques, M.; Lambrozo, J.; Frank, R.; Himbert, C.

    2002-01-01

    The aim of this study was to assess the changes in the behavior of cardiac pacemakers exposed to 50 and 60 Hz magnetic fields generated by industrial current and 20 to 50 khz magnetic fields generated by a household in a booming period - the induction cook top - and to study the incidence of these changes in a population of subjects with implanted pacemakers. This will enabled to give patients advices about dealing with electric transport lines and facilities and with induction cook tops and to advise manufacturers about the risks involved

  5. UNC79 and UNC80, putative auxiliary subunits of the NARROW ABDOMEN ion channel, are indispensable for robust circadian locomotor rhythms in Drosophila.

    Directory of Open Access Journals (Sweden)

    Bridget C Lear

    Full Text Available In the fruit fly Drosophila melanogaster, a network of circadian pacemaker neurons drives daily rhythms in rest and activity. The ion channel NARROW ABDOMEN (NA, orthologous to the mammalian sodium leak channel NALCN, functions downstream of the molecular circadian clock in pacemaker neurons to promote behavioral rhythmicity. To better understand the function and regulation of the NA channel, we have characterized two putative auxiliary channel subunits in Drosophila, unc79 (aka dunc79 and unc80 (aka CG18437. We have generated novel unc79 and unc80 mutations that represent strong or complete loss-of-function alleles. These mutants display severe defects in circadian locomotor rhythmicity that are indistinguishable from na mutant phenotypes. Tissue-specific RNA interference and rescue analyses indicate that UNC79 and UNC80 likely function within pacemaker neurons, with similar anatomical requirements to NA. We observe an interdependent, post-transcriptional regulatory relationship among the three gene products, as loss of na, unc79, or unc80 gene function leads to decreased expression of all three proteins, with minimal effect on transcript levels. Yet despite this relationship, we find that the requirement for unc79 and unc80 in circadian rhythmicity cannot be bypassed by increasing NA protein expression, nor can these putative auxiliary subunits substitute for each other. These data indicate functional requirements for UNC79 and UNC80 beyond promoting channel subunit expression. Immunoprecipitation experiments also confirm that UNC79 and UNC80 form a complex with NA in the Drosophila brain. Taken together, these data suggest that Drosophila NA, UNC79, and UNC80 function together in circadian clock neurons to promote rhythmic behavior.

  6. Postoperative circadian disturbances

    DEFF Research Database (Denmark)

    Gögenur, Ismail

    2010-01-01

    ) in urine the first night after both minor and major surgery. This delay after major surgery was correlated to the duration of surgery. The amplitude in the melatonin rhythm was unchanged the first night but increased in the second night after major surgery. The amplitude in AMT6s was reduced the first...... night after minimally invasive surgery. The core body temperature rhythm was disturbed after both major and minor surgery. There was a change in the sleep wake cycle with a significantly increased duration of REM-sleep in the day and evening time after major surgery compared with preoperatively....... There was also a shift in the autonomic nervous balance after major surgery with a significantly increased number of myocardial ischaemic episodes during the nighttime period. The circadian activity rhythm was also disturbed after both minor and major surgery. The daytime AMT6s excretion in urine after major...

  7. α1B-Adrenergic receptor signaling controls circadian expression of Tnfrsf11b by regulating clock genes in osteoblasts

    Directory of Open Access Journals (Sweden)

    Takao Hirai

    2015-11-01

    Full Text Available Circadian clocks are endogenous and biological oscillations that occur with a period of <24 h. In mammals, the central circadian pacemaker is localized in the suprachiasmatic nucleus (SCN and is linked to peripheral tissues through neural and hormonal signals. In the present study, we investigated the physiological function of the molecular clock on bone remodeling. The results of loss-of-function and gain-of-function experiments both indicated that the rhythmic expression of Tnfrsf11b, which encodes osteoprotegerin (OPG, was regulated by Bmal1 in MC3T3-E1 cells. We also showed that REV-ERBα negatively regulated Tnfrsf11b as well as Bmal1 in MC3T3-E1 cells. We systematically investigated the relationship between the sympathetic nervous system and the circadian clock in osteoblasts. The administration of phenylephrine, a nonspecific α1-adrenergic receptor (AR agonist, stimulated the expression of Tnfrsf11b, whereas the genetic ablation of α1B-AR signaling led to the alteration of Tnfrsf11b expression concomitant with Bmal1 and Per2 in bone. Thus, this study demonstrated that the circadian regulation of Tnfrsf11b was regulated by the clock genes encoding REV-ERBα (Nr1d1 and Bmal1 (Bmal1, also known as Arntl, which are components of the core loop of the circadian clock in osteoblasts.

  8. Treatment of vasovagal syncope: pacemaker or crossing legs?

    NARCIS (Netherlands)

    van Dijk, N.; Harms, M. P.; Linzer, M.; Wieling, W.

    2000-01-01

    A 50-year-old male patient continued to experience syncope after implantation of a pacemaker. During cardiovascular examination, the patient showed a typical vasovagal response, with normal pacemaker function. Leg crossing, which prohibits the pooling of blood in the legs and abdomen, at the onset

  9. State of the art of cardiac pacemaker technology

    International Nuclear Information System (INIS)

    Lambeck, R.

    1978-01-01

    The development of cardiac pacemakers from fixed-frequency to demand pacemakers is reviewed. The latter is described in more detail with regard to its energy sources and its design. The use of radioactive energy sources is illustrated by the example of 238 Pu and 147 promethium and a comparison of the two radiation sources. (AJ) 891 AJ [de

  10. Circadian Rhythm Neuropeptides in Drosophila: Signals for Normal Circadian Function and Circadian Neurodegenerative Disease.

    Science.gov (United States)

    He, Qiankun; Wu, Binbin; Price, Jeffrey L; Zhao, Zhangwu

    2017-04-21

    Circadian rhythm is a ubiquitous phenomenon in many organisms ranging from prokaryotes to eukaryotes. During more than four decades, the intrinsic and exogenous regulations of circadian rhythm have been studied. This review summarizes the core endogenous oscillation in Drosophila and then focuses on the neuropeptides, neurotransmitters and hormones that mediate its outputs and integration in Drosophila and the links between several of these (pigment dispersing factor (PDF) and insulin-like peptides) and neurodegenerative disease. These signaling molecules convey important network connectivity and signaling information for normal circadian function, but PDF and insulin-like peptides can also convey signals that lead to apoptosis, enhanced neurodegeneration and cognitive decline in flies carrying circadian mutations or in a senescent state.

  11. Case of pacemaker pocket infection caused by Finegoldia magna.

    Science.gov (United States)

    Hosseini Dehkordi, Seyed Hamed; Osorio, Georgina

    2017-10-01

    Finegoldia magna (formerly called Peptostreptococcus magnus) is a Gram-positive anaerobic coccus which is increasingly recognized as an opportunistic pathogen. We present a case of F. magna associated non-valvular cardiovascular device-related infection in an 83 year-old male who received a permanent pacemaker for sick sinus syndrome seven weeks prior to his presentation. Five weeks after the implantation, the pacemaker and leads were explanted because of clinical evidence of pacemaker pocket infection. He was initially treated with sulfamethoxazole-trimethoprim based on the Gram stain results from the removed pacemaker. However, two weeks later, he was readmitted with sepsis and was successfully treated with ampicillin-sulbactam. Culture results from the pacemaker and pocket as well as blood cultures grew F. magna. Clinicians should be aware of the possibility of F. magna infection when initial gram stain results show "gram positive cocci". Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Radiation therapy in patients with electric cardiac pacemakers

    International Nuclear Information System (INIS)

    Bisping, H.J.; Stockberg, H.; Meyer, J.; Frik, W.; Technische Hochschule Aachen

    1977-01-01

    In the course of radiation therapy and connected diagnostic measures ionizing radiation and other sources of disturbance may interfere with the function of permanent pacemakers. The conditions of such hazards are investigated in theory and practice making allowance for the different susceptibility to trouble of various models of permanent pacemakers. It appears that no extension of long-term follow-up of the cardiac pacemaker's function is needed with regard to possible late effects of ionizing radiation, but that the follow-up of pacemaker-patients during their first period of treatment should not be neglected, since other sources of electronic interference may be present. Routine checks at radiotherapy installations should also include possible sources of disturbance to electronic pacemakers. (orig.) [de

  13. The cardiac pacemaker patient. Might the pacer be directly irradiated?

    International Nuclear Information System (INIS)

    Tsekos, A.; Momm, F.; Brunner, M.; Guttenberger, R.

    2000-01-01

    According to recommendations listed in a recent review, pacemakers generally should not be irradiated directly. They should be shielded from ionizing radiation or their position changed. Direct irradiation can cause pacemaker failure. There are no clinical signals to indicate a near failure. When controlling pacemaker function, there is often a change in the magnetic frequency before malfunction occurs. If a malfunction results in a partial heart failure only, there would be enough time to implant another pacemaker. As can be seen from a case described here, a policy of 'wait and see' may be adopted even if there are changes in the magnetic frequency. if there is any danger to the patient's life, the feasibility of using an external pacemaker system may be explored, especially in cases where there is a strong need for radiotherapy (severe pain, infiltration of plexus). Risks and benefits should be carefully weighed and discussed with the patient

  14. Pacemaker syndrome with sub-acute left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker: consequence of lead switch at the header.

    Science.gov (United States)

    Khurwolah, Mohammad Reeaze; Vezi, Brian Zwelethini

    In the daily practice of pacemaker insertion, the occurrence of atrial and ventricular lead switch at the pacemaker box header is a rare and unintentional phenomenon, with less than five cases reported in the literature. The lead switch may have dire consequences, depending on the indication for the pacemaker. One of these consequences is pacemaker syndrome, in which the normal sequence of atrial and ventricular activation is impaired, leading to sub-optimal ventricular filling and cardiac output. It is important for the attending physician to recognise any worsening of symptoms in a patient who has recently had a permanent pacemaker inserted. In the case of a dual-chamber pacemaker, switching of the atrial and ventricular leads at the pacemaker box header should be strongly suspected. We present an unusual case of pacemaker syndrome and right ventricular-only pacinginduced left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker.

  15. Circadian Plasticity in the Brain of Insects and Rodents

    Directory of Open Access Journals (Sweden)

    Wojciech Krzeptowski

    2018-05-01

    Full Text Available In both vertebrate and invertebrate brains, neurons, glial cells and synapses are plastic, which means that the physiology and structure of these components are modified in response to internal and external stimuli during development and in mature brains. The term plasticity has been introduced in the last century to describe experience-dependent changes in synapse strength and number. These changes result from local functional and morphological synapse modifications; however, these modifications also occur more commonly in pre- and postsynaptic neurons. As a result, neuron morphology and neuronal networks are constantly modified during the life of animals and humans in response to different stimuli. Nevertheless, it has been discovered in flies and mammals that the number of synapses and size and shape of neurons also oscillate during the day. In most cases, these rhythms are circadian since they are generated by endogenous circadian clocks; however, some rhythmic changes in neuron morphology and synapse number and structure are controlled directly by environmental cues or by both external cues and circadian clocks. When the circadian clock is involved in generating cyclic changes in the nervous system, this type of plasticity is called circadian plasticity. It seems to be important in processing sensory information, in learning and in memory. Disruption of the clock may affect major brain functions.

  16. Toward a complex system understanding of bipolar disorder: A chaotic model of abnormal circadian activity rhythms in euthymic bipolar disorder.

    Science.gov (United States)

    Hadaeghi, Fatemeh; Hashemi Golpayegani, Mohammad Reza; Jafari, Sajad; Murray, Greg

    2016-08-01

    In the absence of a comprehensive neural model to explain the underlying mechanisms of disturbed circadian function in bipolar disorder, mathematical modeling is a helpful tool. Here, circadian activity as a response to exogenous daily cycles is proposed to be the product of interactions between neuronal networks in cortical (cognitive processing) and subcortical (pacemaker) areas of the brain. To investigate the dynamical aspects of the link between disturbed circadian activity rhythms and abnormalities of neurotransmitter functioning in frontal areas of the brain, we developed a novel mathematical model of a chaotic system which represents fluctuations in circadian activity in bipolar disorder as changes in the model's parameters. A novel map-based chaotic system was developed to capture disturbances in circadian activity across the two extreme mood states of bipolar disorder. The model uses chaos theory to characterize interplay between neurotransmitter functions and rhythm generation; it aims to illuminate key activity phenomenology in bipolar disorder, including prolonged sleep intervals, decreased total activity and attenuated amplitude of the diurnal activity rhythm. To test our new cortical-circadian mathematical model of bipolar disorder, we utilized previously collected locomotor activity data recorded from normal subjects and bipolar patients by wrist-worn actigraphs. All control parameters in the proposed model have an important role in replicating the different aspects of circadian activity rhythm generation in the brain. The model can successfully replicate deviations in sleep/wake time intervals corresponding to manic and depressive episodes of bipolar disorder, in which one of the excitatory or inhibitory pathways is abnormally dominant. Although neuroimaging research has strongly implicated a reciprocal interaction between cortical and subcortical regions as pathogenic in bipolar disorder, this is the first model to mathematically represent this

  17. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

    Directory of Open Access Journals (Sweden)

    Julian Lippert

    Full Text Available From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH in comparison to those of healthy controls (HC. Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG and Multiple Sleep Latency Test (MSLT. Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

  18. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

    Science.gov (United States)

    Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

    2014-01-01

    From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

  19. Patients with atrial fibrillation and permanent pacemaker

    DEFF Research Database (Denmark)

    Dalgaard, Frederik; Ruwald, Martin H; Lindhardt, Tommi Bo

    2018-01-01

    BACKGROUND: The management of patients with non-valvular atrial fibrillation (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the last decade, but it is unknown how these changes have affected patients with NVAF with a permanent pacemaker (PPM). METHODS: Through Danish......,261. Thus, the proportional amount of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall 45.9% had atrial fibrillation (AF) duration less than one year and the proportion declined from 55.5% to 42.4% (p

  20. Clear cell hidradenocarcinoma developing in pacemaker pocket.

    Science.gov (United States)

    Reyes, Cesar V

    2008-11-01

    An octagenerian woman developed clear cell hidradenocarcinoma, a rare neoplasm of eccrine sweat gland origin, 4 years following pacemaker implantation in her right lateral chest. The tumor immunohistochemically mimicked a metastatic lobular breast carcinoma, for example, strongly positive estrogen, weakly positive progesterone, and weakly reactive mammoglobin. A complete surgical excision of the tumor was complemented with ipsilateral dissection of involved adjacent axillary lymph nodes. Recommended irradiation was refused by the patient. Retrospective 3-year mammogram review, 2-year postsurgery follow-up, and complete postmortem evaluation failed to prove a primary breast malignancy or other metastatic lesion elsewhere.

  1. Pacemaker implantation complication rates in elderly and young patients

    Directory of Open Access Journals (Sweden)

    Özcan KS

    2013-08-01

    Full Text Available Kazim Serhan Özcan, Damirbek Osmonov, Servet Altay, Cevdet Dönmez, Ersin Yildirim, Ceyhan Türkkan, Baris Güngör, Ahmet Ekmekçi, Ahmet Taha Alper, Kadir Gürkan, İzzet ErdinlerDepartment of Cardiology, Siyami Ersek Cardiovascular and Thoracic Surgery Center, Istanbul, TurkeyAims: To evaluate the complication rate differences between elderly and younger patients who receive a permanent pacemaker implantation.Methods: We reviewed all cases admitted to our institution between January 2008 and June 2009 with symptomatic bradyarrhythmia for whom a permanent pacemaker was implanted. Beginning in June 2009, we prospectively collected data from all patients with the same diagnosis and procedure. The frequency of complications due to the pacemaker implantation procedure was evaluated and compared between young (<70 years old and elderly (≥70 years old patients.Results: Among 574 patients with a permanent pacemaker, 259 patients (45.1% were below and 315 patients (54.9% were above or at 70 years of age. There were 240 (92.7% and 19 (7.3% dual-chamber pacemaker (DDD and single-chamber pacemaker (VVI implanted patients in the younger group, and 291 (76.8% and 73 (23.2% DDD and VVI pacemaker implanted patients in the elderly group, respectively. The complication rate was 39 (15.1% out of 259 young patients and 24 (7.6% out of 315 elderly patients. Postprocedural complications were statistically lower in the elderly patients than in younger patients (P = 0.005.Conclusion: A pacemaker implantation performed by an experienced operator is a safe procedure for patients of advanced age. The patients who are above 70 years old may have less complication rates than the younger patients.Keywords: complications of pacemaker implantation, elderly patients, permanent pacemaker

  2. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock.

    Science.gov (United States)

    Narasimamurthy, Rajesh; Virshup, David M

    2017-01-01

    An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep-wake cycle, feeding-fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks. But, unlike other chemical reactions, the output of the clock system remains nearly constant with fluctuations in ambient temperature, a phenomenon known as temperature compensation. In this brief review, we focus on recent advances in our understanding of the posttranslational modifications, especially a phosphoswitch mechanism controlling the stability of PER2 and its implications for the regulation of temperature compensation.

  3. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock

    Directory of Open Access Journals (Sweden)

    David M. Virshup

    2017-04-01

    Full Text Available An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep–wake cycle, feeding–fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks. But, unlike other chemical reactions, the output of the clock system remains nearly constant with fluctuations in ambient temperature, a phenomenon known as temperature compensation. In this brief review, we focus on recent advances in our understanding of the posttranslational modifications, especially a phosphoswitch mechanism controlling the stability of PER2 and its implications for the regulation of temperature compensation.

  4. Maternal circadian rhythms and the programming of adult health and disease.

    Science.gov (United States)

    Varcoe, Tamara J; Gatford, Kathryn L; Kennaway, David J

    2018-02-01

    The in utero environment is inherently rhythmic, with the fetus subjected to circadian changes in temperature, substrates, and various maternal hormones. Meanwhile, the fetus is developing an endogenous circadian timing system, preparing for life in an external environment where light, food availability, and other environmental factors change predictably and repeatedly every 24 h. In humans, there are many situations that can disrupt circadian rhythms, including shift work, international travel, insomnias, and circadian rhythm disorders (e.g., advanced/delayed sleep phase disorder), with a growing consensus that this chronodisruption can have deleterious consequences for an individual's health and well-being. However, the impact of chronodisruption during pregnancy on the health of both the mother and fetus is not well understood. In this review, we outline circadian timing system ontogeny in mammals and examine emerging research from animal models demonstrating long-term negative implications for progeny health following maternal chronodisruption during pregnancy.

  5. The Effects of Spaceflight on the Rat Circadian Timing System

    Science.gov (United States)

    Fuller, Charles A.; Murakami, Dean M.; Hoban-Higgins, Tana M.; Fuller, Patrick M.; Robinson, Edward L.; Tang, I.-Hsiung

    2003-01-01

    Two fundamental environmental influences that have shaped the evolution of life on Earth are gravity and the cyclic changes occurring over the 24-hour day. Light levels, temperature, and humidity fluctuate over the course of a day, and organisms have adapted to cope with these variations. The primary adaptation has been the evolution of a biological timing system. Previous studies have suggested that this system, named the circadian (circa - about; dies - a day) timing system (CTS), may be sensitive to changes in gravity. The NASA Neurolab spaceflight provided a unique opportunity to evaluate the effects of microgravity on the mammalian CTS. Our experiment tested the hypotheses that microgravity would affect the period, phasing, and light sensitivity of the CTS. Twenty-four Fisher 344 rats were exposed to 16 days of microgravity on the Neurolab STS-90 mission, and 24 Fisher 344 rats were also studied on Earth as one-G controls. Rats were equipped with biotelemetry transmitters to record body temperature (T(sub b)) and heart rate (HR) continuously while the rats moved freely. In each group, 18 rats were exposed to a 24-hour light-dark (LD 12:12) cycle, and six rats were exposed to constant dim red-light (LL). The ability of light to induce a neuronal activity marker (c-fos) in the circadian pacemaker of the brain, the suprachiasmatic nucleus (SCN), was examined in rats studied on flight days two (FD2) and 14 (FD14), and postflight days two (R+1) and 14 (R+13). The flight rats in LD remained synchronized with the LD cycle. However, their T(sub b), rhythm was markedly phase-delayed relative to the LD cycle. The LD flight rats also had a decreased T(sub b) and a change in the waveform of the T(sub b) rhythm compared to controls. Rats in LL exhibited free-running rhythms of T(sub b), and HR; however, the periods were longer in microgravity. Circadian period returned to preflight values after landing. The internal phase angle between rhythms was different in flight than

  6. 21 CFR 870.3680 - Cardiovascular permanent or temporary pacemaker electrode.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiovascular permanent or temporary pacemaker... § 870.3680 Cardiovascular permanent or temporary pacemaker electrode. (a) Temporary pacemaker electrode—(1) Identification. A temporary pacemaker electrode is a device consisting of flexible insulated...

  7. Testing of Common Electromagnetic Environments for Risk of Interference with Cardiac Pacemaker Function

    Directory of Open Access Journals (Sweden)

    Maria Tiikkaja

    2013-09-01

    Conclusions: Modern pacemakers are well shielded against external EMFs, and workers with a pacemaker can most often return to their previous work after having a pacemaker implanted. However, an appropriate risk assessment is still necessary after the implantation of a pacemaker, a change of its generator, or major modification of its programming settings.

  8. Dysglycemia induces abnormal circadian blood pressure variability

    Directory of Open Access Journals (Sweden)

    Kumarasamy Sivarajan

    2011-11-01

    Full Text Available Abstract Background Prediabetes (PreDM in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV. Hypothesis Systemic inflammation and glycemia influence circadian blood pressure variability. Methods Dahl salt-sensitive (S rats (n = 19 after weaning were fed either an American (AD or a standard (SD diet. The AD (high-glycemic-index, high-fat simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG, adipokines (leptin and adiponectin, and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1 and tumor necrosis factor-α (TNF-α] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP and heart rate (HR were recorded by telemetry every 5 minutes during both sleep (day and active (night periods. Pulse pressure (PP was calculated (PP = SBP-DBP. Results [mean(SEM]: The AD fed group displayed significant increase in body weight (after 90 days; p Conclusion These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system which generate abnormal CBPV.

  9. Sleep- and circadian rhythm-associated pathways as therapeutic targets in bipolar disorder.

    Science.gov (United States)

    Bellivier, Frank; Geoffroy, Pierre-Alexis; Etain, Bruno; Scott, Jan

    2015-06-01

    Disruptions in sleep and circadian rhythms are observed in individuals with bipolar disorders (BD), both during acute mood episodes and remission. Such abnormalities may relate to dysfunction of the molecular circadian clock and could offer a target for new drugs. This review focuses on clinical, actigraphic, biochemical and genetic biomarkers of BDs, as well as animal and cellular models, and highlights that sleep and circadian rhythm disturbances are closely linked to the susceptibility to BDs and vulnerability to mood relapses. As lithium is likely to act as a synchronizer and stabilizer of circadian rhythms, we will review pharmacogenetic studies testing circadian gene polymorphisms and prophylactic response to lithium. Interventions such as sleep deprivation, light therapy and psychological therapies may also target sleep and circadian disruptions in BDs efficiently for treatment and prevention of bipolar depression. We suggest that future research should clarify the associations between sleep and circadian rhythm disturbances and alterations of the molecular clock in order to identify critical targets within the circadian pathway. The investigation of such targets using human cellular models or animal models combined with 'omics' approaches are crucial steps for new drug development.

  10. A mathematical model of communication between groups of circadian neurons in Drosophila melanogaster.

    Science.gov (United States)

    Risau-Gusman, Sebastián; Gleiser, Pablo M

    2014-12-01

    In the fruit fly, circadian behavior is controlled by a small number of specialized neurons, whose molecular clocks are relatively well known. However, much less is known about how these neurons communicate among themselves. In particular, only 1 circadian neuropeptide, pigment-dispersing factor (PDF), has been identified, and most aspects of its interaction with the molecular clock remain to be elucidated. Furthermore, it is speculated that many other peptides should contribute to circadian communication. We have developed a relatively detailed model of the 2 main groups of circadian pacemaker neurons (sLNvs and LNds) to investigate these issues. We have proposed many possible mechanisms for the interaction between the synchronization factors and the molecular clock, and we have compared the outputs with the experimental results reported in the literature both for the wild-type and PDF-null mutant. We have studied how different the properties of each neuron should be to account for the observations reported for the sLNvs in the mutant. We have found that only a few mechanisms, mostly related to the slowing down of nuclear entry of a circadian protein, can synchronize neurons that present these differences. Detailed immunofluorescent recordings have suggested that, whereas in the mutant, LNd neurons are synchronized, in the wild-type, a subset of the LNds oscillate faster than the rest. With our model, we find that a more likely explanation for the same observations is that this subset is being driven outside its synchronization range and displays therefore a complex pattern of oscillation.

  11. Evaluating the pacemaker effect with the pump parameter of gated blood-pool imaging

    International Nuclear Information System (INIS)

    Cheng Muhua

    1995-01-01

    13 normal controls and 27 patients with ventricular pacemaker had undergone planar gated blood-pool imaging in different conditions. Result shows: (1) Pump parameters can successfully reflect therapeutic effect of pacemaker among them EMP is the most valuable parameter for evaluating the cardiac pumping effect. (2) After implantation of the ventricular pacemaker, the LVEF did not increase, but the CO and EMP was significantly increased. (3) Compared with right ventricular demand pacemaker, the rate-responsive ventricular pacemaker give better hemodynamic benefit at exercise condition. (4) Through restrained cardiac pacemaker the functional change was analyzed on or off pace, and monitoring the cardiac function itself after the pacemaker was implanted

  12. Familial circadian rhythm disorder in the diurnal primate, Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Irina V Zhdanova

    Full Text Available In view of the inverse temporal relationship of central clock activity to physiological or behavioral outputs in diurnal and nocturnal species, understanding the mechanisms and physiological consequences of circadian disorders in humans would benefit from studies in a diurnal animal model, phylogenetically close to humans. Here we report the discovery of the first intrinsic circadian disorder in a family of diurnal non-human primates, the rhesus monkey. The disorder is characterized by a combination of delayed sleep phase, relative to light-dark cycle, mutual desynchrony of intrinsic rhythms of activity, food intake and cognitive performance, enhanced nighttime feeding or, in the extreme case, intrinsic asynchrony. The phenotype is associated with normal length of intrinsic circadian period and requires an intact central clock, as demonstrated by an SCN lesion. Entrainment to different photoperiods or melatonin administration does not eliminate internal desynchrony, though melatonin can temporarily reinstate intrinsic activity rhythms in the animal with intrinsic asynchrony. Entrainment to restricted feeding is highly effective in animals with intrinsic or SCN lesion-induced asynchrony. The large isolated family of rhesus macaques harboring the disorder provides a powerful new tool for translational research of regulatory circuits underlying circadian disorders and their effective treatment.

  13. Influence of digital and analogue cellular telephones on implanted pacemakers.

    Science.gov (United States)

    Altamura, G; Toscano, S; Gentilucci, G; Ammirati, F; Castro, A; Pandozi, C; Santini, M

    1997-10-01

    The aim of this study was to find out whether digital and analogue cellular 'phones affect patients with pacemakers. The study comprised continuous ECG monitoring of 200 pacemaker patients. During the monitoring certain conditions caused by interference created by the telephone were looked for: temporary or prolonged pacemaker inhibition; a shift to asynchronous mode caused by electromagnetic interference; an increase in ventricular pacing in dual chamber pacemakers, up to the programmed upper rate. The Global System for Mobile Communications system interfered with pacing 97 times in 43 patients (21.5%). During tests on Total Access of Communication System telephones, there were 60 cases of pacing interference in 35 patients (17.5%). There were 131 interference episodes during ringing vs 26 during the on/off phase; (P 4 s) was seen at the pacemaker 'base' sensing value in six patients using the Global system but in only one patient using Total Access. Cellular 'phones may be dangerous for pacemaker patients. However, they can be used safely if patients do not carry the 'phone close to the pacemaker, which is the only place where high risk interference has been observed.

  14. Neck Pain One Week after Pacemaker Generator Replacement.

    Science.gov (United States)

    Graham, Ross F; Wightman, John M

    2015-07-01

    The incidence of cardiac pacemaker implantation has risen markedly in the past three decades, making awareness of possible postprocedural complications critical to the emergency physician. This case is the first documented instance of internal jugular (IJ) deep vein thrombosis (DVT) from an uncomplicated pacemaker generator replacement. A patient presented to an Emergency Department with a 2-day history of mild left temporal headache migrating to his left neck. The patient did not volunteer this information, but review of systems revealed a temporary transvenous pacemaker inserted through the right IJ vein 1 week previously during a routine exchange of a left-sided cardiac pacemaker generator. Manipulation of the existing pacemaker wires entering the left subclavian vein was minimal. Computed tomographic angiography of the neck demonstrated near-complete thrombotic occlusion of the entire length of his left IJ vein. This required hospital admission for observation and treatment with anticoagulation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: DVT, with thrombotic extension into adjacent vessels anywhere along the course of pacemaker wires, should be considered by the emergency provider in the evaluation of head, neck, or upper extremity symptoms after recent or remote implantation or manipulation of a transvenous cardiac pacemaker, including generator replacement. Failure to identify and treat appropriately could result in significant morbidity and mortality from airway edema, septic thrombophlebitis, superior vena cava syndrome, superior sagittal sinus thrombosis, or pulmonary embolism. Published by Elsevier Inc.

  15. Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.

    Science.gov (United States)

    Makki, Nader; Dollery, Jenn; Jones, Danielle; Crestanello, Juan; Lilly, Scott

    Permanent pacemaker (PPM) placement occurs in 5-20% of patients after transcatheter aortic valve replacement (TAVR). Although predictors of pacemaker implantation have been established, features that predispose patients to pacemaker utilization on follow up have not been widely reported. We performed a retrospective review of patients undergoing commercial TAVR between 2011 and 2016. We collated patients that underwent in-hospital PPM implantation and had a follow up of at least 3months. Data abstraction was performed for electrophysiological studies (EPS), pacemaker indication, timing, and device interrogation for pacemaker dependency on follow up. A total of 24 patients received in-hospital PPM post-TAVR (14% of total cohort), and mean follow up was 22months. Indications for PPM included resting complete heart block (CHB; 15/24, 63%), left bundle branch block and abnormal electrophysiological study (EPS; 7/24, 29%), alternating bundle branch block (1/24, 4%) and tachy-brady syndrome (1/24, 4%). Pacemaker dependency (underlying ventricular asystole, complete heart block, or >50% pacing) occurred in 8/24 patients (33%) during follow-up, 7 of whom had resting CHB, and one with CHB invoked during EPS. Pacemaker dependency after TAVR is common among those that exhibited CHB, but not among those with a prolonged HV delay during EPS. Although preliminary, these observations are relevant to management of rhythm disturbances after TAVR, and may inform the practice of EPS-based PPM implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Modern Perspectives on Numerical Modeling of Cardiac Pacemaker Cell

    Science.gov (United States)

    Maltsev, Victor A.; Yaniv, Yael; Maltsev, Anna V.; Stern, Michael D.; Lakatta, Edward G.

    2015-01-01

    Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent “coupled-clock” theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies, such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age. PMID:24748434

  17. Proton Beam Therapy Interference With Implanted Cardiac Pacemakers

    International Nuclear Information System (INIS)

    Oshiro, Yoshiko; Sugahara, Shinji; Noma, Mio; Sato, Masato; Sakakibara, Yuzuru; Sakae, Takeji; Hayashi, Yasutaka; Nakayama, Hidetsugu; Tsuboi, Koji; Fukumitsu, Nobuyoshi; Kanemoto, Ayae; Hashimoto, Takayuki; Tokuuye, Koichi

    2008-01-01

    Purpose: To investigate the effect of proton beam therapy (PBT) on implanted cardiac pacemaker function. Methods and Materials: After a phantom study confirmed the safety of PBT in patients with cardiac pacemakers, we treated 8 patients with implanted pacemakers using PBT to a total tumor dose of 33-77 gray equivalents (GyE) in dose fractions of 2.2-6.6 GyE. The combined total number of PBT sessions was 127. Although all pulse generators remained outside the treatment field, 4 patients had pacing leads in the radiation field. All patients were monitored by means of electrocardiogram during treatment, and pacemakers were routinely examined before and after PBT. Results: The phantom study showed no effect of neutron scatter on pacemaker generators. In the study, changes in heart rate occurred three times (2.4%) in 2 patients. However, these patients remained completely asymptomatic throughout the PBT course. Conclusions: PBT can result in pacemaker malfunctions that manifest as changes in pulse rate and pulse patterns. Therefore, patients with cardiac pacemakers should be monitored by means of electrocardiogram during PBT

  18. Effect of telecobalt irradiation on the function of implantable pacemaker

    International Nuclear Information System (INIS)

    Toyoda, Michiaki

    1986-01-01

    In patients implanted with a pacemaker, radiotherapy may be chosen as the treatment when malignant tumor is complicated. Therefore, on the assumption that the pacemaker apparatus is exposed to X-ray, 21 lithium cells used for CMOS or TTL circuit were collected before expiration date and irradiated with 60 Co. The pacemaker used were 10 apparatuses of unprogrammed model VVI, 9 apparatuses of programmed model VVI and 2 apparatuses programmed model DVI. Irradiation was done up to 1,000 rads in dividing doses or at 1,000 rads as a single dose. Observations were made for effects on intervals, amplitude and wave shape of stimula to pacemaker, power, sensitivity, refractory phase, and program functions. In conclusion, it was found that pacemaker is sure to be affected considerably for various functions, although no functional arrest occurs, under irradiation up to 1,000 rads of 60 Co in dividing dose. When irradiation at 1,000 rads was given as a single dose, dysfunctions of pacemaker developed in some cases indicating that direct irradiation at high doses is contraindicated for pacemakers using much of LSI-CMOS. (author)

  19. A devices' game of thrones: cardiac resynchronization therapy vs. pacemaker.

    Science.gov (United States)

    Moura-Ferreira, Sara; Gonçalves, Helena; Oliveira, Marco; Primo, João; Fonseca, Paulo; Ribeiro, José; Santos, Elisabeth; Pelicano, Nuno; Martins, Dinis; Gama, Vasco

    2017-12-01

    Oversensing can interfere with biventricular pacing. Cardiac Resynchronization Therapy (CRT) output inhibition due to automatic brady mode change from a sensing to a pacing mode of a previously implanted pacemaker as it reached battery capacity depleted indicator has not been previously published in the medical literature. We report the first case of CRT output inhibition in a pacemaker dependent patient due to electrical stimuli from a previously right-sided implanted pacemaker, after unaware reversion of OVO mode (O = no chambers paced; V = ventricular sensing; O = no response to sensing) to backup VVI (V = ventricular pacing; V = ventricular sensing; I = inhibitory response to sensing) when it reached the elective replacement interval. This paper emphasizes the importance of knowing the distinct pacemaker brady mode behaviours after battery capacity depleted indicator has been reached, according to the pacemakers' manufacturer, including the possibility of automatic brady mode change from sensing to pacing mode. It also highlights the potential for severe bradycardia or asystole of this automatic brady mode change from a previously implanted pacemaker in pacemaker dependent patients submitted to CRT upgrade. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  20. Cardiovascular patients’ experiences of living with pacemaker: Qualitative study

    Directory of Open Access Journals (Sweden)

    Morteza Ghojazadeh

    2015-09-01

    Full Text Available BACKGROUND: A pacemaker implantation is considered major life event for cardiovascular patients, so they will probably have very interesting experiences of living with this device. The aim of this study was to explore the experiences of cardiovascular patients living with the pacemaker. METHODS: In this qualitative study, 27 patients were chosen through purposive sampling to achieve data saturation, and their experiences were examined using semi-structured interviews. The patients’ statements were recorded with their consent and analyzed using content analysis method. RESULTS: Participants’ experiences included three main themes: “Problems and limitations,” “feeling and dealing with pacemaker”, and “sources of comfort” and 10 sub-themes including: physical problems, financial problems, social problems, the first encounter, the feeling of living with the pacemaker, how to cope with pacemaker, satisfaction with pacemaker, good family support, hospital and hospital staff performance, and role of religious beliefs. CONCLUSION: Planning to solve social problems, identifying and changing feelings of patients using pacemakers, reinforcing the resources of comfort especially family support seem to be necessary steps for improving quality of life and impact of using pacemaker

  1. Firing Patterns and Transitions in Coupled Neurons Controlled by a Pacemaker

    International Nuclear Information System (INIS)

    Mei-Sheng, Li; Qi-Shao, Lu; Li-Xia, Duan; Qing-Yun, Wang

    2008-01-01

    To reveal the dynamics of neuronal networks with pacemakers, the firing patterns and their transitions are investigated in a ring HR neuronal network with gap junctions under the control of a pacemaker. Compared with the situation without pacemaker, the neurons in the network can exhibit various firing patterns as the external current is applied or the coupling strength of pacemaker varies. The results are beneficial for understanding the complex cooperative behaviour of large neural assemblies with pacemaker control

  2. Acute pericarditis with cardiac tamponade induced by pacemaker implantation.

    Science.gov (United States)

    Shingaki, Masami; Kobayashi, Yutaka; Suzuki, Haruo

    2015-11-01

    An 87-year-old woman was diagnosed with third-degree atrioventricular block and underwent pacemaker implantation. On postoperative day 12, she experienced cardiac tamponade that was suspected on computed tomography to be caused by lead perforation; therefore, we performed open-heart surgery. However, we could not identify a perforation site on the heart, and drained a 400-mL exudative pericardial effusion. Subsequently, we diagnosed the pericardial effusion as due to pericarditis induced by pacemaker implantation. It is sometimes difficult to distinguish pericarditis from pacemaker lead perforation, so both should be included in the differential diagnosis. © The Author(s) 2014.

  3. Cognitive performance as a zeitgeber: cognitive oscillators and cholinergic modulation of the SCN entrain circadian rhythms.

    Directory of Open Access Journals (Sweden)

    Howard J Gritton

    Full Text Available The suprachiasmatic nucleus (SCN is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior.

  4. Age-Related Changes in the Expression of the Circadian Clock Protein PERIOD in Drosophila Glial Cells

    Directory of Open Access Journals (Sweden)

    Dani M. Long

    2018-01-01

    Full Text Available Circadian clocks consist of molecular negative feedback loops that coordinate physiological, neurological, and behavioral variables into “circa” 24-h rhythms. Rhythms in behavioral and other circadian outputs tend to weaken during aging, as evident in progressive disruptions of sleep-wake cycles in aging organisms. However, less is known about the molecular changes in the expression of clock genes and proteins that may lead to the weakening of circadian outputs. Western blot studies have demonstrated that the expression of the core clock protein PERIOD (PER declines in the heads of aged Drosophila melanogaster flies. This age-related decline in PER does not occur in the central pacemaker neurons but has been demonstrated so far in retinal photoreceptors. Besides photoreceptors, clock proteins are also expressed in fly glia, which play important roles in neuronal homeostasis and are further categorized into subtypes based on morphology and function. While previous studies of mammalian glial cells have demonstrated the presence of functional clocks in astrocytes and microglia, it is not known which glial cell types in Drosophila express clock proteins and how their expression may change in aged individuals. Here, we conducted immunocytochemistry experiments to identify which glial subtypes express PER protein suggestive of functional circadian clocks. Glial cell subtypes that showed night-time accumulation and day-time absence in PER consistent with oscillations reported in the pacemaker neurons were selected to compare the level of PER protein between young and old flies. Our data demonstrate that some glial subtypes show rhythmic PER expression and the relative PER levels become dampened with advanced age. Identification of glial cell types that display age-related dampening of PER levels may help to understand the cellular changes that contribute to the loss of homeostasis in the aging brain.

  5. Central control of circadian phase in arousal-promoting neurons.

    Directory of Open Access Journals (Sweden)

    Carrie E Mahoney

    Full Text Available Cells of the dorsomedial/lateral hypothalamus (DMH/LH that produce hypocretin (HCRT promote arousal in part by activation of cells of the locus coeruleus (LC which express tyrosine hydroxylase (TH. The suprachiasmatic nucleus (SCN drives endogenous daily rhythms, including those of sleep and wakefulness. These circadian oscillations are generated by a transcriptional-translational feedback loop in which the Period (Per genes constitute critical components. This cell-autonomous molecular clock operates not only within the SCN but also in neurons of other brain regions. However, the phenotype of such neurons and the nature of the phase controlling signal from the pacemaker are largely unknown. We used dual fluorescent in situ hybridization to assess clock function in vasopressin, HCRT and TH cells of the SCN, DMH/LH and LC, respectively, of male Syrian hamsters. In the first experiment, we found that Per1 expression in HCRT and TH oscillated in animals held in constant darkness with a peak phase that lagged that in AVP cells of the SCN by several hours. In the second experiment, hamsters induced to split their locomotor rhythms by exposure to constant light had asymmetric Per1 expression within cells of the middle SCN at 6 h before activity onset (AO and in HCRT cells 9 h before and at AO. We did not observe evidence of lateralization of Per1 expression in the LC. We conclude that the SCN communicates circadian phase to HCRT cells via lateralized neural projections, and suggests that Per1 expression in the LC may be regulated by signals of a global or bilateral nature.

  6. Endocardial Pacemaker Implantation in Neonates and Infants

    Directory of Open Access Journals (Sweden)

    Canan Ayabakan

    2006-04-01

    Full Text Available Transvenous pacemaker lead implantation is the preferred method of pacing in adult patients. Lead performance and longevity are superior and the implantation approach can be performed under local anaesthetic with a very low morbidity. In children, and especially in neonates and infants, the epicardial route was traditionally chosen until the advent of smaller generators and lead implantation techniques that allowed growth of the child without lead displacement. Endocardial implantation is not universally accepted, however, as there is an incidence of venous occlusion of the smaller veins of neonates and infants with concerns for loss of venous access in the future. Growing experience with lower profile leads, however, reveals that endocardial pacing too can be performed with low morbidity and good long-term results in neonates and infants.

  7. Cardiac pacemaker. [electric-battery powered

    Energy Technology Data Exchange (ETDEWEB)

    Kolenik, S A

    1976-01-02

    The construction of a cardiac pacemaker is described which is characterized by particularly small dimensions, small weight and long life duration. The weight is under 100g, the specific weight under 1.7. Mass inertia forces which occur through acceleration and retardation processes, thus remain below the threshold values, above which one would have to reckon with considerable damaging of the surrounding body tissue. The maintaining of small size and slight weight is achieved by using an oscillator on COSMOS basis, where by considerably lower energy consumption, among others the lifetimes of the batteries used - a lithium anode with thionyl chloride electrolyte - is extended to over 5 years. The reliability can be increased by the use of 2 or more batteries. The designed dimension are 20x60x60 mm/sup 3/.

  8. Circadian rhythms and obesity in mammals.

    Science.gov (United States)

    Froy, Oren

    2012-01-01

    Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders. Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding (RF), calorie restriction (CR), and intermittent fasting (IF), provide a time cue and reset the circadian clock and lead to better health. In contrast, high-fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. This paper focuses on circadian rhythms and their link to obesity.

  9. Neutron absorbed dose in a pacemaker CMOS

    Energy Technology Data Exchange (ETDEWEB)

    Borja H, C. G.; Guzman G, K. A.; Valero L, C. Y.; Banuelos F, A.; Hernandez D, V. M.; Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico); Paredes G, L., E-mail: candy_borja@hotmail.com [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2011-11-15

    The absorbed dose due to neutrons by a Complementary Metal Oxide Semiconductor (CMOS) has been estimated using Monte Carlo methods. Eventually a person with a pacemaker becomes a patient that must be treated by radiotherapy with a linear accelerator; the pacemaker has integrated circuits as CMOS that are sensitive to intense and pulsed radiation fields. When the Linac is working in Bremsstrahlung mode an undesirable neutron field is produced due to photoneutron reactions; these neutrons could damage the CMOS putting the patient at risk during the radiotherapy treatment. In order to estimate the neutron dose in the CMOS a Monte Carlo calculation was carried out where a full radiotherapy vault room was modeled with a W-made spherical shell in whose center was located the source term of photoneutrons produced by a Linac head operating in Bremsstrahlung mode at 18 MV. In the calculations a phantom made of tissue equivalent was modeled while a beam of photoneutrons was applied on the phantom prostatic region using a field of 10 x 10 cm{sup 2}. During simulation neutrons were isotropically transported from the Linac head to the phantom chest, here a 1 {theta} x 1 cm{sup 2} cylinder made of polystyrene was modeled as the CMOS, where the neutron spectrum and the absorbed dose were estimated. Main damages to CMOS are by protons produced during neutron collisions protective cover made of H-rich materials, here the neutron spectrum that reach the CMOS was calculated showing a small peak around 0.1 MeV and a larger peak in the thermal region, both connected through epithermal neutrons. (Author)

  10. Autoreceptor Control of Peptide/Neurotransmitter Corelease from PDF Neurons Determines Allocation of Circadian Activity in Drosophila

    Directory of Open Access Journals (Sweden)

    Charles Choi

    2012-08-01

    Full Text Available Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral-ventral pacemaker neurons (LNvs that secrete the neuropeptide PDF (pigment dispersing factor. Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR-expressing dorsal clock neurons in organizing circadian activity. Although LNvs also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here, we show that (1 PDFR activation in LNvs shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions, and (2 this shift is mediated by stimulation of the Gα,s-cAMP pathway and a consequent change in PDF/neurotransmitter corelease from the LNvs. These results suggest another mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits.

  11. Autoreceptor Modulation of Peptide/Neurotransmitter Co-release from PDF Neurons Determines Allocation of Circadian Activity in Drosophila

    Science.gov (United States)

    Choi, Charles; Cao, Guan; Tanenhaus, Anne K.; McCarthy, Ellena v.; Jung, Misun; Schleyer, William; Shang, Yuhua; Rosbash, Michael; Yin, Jerry C.P.; Nitabach, Michael N.

    2012-01-01

    Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral ventral pacemaker neurons (LNvs) that secrete the neuropeptide PDF (Pigment Dispersing Factor). Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR)-expressing dorsal clock neurons in organizing circadian activity. While LNvs also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here we show that (1) PDFR activation in LNvs shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions and (2) this shift is mediated by stimulation of the Ga,s-cAMP pathway and a consequent change in PDF/neurotransmitter co-release from the LNvs. These results suggest a novel mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits. PMID:22938867

  12. Autoreceptor control of peptide/neurotransmitter corelease from PDF neurons determines allocation of circadian activity in drosophila.

    Science.gov (United States)

    Choi, Charles; Cao, Guan; Tanenhaus, Anne K; McCarthy, Ellena V; Jung, Misun; Schleyer, William; Shang, Yuhua; Rosbash, Michael; Yin, Jerry C P; Nitabach, Michael N

    2012-08-30

    Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral-ventral pacemaker neurons (LN(v)s) that secrete the neuropeptide PDF (pigment dispersing factor). Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR)-expressing dorsal clock neurons in organizing circadian activity. Although LN(v)s also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here, we show that (1) PDFR activation in LN(v)s shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions, and (2) this shift is mediated by stimulation of the Gα,s-cAMP pathway and a consequent change in PDF/neurotransmitter corelease from the LN(v)s. These results suggest another mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Intra-cardiac pacemaker infection: Surgical management and outcome

    Directory of Open Access Journals (Sweden)

    Sameh Elameen

    2016-05-01

    Conclusion: Explantation of the complete pacemaker system has proved a reliable method to eradicate infection. Complications were rare, except in patients who present lately in a critically ill condition and septic shock.

  14. Circadian rhythms in mitochondrial respiration

    NARCIS (Netherlands)

    de Goede, Paul; Wefers, Jakob; Brombacher, Eline Constance; Schrauwen, P; Kalsbeek, A.

    2018-01-01

    Many physiological processes are regulated with a 24h periodicity to anticipate the environmental changes of day to nighttime and vice versa. These 24h regulations, commonly termed circadian rhythms, amongst others control the sleep-wake cycle, locomotor activity and preparation for food

  15. Circadian Clocks: Unexpected Biochemical Cogs.

    Science.gov (United States)

    Mori, Tetsuya; Mchaourab, Hassane; Johnson, Carl Hirschie

    2015-10-05

    A circadian oscillation can be reconstituted in vitro from three proteins that cycles with a period of ∼ 24 h. Two recent studies provide surprising biochemical answers to why this remarkable oscillator has such a long time constant and how it can switch effortlessly between alternating enzymatic modes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Circadian Clocks: Unexpected Biochemical Cogs

    OpenAIRE

    Mori, Tetsuya; Mchaourab, Hassane; Johnson, Carl Hirschie

    2015-01-01

    A circadian oscillation can be reconstituted in vitro from three proteins that cycles with a period of ~24 h. Two recent studies provide surprising biochemical answers to why this remarkable oscillator has such a long time constant and how it can switch effortlessly between alternating enzymatic modes.

  17. Leadless Cardiac Pacemakers: Current status of a modern approach in pacing

    Directory of Open Access Journals (Sweden)

    Skevos Sideris

    2017-11-01

    Full Text Available Since the first transvenous pacemaker implantation, which took place 50 years ago, important progress has been achieved in pacing technology. Consequently, at present, more than 700,000 pacemakers are implanted annually worldwide. However, conventional pacemakers' implantation has a non-negligible risk of periprocedural and long-term complications associated with the transvenous leads and pacemaker pocket. Recently, leadless pacing systems have emerged as a therapeutic alternative to conventional pacing systems that provide therapy for patients with bradyarrhythmias, while eliminating potential transvenous lead- and pacemaker pocket-related complications. Initial studies have demonstrated favorable efficacy and safety of currently developed leadless pacing systems, compared to transvenous pacemakers. In the present paper, we review the current evidence and highlight the advantages and disadvantages of this novel technology. New technological advances may allow the next generation of leadless pacemakers to further expand, thereby offering a wireless cardiac pacing in future. Keywords: cardiac pacing, pacemaker, leadless pacemaker, bradycardia

  18. Intermittent pacemaker dysfunction caused by digital mobile telephones.

    Science.gov (United States)

    Naegeli, B; Osswald, S; Deola, M; Burkart, F

    1996-05-01

    This study was designed to evaluate possible interactions between digital mobile telephones and implanted pacemakers. Electromagnetic fields may interfere with normal pacemaker function. Development of bipolar sensing leads and modern noise filtering techniques have lessened this problem. However, it remains unclear whether these features also protect from high frequency noise arising from digital cellular phones. In 39 patients with an implanted pacemaker (14 dual-chamber [DDD], 8 atrial-synchronized ventricular-inhibited [VDD(R)] and 17 ventricular-inhibited [VVI(R)] pacemakers), four mobile phones with different levels of power output (2 and 8 W) were tested in the standby, dialing and operating mode. During continuous electrocardiographic monitoring, 672 tests were performed in each mode with the phones positioned over the pulse generator, the atrial and the ventricular electrode tip. The tests were carried out at different sensitivity settings and, where possible, in the unipolar and bipolar pacing modes as well. In 7 (18%) of 39 patients, a reproducible interference was induced during 26 (3.9%) of 672 tests with the operating phones in close proximity (phone and at maximal sensitivity of the pacemakers (maximal vs. nominal sensitivity, 6% vs. 1.8% positive test results, p = 0.009). When the bipolar and unipolar pacing modes were compared in the same patients, ventricular inhibition was induced only in the unipolar mode (12.5% positive test results, p = 0.0003). Digital mobile phones in close proximity to implanted pacemakers may cause intermittent pacemaker dysfunction with inappropriate ventricular tracking and potentially dangerous pacemaker inhibition.

  19. Elektrokirurgi hos patienter med pacemaker og implanterbar kardioverter-defibrillator

    DEFF Research Database (Denmark)

    Lønnberg, Ann Sophie Claire; Philberts, Berit Thornvig; Bonde, Christian

    2017-01-01

    Electrosurgery is a very useful tool and one of the most commonly used techniques. However, the technique can interfere with pacemakers and implantable cardioverter defibrillators. This article provides practical recommendations for the use of electrosurgery in these patients.......Electrosurgery is a very useful tool and one of the most commonly used techniques. However, the technique can interfere with pacemakers and implantable cardioverter defibrillators. This article provides practical recommendations for the use of electrosurgery in these patients....

  20. Successful pacing using a batteryless sunlight-powered pacemaker.

    Science.gov (United States)

    Haeberlin, Andreas; Zurbuchen, Adrian; Schaerer, Jakob; Wagner, Joerg; Walpen, Sébastien; Huber, Christoph; Haeberlin, Heinrich; Fuhrer, Juerg; Vogel, Rolf

    2014-10-01

    Today's cardiac pacemakers are powered by batteries with limited energy capacity. As the battery's lifetime ends, the pacemaker needs to be replaced. This surgical re-intervention is costly and bears the risk of complications. Thus, a pacemaker without primary batteries is desirable. The goal of this study was to test whether transcutaneous solar light could power a pacemaker. We used a three-step approach to investigate the feasibility of sunlight-powered cardiac pacing. First, the harvestable power was estimated. Theoretically, a subcutaneously implanted 1 cm(2) solar module may harvest ∼2500 µW from sunlight (3 mm implantation depth). Secondly, ex vivo measurements were performed with solar cells placed under pig skin flaps exposed to a solar simulator and real sunlight. Ex vivo measurements under real sunlight resulted in a median output power of 4941 µW/cm(2) [interquartile range (IQR) 3767-5598 µW/cm(2), median skin flap thickness 3.0 mm (IQR 2.7-3.3 mm)]. The output power strongly depended on implantation depth (ρSpearman = -0.86, P pacemaker powered by a 3.24 cm(2) solar module was implanted in vivo in a pig to measure output power and to pace. In vivo measurements showed a median output power of >3500 µW/cm(2) (skin flap thickness 2.8-3.84 mm). Successful batteryless VVI pacing using a subcutaneously implanted solar module was performed. Based on our results, we estimate that a few minutes of direct sunlight (irradiating an implanted solar module) allow powering a pacemaker for 24 h using a suitable energy storage. Thus, powering a pacemaker by sunlight is feasible and may be an alternative energy supply for tomorrow's pacemakers. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  1. ARTERIAL HYPERTENSION AND MEDICAL SUPPORT OF PATIENTS WITH PERMANENT PACEMAKERS

    Directory of Open Access Journals (Sweden)

    T. A. Derienko

    2016-06-01

    Full Text Available The review is devoted to clinical problems of arterial hypertension (AH in patients with implanted pacemakers (EKS and cardiac resynchronization therapy (CRT. Indications for pacemaker implantation and CRT are considered, especially the purpose and effectiveness of angiotensin-converting enzyme (ACE inhibitors, angiotensin II receptor antagonists (ARA, sartans, beta-blockers (BAB, diuretics, calcium channel blockers. We prove that the CRT and cardiac pacing and do not cancel, bur modify drug therapy of AH.

  2. Circadian Clock Dysfunction and Psychiatric Disease: Could Fruit Flies have a Say?

    Science.gov (United States)

    Zordan, Mauro Agostino; Sandrelli, Federica

    2015-01-01

    There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system leads to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here, we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e., a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia, and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes, which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions, and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease.

  3. Circadian clock dysfunction and psychiatric disease: could fruit flies have a say?

    Directory of Open Access Journals (Sweden)

    Mauro Agostino Zordan

    2015-04-01

    Full Text Available There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system lead to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e. a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease.

  4. Pacemaker implantation after catheter ablation for atrial fibrillation.

    Science.gov (United States)

    Deshmukh, Abhishek J; Yao, Xiaoxi; Schilz, Stephanie; Van Houten, Holly; Sangaralingham, Lindsey R; Asirvatham, Samuel J; Friedman, Paul A; Packer, Douglas L; Noseworthy, Peter A

    2016-01-01

    Sinus node dysfunction requiring pacemaker implantation is commonly associated with atrial fibrillation (AF), but may not be clinically apparent until restoration of sinus rhythm with ablation or cardioversion. We sought to determine frequency, time course, and predictors for pacemaker implantation after catheter ablation, and to compare the overall rates to a matched cardioversion cohort. We conducted a retrospective analysis using a large US commercial insurance database and identified 12,158 AF patients who underwent catheter ablation between January 1, 2005 and December 31, 2012. Over an average of 2.4 years of follow-up, 5.6 % of the patients underwent pacemaker implantation. Using the Cox proportional hazards models, we found that risk of risks of pacemaker implantation was associated with older age (50-64 and ≥65 versus pacemaker implantation between ablation patients and propensity score (PS)-matched cardioversion groups (3.5 versus. 4.1 % at 1 year and 8.8 versus 8.3 % at 5 years). Overall, pacemaker implantation occurs in about 1/28 patients within 1 year of catheter ablation. The overall implantation rate decreased between 2005 and 2012. Furthermore, the risk after ablation is similar to cardioversion, suggesting that patients require pacing due to a common underlying electrophysiologic substrate, rather than the ablation itself.

  5. Effects of irradiation on the components of implantable pacemakers

    International Nuclear Information System (INIS)

    Kawamura, Shinji; Ono, Seiji; Kuga, Noriyuki; Shiba, Tooru; Hirose, Tetsuo; Matoba, Masaru

    2003-01-01

    The purpose of this study was to examine the effects of irradiation on implantable pacemaker components. The pacemaker was divided into three components: lead wire and electrode, battery, and electrical circuit, and each component was irradiated by X-ray and electron beams, respectively. The pacemaker parameters were measured by both telemetry data of the programmer and directly measured data from the output terminal. The following results were obtained. For the lead wire and electrode, there was no effect on the pacemaker function due to irradiation by X-ray and electron beams. In the case of battery irradiation, there was no change in battery voltage or current up to 236 Gy X-ray dose. In the electrical circuit, the pacemaker reverted to the regular beating rate (fixed-rate mode) immediately after the start of X-ray irradiation, and it continued in this mode during irradiation. In patients with their own heartbeat rhythm, changing to the fixed-rate mode may cause dangerous conditions such as ventricular fibrillation. When the accumulated irradiation dose is increased, another failure can be seen in the output voltage of the pacemaker. The pacing output voltage dropped rapidly by about 40% at 30-88 Gy. Decreasing the output voltage results in pacing disorders, and heart failure may occur. In the telemetry data of the programmer, no change in output voltage could be detected, highlighting the difference between telemetry data and actual pacing data. (author)

  6. Selective interference with pacemaker activity by electrical dental devices.

    Science.gov (United States)

    Miller, C S; Leonelli, F M; Latham, E

    1998-01-01

    We sought to determine whether electromagnetic interference with cardiac pacemakers occurs during the operation of contemporary electrical dental equipment. Fourteen electrical dental devices were tested in vitro for their ability to interfere with the function of two Medtronics cardiac pacemakers (one a dual-chamber, bipolar Thera 7942 pacemaker, the other a single-chamber, unipolar Minix 8340 pacemaker). Atrial and ventricular pacemaker output and electrocardiographic activity were monitored by means of telemetry with the use of a Medtronics 9760/90 programmer. Atrial and ventricular pacing were inhibited by electromagnetic interference produced by the electrosurgical unit up to a distance of 10 cm, by the ultrasonic bath cleaner up to 30 cm, and by the magnetorestrictive ultrasonic scalers up to 37.5 cm. In contrast, operation of the amalgamator, electric pulp tester, composite curing light, dental handpieces, electric toothbrush, microwave oven, dental chair and light, ENAC ultrasonic instrument, radiography unit, and sonic scaler did not alter pacing rate or rhythm. These results suggest that certain electrosurgical and ultrasonic instruments may produce deleterious effects in medically fragile patients with cardiac pacemakers.

  7. Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.

    Science.gov (United States)

    Griggs, Chanel A; Malm, Scott W; Jaime-Frias, Rosa; Smith, Catharine L

    2018-01-15

    Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop. In cells with an unsynchronized clock, VPA simultaneously upregulated the expression of genes encoding core circadian transcription factors that regulate the positive and negative limbs of the feedback loop. Using low dose glucocorticoid, we synchronized cultured fibroblast cells to a circadian oscillatory pattern. Whether VPA was added at the time of synchronization or 12h later at CT12, we found that VPA disrupted the oscillatory expression of multiple genes encoding essential transcription factors that regulate circadian rhythm. Therefore, we conclude that VPA has a potent effect on the circadian rhythm transcription-translation feedback loop that may be linked to negative VPA side effects in humans. Furthermore, our study suggests potential chronopharmacology implications of VPA usage. Copyright © 2017. Published by Elsevier Inc.

  8. Paternal irradiation perturbs the expression of circadian genes in offspring

    International Nuclear Information System (INIS)

    Gomes, Andre M.G.F.; Barber, Ruth C.; Dubrova, Yuri E.

    2015-01-01

    Highlights: • We have analysed gene expression in the offspring of irradiated male mice. • CBA/Ca and BALB/c male mice were used in our study. • The pattern of gene expression was established in four tissues. • Expression of genes in involved in rhythmic process/circadian rhythm is compromised. • Our data may explain the phenomenon of transgenerational genomic instability. - Abstract: The circadian system represents a complex network which influences the timing of many biological processes. Recent studies have established that circadian alterations play an important role in the susceptibility to many human diseases, including cancer. Here we report that paternal irradiation in mice significantly affects the expression of genes involved in rhythmic processes in their first-generation offspring. Using microarrays, the patterns of gene expression were established for brain, kidney, liver and spleen samples from the non-exposed offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented categories among the genes differentially expressed in the offspring of control and irradiated males were those involved in rhythmic process, circadian rhythm and DNA-dependent regulation of transcription. The results of our study therefore provide a plausible explanation for the transgenerational effects of paternal irradiation, including increased transgenerational carcinogenesis described in other studies

  9. Paternal irradiation perturbs the expression of circadian genes in offspring

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Andre M.G.F.; Barber, Ruth C.; Dubrova, Yuri E., E-mail: yed2@le.ac.uk

    2015-05-15

    Highlights: • We have analysed gene expression in the offspring of irradiated male mice. • CBA/Ca and BALB/c male mice were used in our study. • The pattern of gene expression was established in four tissues. • Expression of genes in involved in rhythmic process/circadian rhythm is compromised. • Our data may explain the phenomenon of transgenerational genomic instability. - Abstract: The circadian system represents a complex network which influences the timing of many biological processes. Recent studies have established that circadian alterations play an important role in the susceptibility to many human diseases, including cancer. Here we report that paternal irradiation in mice significantly affects the expression of genes involved in rhythmic processes in their first-generation offspring. Using microarrays, the patterns of gene expression were established for brain, kidney, liver and spleen samples from the non-exposed offspring of irradiated CBA/Ca and BALB/c male mice. The most over-represented categories among the genes differentially expressed in the offspring of control and irradiated males were those involved in rhythmic process, circadian rhythm and DNA-dependent regulation of transcription. The results of our study therefore provide a plausible explanation for the transgenerational effects of paternal irradiation, including increased transgenerational carcinogenesis described in other studies.

  10. The Importance of the Circadian Clock in Regulating Plant Metabolism

    Directory of Open Access Journals (Sweden)

    Jin A Kim

    2017-12-01

    Full Text Available Carbohydrates are the primary energy source for plant development. Plants synthesize sucrose in source organs and transport them to sink organs during plant growth. This metabolism is sensitive to environmental changes in light quantity, quality, and photoperiod. In the daytime, the synthesis of sucrose and starch accumulates, and starch is degraded at nighttime. The circadian clock genes provide plants with information on the daily environmental changes and directly control many developmental processes, which are related to the path of primary metabolites throughout the life cycle. The circadian clock mechanism and processes of metabolism controlled by the circadian rhythm were studied in the model plant Arabidopsis and in the crops potato and rice. However, the translation of molecular mechanisms obtained from studies of model plants to crop plants is still difficult. Crop plants have specific organs such as edible seed and tuber that increase the size or accumulate valuable metabolites by harvestable metabolic components. Human consumers are interested in the regulation and promotion of these agriculturally significant crops. Circadian clock manipulation may suggest various strategies for the increased productivity of food crops through using environmental signal or overcoming environmental stress.

  11. Final generic environmental statement on the routine use of plutonium-powered cardiac pacemakers. Update of information on power sources for pacemakers

    International Nuclear Information System (INIS)

    1979-05-01

    The Final Environmental Statement on Routine Use of Plutonium-Powered Cardiac Pacemakers (FES) was issued in July 1976. Supplement 1, prepared in 1978, updates the FES with respect to power sources for pacemakers. Particular attention is given to the non-nuclear lithium batteries as alternatives to 238-Pu power sources in pacemakers. Supplement 1 also considers the current extent of pacemaker use and makeup of the patient population and concludes that the FES' conclusion is still valid that distribution of 238-Pu powered pacemakers for routine use should be authorized subject to specific conditions

  12. Impact of Pacemaker Lead Characteristics on Pacemaker Related Infection and Heart Perforation: A Nationwide Population-Based Cohort Study.

    Science.gov (United States)

    Lin, Yu-Sheng; Chen, Tien-Hsing; Hung, Sheng-Ping; Chen, Dong Yi; Mao, Chun-Tai; Tsai, Ming-Lung; Chang, Shih-Tai; Wang, Chun-Chieh; Wen, Ming-Shien; Chen, Mien-Cheng

    2015-01-01

    Several risk factors for pacemaker (PM) related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications. Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07-0.80; P = 0.020) or the passive fixation group (OR, 0.26; 95% CI, 0.08-0.83; P = 0.023). There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.

  13. Impact of Pacemaker Lead Characteristics on Pacemaker Related Infection and Heart Perforation: A Nationwide Population-Based Cohort Study.

    Directory of Open Access Journals (Sweden)

    Yu-Sheng Lin

    Full Text Available Several risk factors for pacemaker (PM related complications have been reported. However, no study has investigated the impact of lead characteristics on pacemaker-related complications.Patients who received a new pacemaker implant from January 1997 to December 2011 were selected from the Taiwan National Health Insurance Database. This population was grouped according to the pacemaker lead characteristics in terms of fixation and insulation. The impact of the characteristics of leads on early heart perforation was analyzed by multivariable logistic regression analysis, while the impact of the lead characteristics on early and late infection and late heart perforation over a three-year period were analyzed using Cox regression. This study included 36,104 patients with a mean age of 73.4±12.5 years. In terms of both early and late heart perforations, there were no significant differences between groups across the different types of fixation and insulations. In the multivariable Cox regression analysis, the pacemaker-related infection rate was significantly lower in the active fixation only group compared to either the both fixation (OR, 0.23; 95% CI, 0.07-0.80; P = 0.020 or the passive fixation group (OR, 0.26; 95% CI, 0.08-0.83; P = 0.023.There was no difference in heart perforation between active and passive fixation leads. Active fixation leads were associated with reduced risk of pacemaker-related infection.

  14. Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits.

    Directory of Open Access Journals (Sweden)

    Erika Navarrete

    Full Text Available Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB. We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1, pups were randomly assigned to one of the following conditions: intact pups (INT, intact pups fed by enteral gavage (INT+ENT, sham operated pups (SHAM, pups with unilateral lesions of the olfactory bulb (OBx-UNI, and pups with bilateral lesions of the olfactory bulb (OBx-BI. At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00, and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb.

  15. The relationship between circadian disruption and the development of metabolic syndrome and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Karatsoreos IN

    2014-12-01

    Full Text Available Ilia N Karatsoreos Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA Abstract: Circadian (daily rhythms are pervasive in nature, and expressed in nearly every behavioral and physiological process. In mammals, circadian rhythms are regulated by the master brain clock in the suprachiasmatic nucleus of the hypothalamus that coordinates the activity of “peripheral” oscillators throughout the brain and body. While much progress has been made in understanding the basic functioning of the circadian clock at the level of genes, molecules, and cells, our understanding of how these clocks interact with complex systems is still in its infancy. Much recent work has focused on the role of circadian clocks in the etiology of disorders as diverse as cancer, diabetes, and obesity. Given the rapid rise in obesity, and the economic costs involved in treating its associated cardiometabolic disorders such as heart disease and diabetes mellitus, understanding the development of obesity and metabolic dysregulation is crucial. Significant epidemiological data indicate a role for circadian rhythms in metabolic disorders. Shift workers have a higher incidence of obesity and diabetes, and laboratory studies in humans show misaligning sleep and the circadian clock leads to hyperinsulinemia. In animal models, body-wide “clock gene” knockout mice are prone to obesity. Further, disrupting the circadian clock by manipulating the light–dark cycle can result in metabolic dysregulation and development of obesity. At the molecular level, elegant studies have shown that targeted disruption of the genetic circadian clock in the pancreas leads to diabetes, highlighting the fact that the circadian clock is directly coupled to metabolism at the cellular level. Keywords: glucose, metabolism, sleep, rhythms, obesity

  16. Drosophila spaghetti and doubletime link the circadian clock and light to caspases, apoptosis and tauopathy.

    Directory of Open Access Journals (Sweden)

    John C Means

    2015-05-01

    Full Text Available While circadian dysfunction and neurodegeneration are correlated, the mechanism for this is not understood. It is not known if age-dependent circadian dysfunction leads to neurodegeneration or vice-versa, and the proteins that mediate the effect remain unidentified. Here, we show that the knock-down of a regulator (spag of the circadian kinase Dbt in circadian cells lowers Dbt levels abnormally, lengthens circadian rhythms and causes expression of activated initiator caspase (Dronc in the optic lobes during the middle of the day or after light pulses at night. Likewise, reduced Dbt activity lengthens circadian period and causes expression of activated Dronc, and a loss-of-function mutation in Clk also leads to expression of activated Dronc in a light-dependent manner. Genetic epistasis experiments place Dbt downstream of Spag in the pathway, and Spag-dependent reductions of Dbt are shown to require the proteasome. Importantly, activated Dronc expression due to reduced Spag or Dbt activity occurs in cells that do not express the spag RNAi or dominant negative Dbt and requires PDF neuropeptide signaling from the same neurons that support behavioral rhythms. Furthermore, reduction of Dbt or Spag activity leads to Dronc-dependent Drosophila Tau cleavage and enhanced neurodegeneration produced by human Tau in a fly eye model for tauopathy. Aging flies with lowered Dbt or Spag function show markers of cell death as well as behavioral deficits and shortened lifespans, and even old wild type flies exhibit Dbt modification and activated caspase at particular times of day. These results suggest that Dbt suppresses expression of activated Dronc to prevent Tau cleavage, and that the circadian clock defects confer sensitivity to expression of activated Dronc in response to prolonged light. They establish a link between the circadian clock factors, light, cell death pathways and Tau toxicity, potentially via dysregulation of circadian neuronal remodeling in

  17. Dim light at night disrupts molecular circadian rhythms and increases body weight.

    Science.gov (United States)

    Fonken, Laura K; Aubrecht, Taryn G; Meléndez-Fernández, O Hecmarie; Weil, Zachary M; Nelson, Randy J

    2013-08-01

    With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms that are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electric lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however, the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to dim light at night and investigated changes in the circadian system and metabolism. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night altered core circadian clock rhythms in the hypothalamus at both the gene and protein level. Circadian rhythms in clock expression persisted during light at night; however, the amplitude of Per1 and Per2 rhythms was attenuated in the hypothalamus. Circadian oscillations were also altered in peripheral tissues critical for metabolic regulation. Exposure to dimly illuminated, as compared to dark, nights decreased the rhythmic expression in all but one of the core circadian clock genes assessed in the liver. Additionally, mice exposed to dim light at night attenuated Rev-Erb expression in the liver and adipose tissue. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide evidence that mild changes in environmental lighting can alter circadian and metabolic function. Detailed analysis of temporal changes induced by nighttime light exposure may provide insight into the onset and progression of obesity and metabolic syndrome, as well as other disorders involving sleep and circadian rhythm disruption.

  18. Influence of internal current and pacing current on pacemaker longevity.

    Science.gov (United States)

    Schuchert, A; Kuck, K H

    1994-01-01

    The effects of lower pulse amplitude on battery current and pacemaker longevity were studied comparing the new, small-sized VVI pacemaker, Minix 8341, with the former model, Pasys 8329. Battery current was telemetrically measured at 0.8, 1.6, 2.5, and 5.0 V pulse amplitude and 0.05, 0.25, 0.5, and 1.0 msec pulse duration. Internal current was assumed to be equal to the battery current at 0.8 V and 0.05 msec. Pacing current was calculated subtracting internal current from battery current. The Minix pacemaker had a significantly lower battery current because of a lower internal current (Minix: 4.1 +/- 0.1 microA; Pasys: 16.1 +/- 0.1 microA); pacing current of both units was similar. At 0.5 msec pulse duration, the programming from 5.0-2.5 V pulse amplitude resulted in a greater relative reduction of battery current in the newer pacemaker (51% vs 25%). Projected longevity of each pacemaker was 7.9 years at 5.0 V and 0.5 msec. The programming from 5.0-2.5 V extended the projected longevity by 2.3 years (Pasys) and by 7.1 years (Minix). The longevity was negligibly longer after programming to 1.6 V. extension of pacemaker longevity can be achieved with the programming to 2.5 V or less if the connected pacemakers need a low internal current for their circuitry.

  19. Circadian Rhythm Control: Neurophysiological Investigations

    Science.gov (United States)

    Glotzbach, S. F.

    1985-01-01

    The suprachiasmatic nucleus (SCN) was implicated as a primary component in central nervous system mechanisms governing circadian rhythms. Disruption of the normal synchronization of temperature, activity, and other rhythms is detrimental to health. Sleep wake disorders, decreases in vigilance and performance, and certain affective disorders may result from or be exacerbated by such desynchronization. To study the basic neurophysiological mechanisms involved in entrainment of circadian systems by the environment, Parylene-coated, etched microwire electrode bundles were used to record extracellular action potentials from the small somata of the SCN and neighboring hypothalamic nuclei in unanesthetized, behaving animals. Male Wistar rats were anesthetized and chronically prepared with EEG ane EMG electrodes in addition to a moveable microdrive assembly. The majority of cells had firing rates 10 Hz and distinct populations of cells which had either the highest firing rate or lowest firing rate during sleep were seen.

  20. [Right heart failure after pacemaker implantation].

    Science.gov (United States)

    Gallego Galiana, Juan; López Castellanos, Genoveva; Gioia, Francesca; Ruiz Ortega, Raúl Antonio; Cobo Reinoso, Maria Eugenia; Manzano Espinosa, Luis

    2015-06-22

    Severe tricuspid regurgitation (TR) secondary to interference pacemaker (PM) cable is a rare cause of progressive right heart failure (HF), which can worsen patient outcomes. We present 3 clinical cases of right HF secondary to TR after PM implantation. In these patients the clinic is right HF, which can appear early, as in our second patient, or after years of implementation of the PM, as in the first and third patients. The diagnosis is confirmed by echocardiography, the most accurate 3D, followed by transesophageal. The 2D transthoracic can not detect it, because it has low sensitivity for TR associated with PM. Medical treatment is always the first choice, since any other procedure carries significant morbidity and mortality. Probably this is a condition that we will diagnose with increasing frequency, because there are more and more patients with devices and, at the same time, the diagnostic tools are improving. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  1. Radioisotope thermoelectric generators for implanted pacemakers

    Energy Technology Data Exchange (ETDEWEB)

    Pustovalov, A.A.; Bovin, A.V.; Fedorets, V.I.; Shapovalov, V.P.

    1986-08-01

    This paper discusses the development and application of long-life lithium batteries and the problems associated with miniature radioisotope thermoelectric generators (RITEG) with service lives of 10 years or longer. On eof the main problems encountered when devising a radioisotope heat source (RHS) for an RITEG is to obtain biomedical /sup 238/PuO/sub 2/ with a specific neutron yield of 3.10/sup 3/-4.10/sup 3/ (g /SUP ./ sec)/sup -1/, equivalent to metallic Pu 238, and with a content of gamma impurities sufficient to ensure a permissible exposure a permissible exposure does rate (EDR) of a mixture of neutron and gamma radiation. After carrying out the isotope exchange and purifying the initial sample of its gamma impurity elements, the authors obtain biomedical Pu 238 satisfying the indicated requirements king suitable for use in the power packs of medical devices. Taking the indicated specifications into account, the Ritm-1o and gamma radioisotope heat sources were designed, built, tested in models and under natural conditions, and then into production as radioisotope thermoelectric generators designed to power the electronic circuits of implanted pacemakers. The Ritm-MT and Gemma radioisotope thermoelectric generators described are basic units, which can be used as self-contained power supplies for electronic equipment with power requirements in the micromilliwatt range.

  2. Circadian Rhythm Sleep-Wake Disorders.

    Science.gov (United States)

    Abbott, Sabra M; Reid, Kathryn J; Zee, Phyllis C

    2015-12-01

    The circadian system regulates the timing and expression of nearly all biological processes, most notably, the sleep-wake cycle, and disruption of this system can result in adverse effects on both physical and mental health. The circadian rhythm sleep-wake disorders (CRSWDs) consist of 5 disorders that are due primarily to pathology of the circadian clock or to a misalignment of the timing of the endogenous circadian rhythm with the environment. This article outlines the nature of these disorders, the association of many of these disorders with psychiatric illness, and available treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Tunability of the circadian action of tetrachromatic solid-state light sources

    International Nuclear Information System (INIS)

    Žukauskas, A.; Vaicekauskas, R.

    2015-01-01

    An approach to the optimization of the spectral power distribution of solid-state light sources with the tunable non-image forming photobiological effect on the human circadian rhythm is proposed. For tetrachromatic clusters of model narrow-band (direct-emission) light-emitting diodes (LEDs), the limiting tunability of the circadian action factor (CAF), which is the ratio of the circadian efficacy to luminous efficacy of radiation, was established as a function of constraining color fidelity and luminous efficacy of radiation. For constant correlated color temperatures (CCTs), the CAF of the LED clusters can be tuned above and below that of the corresponding blackbody radiators, whereas for variable CCT, the clusters can have circadian tunability covering that of a temperature-tunable blackbody radiator

  4. Tunability of the circadian action of tetrachromatic solid-state light sources

    Energy Technology Data Exchange (ETDEWEB)

    Žukauskas, A., E-mail: arturas.zukauskas@ff.vu.lt [Institute of Applied Research, Vilnius University, Saulėtekio al. 9-III, LT-10222 Vilnius (Lithuania); Vaicekauskas, R. [Department of Computer Science, Vilnius University, Didlaukio g. 47, Vilnius LT-08303 (Lithuania)

    2015-01-26

    An approach to the optimization of the spectral power distribution of solid-state light sources with the tunable non-image forming photobiological effect on the human circadian rhythm is proposed. For tetrachromatic clusters of model narrow-band (direct-emission) light-emitting diodes (LEDs), the limiting tunability of the circadian action factor (CAF), which is the ratio of the circadian efficacy to luminous efficacy of radiation, was established as a function of constraining color fidelity and luminous efficacy of radiation. For constant correlated color temperatures (CCTs), the CAF of the LED clusters can be tuned above and below that of the corresponding blackbody radiators, whereas for variable CCT, the clusters can have circadian tunability covering that of a temperature-tunable blackbody radiator.

  5. Circadian organization in hemimetabolous insects.

    Science.gov (United States)

    Tomioka, Kenji; Abdelsalam, Salaheldin

    2004-12-01

    The circadian system of hemimetabolous insects is reviewed in respect to the locus of the circadian clock and multioscillatory organization. Because of relatively easy access to the nervous system, the neuronal organization of the clock system in hemimetabolous insects has been studied, yielding identification of the compound eye as the major photoreceptor for entrainment and the optic lobe for the circadian clock locus. The clock site within the optic lobe is inconsistent among reported species; in cockroaches the lobula was previously thought to be a most likely clock locus but accessory medulla is recently stressed to be a clock center, while more distal part of the optic lobe including the lamina and the outer medulla area for the cricket. Identification of the clock cells needs further critical studies. Although each optic lobe clock seems functionally identical, in respect to photic entrainment and generation of the rhythm, the bilaterally paired clocks form a functional unit. They interact to produce a stable time structure within individual insects by exchanging photic and temporal information through neural pathways, in which serotonin and pigment-dispersing factor (PDF) are involved as chemical messengers. The mutual interaction also plays an important role in seasonal adaptation of the rhythm.

  6. Spiral–pacemaker interactions in a mathematical model of excitable medium

    International Nuclear Information System (INIS)

    Shajahan, T K; Borek, Bartłomiej; Shrier, Alvin; Glass, Leon

    2013-01-01

    Interactions of a spiral wave with a pacemaker is studied in a mathematical model of two dimensional excitable medium. Faster pacemakers emitting target waves can abolish spirals by driving them to the border of the medium. Our study shows that a slower pacemaker can modify spiral wave behavior by changing the motion of the spiral core. We analyze the dynamics of the spiral wave near the spiral core and away from the core as a function of size and period of the pacemaker. The pacemaker can cause the spiral wave to drift towards it, and either speed up or slow down the reentrant activity. Furthermore, the drift induced by the pacemaker can result in irregular or quasiperiodic dynamics even at sites away from the pacemaker. These results highlight the influence of pacemakers on complex spiral wave dynamics. (paper)

  7. Effects of irradiation on the components of implantable pacemakers

    CERN Document Server

    Kawamura, S; Kuga, N; Shiba, T; Hirose, T; Fujimoto, H; Toyoshima, T; Hyodo, K; Matoba, M

    2003-01-01

    The purpose of this study was to examine the effects of irradiation on implantable pacemaker components. The pacemaker was divided into three components: lead wire and electrode, battery, and electrical circuit, and each component was irradiated by X-ray and electron beams, respectively. The pacemaker parameters were measured by both telemetry data of the programmer and directly measured data from the output terminal. The following results were obtained. For the lead wire and electrode, there was no effect on the pacemaker function due to irradiation by X-ray and electron beams. In the case of battery irradiation, there was no change in battery voltage or current up to 236 Gy X-ray dose. In the electrical circuit, the pacemaker reverted to the regular beating rate (fixed-rate mode) immediately after the start of X-ray irradiation, and it continued in this mode during irradiation. In patients with their own heartbeat rhythm, changing to the fixed-rate mode may cause dangerous conditions such as ventricular fib...

  8. Patients exposure from fluoroscopic guided pacemaker implantation procedures

    Energy Technology Data Exchange (ETDEWEB)

    Alkhorayef, M.; Babikir, E. [King Saud University, College of Applied Sciences, Radiological Sciences Department, P. O. Box 10219, Riyadh 11433 (Saudi Arabia); Sulieman, A. [Prince Sattam bin Abdulaziz University, College of Applied Medical Sciences, Radiology and Medical Imaging Department, P. O. Box 422, Alkharj 11942 (Saudi Arabia); Daar, E. [University of Jordan, Faculty of Science, Department of Physics, Amman 11942 (Jordan); Alnaaimi, M.; Alduaij, M. [Kuwait Cancer Control Centre, Department of Nuclear Medicine, Shwiekh (Kuwait); Bradley, D., E-mail: malkhorayef@ksu.edu.sa [University of Surrey, Centre for Nuclear and Radiation Physics, Guildford, Surrey, GU2 7XH (United Kingdom)

    2016-10-15

    A pacemaker, which is used for heart re synchronization with electrical impulses, is used to manage many clinical conditions. Recently, the frequency of the pacemaker implantation procedures increased 50% worldwide. During this procedure, patients and staff can be exposed to excessive radiation exposure. Wide range of doses was reported in previous studies, suggesting that optimization of this procedure is not fulfilled yet. This study aims to evaluate the patient and staff radiation doses during cardiac pacemaker procedure and quantify the patient effective dose. A total of 145 procedures were performed for five pacemakers procedures (VVI, VVIR, VVD, VVDR and DDDR) two hospitals were evaluated. Patients doses were measured using the kerma-area product meter. Effective doses were estimated using software based on Monte Carlo simulation from National Radiological Protection Board. The effective dose values were used to estimate the cancer risk from pacemaker procedure. Patients demographic data, exposure parameters for both fluoroscopy and radiography were quantified. The mean patients doses (Gy. cm{sup 2}) for VVI, VVIR, VVD, VVDR and DDDR was 1.52±0.13 (1.43-1.61), 3.28±2.34 (0.29-8.73), 3.04±1.67 (1.57-4.86), 6.04±2.326 and 19.2±3.6 (5.43-30.2), respectively, per procedure. The overall patients effective dose is 1.1 mSv per procedure. (Author)

  9. Safety of Laser Interstitial Thermal Therapy in Patients With Pacemakers.

    Science.gov (United States)

    Grewal, Sanjeet S; Gorny, Krzysztof R; Favazza, Christopher P; Watson, Robert E; Kaufmann, Timothy J; Van Gompel, Jamie J

    2018-02-10

    Laser interstitial thermal therapy (LiTT) has increasingly been used as a treatment option for medically refractory epilepsy, tumors, and radiation necrosis. The use of LiTT requires intraoperative magnetic resonance (MR) thermography. This can become an issue in patients with other implanted therapeutic devices such as pacemakers and vagal nerve stimulators due to concerns regarding increases in the specific absorption rate (SAR). This is a technical case report demonstrating a successfully and safely performed LiTT in a 1.5-T magnetic resonance imaging (MRI) in a patient with a pacemaker for mesial temporal sclerosis. An 83-yr-old gentleman who had an implanted cardiac pacemaker presented with medically intractable epilepsy and was confirmed to have mesial temporal sclerosis on imaging. Video electroencephalography demonstrated concordant ipsilateral seizures and semiology. He underwent LiTT for ablation of the mesial temporal lobe. This was performed with the below described protocol with a cardiology nurse monitoring the patient's cardiac condition and a physicist monitoring SAR, and MR imaging quality without any adverse events. This study reports on a protocol of cardiac and MR SAR to safely perform MR-guided LiTT in the setting of traditional pacemakers in patients who are not pacemaker dependent. Copyright © 2018 by the Congress of Neurological Surgeons

  10. Sacral Neuromodulation in Patients With a Cardiac Pacemaker

    Directory of Open Access Journals (Sweden)

    Abdullah A. Gahzi

    2016-09-01

    Full Text Available The objective of this study was to describe our experience using sacral neuromodulation to treat urinary urgency, frequency, urge incontinence, and chronic urinary retention in patients with cardiac pacemakers. With the increasingly widespread use of InterStim for bladder function restoration, we are seeing more complex patients with multiple comorbidities, including cardiac conditions. Herein, we report 3 cases of individuals with cardiac pacemakers who underwent InterStim implantation to treat urinary conditions. This study is a case series of 3 patients with cardiac pacemakers who underwent sacral neuromodulation to treat refractory voiding dysfunction. The initial patient screening for InterStim therapy involved percutaneous nerve evaluation (PNE, in which a temporary untined lead wire was placed through the S3 foramen. Patients who did not respond to PNE proceeded to a staged implant. All patients in this study had a greater than 50% improvement of their urinary symptoms during the initial trial and underwent placement of the InterStim implantable pulse generator (IPG. Postoperative programming was done under electrocardiogram monitoring by a cardiologist. No interference was observed between the Inter-Stim IPG and the cardiac pacemaker. In this group of patients, sacral neuromodulation in the presence of a cardiac pacemaker appears to have been safe.

  11. Patients exposure from fluoroscopic guided pacemaker implantation procedures

    International Nuclear Information System (INIS)

    Alkhorayef, M.; Babikir, E.; Sulieman, A.; Daar, E.; Alnaaimi, M.; Alduaij, M.; Bradley, D.

    2016-10-01

    A pacemaker, which is used for heart re synchronization with electrical impulses, is used to manage many clinical conditions. Recently, the frequency of the pacemaker implantation procedures increased 50% worldwide. During this procedure, patients and staff can be exposed to excessive radiation exposure. Wide range of doses was reported in previous studies, suggesting that optimization of this procedure is not fulfilled yet. This study aims to evaluate the patient and staff radiation doses during cardiac pacemaker procedure and quantify the patient effective dose. A total of 145 procedures were performed for five pacemakers procedures (VVI, VVIR, VVD, VVDR and DDDR) two hospitals were evaluated. Patients doses were measured using the kerma-area product meter. Effective doses were estimated using software based on Monte Carlo simulation from National Radiological Protection Board. The effective dose values were used to estimate the cancer risk from pacemaker procedure. Patients demographic data, exposure parameters for both fluoroscopy and radiography were quantified. The mean patients doses (Gy. cm 2 ) for VVI, VVIR, VVD, VVDR and DDDR was 1.52±0.13 (1.43-1.61), 3.28±2.34 (0.29-8.73), 3.04±1.67 (1.57-4.86), 6.04±2.326 and 19.2±3.6 (5.43-30.2), respectively, per procedure. The overall patients effective dose is 1.1 mSv per procedure. (Author)

  12. Implantable Cardiac Pacemakers – 50 Years from the First Implantation

    Directory of Open Access Journals (Sweden)

    Ratko Magjarević

    2010-01-01

    Overview: Development of implantable cardiac pacemaker was enabled by another important invention, the silicon transistor. h ough the invention of suitable lithium cells as appropriate power supply was essential for prolongation of battery life cycle and for increased reliability of pacemakers, main milestones in the development were associated with technological breakthroughs in electronics: from transistors, which introduced such features as small size and low power consumption, to hybrid and integrated circuits, which enabled programmability, microprocessors, which added more options in programming (multiprogrammability, diagnostics and telemetry, and the ICT (information communication technology that enabled physicians remote access to patients and interrogation of their implantable devices. Conclusions: Implantable pacemakers are reliable devices indicated for a wide range of dif erent therapies of cardiac rhythm disorders and heart failure. h ere is still a lot to learn about the physiology of a normal heart and even more about the failing heart. Modern pacemakers provide physicians valuable information from pacemakers’ memory via the built-in telemetry system. h ese information help physicians to better understand pathologic processes within the heart, thus contributing to the development of new ideas for treatment of diseases and for precise tailoring of the therapy to the patient’s needs. Although implantable pacemakers have reached the level of mature technology, they will continue to develop with therapies and diagnostics to facilitate a higher quality of life.

  13. Pacemaker lead fracture associated with weightlifting: a report of two cases.

    Science.gov (United States)

    Deering, J A; Pederson, D N

    1993-12-01

    Two cases of pacemaker lead fracture associated with weight-lifting are presented. This is a rare association which has only recently been described in the literature. In both cases, the pacemaker lead was fractured between the clavicle and the first rib, suggesting crush injury. The chest X-ray, pacemaker telemetry with measurement of lead impedance, and pacemaker reprogramming were all helpful in management.

  14. Metabolic influences on circadian rhythmicity in Siberian and Syrian hamsters exposed to long photoperiods.

    Science.gov (United States)

    Challet, E; Kolker, D E; Turek, F W

    2000-01-01

    Calorie restriction and other situations of reduced glucose availability in rodents alter the entraining effects of light on the circadian pacemaker located in the suprachiasmatic nuclei. Siberian and Syrian hamsters are photoperiodic species that are sexually active when exposed to long summer-like photoperiods, while both species show opposite changes in body mass when transferred from long to short or short to long days. Because metabolic cues may fine tune the photoperiodic responses via the suprachiasmatic nuclei, we tested whether timed calorie restriction can alter the photic synchronization of the light-entrainable pacemaker in these two hamster species exposed to long photoperiods. Siberian and Syrian hamsters were exposed to 16 h:8 h light:dark cycles and received daily hypocaloric (75% of daily food intake) or normocaloric diet (100% of daily food intake) 4 h after light onset. Four weeks later, hamsters were transferred to constant darkness and fed ad libitum. The onset of the nocturnal pattern of locomotor activity was phase advanced by 1.5 h in calorie-restricted Siberian hamsters, but not in Syrian hamsters. The lack of phase change in calorie-restricted Syrian hamsters was also observed in individuals exposed to 14 h:10 h dim light:dark cycles and fed with lower hypocaloric food (i.e. 60% of daily food intake) 2 h after light onset. Moreover, in hamsters housed in constant darkness and fed ad lib., light-induced phase shifts of the locomotor activity in Siberian hamsters, but not in Syrian hamsters were significantly reduced when glucose utilization was blocked by pretreatment with 500 mg/kg i.p. 2-deoxy-D-glucose. Taken together, these results show that the photic synchronization of the light-entrainable pacemaker can be modulated by metabolic cues in Siberian hamsters, but not in Syrian hamsters maintained on long days.

  15. The influence of anatomical and physiological parameters on the interference voltage at the input of unipolar cardiac pacemakers in low frequency electric fields

    Energy Technology Data Exchange (ETDEWEB)

    Joosten, S; Pammler, K; Silny, J [Research Center for Bioelectromagnetic Interaction (FEMU), University Hospital, Aachen University (Germany)], E-mail: joosten@femu.rwth-aachen.de

    2009-02-07

    The problem of electromagnetic interference of electronic implants such as cardiac pacemakers has been well known for many years. An increasing number of field sources in everyday life and occupational environment leads unavoidably to an increased risk for patients with electronic implants. However, no obligatory national or international safety regulations exist for the protection of this patient group. The aim of this study is to find out the anatomical and physiological worst-case conditions for patients with an implanted pacemaker adjusted to unipolar sensing in external time-varying electric fields. The results of this study with 15 volunteers show that, in electric fields, variation of the interference voltage at the input of a cardiac pacemaker adds up to 200% only because of individual factors. These factors should be considered in human studies and in the setting of safety regulations.

  16. The influence of anatomical and physiological parameters on the interference voltage at the input of unipolar cardiac pacemakers in low frequency electric fields

    International Nuclear Information System (INIS)

    Joosten, S; Pammler, K; Silny, J

    2009-01-01

    The problem of electromagnetic interference of electronic implants such as cardiac pacemakers has been well known for many years. An increasing number of field sources in everyday life and occupational environment leads unavoidably to an increased risk for patients with electronic implants. However, no obligatory national or international safety regulations exist for the protection of this patient group. The aim of this study is to find out the anatomical and physiological worst-case conditions for patients with an implanted pacemaker adjusted to unipolar sensing in external time-varying electric fields. The results of this study with 15 volunteers show that, in electric fields, variation of the interference voltage at the input of a cardiac pacemaker adds up to 200% only because of individual factors. These factors should be considered in human studies and in the setting of safety regulations.

  17. Pacemaker Dependency after Cardiac Surgery: A Systematic Review of Current Evidence.

    Science.gov (United States)

    Steyers, Curtis M; Khera, Rohan; Bhave, Prashant

    2015-01-01

    Severe postoperative conduction disturbances requiring permanent pacemaker implantation frequently occur following cardiac surgery. Little is known about the long-term pacing requirements and risk factors for pacemaker dependency in this population. We performed a systematic review of the literature addressing rates and predictors of pacemaker dependency in patients requiring permanent pacemaker implantation after cardiac surgery. Using a comprehensive search of the Medline, Web of Science and EMBASE databases, studies were selected for review based on predetermined inclusion and exclusion criteria. A total of 8 studies addressing the endpoint of pacemaker-dependency were identified, while 3 studies were found that addressed the recovery of atrioventricular (AV) conduction endpoint. There were 10 unique studies with a total of 780 patients. Mean follow-up ranged from 6-72 months. Pacemaker dependency rates ranged from 32%-91% and recovery of AV conduction ranged from 16%-42%. There was significant heterogeneity with respect to the definition of pacemaker dependency. Several patient and procedure-specific variables were found to be independently associated with pacemaker dependency, but these were not consistent between studies. Pacemaker dependency following cardiac surgery occurs with variable frequency. While individual studies have identified various perioperative risk factors for pacemaker dependency and non-resolution of AV conduction disease, results have been inconsistent. Well-conducted studies using a uniform definition of pacemaker dependency might identify patients who will benefit most from early permanent pacemaker implantation after cardiac surgery.

  18. [TRENDS OF PERMANENT PACEMAKER IMPLANTATION IN A SINGLE CENTER OVER A 20-YEAR PERIOD].

    Science.gov (United States)

    Antonelli, Dante; Ilan, Limor Bushar; Freedberg, Nahum A; Feldman, Alexander; Turgeman, Yoav

    2015-05-01

    To review the changes in permanent pacemaker implantation indications, pacing modes and patients' demographics over a 20-year period. We retrospectively retrieved data on patients who underwent first implantation of the pacemaker between 1-1-1991 and 31-12-2010. One thousand and nine (1,009) patients underwent a first pacemaker implantation during that period; 535 were men (53%), their mean age was 74.6±19.5 years; the highest rate of implanted pacemaker was in patients ranging in age from 70-79 years, however there was an increasing number of patients aged over 80 years. The median survival time after initial pacemaker implantation was 8 years. Syncope was the most common symptom (62.5%) and atrioventricular block was the most common electrocardiographic indication (56.4%) leading to pacemaker implantation. There was increased utilization of dual chamber and rate responsive pacemakers over the years. There was no difference regarding mode selection between genders. Pacemaker implantation rates have increased over a 20-year period. Dual chamber replaced most of the single ventricular chamber pacemaker and rate responsive pacemakers became the norm. The data of a small volume center are similar to those reported in pacemaker surveys of high volume pacemaker implantation centers. They confirm adherence to the published guidelines for pacing.

  19. Distinct functions of Period2 and Period3 in the mouse circadian system revealed by in vitro analysis.

    Directory of Open Access Journals (Sweden)

    Julie S Pendergast

    2010-01-01

    Full Text Available The mammalian circadian system, which is composed of a master pacemaker in the suprachiasmatic nuclei (SCN as well as other oscillators in the brain and peripheral tissues, controls daily rhythms of behavior and physiology. Lesions of the SCN abolish circadian rhythms of locomotor activity and transplants of fetal SCN tissue restore rhythmic behavior with the periodicity of the donor's genotype, suggesting that the SCN determines the period of the circadian behavioral rhythm. According to the model of timekeeping in the SCN, the Period (Per genes are important elements of the transcriptional/translational feedback loops that generate the endogenous circadian rhythm. Previous studies have investigated the functions of the Per genes by examining locomotor activity in mice lacking functional PERIOD proteins. Variable behavioral phenotypes were observed depending on the line and genetic background of the mice. In the current study we assessed both wheel-running activity and Per1-promoter-driven luciferase expression (Per1-luc in cultured SCN, pituitary, and lung explants from Per2(-/- and Per3(-/- mice congenic with the C57BL/6J strain. We found that the Per2(-/- phenotype is enhanced in vitro compared to in vivo, such that the period of Per1-luc expression in Per2(-/- SCN explants is 1.5 hours shorter than in Per2+/+ SCN, while the free-running period of wheel-running activity is only 11 minutes shorter in Per2(-/- compared to Per2+/+ mice. In contrast, circadian rhythms in SCN explants from Per3(-/- mice do not differ from Per3+/+ mice. Instead, the period and phase of Per1-luc expression are significantly altered in Per3(-/- pituitary and lung explants compared to Per3+/+ mice. Taken together these data suggest that the function of each Per gene may differ between tissues. Per2 appears to be important for period determination in the SCN, while Per3 participates in timekeeping in the pituitary and lung.

  20. Ductal carcinoma of the breast in the pacemaker generator's pocket.

    Science.gov (United States)

    Zonca, P; Herokova, J; Cambal, M; Jacobi, C A

    2009-01-01

    Authors present a case of a 78-year-old female patient with invasive ductal adenocarcinoma in the pacemaker, s pocket. A decubitus-like tumor had developed in this place, and has been missinterpretated as a benign lesion for 5 months. Diagnosis was done with a time delay. An excisional biopsy revealed annvasive ductal adenocarcinoma. The first step was the implantation of a new pacemaker generator performed on the opposite side. The second step was a modified radical mastectomy, according to Madden, and the removal of the originally implanted pacemaker generator. Radiotherapy and hormonal adjuvant therapy were applied after surgery. The patient was followed-up at an out-patient clinic, and died 25 months after diagnosis because of generalization of the disease (Fig. 2, Ref. 35). Full Text (Free, PDF) www.bmj.sk.

  1. Automatic Capture Verification in Pacemakers (Autocapture – Utility and Problems

    Directory of Open Access Journals (Sweden)

    Ruth Kam

    2004-04-01

    Full Text Available The concept of a closed – loop feedback system, that would automatically assess pacing threshold and self -adjust pacing output to ensure consistent myocardial capture, has many appeals. Enhancing patient safety in cases of an unexpected rise in threshold, reduced current drain, hence prolonging battery longevity and reducing the amount of physician intervention required are just some of the advantages. Autocapture (AC is a proprietary algorithm developed by St Jude Medical CRMD, Sylmar, CA, USA, (SJM that was the first to commercially provide these automatic functions in a single chamber pacemaker (Microny and Regency, and subsequently in a dual chamber pacemaker (Affinity, Entity and Identity family of pacemakers. This article reviews the conditions necessary for AC verification and performance and the problems encountered in clinical practice.

  2. [11C]Doxepin binding to histamine H1 receptors in living human brain in association with attentive waking and circadian rhythm

    Directory of Open Access Journals (Sweden)

    Kazuhiko eYanai

    2012-06-01

    Full Text Available Molecular imaging in neuroscience is a new research field that enables visualization of the impact of molecular events on brain structure and function in humans. While magnetic resonance-based imaging techniques can provide complex information at the level of system, positron emission tomography (PET enables determination of the distribution and density of receptor and enzyme in the human brain. Previous studies using [11C]raclopride revealed that the release of neuronal dopamine was increased in human brain by psychostimulants or reward stimuli. Following on from these previous studies, we examined whether the levels of neuronal release of histamine might change [11C]doxepin binding to the H1 receptors under the influence of physiological stimuli. The purpose of the present study was to evaluate the test-retest reliability of quantitative measurement of [11C]doxepin binding between morning and afternoon and between resting and attentive waking conditions in healthy human subjects. There was a trend for a decrease in [11C]doxepin binding during attentive calculation tasks compared with that in resting conditions, but the difference (approximately 10% was not significant. In contrast, the binding potential of [11C]doxepin in the anterior cingulate gyrus was significantly higher in the morning than that in the afternoon (approximately 19%, suggesting that higher histamine release in the morning would decrease the [11C]doxepin binding in the afternoon. This study suggests that non-invasive measurement of neuronal histamine release is feasible in humans by PET ligand-activation study, although the development of a tracer with better signal-to-noise properties is needed.

  3. Global health resource utilization associated with pacemaker complications.

    Science.gov (United States)

    Waweru, Catherine; Steenrod, Anna; Wolff, Claudia; Eggington, Simon; Wright, David Jay; Wyrwich, Kathleen W

    2017-07-01

    To estimate health resource utilization (HRU) associated with the management of pacemaker complications in various healthcare systems. Electrophysiologists (EPs) from four geographical regions (Western Europe, Australia, Japan, and North America) were invited to participate. Survey questions focused on HRU in the management of three chronic pacemaker complications (i.e. pacemaker infections requiring extraction, lead fractures/insulation breaches requiring replacement, and upper extremity deep venous thrombosis [DVT]). Panelists completed a maximum of two web-based surveys (iterative rounds). Mean, median values, and interquartile ranges were calculated and used to establish consensus. Overall, 32 and 29 panelists participated in the first and second rounds of the Delphi panel, respectively. Consensus was reached on treatment and HRU associated with a typical pacemaker implantation and complications. HRU was similar across regions, except for Japan, where panelists reported the longest duration of hospital stay in all scenarios. Infections were the most resource-intensive complications and were characterized by intravenous antibiotics days of 9.6?13.5 days and 21.3?29.2 days for pocket and lead infections respectively; laboratory and diagnostic tests, and system extraction and replacement procedures. DVT, on the other hand, was the least resource intensive complication. The results of the panel represent the views of the respondents who participated and may not be generalizable outside of this panel. The surveys were limited in scope and, therefore, did not include questions on management of acute complications (e.g. hematoma, pneumothorax). The Delphi technique provided a reliable and efficient approach to estimating resource utilization associated with chronic pacemaker complications. Estimates from the Delphi panel can be used to generate costs of pacemaker complications in various regions.

  4. Development of a circadian light source

    Science.gov (United States)

    Nicol, David B.; Ferguson, Ian T.

    2002-11-01

    Solid state lighting presents a new paradigm for lighting - controllability. Certain characteristics of the lighting environment can be manipulated, because of the possibility of using multiple LEDs of different emission wavelengths as the illumination source. This will provide a new, versatile, general illumination source due to the ability to vary the spectral power distribution. New effects beyond the visual may be achieved that are not possible with conventional light sources. Illumination has long been the primary function of lighting but as the lighting industry has matured the psychological aspects of lighting have been considered by designers; for example, choosing a particular lighting distribution or color variation in retail applications. The next step in the evolution of light is to consider the physiological effects of lighting that cause biological changes in a person within the environment. This work presents the development of a source that may have important bearing on this area of lighting. A circadian light source has been developed to provide an illumination source that works by modulating its correlated color temperature to mimic the changes in natural daylight through the day. In addition, this source can cause or control physiological effects for a person illuminated by it. The importance of this is seen in the human circadian rhythm's peak response corresponding to blue light at ~460 nm which corresponds to the primary spectral difference in increasing color temperature. The device works by adding blue light to a broadband source or mixing polychromatic light to mimic the variation of color temperature observed for the Planckian Locus on the CIE diagram. This device can have several applications including: a tool for researchers in this area, a general illumination lighting technology, and a light therapy device.

  5. Development of cortisol circadian rhythm in infancy.

    NARCIS (Netherlands)

    Weerth, C. de; Zijl, R.H.

    2003-01-01

    BACKGROUND AND AIMS: Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not

  6. Experimental evidence of a chaotic region in a neural pacemaker

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Hua-Guang, E-mail: guhuaguang@tongji.edu.cn [School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai 200092 (China); Department of Electronic Engineering, City University of Hong Kong, Hong Kong SAR (China); Jia, Bing [School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai 200092 (China); Chen, Guan-Rong [Department of Electronic Engineering, City University of Hong Kong, Hong Kong SAR (China)

    2013-03-15

    In this Letter, we report the finding of period-adding scenarios with chaos in firing patterns, observed in biological experiments on a neural pacemaker, with fixed extra-cellular potassium concentration at different levels and taken extra-cellular calcium concentration as the bifurcation parameter. The experimental bifurcations in the two-dimensional parameter space demonstrate the existence of a chaotic region interwoven with the periodic region thereby forming a period-adding sequence with chaos. The behavior of the pacemaker in this region is qualitatively similar to that of the Hindmarsh–Rose neuron model in a well-known comb-shaped chaotic region in two-dimensional parameter spaces.

  7. [Management of surgery patients with implanted cardiac pacemakers].

    Science.gov (United States)

    Ugljen, R; Dadić, D; Ferek-Petrić, B; Jelić, I; Letica, D; Anić, D; Husar, J

    1995-01-01

    Patients having cardiac pacemaker implanted may be subjected to various general surgery procedures. Application of electrosurgery for the purpose of resection and coagulation, provides a high frequency electric field which produces electric voltage on the electrodes of the pacing system. This voltage may be detected within the pacing system, and various arrhythmias can be provoked in correlation with underlying rhythm and mode of pacing. Preoperative patient control and proper pacemaker programming can prevent the pacing malfunctions due to the electrosurgery application. Appropriate positioning of the neutral electrode in relation to the pacing system avoids the electric fields intersection and decreases their interference.

  8. A leadless pacemaker in the real-world setting

    DEFF Research Database (Denmark)

    Roberts, Paul R.; Clementy, Nicolas; Al Samadi, Faisal

    2017-01-01

    , telemetry, and battery issues. Objective The acute performance of the Micra transcatheter pacemaker from a worldwide Post-Approval Registry is reported. Methods The registry is an ongoing prospective single-arm observational study designed to assess the safety and effectiveness of Micra in the post...... were low and stable. Conclusion Performance of the Micra transcatheter pacemaker in a real-world setting demonstrates a high rate (99.6%) of implant success and low rate (1.51%) of major complications through 30 days post implant. In particular, the rates of pericardial effusion, device dislodgement...

  9. Circadian rhythms, time-restricted feeding, and healthy aging.

    Science.gov (United States)

    Manoogian, Emily N C; Panda, Satchidananda

    2017-10-01

    Circadian rhythms optimize physiology and health by temporally coordinating cellular function, tissue function, and behavior. These endogenous rhythms dampen with age and thus compromise temporal coordination. Feeding-fasting patterns are an external cue that profoundly influence the robustness of daily biological rhythms. Erratic eating patterns can disrupt the temporal coordination of metabolism and physiology leading to chronic diseases that are also characteristic of aging. However, sustaining a robust feeding-fasting cycle, even without altering nutrition quality or quantity, can prevent or reverse these chronic diseases in experimental models. In humans, epidemiological studies have shown erratic eating patterns increase the risk of disease, whereas sustained feeding-fasting cycles, or prolonged overnight fasting, is correlated with protection from breast cancer. Therefore, optimizing the timing of external cues with defined eating patterns can sustain a robust circadian clock, which may prevent disease and improve prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Transcatheter leadless pacemaker implantation in a patient with a transvenous dual-chamber pacemaker already in place.

    Science.gov (United States)

    Karjalainen, Pasi P; Nammas, Wail; Paana, Tuomas

    2016-01-01

    An 83-year-old lady had a DDDR pacemaker inserted in 1997 for symptomatic atrioventricular block. She underwent battery replacement in 2008. In 2010, she developed atrial fibrillation; the pacemaker was switched to VVIR mode. During the last 2years, ventricular lead threshold increased progressively. In December 2015, she presented for elective battery replacement. After successful battery replacement, the ventricular lead threshold remained high; therefore, we implanted a leadless transcatheter pacemaker, via femoral vein access, using a dedicated catheter delivery system. Electrical measurements at this stage revealed a pacing threshold of 0.28V at 0.24msec, and an impedance of 650Ω. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

    Science.gov (United States)

    El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

    2018-06-20

    Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Cancer Clocks Out for Lunch: Disruption of Circadian Rhythm and Metabolic Oscillation in Cancer.

    Science.gov (United States)

    Altman, Brian J

    2016-01-01

    Circadian rhythms are 24-h oscillations present in most eukaryotes and many prokaryotes that synchronize activity to the day-night cycle. They are an essential feature of organismal and cell physiology that coordinate many of the metabolic, biosynthetic, and signal transduction pathways studied in biology. The molecular mechanism of circadian rhythm is controlled both by signal transduction and gene transcription as well as by metabolic feedback. The role of circadian rhythm in cancer cell development and survival is still not well understood, but as will be discussed in this Review, accumulated research suggests that circadian rhythm may be altered or disrupted in many human cancers downstream of common oncogenic alterations. Thus, a complete understanding of the genetic and metabolic alterations in cancer must take potential circadian rhythm perturbations into account, as this disruption itself will influence how gene expression and metabolism are altered in the cancer cell compared to its non-transformed neighbor. It will be important to better understand these circadian changes in both normal and cancer cell physiology to potentially design treatment modalities to exploit this insight.

  13. Dim Light at Night Disrupts Molecular Circadian Rhythms and Affects Metabolism

    Science.gov (United States)

    Fonken, Laura K.; Aubrecht, Taryn G.; Meléndez-Fernández, O. Hecmarie; Weil, Zachary M.; Nelson, Randy J.

    2014-01-01

    With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms which are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electrical lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to nighttime light and investigated changes in the circadian system and body weight. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night attenuate core circadian clock rhythms in the SCN at both the gene and protein level. Moreover, circadian clock rhythms were perturbed in the liver by nighttime light exposure. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide mechanistic evidence for how mild changes in environmental lighting can alter circadian and metabolic function. PMID:23929553

  14. Discuss the cause and treatment of pacemaker lead dislocation and deal with

    International Nuclear Information System (INIS)

    Chen Yueguang; Zhang Dadong; Lu Jie; Yang Hui; Liu Chunyan; Zhang Wei

    2003-01-01

    Objective: To follow up the patients with pacemaker, observe the condition of pacemaker lead, to explore the cause of lead dislocation, to find out and prevent its occurrence. Methods: Summarizing the clinical data of 6 patients with pacemaker, 7 pacemaker leads with 8 time dislocation, pacemaker 2 DDDR, 2 DDD, 2 VVI. Results: Four patients were punctured from right subclavian vein, one from left subclavian vein and one from right brachiocephalic vein; four leads were dislocation in atrium and one mildly dislocation; four leads dislocation in ventricle and two mildly dislocation; There were 3 old women with 4 leads and 5 times of dislocation

  15. Circadian Clock Genes Are Essential for Normal Adult Neurogenesis, Differentiation, and Fate Determination.

    Directory of Open Access Journals (Sweden)

    Astha Malik

    Full Text Available Adult neurogenesis creates new neurons and glia from stem cells in the human brain throughout life. It is best understood in the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ. Circadian rhythms have been identified in the hippocampus, but the role of any endogenous circadian oscillator cells in hippocampal neurogenesis and their importance in learning or memory remains unclear. Any study of stem cell regulation by intrinsic circadian timing within the DG is complicated by modulation from circadian clocks elsewhere in the brain. To examine circadian oscillators in greater isolation, neurosphere cultures were prepared from the DG of two knockout mouse lines that lack a functional circadian clock and from mPer1::luc mice to identify circadian oscillations in gene expression. Circadian mPer1 gene activity rhythms were recorded in neurospheres maintained in a culture medium that induces neurogenesis but not in one that maintains the stem cell state. Although the differentiating neural stem progenitor cells of spheres were rhythmic, evidence of any mature neurons was extremely sparse. The circadian timing signal originated in undifferentiated cells within the neurosphere. This conclusion was supported by immunocytochemistry for mPER1 protein that was localized to the inner, more stem cell-like neurosphere core. To test for effects of the circadian clock on neurogenesis, media conditions were altered to induce neurospheres from BMAL1 knockout mice to differentiate. These cultures displayed unusually high differentiation into glia rather than neurons according to GFAP and NeuN expression, respectively, and very few BetaIII tubulin-positive, immature neurons were observed. The knockout neurospheres also displayed areas visibly devoid of cells and had overall higher cell death. Neurospheres from arrhythmic mice lacking two other core clock genes, Cry1 and Cry2, showed significantly reduced growth and increased astrocyte

  16. Differential effects of ionizing radiation on the circadian oscillator and other functions in the eye of Aplysia

    International Nuclear Information System (INIS)

    Woolum, J.C.; Strumwasser, F.

    1980-01-01

    Ionizing radiation has been used to selectively separate the circadian oscillator function of the eye of Aplysia from some of its other functions-synchronous compound action potential (CAP) generation, the light response, synaptic transmission between photoreceptors and output neurons, and the bursting pacemaker mechanism. Doses of 4-krad (50 kV peak) x-rays have a minimal effect on the circadian rhythm of CAP frequency, measured from the optic nerve, whereas irradiation with a 40-krad dose abolishes the rhythm without affecting any of the four other functions of this eye. We estimate a 50% survival of the oscillator function at doses of about 6 krad. The results, including those from selective irradiation of the anterior or posterior poles of the eye, suggest that there are a number of circadian oscillators in the eye-most of them in the posterior portion near the optic nerve. An approximate target size has been obtained from target theory, approx. =10 8 A 3 , which is somewhat larger than the target size for viral infectivity function, as one example. However, this approximate target size and the fact that recovery or repair can occur in vivo suggest that the oscillator may involve nucleic acid molecules

  17. Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2

    Directory of Open Access Journals (Sweden)

    Yaoming Yang

    2012-06-01

    Endogenous 24-hour rhythms are generated by circadian clocks located in most tissues. The molecular clock mechanism is based on feedback loops involving clock genes and their protein products. Post-translational modifications, including ubiquitination, are important for regulating the clock feedback mechanism. Previous work has focused on the role of ubiquitin ligases in the clock mechanism. Here we show a role for the rhythmically-expressed deubiquitinating enzyme ubiquitin specific peptidase 2 (USP2 in clock function. Mice with a deletion of the Usp2 gene (Usp2 KO display a longer free-running period of locomotor activity rhythms and altered responses of the clock to light. This was associated with altered expression of clock genes in synchronized Usp2 KO mouse embryonic fibroblasts and increased levels of clock protein PERIOD1 (PER1. USP2 can be coimmunoprecipitated with several clock proteins but directly interacts specifically with PER1 and deubiquitinates it. Interestingly, this deubiquitination does not alter PER1 stability. Taken together, our results identify USP2 as a new core component of the clock machinery and demonstrate a role for deubiquitination in the regulation of the circadian clock, both at the level of the core pacemaker and its response to external cues.

  18. What Pacemakers Can Teach Us about the Ethics of Maintaining Artificial Organs.

    Science.gov (United States)

    Hutchison, Katrina; Sparrow, Robert

    2016-11-01

    One day soon it may be possible to replace a failing heart, liver, or kidney with a long-lasting mechanical replacement or perhaps even with a 3-D printed version based on the patient's own tissue. Such artificial organs could make transplant waiting lists and immunosuppression a thing of the past. Supposing that this happens, what will the ongoing care of people with these implants involve? In particular, how will the need to maintain the functioning of artificial organs over an extended period affect patients and their doctors and the responsibilities of those who manufacture such devices? Drawing on lessons from the history of the cardiac pacemaker, this article offers an initial survey of the ethical issues posed by the need to maintain and service artificial organs. We briefly outline the nature and history of cardiac pacemakers, with a particular focus on the need for technical support, maintenance, and replacement of these devices. Drawing on the existing medical literature and on our conversations and correspondence with cardiologists, regulators, and manufacturers, we describe five sources of ethical issues associated with pacemaker maintenance: the location of the devices inside the human body, such that maintenance generates surgical risks; the complexity of the devices, which increases the risk of harms to patients as well as introducing potential injustices in access to treatment; the role of software-particularly software that can be remotely accessed-in the functioning of the devices, which generates privacy and security issues; the impact of continual development and improvement of the device; and the influence of commercial interests in the context of a medical device market in which there are several competing products. Finally, we offer some initial suggestions as to how these questions should be answered. © 2016 The Hastings Center.

  19. Study of electrochemical properties of thin film materials obtained using plasma technologies for production of electrodes for pacemakers

    International Nuclear Information System (INIS)

    Obrezkov, O I; Vinogradov, V P; Krauz, V I; Mozgrin, D V; Guseva, I A; Andreev, E S; Zverev, A A; Starostin, A L

    2016-01-01

    Studies of thin film materials (TFM) as coatings of tips of pacemaker electrodes implanted into the human heart have been performed. TFM coatings were deposited in vacuum by arc magnetron discharge plasma, by pulsed discharge of “Plasma Focus”, and by electron beam evaporation. Simulation of electric charge transfer to the heart in physiological blood- imitator solution and determination of electrochemical properties of the coatings were carried out. TFM of highly developed surface of contact with tissue was produced by argon plasma spraying of titanium powder with subsequent coating by titanium nitride in vacuum arc assisted by Ti ion implantation. The TFM coatings of pacemaker electrode have passed necessary clinical tests and were used in medical practice. They provide low voltage myocardium stimulation thresholds within the required operating time. (paper)

  20. Cryptochrome mediates light-dependent magnetosensitivity of Drosophila's circadian clock.

    Directory of Open Access Journals (Sweden)

    Taishi Yoshii

    2009-04-01

    Full Text Available Since 1960, magnetic fields have been discussed as Zeitgebers for circadian clocks, but the mechanism by which clocks perceive and process magnetic information has remained unknown. Recently, the radical-pair model involving light-activated photoreceptors as magnetic field sensors has gained considerable support, and the blue-light photoreceptor cryptochrome (CRY has been proposed as a suitable molecule to mediate such magnetosensitivity. Since CRY is expressed in the circadian clock neurons and acts as a critical photoreceptor of Drosophila's clock, we aimed to test the role of CRY in magnetosensitivity of the circadian clock. In response to light, CRY causes slowing of the clock, ultimately leading to arrhythmic behavior. We expected that in the presence of applied magnetic fields, the impact of CRY on clock rhythmicity should be altered. Furthermore, according to the radical-pair hypothesis this response should be dependent on wavelength and on the field strength applied. We tested the effect of applied static magnetic fields on the circadian clock and found that flies exposed to these fields indeed showed enhanced slowing of clock rhythms. This effect was maximal at 300 muT, and reduced at both higher and lower field strengths. Clock response to magnetic fields was present in blue light, but absent under red-light illumination, which does not activate CRY. Furthermore, cry(b and cry(OUT mutants did not show any response, and flies overexpressing CRY in the clock neurons exhibited an enhanced response to the field. We conclude that Drosophila's circadian clock is sensitive to magnetic fields and that this sensitivity depends on light activation of CRY and on the applied field strength, consistent with the radical pair mechanism. CRY is widespread throughout biological systems and has been suggested as receptor for magnetic compass orientation in migratory birds. The present data establish the circadian clock of Drosophila as a model system

  1. [Circadian markers and genes in bipolar disorder].

    Science.gov (United States)

    Yeim, S; Boudebesse, C; Etain, B; Belliviera, F

    2015-09-01

    Bipolar disorder is a severe and complex multifactorial disease, characterized by alternance of acute episodes of depression and mania/hypomania, interspaced by euthymic periods. The etiological determinants of bipolar disorder yet, are still poorly understood. For the last 30 years, chronobiology is an important field of investigation to better understand the pathophysiology of bipolar disorder. We conducted a review using Medline, ISI Database, EMBase, PsyInfo up to January 2015, using the following keywords combinations: "mood disorder", "bipolar disorder", "depression", "unipolar disorder", "major depressive disorder", "affective disorder", for psychiatric conditions; and "circadian rhythms", "circadian markers", "circadian gene", "clock gene", "melatonin" for circadian rhythms. The search critera was presence of word in any field of the article. Quantitative and qualitative circadian abnormalities are associated with bipolar disorders both during acute episodes and euthymic periods, suggesting that these altered circadian rhythms may represent biological trait markers of the disorder. These circadian dysfunctions were assessed by various validated tools including polysomnography, actigraphy, sleep diaries, chronotype assessments and blood melatonin/cortisol measures. Other altered endogenous circadian activities have also been reported in bipolar patients, such as hormones secretion, core body temperature or fibroblasts activity. Moreover, these markers were also altered in healthy relatives of bipolar patients, suggesting a degree of heritability. Several genetic association studies have also showed associations between multiple circadian genes and bipolar disorder, such as CLOCK, ARTNL1, GSK3β, PER3, NPAS2, NR1D1, TIMELESS, RORA, RORB, and CSNK1ε. Thus, these circadian gene variants may contribute to the genetic susceptibility of the disease. Furthermore, the study of the clock system may help to better understand some phenotypic aspects like the

  2. Circadian Regulation of Glutamate Transporters

    Directory of Open Access Journals (Sweden)

    Donají Chi-Castañeda

    2018-06-01

    Full Text Available L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS. This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation of glutamate transport in neuronal and glial cells, and their consequence in brain function.

  3. Deactivation of Pacemaker: Ethical Approach or Managerial Failure?

    Directory of Open Access Journals (Sweden)

    Macková Marie

    2017-12-01

    Full Text Available The decision about the deactivation of a pacemaker must be the result of a multicriteria decision-making process where the legal, ethical and effectiveness aspects must be taken into account and delicately balanced, while also considering the risk of managerial failure. Academic as well as professional discussion is necessary because there is a whole range of question marks on this topic and all the aspects mentioned above. The aim of this paper is to contribute to the debate by presenting the views of Czech physicians about the possibility of deactivation of the pacemaker in patients in terminal states. Based on the results of our research, the following steps are recommended to enable the deactivation of pacemakers in the Czech environment. Before the patient’s own indication of pacemaker therapy, treatment should be discussed with the patient in detail, including complications and deactivation options. Czech ethical consultant services should be set up in Czech hospitals. And last but not least, they should take an opinion on this issue as well as the professional society.

  4. Pacemaker dislocation - Truly ectopic activation necessitating surgical treatment

    NARCIS (Netherlands)

    de Kroon, TL; Witsenburg, M; Bogerts, AJJC

    Intra-abdominal migration of a generator from an epicardial pacemaker system is a rare but potentially life-threatening complication. We report on a case of a 2-year-old child in whom the generator silently migrated from the sheath of the rectus abdominis muscle in the upper abdominal wall down into

  5. Neutron spectra from radionuclide sources for cardiac pacemakers

    International Nuclear Information System (INIS)

    Kluge, H.

    1975-01-01

    Neutron spectra from Plutonium 238 radioisotope batteries powering cardiac pacemakers are measured in the energy range above 0.7 MeV. The results are used to calculate radiation doses within a cylindrical phantom. There are only minor differences between the different types of plutonium 238-batteries and californium 252-batteries

  6. Prophylactic antibiotic for pacemaker surgery: what is optimal ...

    African Journals Online (AJOL)

    One of them, a bed-ridden patient developed severe pocket infection necessitating explantation and replacement 3 weeks later. Conclusions: We noted with satisfaction that short regime of prophylactic parentral ceftriaxone is effective in preventing pacemaker infection and there is no need for the long regimen. Niger Med J.

  7. 238Pu sources for cardiac pacemakers. II. Control

    International Nuclear Information System (INIS)

    Pottier, R.; Merigot, S.

    1976-01-01

    The method and the apparatus used for thermal (power) and radioactive control of radioisotopic sources for pacemakers are briefly described. The cybernetic system is also presented, which assumes almost automatically the monitoring of control, mechanical and electronic works, data processing, the measurements and computations, and the works related to quality control [fr

  8. Cost Issues in Pacemaker Surgery in Nigeria | Thomas | Nigerian ...

    African Journals Online (AJOL)

    Permanent pacemakers are being implanted worldwide for prolongation and improvement of lives of patients who have conduction defects. Even though the average cost of pacing has reduced significantly over the years, procurement of the all important treatment modality remains a major financial drain especially in a ...

  9. [Aspergillus fumigatus endocarditis in a patient with a biventricular pacemaker].

    Science.gov (United States)

    Cuesta, José M; Fariñas, María C; Rodilla, Irene G; Salesa, Ricardo; de Berrazueta, José R

    2005-05-01

    Aspergillus fumigatus endocarditis is one of the rarest and severest complications in cardiological patients. We describe a patient with an intracardial pacemaker who was diagnosed as having Aspergillus fumigatus endocarditis. Postmortem examination showed a large, Aspergillus-infected thrombus encased in the right ventricle, pulmonary trunk and main pulmonary branches.

  10. Circadian Clocks for All Meal-Times: Anticipation of 2 Daily Meals in Rats

    Science.gov (United States)

    Mistlberger, Ralph E.; Kent, Brianne A.; Chan, Sofina; Patton, Danica F.; Weinberg, Alexander; Parfyonov, Maksim

    2012-01-01

    Anticipation of a daily meal in rats has been conceptualized as a rest-activity rhythm driven by a food-entrained circadian oscillator separate from the pacemaker generating light-dark (LD) entrained rhythms. Rats can also anticipate two daily mealtimes, but whether this involves independently entrained oscillators, one ‘continuously consulted’ clock, cue-dependent non-circadian interval timing or a combination of processes, is unclear. Rats received two daily meals, beginning 3-h (meal 1) and 13-h (meal 2) after lights-on (LD 14∶10). Anticipatory wheel running began 68±8 min prior to meal 1 and 101±9 min prior to meal 2 but neither the duration nor the variability of anticipation bout lengths exhibited the scalar property, a hallmark of interval timing. Meal omission tests in LD and constant dark (DD) did not alter the timing of either bout of anticipation, and anticipation of meal 2 was not altered by a 3-h advance of meal 1. Food anticipatory running in this 2-meal protocol thus does not exhibit properties of interval timing despite the availability of external time cues in LD. Across all days, the two bouts of anticipation were uncorrelated, a result more consistent with two independently entrained oscillators than a single consulted clock. Similar results were obtained for meals scheduled 3-h and 10-h after lights-on, and for a food-bin measure of anticipation. Most rats that showed weak or no anticipation to one or both meals exhibited elevated activity at mealtime during 1 or 2 day food deprivation tests in DD, suggesting covert operation of circadian timing in the absence of anticipatory behavior. A control experiment confirmed that daytime feeding did not shift LD-entrained rhythms, ruling out displaced nocturnal activity as an explanation for daytime activity. The results favor a multiple oscillator basis for 2-meal anticipatory rhythms and provide no evidence for involvement of cue-dependent interval timing. PMID:22355393

  11. A circadian clock in the olfactory bulb anticipates feeding during food anticipatory activity.

    Science.gov (United States)

    Nolasco, Nahum; Juárez, Claudia; Morgado, Elvira; Meza, Enrique; Caba, Mario

    2012-01-01

    Rabbit pups ingest food, in this case milk, once a day with circadian periodicity and are a natural model of food anticipatory activity. During nursing, several sensory systems receive information about properties of the food, one of them being the olfactory system, which has received little attention in relation to synchronization by food. In addition, the olfactory bulb has a circadian pacemaker that exhibits rhythms independently of the suprachiasmatic nucleus, but the biological functions of these rhythms are largely unknown. In the present contribution, we hypothesized that circadian suckling of milk synchronizes rhythms in the olfactory bulb. To this aim we explored by immunohistochemistry, rhythms of FOS and PER1 proteins, as indicators of activation and reporter of oscillations, respectively, through a complete 24-h cycle in periglomerular, mitral and granular cell layers of both the main and the accessory olfactory bulb. Subjects were 7-day-old rabbit pups scheduled to nurse during the night (02:00 h) or day (10:00 h), and also fasted subjects, to explore the possible persistence of oscillations. In the three layers of the main olfactory bulb, FOS was high at time of nursing, then further increased 1.5 h afterward, and then decreased to increase again in advance of the next nursing bout. This pattern persisted, without the postprandial increase, in fasted subjects with a shift in subjects nursed at 02:00. PER1 was increased 2-8 h after nursing and this increase persisted in most cell layers, with a shift, in fasted subjects. In the accessory olfactory bulb we only observed a consistent pattern of FOS expression in the mitral cell layer of nursed subjects, similar to that of the main olfactory bulb. We conclude that the main olfactory bulb is synchronized during milk ingestion, but during fasting its oscillations perhaps are modulated by the suprachiasmatic nucleus, as proposed for rodents.

  12. A circadian clock in the olfactory bulb anticipates feeding during food anticipatory activity.

    Directory of Open Access Journals (Sweden)

    Nahum Nolasco

    Full Text Available Rabbit pups ingest food, in this case milk, once a day with circadian periodicity and are a natural model of food anticipatory activity. During nursing, several sensory systems receive information about properties of the food, one of them being the olfactory system, which has received little attention in relation to synchronization by food. In addition, the olfactory bulb has a circadian pacemaker that exhibits rhythms independently of the suprachiasmatic nucleus, but the biological functions of these rhythms are largely unknown. In the present contribution, we hypothesized that circadian suckling of milk synchronizes rhythms in the olfactory bulb. To this aim we explored by immunohistochemistry, rhythms of FOS and PER1 proteins, as indicators of activation and reporter of oscillations, respectively, through a complete 24-h cycle in periglomerular, mitral and granular cell layers of both the main and the accessory olfactory bulb. Subjects were 7-day-old rabbit pups scheduled to nurse during the night (02:00 h or day (10:00 h, and also fasted subjects, to explore the possible persistence of oscillations. In the three layers of the main olfactory bulb, FOS was high at time of nursing, then further increased 1.5 h afterward, and then decreased to increase again in advance of the next nursing bout. This pattern persisted, without the postprandial increase, in fasted subjects with a shift in subjects nursed at 02:00. PER1 was increased 2-8 h after nursing and this increase persisted in most cell layers, with a shift, in fasted subjects. In the accessory olfactory bulb we only observed a consistent pattern of FOS expression in the mitral cell layer of nursed subjects, similar to that of the main olfactory bulb. We conclude that the main olfactory bulb is synchronized during milk ingestion, but during fasting its oscillations perhaps are modulated by the suprachiasmatic nucleus, as proposed for rodents.

  13. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes-A model

    Energy Technology Data Exchange (ETDEWEB)

    Kanani, S. [Institut Genomique Fonctionelle, 141 Rue de la Cardonille, 34396 Montpellier (France); Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Pumir, A. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Laboratoire J.A. Dieudonne, CNRS and Universite de Nice, Parc Valrose, 06108 Nice (France)], E-mail: alain.pumir@unice.fr; Krinsky, V. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France)

    2008-01-07

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler-Reuter model, as well as with the elaborate dynamic Luo-Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin-Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I{sub K1} channels is low enough. At too high an expression level of I{sub K1} channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I{sub K1} channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I{sub K1} channels observed in ventricular myocytes, both in the Beeler-Reuter and in the dynamic Luo-Rudy models are too high to allow to observe oscillations. With expression levels below {approx}1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I{sub K1} has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  14. Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes—A model

    Science.gov (United States)

    Kanani, S.; Pumir, A.; Krinsky, V.

    2008-01-01

    One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler Reuter model, as well as with the elaborate dynamic Luo Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I channels is low enough. At too high an expression level of I channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I channels observed in ventricular myocytes, both in the Beeler Reuter and in the dynamic Luo Rudy models are too high to allow to observe oscillations. With expression levels below ˜1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

  15. Circadian Rhythm Disruption Promotes Lung Tumorigenesis.

    Science.gov (United States)

    Papagiannakopoulos, Thales; Bauer, Matthew R; Davidson, Shawn M; Heimann, Megan; Subbaraj, Lakshmipriya; Bhutkar, Arjun; Bartlebaugh, Jordan; Vander Heiden, Matthew G; Jacks, Tyler

    2016-08-09

    Circadian rhythms are 24-hr oscillations that control a variety of biological processes in living systems, including two hallmarks of cancer, cell division and metabolism. Circadian rhythm disruption by shift work is associated with greater risk for cancer development and poor prognosis, suggesting a putative tumor-suppressive role for circadian rhythm homeostasis. Using a genetically engineered mouse model of lung adenocarcinoma, we have characterized the effects of circadian rhythm disruption on lung tumorigenesis. We demonstrate that both physiologic perturbation (jet lag) and genetic mutation of the central circadian clock components decreased survival and promoted lung tumor growth and progression. The core circadian genes Per2 and Bmal1 were shown to have cell-autonomous tumor-suppressive roles in transformation and lung tumor progression. Loss of the central clock components led to increased c-Myc expression, enhanced proliferation, and metabolic dysregulation. Our findings demonstrate that both systemic and somatic disruption of circadian rhythms contribute to cancer progression. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Toward a detailed computational model for the mammalian circadian clock

    Science.gov (United States)

    Leloup, Jean-Christophe; Goldbeter, Albert

    2003-06-01

    We present a computational model for the mammalian circadian clock based on the intertwined positive and negative regulatory loops involving the Per, Cry, Bmal1, Clock, and Rev-Erb genes. In agreement with experimental observations, the model can give rise to sustained circadian oscillations in continuous darkness, characterized by an antiphase relationship between Per/Cry/Rev-Erb and Bmal1 mRNAs. Sustained oscillations correspond to the rhythms autonomously generated by suprachiasmatic nuclei. For other parameter values, damped oscillations can also be obtained in the model. These oscillations, which transform into sustained oscillations when coupled to a periodic signal, correspond to rhythms produced by peripheral tissues. When incorporating the light-induced expression of the Per gene, the model accounts for entrainment of the oscillations by light-dark cycles. Simulations show that the phase of the oscillations can then vary by several hours with relatively minor changes in parameter values. Such a lability of the phase could account for physiological disorders related to circadian rhythms in humans, such as advanced or delayed sleep phase syndrome, whereas the lack of entrainment by light-dark cycles can be related to the non-24h sleep-wake syndrome. The model uncovers the possible existence of multiple sources of oscillatory behavior. Thus, in conditions where the indirect negative autoregulation of Per and Cry expression is inoperative, the model indicates the possibility that sustained oscillations might still arise from the negative autoregulation of Bmal1 expression.

  17. Circadian Gating of Epithelial-to-Mesenchymal Transition in Breast Cancer Cells Via Melatonin-Regulation of GSK3β

    Science.gov (United States)

    Mao, Lulu; Dauchy, Robert T.; Blask, David E.; Slakey, Lauren M.; Xiang, Shulin; Yuan, Lin; Dauchy, Erin M.; Shan, Bin; Brainard, George C.; Hanifin, John P.; Duplessis, Tamika T.; Hill, Steven M.

    2012-01-01

    Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3β (GSK3β), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhythm of GSK3β phosphorylation. Melatonin activates GSK3β by inhibiting the serine-threonine kinase Akt phosphorylation, inducing β-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3β activity and driving epithelial-to-mesenchymal transition in breast cancer patients. PMID:23002080

  18. Circadian Rhythms, Sleep, and Disorders of Aging.

    Science.gov (United States)

    Mattis, Joanna; Sehgal, Amita

    2016-04-01

    Sleep-wake cycles are known to be disrupted in people with neurodegenerative disorders. These findings are now supported by data from animal models for some of these disorders, raising the question of whether the disrupted sleep/circadian regulation contributes to the loss of neural function. As circadian rhythms and sleep consolidation also break down with normal aging, changes in these may be part of what makes aging a risk factor for disorders like Alzheimer's disease (AD). Mechanisms underlying the connection between circadian/sleep dysregulation and neurodegeneration remain unclear, but several recent studies provide interesting possibilities. While mechanistic analysis is under way, it is worth considering treatment of circadian/sleep disruption as a means to alleviate symptoms of neurodegenerative disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Circadian Rhythm Management System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The value of measuring sleep-wake cycles is significantly enhanced by measuring other physiological signals that depend on circadian rhythms (such as heart rate and...

  20. Mathematical Modeling of Circadian/Performance Countermeasures

    Data.gov (United States)

    National Aeronautics and Space Administration — We developed and refined our current mathematical model of circadian rhythms to incorporate melatonin as a marker rhythm. We used an existing physiologically based...

  1. Effects of light exposure and sleep displacement on dim light melatonin onset

    NARCIS (Netherlands)

    Gordijn, MCM; Beersma, DGM; Korte, HJ; Van den Hoofdakker, RH

    The purpose of the study was to induce in two different ways, a phase-angle difference between the circadian pacemaker and the imposed sleep-wake cycle in humans, we intended to: (i) shift the circadian pacemaker by exposure to bright light and keep the timing of the sleep-wake cycle fixed; and (ii)

  2. Modulation of learning and memory by the targeted deletion of the circadian clock gene Bmal1 in forebrain circuits.

    Science.gov (United States)

    Snider, Kaitlin H; Dziema, Heather; Aten, Sydney; Loeser, Jacob; Norona, Frances E; Hoyt, Kari; Obrietan, Karl

    2016-07-15

    A large body of literature has shown that the disruption of circadian clock timing has profound effects on mood, memory and complex thinking. Central to this time keeping process is the master circadian pacemaker located within the suprachiasmatic nucleus (SCN). Of note, within the central nervous system, clock timing is not exclusive to the SCN, but rather, ancillary oscillatory capacity has been detected in a wide range of cell types and brain regions, including forebrain circuits that underlie complex cognitive processes. These observations raise questions about the hierarchical and functional relationship between the SCN and forebrain oscillators, and, relatedly, about the underlying clock-gated synaptic circuitry that modulates cognition. Here, we utilized a clock knockout strategy in which the essential circadian timing gene Bmal1 was selectively deleted from excitatory forebrain neurons, whilst the SCN clock remained intact, to test the role of forebrain clock timing in learning, memory, anxiety, and behavioral despair. With this model system, we observed numerous effects on hippocampus-dependent measures of cognition. Mice lacking forebrain Bmal1 exhibited deficits in both acquisition and recall on the Barnes maze. Notably, loss of forebrain Bmal1 abrogated time-of-day dependent novel object location memory. However, the loss of Bmal1 did not alter performance on the elevated plus maze, open field assay, and tail suspension test, indicating that this phenotype specifically impairs cognition but not affect. Together, these data suggest that forebrain clock timing plays a critical role in shaping the efficiency of learning and memory retrieval over the circadian day. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Circadian Rhythms and Obesity in Mammals

    OpenAIRE

    Froy, Oren

    2012-01-01

    Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating the circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabol...

  4. Evolution of circadian organization in vertebrates

    Directory of Open Access Journals (Sweden)

    M. Menaker

    1997-03-01

    Full Text Available Circadian organization means the way in which the entire circadian system above the cellular level is put together physically and the principles and rules that determine the interactions among its component parts which produce overt rhythms of physiology and behavior. Understanding this organization and its evolution is of practical importance as well as of basic interest. The first major problem that we face is the difficulty of making sense of the apparently great diversity that we observe in circadian organization of diverse vertebrates. Some of this diversity falls neatly into place along phylogenetic lines leading to firm generalizations: i in all vertebrates there is a "circadian axis" consisting of the retinas, the pineal gland and the suprachiasmatic nucleus (SCN, ii in many non-mammalian vertebrates of all classes (but not in any mammals the pineal gland is both a photoreceptor and a circadian oscillator, and iii in all non-mammalian vertebrates (but not in any mammals there are extraretinal (and extrapineal circadian photoreceptors. An interesting explanation of some of these facts, especially the differences between mammals and other vertebrates, can be constructed on the assumption that early in their evolution mammals passed through a "nocturnal bottleneck". On the other hand, a good deal of the diversity among the circadian systems of vertebrates does not fall neatly into place along phylogenetic lines. In the present review we will consider how we might better understand such "phylogenetically incoherent" diversity and what sorts of new information may help to further our understanding of the evolution of circadian organization in vertebrates

  5. Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

    International Nuclear Information System (INIS)

    Demel, A.W.

    1990-12-01

    Since blood cortisol (F) and melatonin (MLT) display a circadian secretion pattern and since the saliva concentration of this hormones is an excellent indicator of its blood levels the measurement of salivary F and MLT may be used for examining circadian rhythmicity. In this study the relationship between salivary F and MLT was explored. For this purpose it was necessary first to establish and validate a radioimmunoassay for F in saliva: salivary F was determined by a direct radioimmunoassay using cortisol-3-(O-carboxymethyl) oximino-(2-( 125 I)iodohistamin) as tracer and cortisol-3-CMO-BSA antiserum. The parallel measurement of F levels in saliva and serum of adults gave an excellent correlation (r=0.87, p 0.00956x ). Serum F was assayed on the Abott TDX-System using a radioimmunofluorescence method. Secondly, using this assay the circadian saliva F pattern was determined as well as the pattern of salivary MLT in 9 young, healthy volunteers. For saliva MLT estimations a previously published method was applied (Schulz et al 1990). Using a computerized program (RHYTHM) written by Eve v. Cauter (1979), the hormone data of each individuum were examined for circadian rhythmicity and its acrophase (time of occurrence of the maximum of a sinusoid fitted to the data). The F acrophase occurred between 7:00 and 12:00 h (mean: 3:33 h, SD: 104.4 min). The easy stress-free non invasive nature of saliva collection makes saliva to one of the most accessible body fluids and of high value in studying the circadian system in healthy humans as well as in infants, children, pregnant women and anaemic patients. Measurements of salivary F and MLT may help to elucidate not only the circadian rhythms of these hormones under normal and pathological conditions but it may also provide insight in physiology and pathology of the circadian system in general. (author)

  6. Radioimmunological analysis of circadian rhythms of cortisol and melatonin in saliva

    International Nuclear Information System (INIS)

    Demel, A.W.

    1990-12-01

    Since blood cortisol (F) and melatonin (MLT) display a circadian secretion pattern and since the saliva concentration of this hormones is an excellent indicator of its blood levels the measurement of salivary F and MLT may be user for examining circadian rhythmicity. In this study the relationship between salivary F and MLT was explored. For this purpose it was necessary first to establish and validate a radioimmunoassay for F in saliva: salivary F was determined by a direct radioimmunoassay using cortisol-3-(O-carb oxymethyl) oximino-(2-( 125 I)iodohistamin) as tracer and cortisol-3-CMO-BSA antiserum. The parallel measurement of F levels in saliva and serum of adults gave an excellent correlation (r=0.87, p 0.00956x ). Serum F was assayed on the Abott TDX-System using a radioimmunofluorescence method. Secondly, using this assay the circadian saliva F pattern was determined as well as the pattern of salivary MLT in 9 young, healthy volunteers. For saliva MLT estimations a previously published method was applied (SCHULZ et al 1990). Using a computerized program (RHYTHM) written by EVE v. CAUTER (1979), the hormone data of each individuum were examined for circadian rhythmicity and its acrophase (time of occurence of the maximum of a sinusoid fitted to the data). The F acrophase occured between 7:00 and 12:00 h (Mean: 3:33 h, SD: 104.4 min). The easy stress-free non invasive nature of saliva collection makes saliva to one of the most accessible body fluids and of high value in studying the circadian system in healthy humans as well as in infants, children, pregnant women and anaemic patients. Measurements of salivary F and MLT may help to elucidate not only the circadian rhythms of these hormones under normal and pathological conditions but it may also provide insight in physiology and pathology of the circadian system in general. (author)

  7. The effects of hydrogen peroxide on the circadian rhythms of Microcystis aeruginosa.

    Directory of Open Access Journals (Sweden)

    Haifeng Qian

    Full Text Available BACKGROUND: The cyanobacterium Microcystis aeruginosa is one of the principal bloom-forming cyanobacteria present in a wide range of freshwater ecosystems. M. aeruginosa produces cyanotoxins, which can harm human and animal health. Many metabolic pathways in M. aeruginosa, including photosynthesis and microcystin synthesis, are controlled by its circadian rhythms. However, whether xenobiotics affect the cyanobacterial circadian system and change its growth, physiology and biochemistry is unknown. We used real-time PCR to study the effect of hydrogen peroxide (H(2O(2 on the expression of clock genes and some circadian genes in M. aeruginosa during the light/dark (LD cycle. RESULTS: The results revealed that H(2O(2 changes the expression patterns of clock genes (kaiA, kaiB, kaiC and sasA and significantly decreases the transcript levels of kaiB, kaiC and sasA. H(2O(2 treatment also decreased the transcription of circadian genes, such as photosynthesis-related genes (psaB, psbD1 and rbcL and microcystin-related genes (mcyA, mcyD and mcyH, and changed their circadian expression patterns. Moreover, the physiological functions of M. aeruginosa, including its growth and microcystin synthesis, were greatly influenced by H(2O(2 treatment during LD. These results indicate that changes in the cyanobacterial circadian system can affect its physiological and metabolic pathways. CONCLUSION: Our findings show that a xenobiotic can change the circadian expression patterns of its clock genes to influence clock-controlled gene regulation, and these influences are evident at the level of cellular physiology.

  8. Circadian rhythm disruption was observed in hand, foot, and mouth disease patients.

    Science.gov (United States)

    Zhu, Yu; Jiang, Zhou; Xiao, Guoguang; Cheng, Suting; Wen, Yang; Wan, Chaomin

    2015-03-01

    Hand, foot, and mouth disease (HFMD) with central nerve system complications may rapidly progress to fulminated cardiorespiratory failure, with higher mortality and worse prognosis. It has been reported that circadian rhythms of heart rate (HR) and respiratory rate are useful in predicting prognosis of severe cardiovascular and neurological diseases. The present study aims to investigate the characteristics of the circadian rhythms of HR, respiratory rate, and temperature in HFMD patients with neurological complications. Hospitalized HFMD patients including 33 common cases (common group), 61 severe cases (severe group), and 9 critical cases (critical group) were contrasted retrospectively. Their HR, respiratory rate, and temperatures were measured every 4 hours during the first 48-hour in the hospital. Data were analyzed with the least-squares fit of a 24-hour cosine function by the single cosinor and population-mean cosinor method. Results of population-mean cosinor analysis demonstrated that the circadian rhythm of HR, respiratory rate, and temperature was present in the common and severe group, but absent in the critical group. The midline-estimating statistic of rhythm (MESOR) (P = 0.016) and acrophase (P circadian characteristics of HR among 3 groups. Compared with the common group, the MESOR of temperature and respiratory rate was significantly higher, and acrophase of temperature and respiratory rate was 2 hours ahead in the severe group, critical HFMD patients lost their population-circadian rhythm of temperature, HR, and respiratory rate. The high values of temperature and respiratory rate for the common group were concentrated between 3 and 9 PM, whereas those for the severe group were more dispersive. And the high values for the critical group were equally distributed in 24 hours of the day. Circadian rhythm of patients' temperature in the common group was the same as the normal rhythm of human body temperature. Circadian rhythm of patients

  9. Disruption of the circadian period of body temperature by the anesthetic propofol.

    Science.gov (United States)

    Touitou, Yvan; Mauvieux, Benoit; Reinberg, Alain; Dispersyn, Garance

    2016-01-01

    The circadian time structure of an organism can be desynchronized in a large number of instances, including the intake of specific drugs. We have previously found that propofol, which is a general anesthetic, induces a desynchronization of the circadian time structure in rats, with a 60-80 min significant phase advance of body temperature circadian rhythm. We thus deemed it worthwhile to examine whether this phase shift of body temperature was related to a modification of the circadian period Tau. Propofol was administered at three different Zeitgeber Times (ZTs): ZT6 (middle of the rest period), ZT10 (2 h prior to the beginning of activity period), ZT16 (4 h after the beginning of the activity period), with ZT0 being the beginning of the rest period (light onset) and ZT12 being the beginning of the activity period (light offset). Control rats (n = 20) were injected at the same ZTs with 10% intralipid, which is a control lipidic solution. Whereas no modification of the circadian period of body temperature was observed in the control rats, propofol administration resulted in a significant shortening of the period by 96 and 180 min at ZT6 and ZT10, respectively. By contrast, the period was significantly lengthened by 90 min at ZT16. We also found differences in the time it took for the rats to readjust their body temperature to the original 24-h rhythm. At ZT16, the speed of readjustment was more rapid than at the two other ZTs that we investigated. This study hence shows (i) the disruptive effects of the anesthetic propofol on the body temperature circadian rhythm, and it points out that (ii) the period Tau for body temperature responds to this anesthetic drug according to a Tau-response curve. By sustaining postoperative sleep-wake disorders, the disruptive effects of propofol on circadian time structure might have important implications for the use of this drug in humans.

  10. Linking Core Promoter Classes to Circadian Transcription.

    Directory of Open Access Journals (Sweden)

    Pål O Westermark

    2016-08-01

    Full Text Available Circadian rhythms in transcription are generated by rhythmic abundances and DNA binding activities of transcription factors. Propagation of rhythms to transcriptional initiation involves the core promoter, its chromatin state, and the basal transcription machinery. Here, I characterize core promoters and chromatin states of genes transcribed in a circadian manner in mouse liver and in Drosophila. It is shown that the core promoter is a critical determinant of circadian mRNA expression in both species. A distinct core promoter class, strong circadian promoters (SCPs, is identified in mouse liver but not Drosophila. SCPs are defined by specific core promoter features, and are shown to drive circadian transcriptional activities with both high averages and high amplitudes. Data analysis and mathematical modeling further provided evidence for rhythmic regulation of both polymerase II recruitment and pause release at SCPs. The analysis provides a comprehensive and systematic view of core promoters and their link to circadian mRNA expression in mouse and Drosophila, and thus reveals a crucial role for the core promoter in regulated, dynamic transcription.

  11. Circadian clocks are resounding in peripheral tissues.

    Directory of Open Access Journals (Sweden)

    Andrey A Ptitsyn

    2006-03-01

    Full Text Available Circadian rhythms are prevalent in most organisms. Even the smallest disturbances in the orchestration of circadian gene expression patterns among different tissues can result in functional asynchrony, at the organism level, and may to contribute to a wide range of physiologic disorders. It has been reported that as many as 5%-10% of transcribed genes in peripheral tissues follow a circadian expression pattern. We have conducted a comprehensive study of circadian gene expression on a large dataset representing three different peripheral tissues. The data have been produced in a large-scale microarray experiment covering replicate daily cycles in murine white and brown adipose tissues as well as in liver. We have applied three alternative algorithmic approaches to identify circadian oscillation in time series expression profiles. Analyses of our own data indicate that the expression of at least 7% to 21% of active genes in mouse liver, and in white and brown adipose tissues follow a daily oscillatory pattern. Indeed, analysis of data from other laboratories suggests that the percentage of genes with an oscillatory pattern may approach 50% in the liver. For the rest of the genes, oscillation appears to be obscured by stochastic noise. Our phase classification and computer simulation studies based on multiple datasets indicate no detectable boundary between oscillating and non-oscillating fractions of genes. We conclude that greater attention should be given to the potential influence of circadian mechanisms on any biological pathway related to metabolism and obesity.

  12. Circadian rhythms, food timing and obesity.

    Science.gov (United States)

    Lopez-Minguez, J; Gómez-Abellán, P; Garaulet, M

    2016-11-01

    It is known that our physiology changes throughout the day and that several physiological hormones display circadian rhythmicity. The alteration of this normal pattern is called chronodisruption (CD). In recent years, it has been demonstrated that CD is related to obesity. Although several factors may be causing CD, one important aspect to consider is the failure in our internal clock. Indeed, studies performed in mutant animals have demonstrated that mutations in clock genes are related to obesity. In human subjects, mutations are rare (obesity and weight loss. Taking into account that genetics is behind CD, as has already been demonstrated in twins' models, the question is: Are we predestinated? We will see along these lines that nutrigenetics and epigenetics answer: 'No, we are not predestinated'. Through nutrigenetics we know that our behaviours may interact with our genes and may decrease the deleterious effect of one specific risk variant. From epigenetics the message is even more positive: it is demonstrated that by changing our behaviours we can change our genome. Herein, we propose modifying 'what, how, and when we eat' as an effective tool to decrease our genetic risk, and as a consequence to diminish CD and decrease obesity. This is a novel and very promising area in obesity prevention and treatment.

  13. Generic environmental statement on the routine use of plutonium-powered cardiac pacemakers

    International Nuclear Information System (INIS)

    Shoup, R.L.; Robinson, T.W.; O'Donnell, F.R.

    1976-01-01

    The purpose of a continuing program at ORNL is to provide technical assistance to the NRC on writing and editing of the final environmental statement on the routine use of nuclear-powered (primarily 238 Pu) cardiac pacemakers. This environmental statement defines the safety and reliability standards that nuclear-powered pacemakers are required to meet. All aspects of the risks to the patients, the public, and the environment are evaluated both for the routine use of plutonium-powered pacemakers and for postulated accidents involving pacemaker patients. Benefits derived from the use of plutonium-powered units are discussed and weighed against the risks in order to determine whether routine use is justified. Available alternative pacemakers with various performance characteristics are compared with respect to costs and to the needs of pacemaker patients

  14. Subjective consequences of permanent pacemaker therapy in patients under the age of retirement

    DEFF Research Database (Denmark)

    Mickley, H; Petersen, J; Nielsen, B L

    1989-01-01

    During a 5-year period, 81 patients ages 20 to 60 years old had implantation of a permanent cardiac pacemaker at the University Hospital, Odense. At follow-up, during 1985, the 73 survivors received a semi-structured questionnaire regarding subjective consequences of pacemaker therapy, and 72...... people (98.6%) agreed to participate. The mean pacing period (range) was 33.8 (11-72) months. Surgical intervention was required in 14 patients (19.4%) during follow-up. Regarding all symptoms 67 patients (93.1%) perceived benefit from the pacemaker. The effectiveness of cardiac pacing was most...... or a sensation of "impulses"/palpitations. To the majority (49 patients or 68.1%) pacemaker treatment did not influence quality of sexual activity. Six patients (8.3%) perceived an improvement, whereas a corresponding number felt deterioration in sexual activity following pacemaker implantation. Pacemaker...

  15. Semiconductor measurement technology: reliability technology for cardiac pacemakers 2: a workshop report, 1976

    International Nuclear Information System (INIS)

    Schafft, H.A.

    1977-01-01

    Summaries are presented of 12 invited talks on the following topics: the procurement and assurance of high reliability electronic parts, leak rate and moisture measurements, pacemaker batteries, and pacemaker leads. The workshop, second in a series, was held in response to strong interest expressed by the pacemaker community to address technical questions relevant to the enhancement and assurance of cardiac pacemaker reliability. Discussed at the workshop were a process validation wafer concept for assuring process uniformity in device chips; screen tests for assuring reliable electronic parts; reliability prediction; reliability comparison of semiconductor technologies; mechanisms of short-circuiting dendritic growths; details of helium and radioisotope leak test methods; a study to correlate package leak rates, as measured with test gasses, and actual moisture infusion; battery life prediction; microcalorimetric measurements to nondestructively evaluate batteries for pacemakers; and an engineer's and a physician's view of the present status of pacemaker leads. References are included with most of the reports

  16. Possible health hazards for cardiac pacemaker wearers from exposure to electromagnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    1988-03-01

    Cardiac pacemakers are used to provide electrical stimulation to the heart when the heart's natural rhythm is interrupted. This study shows that they can be susceptible to electromagnetic fields. Pacemakers are well protected against common electromagnetic fields, such as those from household appliances. But intense electomagnetic fields, such as those found in some industrial settings, could affect the functioning of the pacemaker. Such interference may cause the pacemaker wearer to feel dizzy or experience an accelerated heartbeat. While this is not fatal, the pacemaker wearer should try to move away from the source of the interfering field and avoid situations in which interference could arise. After experiencing any of these symptoms, the pacemaker wearer should contact a physician. Potential sources of electromagnetic interference should be identified and characterized to determine if there could be an interference hazard. Exposure to interfering electomagnetic fields should be minimized. 7 refs., 1 fig.

  17. Sleep deprivation decreases phase-shift responses of circadian rhythms to light in the mouse: role of serotonergic and metabolic signals.

    Science.gov (United States)

    Challet, E; Turek, F W; Laute, M; Van Reeth, O

    2001-08-03

    The circadian pacemaker in the suprachiasmatic nuclei is primarily synchronized to the daily light-dark cycle. The phase-shifting and synchronizing effects of light can be modulated by non-photic factors, such as behavioral, metabolic or serotonergic cues. The present experiments examine the effects of sleep deprivation on the response of the circadian pacemaker to light and test the possible involvement of serotonergic and/or metabolic cues in mediating the effects of sleep deprivation. Photic phase-shifting of the locomotor activity rhythm was analyzed in mice transferred from a light-dark cycle to constant darkness, and sleep-deprived for 8 h from Zeitgeber Time 6 to Zeitgeber Time 14. Phase-delays in response to a 10-min light pulse at Zeitgeber Time 14 were reduced by 30% in sleep-deprived mice compared to control mice, while sleep deprivation without light exposure induced no significant phase-shifts. Stimulation of serotonin neurotransmission by fluoxetine (10 mg/kg), a serotonin reuptake inhibitor that decreases light-induced phase-delays in non-deprived mice, did not further reduce light-induced phase-delays in sleep-deprived mice. Impairment of serotonin neurotransmission with p-chloroamphetamine (three injections of 10 mg/kg), which did not increase light-induced phase-delays in non-deprived mice significantly, partially normalized light-induced phase-delays in sleep-deprived mice. Injections of glucose increased light-induced phase-delays in control and sleep-deprived mice. Chemical damage of the ventromedial hypothalamus by gold-thioglucose (600 mg/kg) prevented the reduction of light-induced phase-delays in sleep-deprived mice, without altering phase-delays in control mice. Taken together, the present results indicate that sleep deprivation can reduce the light-induced phase-shifts of the mouse suprachiasmatic pacemaker, due to serotonergic and metabolic changes associated with the loss of sleep.

  18. Social memory in the rat: circadian variation and effect of circadian rhythm disruption

    NARCIS (Netherlands)

    Reijmers, L.G.J.E.; Leus, I.E.; Burbach, J.P.H.; Spruijt, B.M.; Ree, van J.M.

    2001-01-01

    Disruption of circadian rhythm can impair long-term passive avoidance memory of rats and mice. The present study investigated whether disruption of circadian rhythm can also impair social memory of male rats. Social memory was assessed using the social discrimination test, in which a short-term

  19. Complex regional pain syndrome type I following pacemaker implantation

    Directory of Open Access Journals (Sweden)

    Sangita Kamath

    2015-12-01

    Full Text Available A 70-year-old woman presented with burning pain and swelling over dorsum of right hand and small joints of the fingers, associated with redness, feeling of warmth, and stiffness of the fingers, with inability to bend the fingers since 2 months. The symptoms were progressively increasing in intensity for the past 1 month. There was no history of fever or trauma to the hand. Two months before her symptoms started, she had permanent pacemaker implanted for complete heart block with syncope. She was hypertensive and was on regular medication. Her X-ray of right hand showed decreased bone density (demineralisation, suggestive of osteopenia. A diagnosis of reflex sympathetic dystrophy syndrome or complex regional pain syndrome type I induced by pacemaker insertion was made. She was treated with amitriptyline and steroids, after which her symptoms improved dramatically.

  20. Percutaneously Inject able Fetal Pacemaker: Electrodes, Mechanical Design and Implantation*

    Science.gov (United States)

    Zhou, Li; Chmait, Ramen; Bar-Cohen, Yaniv; Peck, Raymond A.; Loeb, Gerald E.

    2015-01-01

    We are developing a self-contained cardiac pacemaker with a small, cylindrical shape (~3×20mm) that permits it to be implanted percutaneously into a fetus to treat complete heart block and consequent hydrops fetalis, which is otherwise fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. The feasibility of implanting the device percutaneously under ultrasonic imaging guidance was demonstrated in acute adult rabbit experiments. PMID:23367442

  1. Percutaneously injectable fetal pacemaker: electrodes, mechanical design and implantation.

    Science.gov (United States)

    Zhou, Li; Chmait, Ramen; Bar-Cohen, Yaniv; Peck, Raymond A; Loeb, Gerald E

    2012-01-01

    We are developing a self-contained cardiac pacemaker with a small, cylindrical shape (~3 × 20 mm) that permits it to be implanted percutaneously into a fetus to treat complete heart block and consequent hydrops fetalis, which is otherwise fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. The feasibility of implanting the device percutaneously under ultrasonic imaging guidance was demonstrated in acute adult rabbit experiments.

  2. A minimal model for a slow pacemaking neuron

    International Nuclear Information System (INIS)

    Zakharov, D.G.; Kuznetsov, A.

    2012-01-01

    Highlights: ► We have constructed a phenomenological model for slow pacemaking neurons. ► The model implements a nonlinearity introduced by an ion-dependent current. ► The new nonlinear dependence allows for differentiating responses to various stimuli. ► We discuss implications of our results for a broad class of neurons. - Abstract: We have constructed a phenomenological model for slow pacemaking neurons. These are neurons that generate very regular periodic oscillations of the membrane potential. Many of these neurons also differentially respond to various types of stimulation. The model is based on FitzHugh–Nagumo (FHN) oscillator and implements a nonlinearity introduced by a current that depends on an ion concentration. The comparison with the original FHN oscillator has shown that the new nonlinear dependence allows for differentiating responses to various stimuli. We discuss implications of our results for a broad class of neurons.

  3. Dual chamber pacemaker implants - a new opportunity in Pakistan for children with congenital and acquired complete heart block

    International Nuclear Information System (INIS)

    Ashfaq, A.; Khan, M.A.; Atiq, M.

    2011-01-01

    Implantation of cardiac pacemakers has been practiced for at least five decades with continuous developments of the hardware. The invention of dual chamber pacemakers has initiated a debate concerning its superiority over single chamber ventricular pacemakers. Throughout the world, surgeons have been using dual chambered permanent pacemakers with successful follow ups. However, Pakistan has not yet taken the advantage of such pacemaker devices till now. We report three cases that underwent a dual chamber permanent pacemaker implantation for the first time in children less than 8 kg with successful follow ups. (author)

  4. Post-transcriptional control of the mammalian circadian clock: implications for health and disease.

    Science.gov (United States)

    Preußner, Marco; Heyd, Florian

    2016-06-01

    Many aspects of human physiology and behavior display rhythmicity with a period of approximately 24 h. Rhythmic changes are controlled by an endogenous time keeper, the circadian clock, and include sleep-wake cycles, physical and mental performance capability, blood pressure, and body temperature. Consequently, many diseases, such as metabolic, sleep, autoimmune and mental disorders and cancer, are connected to the circadian rhythm. The development of therapies that take circadian biology into account is thus a promising strategy to improve treatments of diverse disorders, ranging from allergic syndromes to cancer. Circadian alteration of body functions and behavior are, at the molecular level, controlled and mediated by widespread changes in gene expression that happen in anticipation of predictably changing requirements during the day. At the core of the molecular clockwork is a well-studied transcription-translation negative feedback loop. However, evidence is emerging that additional post-transcriptional, RNA-based mechanisms are required to maintain proper clock function. Here, we will discuss recent work implicating regulated mRNA stability, translation and alternative splicing in the control of the mammalian circadian clock, and its role in health and disease.

  5. Epigenetic control and the circadian clock: linking metabolism to neuronal responses.

    Science.gov (United States)

    Orozco-Solis, R; Sassone-Corsi, P

    2014-04-04

    Experimental and epidemiological evidence reveal the profound influence that industrialized modern society has imposed on human social habits and physiology during the past 50 years. This drastic change in life-style is thought to be one of the main causes of modern diseases including obesity, type 2 diabetes, mental illness such as depression, sleep disorders, and certain types of cancer. These disorders have been associated to disruption of the circadian clock, an intrinsic time-keeper molecular system present in virtually all cells and tissues. The circadian clock is a key element in homeostatic regulation by controlling a large array of genes implicated in cellular metabolism. Importantly, intimate links between epigenetic regulation and the circadian clock exist and are likely to prominently contribute to the plasticity of the response to the environment. In this review, we summarize some experimental and epidemiological evidence showing how environmental factors such as stress, drugs of abuse and changes in circadian habits, interact through different brain areas to modulate the endogenous clock. Furthermore we point out the pivotal role of the deacetylase silent mating-type information regulation 2 homolog 1 (SIRT1) as a molecular effector of the environment in shaping the circadian epigenetic landscape. Published by Elsevier Ltd.

  6. Dim Light Melatonin Onset and Affect in Adolescents With an Evening Circadian Preference.

    Science.gov (United States)

    Dolsen, Michael R; Harvey, Allison G

    2018-01-01

    A shift toward an evening circadian preference and the onset of mood problems often occur during adolescence. Although these changes are linked to poorer outcomes, few studies have considered how positive and negative affect are related to the circadian rhythm during adolescence. This study examined the relationship between evening and morning affect ratings and dim light melatonin onset (DLMO), a measure of endogenous circadian rhythm. Age and sex were tested as moderators. This study is based on a subset of 163 (94 female, age = 14.7) adolescents with an evening circadian preference from a National Institute of Child Health and Human Development-funded study. Participants provided saliva for melatonin analysis and rated evening and morning affect. Higher evening negative affect was related to a later DLMO. Evening positive affect was not significantly related to DLMO timing. Age but not sex was a significant moderator such that higher negative and lower positive affect were related to a later DLMO for 10- to 13-year-olds, whereas higher positive affect was related to a later DLMO for 17- to 18-year-olds. DLMO was not significantly related to morning affect ratings. There is evidence that higher negative and lower positive affect may be related to the shift toward an evening circadian preference observed in adolescents, particularly for younger adolescents. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  7. Analysis of circadian properties and healthy levels of blue light from smartphones at night

    Science.gov (United States)

    Oh, Ji Hye; Yoo, Heeyeon; Park, Hoo Keun; Do, Young Rag

    2015-06-01

    This study proposes representative figures of merit for circadian and vision performance for healthy and efficient use of smartphone displays. The recently developed figures of merit for circadian luminous efficacy of radiation (CER) and circadian illuminance (CIL) related to human health and circadian rhythm were measured to compare three kinds of commercial smartphone displays. The CIL values for social network service (SNS) messenger screens from all three displays were higher than 41.3 biolux (blx) in a dark room at night, and the highest CIL value reached 50.9 blx. These CIL values corresponded to melatonin suppression values (MSVs) of 7.3% and 11.4%, respectively. Moreover, smartphone use in a bright room at night had much higher CIL and MSV values (58.7 ~ 105.2 blx and 15.4 ~ 36.1%, respectively). This study also analyzed the nonvisual and visual optical properties of the three smartphone displays while varying the distance between the screen and eye and controlling the brightness setting. Finally, a method to possibly attenuate the unhealthy effects of smartphone displays was proposed and investigated by decreasing the emitting wavelength of blue LEDs in a smartphone LCD backlight and subsequently reducing the circadian effect of the display.

  8. Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Makoto Akashi

    2017-06-01

    Full Text Available Hypercholesterolemia is a well-known risk factor for a wide range of diseases in developed countries. Here, we report that mice lacking functional LDLR (low density lipoprotein receptor, an animal model of human familial hypercholesterolemia, show circadian abnormalities. In free running behavioral experiments in constant darkness, these mice showed a prolonged active phase and distinctly bimodal rhythms. Even when the circadian rhythms were entrained by light and dark cycles, these mice showed a significant attenuation of behavioral onset intensity at the start of the dark period. Further, we hypothesized that the combination of hypercholesterolemia and circadian abnormalities may affect cardiovascular disease progression. To examine this possibility, we generated LDLR-deficient mice with impaired circadian rhythms by simultaneously introducing a mutation into Period2, a core clock gene, and found that these mice showed a significant enlargement of artery plaque area with an increase in inflammatory cytokine IL-6 levels. These results suggest that circadian dysfunction may be associated with the development or progression of cardiovascular diseases.

  9. Leadless pacemaker extraction from a single-center perspective.

    Science.gov (United States)

    González Villegas, Elkin; Al Razzo, Omar; Silvestre García, Jorge; Mesa García, José

    2018-02-01

    Leadless pacemaker can be considered as a technical revolution in cardiac pacing devices, with clear advantages over conventional pacemakers in overcoming all lead-related complications. However, the management of these devices once they reach the end of life (EOL) of the battery is still controversial. In the next years, there will be an increase in the need to define a clear strategy in the management of leadless PM once they reach their EOL. Safe extraction of these devices will define in a great manner this strategy METHODS: We performed the extraction of three functioning Nanostim leadless pacemaker prophylactically in two females and one male patients as part of the Nanostim battery depletion field action recommendation. All patients had a prior transesophageal 3D echocardiography to determine the device intracardiac mobility and the extent of possible endothelialization. For the extractions, we used the Nanostim Retrieval Catheter S1RSIN (St. Jude Medical, St. Paul, MN, USA), which is a proprietary catheter provided by the manufacturing company based on a lasso. Complete extraction of the devices was achieved in all patients using a relatively short fluoroscopic time (16, 19, and 12 minutes). The extraction of leadless pacemakers can be considered as a safe and feasible procedure using the tools provided by the manufacturer and designed for the extraction. However, a very low threshold must be maintained to avoid any risk to the patients. Our extraction time ranges are between 983 and 1,070 days, nevertheless it is necessary to gather more long-term data to assess the feasibility and safety of these procedures. © 2017 Wiley Periodicals, Inc.

  10. Integrative Modeling of Electrical Properties of Pacemaker Cardiac Cells

    Science.gov (United States)

    Grigoriev, M.; Babich, L.

    2016-06-01

    This work represents modeling of electrical properties of pacemaker (sinus) cardiac cells. Special attention is paid to electrical potential arising from transmembrane current of Na+, K+ and Ca2+ ions. This potential is calculated using the NaCaX model. In this respect, molar concentration of ions in the intercellular space which is calculated on the basis of the GENTEX model is essential. Combined use of two different models allows referring this approach to integrative modeling.

  11. Identification and functional characterization of cardiac pacemaker cells in zebrafish.

    Directory of Open Access Journals (Sweden)

    Federico Tessadori

    Full Text Available In the mammalian heart a conduction system of nodes and conducting cells generates and transduces the electrical signals evoking myocardial contractions. Specialized pacemaker cells initiating and controlling cardiac contraction rhythmicity are localized in an anatomically identifiable structure of myocardial origin, the sinus node. We previously showed that in mammalian embryos sinus node cells originate from cardiac progenitors expressing the transcription factors T-box transcription factor 3 (Tbx3 and Islet-1 (Isl1. Although cardiac development and function are strikingly conserved amongst animal classes, in lower vertebrates neither structural nor molecular distinguishable components of a conduction system have been identified, questioning its evolutionary origin. Here we show that zebrafish embryos lacking the LIM/homeodomain-containing transcription factor Isl1 display heart rate defects related to pacemaker dysfunction. Moreover, 3D reconstructions of gene expression patterns in the embryonic and adult zebrafish heart led us to uncover a previously unidentified, Isl1-positive and Tbx2b-positive region in the myocardium at the junction of the sinus venosus and atrium. Through their long interconnecting cellular protrusions the identified Isl1-positive cells form a ring-shaped structure. In vivo labeling of the Isl1-positive cells by transgenic technology allowed their isolation and electrophysiological characterization, revealing their unique pacemaker activity. In conclusion we demonstrate that Isl1-expressing cells, organized as a ring-shaped structure around the venous pole, hold the pacemaker function in the adult zebrafish heart. We have thereby identified an evolutionary conserved, structural and molecular distinguishable component of the cardiac conduction system in a lower vertebrate.

  12. Clinicohemodynamic and roentgenologic correlations in patients with artificial pacemakers

    International Nuclear Information System (INIS)

    Tatarchenko, I.P.; Iskenderov, B.G.; Koledinov, V.I.; Zhivotovskaya, G.G.

    1987-01-01

    The clinical pattern, central hemodynamics and roentgenologic data are studied in 34 patients with artificial cardiac pacemaker (ACP) to solve the problem on adequate medicamental therapy of heart failure (HF). Heart sizes and the state of a pulmonary image are estimated roentgenologically. Two types of cardiac-vessel system reactions on physical load: adequate and nonadequate - are detected. Implantation of ACP in patients with the nonadequate reaction does not lead to total liquidation of HF

  13. Clinicohemodynamic and roentgenologic correlations in patients with artificial pacemakers

    Energy Technology Data Exchange (ETDEWEB)

    Tatarchenko, I P; Iskenderov, B G; Koledinov, V I; Zhivotovskaya, G G

    1987-05-01

    The clinical pattern, central hemodynamics and roentgenologic data are studied in 34 patients with artificial cardiac pacemaker (ACP) to solve the problem on adequate medicamental therapy of heart failure (HF). Heart sizes and the state of a pulmonary image are estimated roentgenologically. Two types of cardiac-vessel system reactions on physical load: adequate and nonadequate - are detected. Implantation of ACP in patients with the nonadequate reaction does not lead to total liquidation of HF.

  14. ON THE ROLE OF PERIOD-2 IN THE CIRCADIAN AND HOMEOSTATIC REGULATION OF SLEEP

    OpenAIRE

    La Spada, F.

    2013-01-01

    Humans spend one third of their life sleeping, then we could raise the basic question: Why do we sleep? Despite the fact that we still don't fully understand its function, we made much progress in understanding at different levels how sleep is regulated. One model suggests that sleep is regulated by two processes: a homeostatic process that tracks the need for sleep and by a circadian rhythm that determines the preferred time-of-day sleep occurs. At the molecular level circadian rhythms ar...

  15. A Systematic Review of Economic Evaluations of Pacemaker Telemonitoring Systems.

    Science.gov (United States)

    López-Villegas, Antonio; Catalán-Matamoros, Daniel; Martín-Saborido, Carlos; Villegas-Tripiana, Irene; Robles-Musso, Emilio

    2016-02-01

    Over the last decade, telemedicine applied to pacemaker monitoring has undergone extraordinary growth. It is not known if telemonitoring is more or less efficient than conventional monitoring. The aim of this study was to carry out a systematic review analyzing the available evidence on resource use and health outcomes in both follow-up modalities. We searched 11 databases and included studies published up until November 2014. The inclusion criteria were: a) experimental or observational design; b) studies based on complete economic evaluations; c) patients with pacemakers, and d) telemonitoring compared with conventional hospital monitoring. Seven studies met the inclusion criteria, providing information on 2852 patients, with a mean age of 81 years. The main indication for device implantation was atrioventricular block. With telemonitoring, cardiovascular events were detected and treated 2 months earlier than with conventional monitoring, thus reducing length of hospital stay by 34% and reducing routine and emergency hospital visits as well. There were no significant intergroup differences in perceived quality of life or number of adverse events. The cost of telemonitoring was 60% lower than that of conventional hospital monitoring. Compared with conventional monitoring, cardiovascular events were detected earlier and the number or hospitalizations and hospital visits was reduced with pacemaker telemonitoring. In addition, the costs associated with follow-up were lower with telemonitoring. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Permanent and temporary pacemaker implantation after orthotopic heart transplantation

    Directory of Open Access Journals (Sweden)

    Bacal Fernando

    2000-01-01

    Full Text Available PURPOSE:To determine the indication for and incidence and evolution of temporary and permanent pacemaker implantation in cardiac transplant recipients. METHODS: A retrospective review of 114 patients who underwent orthotopic heart transplantation InCor (Heart Institute USP BR between March 1985 and May 1993. We studied the incidence of and indication for temporary pacing, the relationship between pacing and rejection, the need for pemanent pacing and the clinical follow-up. RESULTS: Fourteen of 114 (12%heart transplant recipients required temporary pacing and 4 of 114 (3.5% patients required permanent pacing. The indication for temporary pacing was sinus node dysfunction in 11 patients (78.5% and atrioventricular (AV block in 3 patients (21.4%. The indication for permanent pacemaker implantation was sinus node dysfunction in 3 patients (75% and atrioventricular (AV block in 1 patient (25%. We observed rejection in 3 patients (21.4% who required temporary pacing and in 2 patients (50% who required permanent pacing. The previous use of amiodarone was observed in 10 patients (71.4% with temporary pacing. Seven of the 14 patients (50% died during follow-up. CONCLUSION: Sinus node dysfunction was the principal indication for temporary and permanent pacemaker implantation in cardiac transplant recipients. The need for pacing was related to worse prognosis after cardiac transplantation.

  17. Continued evaluation of cardiac pacemakers. Annual report Jun 73-31 Aug 75

    International Nuclear Information System (INIS)

    Brueschke, E.E.; Uretz, E.F.; Hauser, R.G.

    1976-01-01

    The nuclear powered pacemaker evaluation was designed to characterize the operating characteristics of such pacemakers and identify potential failure mechanisms. More than 30 nuclear powered pacemakers were implanted in dogs and 15 were subjected to high stress bench tests. This evaluation resulted in the identification of several basic pacemaker problem areas for the batteries under test. These included abrupt and gradual nuclear battery failures, weld seam defects (in one model) resulting in pulse generator failures, pulse generator lead connector defects and pulse generator electronic malfunctions

  18. Swim pacemakers in box jellyfish are modulated by the visual input

    DEFF Research Database (Denmark)

    Garm, Anders Lydik; Bielecki, Jan

    2008-01-01

    A major part of the cubozoan central nervous system is situated in the eye-bearing rhopalia. One of the neuronal output channels from the rhopalia carries a swim pacemaker signal, which has a one-to-one relation with the swim contractions of the bell shaped body. Given the advanced visual system...... of box jellyfish and that the pacemaker signal originates in the vicinity of these eyes, it seems logical to assume that the pacemakers are modified by the visual input. Here, the firing frequency and distribution of inter-signal intervals (ISIs) of single pacemakers are examined in the Caribbean box...

  19. Permanent Pacemaker Lead Induced Severe Tricuspid Regurgitation in Patient Undergoing Multiple Valve Surgery

    Directory of Open Access Journals (Sweden)

    Jung Hee Lee

    2015-04-01

    Full Text Available Severe and permanent tricuspid regurgitation induced by pacemaker leads is rarely reported in the literature. The mechanism of pacemaker-induced tricuspid regurgitation has been identified, but its management has not been well established. Furthermore, debate still exists regarding the proper surgical approach. We present the case of a patient with severe tricuspid regurgitation induced by a pacemaker lead, accompanied by triple valve disease. The patient underwent double valve replacement and tricuspid valve repair without removal of the pre-existing pacemaker lead. The operation was successful and the surgical procedure is discussed in detail.

  20. Permanent pacemaker lead induced severe tricuspid regurgitation in patient undergoing multiple valve surgery.

    Science.gov (United States)

    Lee, Jung Hee; Kim, Tae Ho; Kim, Wook Sung

    2015-04-01

    Severe and permanent tricuspid regurgitation induced by pacemaker leads is rarely reported in the literature. The mechanism of pacemaker-induced tricuspid regurgitation has been identified, but its management has not been well established. Furthermore, debate still exists regarding the proper surgical approach. We present the case of a patient with severe tricuspid regurgitation induced by a pacemaker lead, accompanied by triple valve disease. The patient underwent double valve replacement and tricuspid valve repair without removal of the pre-existing pacemaker lead. The operation was successful and the surgical procedure is discussed in detail.

  1. Radiation therapy planning of a breast cancer patient with in situ pacemaker-challenges and lessons

    Energy Technology Data Exchange (ETDEWEB)

    Munshi, Anusheel; Wadasadawala, Tabassum; Budrukkar, Ashwini; Jalali, Rakesh; Dinshaw, Ketayun A [Dept. of Radiation Oncology, Tata Memorial Hospital, Mumbai (India); Sharma, Pramod Kumar; Sharma, Dayananda [Dept. of Radiation Physics, Tata Memorial Hospital, Mumbai (India)

    2008-02-15

    A postmenopausal lady with an in situ pacemaker developed a lump in the left breast and was diagnosed to have breast cancer. The patient underwent breast conservative surgery and was planned for post operative radiotherapy. The location of the tumor relative to the pacemaker provided a unique challenge in planning radiotherapy and the patient had an uneventful post radiotherapy course. A literature review revealed that modern generation pacemakers are very sensitive to radiation compared to their older counterparts. The present article makes suggestions towards reducing dose in radiotherapy planning in pacemaker patients

  2. Radiation therapy planning of a breast cancer patient with in situ pacemaker-challenges and lessons

    International Nuclear Information System (INIS)

    Munshi, Anusheel; Wadasadawala, Tabassum; Budrukkar, Ashwini; Jalali, Rakesh; Dinshaw, Ketayun A.; Sharma, Pramod Kumar; Sharma, Dayananda

    2008-01-01

    A postmenopausal lady with an in situ pacemaker developed a lump in the left breast and was diagnosed to have breast cancer. The patient underwent breast conservative surgery and was planned for post operative radiotherapy. The location of the tumor relative to the pacemaker provided a unique challenge in planning radiotherapy and the patient had an uneventful post radiotherapy course. A literature review revealed that modern generation pacemakers are very sensitive to radiation compared to their older counterparts. The present article makes suggestions towards reducing dose in radiotherapy planning in pacemaker patients

  3. The mammalian circadian clock and its entrainment by stress and exercise.

    Science.gov (United States)

    Tahara, Yu; Aoyama, Shinya; Shibata, Shigenobu

    2017-01-01

    The mammalian circadian clock regulates day-night fluctuations in various physiological processes. The circadian clock consists of the central clock in the suprachiasmatic nucleus of the hypothalamus and peripheral clocks in peripheral tissues. External environmental cues, including light/dark cycles, food intake, stress, and exercise, provide important information for adjusting clock phases. This review focuses on stress and exercise as potent entrainment signals for both central and peripheral clocks, especially in regard to the timing of stimuli, types of stressors/exercises, and differences in the responses of rodents and humans. We suggest that the common signaling pathways of clock entrainment by stress and exercise involve sympathetic nervous activation and glucocorticoid release. Furthermore, we demonstrate that physiological responses to stress and exercise depend on time of day. Therefore, using exercise to maintain the circadian clock at an appropriate phase and amplitude might be effective for preventing obesity, diabetes, and cardiovascular disease.

  4. Plasma FGF21 displays a circadian rhythm during a 72-h fast in healthy female volunteers

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Beck-Nielsen, Henning; Højlund, Kurt

    2011-01-01

    Fibroblast growth factor (FGF21) is a potent regulator of glucose and lipid metabolism. In rodents, the hepatic expression of FGF21 is controlled by fasting and a circadian regulation, but the physiological role and regulation of FGF21 in humans is not well established. Therefore, the objective...

  5. Electroencephalogram Power Density and Slow Wave Sleep as a Function of Prior Waking and Circadian Phase

    NARCIS (Netherlands)

    Dijk, Derk-Jan; Brunner, Daniel P.; Beersma, Domien G.M.; Borbély, Alexander A.

    1990-01-01

    Human sleep electroencephalograms, recorded in four experiments, were subjected to spectral analysis. Waking prior to sleep varied from 12 to 36 h and sleep was initiated at different circadian phases. Power density of delta and theta frequencies in rapid-eye-movement (REM) sleep and non-REM (NREM)

  6. Conceptual design of GaN betavoltaic battery using in cardiac pacemaker

    International Nuclear Information System (INIS)

    Mohamadian, M.; Feghhi, S.A. H.; Afarideh, H.

    2007-01-01

    Introduction: Pacemaker is an electronic biomedical device which stimulates and regulates or amplify the human heartbeat by delivering weak electrical pulses to the cardiac muscle at regular intervals when its natural regulating mechanisms break down. Developments in design and implementation of power source in adjacent to advances in electronic circuitry is an important aspect in optimization of pacemakers. For instance, many implant patients continue to outlive their batteries and require costly and risky replacement surgery. So such device needs to have high energy density power source and maintain a stable current and voltage for a long period of time to avoid frequent replacements. In addition, the size is also an important consideration for implantable batteries. Betavoltaic batteries are being researched as a suitable source for these applications. Also, these batteries have vast application in which the replacement of batteries is highly inconvenient, such as in oil and mining industries, which often place sensors in dangerous or hard-to-reach locations. The purpose of the present investigation is determination of the optimal parameters of low energy GaN betavoltaic battery in artificial cardiac pacemakers using MCNP code which have higher efficiency than those available with previous devices, especially thermoelectric converters (∼15%). Material and Methods: In this design, two p-n diode structures from GaN semiconductor were used to collect the charge from a layer of 6 3Ni as a source which is centered between the two p-n junctions. MCNP simulation results have been used to determine the amount of electron current from interaction of beta particles in p-n junctions. Results and Discussion: Calculation results indicate that the short circuit current, open circuit voltage and efficiency of a single device are 1.1 μA/cm 2 , 2.7 volt and 25%, respectively. Also, it's concluded that with suitable arrangement of these single devices, one could construct a

  7. Time-of-day- and light-dependent expression of ubiquitin protein ligase E3 component N-recognin 4 (UBR4 in the suprachiasmatic nucleus circadian clock.

    Directory of Open Access Journals (Sweden)

    Harrod H Ling

    Full Text Available Circadian rhythms of behavior and physiology are driven by the biological clock that operates endogenously but can also be entrained to the light-dark cycle of the environment. In mammals, the master circadian pacemaker is located in the suprachiasmatic nucleus (SCN, which is composed of individual cellular oscillators that are driven by a set of core clock genes interacting in transcriptional/translational feedback loops. Light signals can trigger molecular events in the SCN that ultimately impact on the phase of expression of core clock genes to reset the master pacemaker. While transcriptional regulation has received much attention in the field of circadian biology in the past, other mechanisms including targeted protein degradation likely contribute to the clock timing and entrainment process. In the present study, proteome-wide screens of the murine SCN led to the identification of ubiquitin protein ligase E3 component N-recognin 4 (UBR4, a novel E3 ubiquitin ligase component of the N-end rule pathway, as a time-of-day-dependent and light-inducible protein. The spatial and temporal expression pattern of UBR4 in the SCN was subsequently characterized by immunofluorescence microscopy. UBR4 is expressed across the entire rostrocaudal extent of the SCN in a time-of-day-dependent fashion. UBR4 is localized exclusively to arginine vasopressin (AVP-expressing neurons of the SCN shell. Upon photic stimulation in the early subjective night, the number of UBR4-expressing cells within the SCN increases. This study is the first to identify a novel E3 ubiquitin ligase component, UBR4, in the murine SCN and to implicate the N-end rule degradation pathway as a potential player in regulating core clock mechanisms and photic entrainment.

  8. Circadian Rhythm of Pyrocystis fusiformis

    Science.gov (United States)

    Weishaar, B.

    2016-12-01

    For the Academy of Science St. Louis Science Fair, I tested how different photoperiods affect the morphology of Pyrocystis fusiformis with respect to the placement and formation of the chloroplasts. I set up four different rooms to observe the effect the different times in the photoperiod on location of chloroplasts in the cell. At 3:00pm, one room has been in the dark for 12 hours, one for 6 hours, one had been in the light phase for 12 hours and the fourth in the light phase for 6 hours. P fusiformis samples were obtained from each room, observed, photographed at X100 power, and categorized as being a 1, 2, 3, or 4 depending on the position of the chloroplasts. The samples in the different rooms were observed once a week for two weeks, then the samples were rotated to see if P. fusiformis would synchronize the same to the new photoperiod. It was observed that the cells changed morphological stages in the circadian cycle, the chloroplasts moved further away from the nucleus when exposed to light and moved closer to the nucleus when experiencing no light.

  9. Connectivity of Pacemaker Neurons in the Neonatal Rat Superficial Dorsal Horn

    Science.gov (United States)

    Ford, Neil C.; Arbabi, Shahriar; Baccei, Mark L.

    2014-01-01

    Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing have been characterized in lamina I of the neonatal spinal cord, where they are innervated by high-threshold sensory afferents. However, little is known about the output of these pacemakers, as the neuronal populations which are targeted by pacemaker axons have yet to be identified. The present study combines patch clamp recordings in the intact neonatal rat spinal cord with tract-tracing to demonstrate that lamina I pacemaker neurons contact multiple spinal motor pathways during early life. Retrograde labeling of premotor interneurons with the trans-synaptic virus PRV-152 revealed the presence of burst-firing in PRV-infected lamina I neurons, thereby confirming that pacemakers are synaptically coupled to motor networks in the spinal ventral horn. Notably, two classes of pacemakers could be distinguished in lamina I based on cell size and the pattern of their axonal projections. While small pacemaker neurons possessed ramified axons which contacted ipsilateral motor circuits, large pacemaker neurons had unbranched axons which crossed the midline and ascended rostrally in the contralateral white matter. Recordings from identified spino-parabrachial and spino-PAG neurons indicated the presence of pacemaker activity within neonatal lamina I projection neurons. Overall, these results show that lamina I pacemakers are positioned to regulate both the level of activity in developing motor circuits as well as the ascending flow of nociceptive information to the brain, thus highlighting a potential role for pacemaker activity in the maturation of pain and sensorimotor networks in the CNS. PMID:25380417

  10. A novel animal model linking adiposity to altered circadian rhythms

    Science.gov (United States)

    Researchers have provided evidence for a link between obesity and altered circadian rhythms (e.g., shift work, disrupted sleep), but the mechanism for this association is still unknown. Adipocytes possess an intrinsic circadian clock, and circadian rhythms in adipocytokines and adipose tissue metab...

  11. Intact interval timing in circadian CLOCK mutants.

    Science.gov (United States)

    Cordes, Sara; Gallistel, C R

    2008-08-28

    While progress has been made in determining the molecular basis for the circadian clock, the mechanism by which mammalian brains time intervals measured in seconds to minutes remains a mystery. An obvious question is whether the interval-timing mechanism shares molecular machinery with the circadian timing mechanism. In the current study, we trained circadian CLOCK +/- and -/- mutant male mice in a peak-interval procedure with 10 and 20-s criteria. The mutant mice were more active than their wild-type littermates, but there were no reliable deficits in the accuracy or precision of their timing as compared with wild-type littermates. This suggests that expression of the CLOCK protein is not necessary for normal interval timing.

  12. Molecular cogs of the insect circadian clock.

    Science.gov (United States)

    Shirasu, Naoto; Shimohigashi, Yasuyuki; Tominaga, Yoshiya; Shimohigashi, Miki

    2003-08-01

    During the last five years, enormous progress has been made in understanding the molecular basis of circadian systems, mainly by molecular genetic studies using the mouse and fly. Extensive evidence has revealed that the core clock machinery involves "clock genes" and "clock proteins" functioning as molecular cogs. These participate in transcriptional/translational feedback loops and many homologous clock-components in the fruit fly Drosophila are also expressed in mammalian clock tissues with circadian rhythms. Thus, the mechanisms of the central clock seem to be conserved across animal kingdom. However, some recent studies imply that the present widely accepted molecular models of circadian clocks may not always be supported by the experimental evidence.

  13. Age-related changes in sleep and circadian rhythms: impact on cognitive performance and underlying neuroanatomical networks

    Directory of Open Access Journals (Sweden)

    Christina eSchmidt

    2012-07-01

    Full Text Available Circadian and homeostatic sleep-wake regulatory processes interact in a fine tuned manner to modulate human cognitive performance. Dampening of the circadian alertness signal and attenuated deterioration of psychomotor vigilance in response to elevated sleep pressure with aging change this interaction pattern. As evidenced by neuroimaging studies, both homeostatic sleep pressure and circadian sleep-wake promotion impact on cognition-related cortical and arousal-promoting subcortical brain regions including the thalamus, the anterior hypothalamus and the brainstem locus coeruleus (LC. However, how age- related changes in circadian and homeostatic processes impact on the cerebral activity subtending waking performance remains largely unexplored. Post-mortem studies point to neuronal degeneration in the SCN and age-related modifications to aging in the arousal-promoting LC. Alongside, cortical frontal brain areas are particularly susceptible both to aging and misalignment between circadian and homeostatic processes. In this perspective, we summarise and discuss here the potential neuroanatomical networks underlying age-related changes in circadian and homeostatic modulation of waking performance, ranging from basic arousal to higher order cognitive behaviours.

  14. The biological clock modulates the human cortisol response in a multiplicative fashion

    NARCIS (Netherlands)

    van de Werken, Maan; Booij, Sanne H.; van der Zwan, J Esi; Simons, Mirre J. P.; Gordijn, Marijke C. M.; Beersma, Domien G. M.

    Human cortisol levels follow a clear circadian rhythm. We investigated the contribution of alternation of sleep and wakefulness and the circadian clock, using forced desynchrony. Cortisol levels were best described by a multiplication of a circadian and a wake-time component. The human cortisol

  15. Chronotherapeutic drug delivery systems: an approach to circadian rhythms diseases.

    Science.gov (United States)

    Sunil, S A; Srikanth, M V; Rao, N Sreenivasa; Uhumwangho, M U; Latha, K; Murthy, K V Ramana

    2011-11-01

    The purpose of writing this review on chronotherapeutic drug delivery systems (ChrDDs) is to review the literatures with special focus on ChrDDs and the various dosage forms, techniques that are used to target the circadian rhythms (CR) of various diseases. Many functions of the human body vary considerably in a day. ChrDDs refers to a treatment method in which in vivo drug availability is timed to match circadian rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Several techniques have been developed but not many dosage forms for all the diseases are available in the market. ChrDDs are gaining importance in the field of pharmaceutical technology as these systems reduce dosing frequency, toxicity and deliver the drug that matches the CR of that particular disease when the symptoms are maximum to worse. Finally, the ultimate benefit goes to the patient due the compliance and convenience of the dosage form. Some diseases that follow circadian rhythms include cardiovascular diseases, asthma, arthritis, ulcers, diabetes etc. ChrDDs in the market were also discussed and the current technologies used to formulate were also stated. These technologies include Contin® , Chronotopic®, Pulsincaps®, Ceform®, Timerx®, Oros®, Codas®, Diffucaps®, Egalet®, Tablet in capsule device, Core-in-cup tablet technology. A coated drug-core tablet matrix, A bi-layered tablet, Multiparticulate-based chronotherapeutic drug delivery systems, Chronoset and Controlled release microchips.

  16. The importance of hormonal circadian rhythms in daily feeding patterns: An illustration with simulated pigs.

    Science.gov (United States)

    Boumans, Iris J M M; de Boer, Imke J M; Hofstede, Gert Jan; la Fleur, Susanne E; Bokkers, Eddie A M

    2017-07-01

    The interaction between hormonal circadian rhythms and feeding behaviour is not well understood. This study aimed to deepen our understanding of mechanisms underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a case study. Pigs show an alternans feeding pattern, that is, a small peak of feed intake at the beginning of the day and a larger peak at the end of the day. We simulated the feeding behaviour of pigs over a 24h period. The simulation model contained mechanisms that regulate feeding behaviour of animals, including: processing of feed in the gastrointestinal tract, fluctuation in energy balance, circadian rhythms of melatonin and cortisol and motivational decision-making. From the interactions between these various processes, feeding patterns (e.g. feed intake, meal frequency, feeding rate) emerge. These feeding patterns, as well as patterns for the underlying mechanisms (e.g. energy expenditure), fitted empirical data well, indicating that our model contains relevant mechanisms. The circadian rhythms of cortisol and melatonin explained the alternans pattern of feeding in pigs. Additionally, the timing and amplitude of cortisol peaks affected the diurnal and nocturnal peaks in feed intake. Furthermore, our results suggest that circadian rhythms of other hormones, such as leptin and ghrelin, are less important in circadian regulation of feeding behaviour than previously thought. These results are relevant to animal species with a metabolic and endocrine system similar to that of pigs, such as humans. Moreover, the modelling approach to understand feeding behaviour can be applied to other animal species. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Coordination of the maize transcriptome by a conserved circadian clock

    Directory of Open Access Journals (Sweden)

    Harmon Frank G

    2010-06-01

    Full Text Available Abstract Background The plant circadian clock orchestrates 24-hour rhythms in internal physiological processes to coordinate these activities with daily and seasonal changes in the environment. The circadian clock has a profound impact on many aspects of plant growth and development, including biomass accumulation and flowering time. Despite recent advances in understanding the circadian system of the model plant Arabidopsis thaliana, the contribution of the circadian oscillator to important agronomic traits in Zea mays and other cereals remains poorly defined. To address this deficit, this study investigated the transcriptional landscape of the maize circadian system. Results Since transcriptional regulation is a fundamental aspect of circadian systems, genes exhibiting circadian expression were identified in the sequenced maize inbred B73. Of the over 13,000 transcripts examined, approximately 10 percent displayed circadian expression patterns. The majority of cycling genes had peak expression at subjective dawn and dusk, similar to other plant circadian systems. The maize circadian clock organized co-regulation of genes participating in fundamental physiological processes, including photosynthesis, carbohydrate metabolism, cell wall biogenesis, and phytohormone biosynthesis pathways. Conclusions Circadian regulation of the maize genome was widespread and key genes in several major metabolic pathways had circadian expression waveforms. The maize circadian clock coordinated transcription to be coincident with oncoming day or night, which was consistent with the circadian oscillator acting to prepare the plant for these major recurring environmental changes. These findings highlighted the multiple processes in maize plants under circadian regulation and, as a result, provided insight into the important contribution this regulatory system makes to agronomic traits in maize and potentially other C4 plant species.

  18. Zebrafish heart as a model to study the integrative autonomic control of pacemaker function

    Science.gov (United States)

    Stoyek, Matthew R.; Quinn, T. Alexander; Croll, Roger P.

    2016-01-01

    The cardiac pacemaker sets the heart's primary rate, with pacemaker discharge controlled by the autonomic nervous system through intracardiac ganglia. A fundamental issue in understanding the relationship between neural activity and cardiac chronotropy is the identification of neuronal populations that control pacemaker cells. To date, most studies of neurocardiac control have been done in mammalian species, where neurons are embedded in and distributed throughout the heart, so they are largely inaccessible for whole-organ, integrative studies. Here, we establish the isolated, innervated zebrafish heart as a novel alternative model for studies of autonomic control of heart rate. Stimulation of individual cardiac vagosympathetic nerve trunks evoked bradycardia (parasympathetic activation) and tachycardia (sympathetic activation). Simultaneous stimulation of both vagosympathetic nerve trunks evoked a summative effect. Effects of nerve stimulation were mimicked by direct application of cholinergic and adrenergic agents. Optical mapping of electrical activity confirmed the sinoatrial region as the site of origin of normal pacemaker activity and identified a secondary pacemaker in the atrioventricular region. Strong vagosympathetic nerve stimulation resulted in a shift in the origin of initial excitation from the sinoatrial pacemaker to the atrioventricular pacemaker. Putative pacemaker cells in the sinoatrial and atrioventricular regions expressed adrenergic β2 and cholinergic muscarinic type 2 receptors. Collectively, we have demonstrated that the zebrafish heart contains the accepted hallmarks of vertebrate cardiac control, establishing this preparation as a viable model for studies of integrative physiological control of cardiac function by intracardiac neurons. PMID:27342878

  19. Noise-induced effects on multicellular biopacemaker spontaneous activity: Differences between weak and strong pacemaker cells

    Science.gov (United States)

    Aghighi, Alireza; Comtois, Philippe

    2017-09-01

    Self-organization of spontaneous activity of a network of active elements is important to the general theory of reaction-diffusion systems as well as for pacemaking activity to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes, consisting of resting and pacemaker cells, exhibit spontaneous activation of their electrical activity. Similarly, one proposed approach to the development of biopacemakers as an alternative to electronic pacemakers for cardiac therapy is based on heterogeneous cardiac cells with resting and spontaneously beating phenotypes. However, the combined effect of pacemaker characteristics, density, and spatial distribution of the pacemaker cells on spontaneous activity is unknown. Using a simple stochastic pattern formation algorithm, we previously showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of pacemaker cells. In this study, we show that this behavior is dependent on the pacemaker cell characteristics, with weaker pacemaker cells requiring higher density and larger clusters to sustain multicellular activity. These multicellular structures also demonstrated an increased sensitivity to voltage noise that favored spontaneous activity at lower density while increasing temporal variation in the period of activity. This information will help researchers overcome the current limitations of biopacemakers.

  20. I-123 metaiodobenzylguanidine cardiac scintigraphy in patients with an implanted permanent pacemaker

    International Nuclear Information System (INIS)

    Nakata, Akio; Hirota, Satoshi; Tsuji, Hiroshi; Takazakura, Eisuke

    1995-01-01

    Tl scintigraphic abnormalities have been reported in patients with an implanted permanent pacemaker, but little is known about the MIBG scintigraphic findings in such patients. This study was performed to assess the MIBG scintigraphic findings in patients with an implanted permanent pacemaker, and to test the hypothesis that imaging characteristics of MIBG scintigraphy differ according to its mode. Twelve patients (4 men and 8 women, mean age: 72.4±9.5 years), who had undergone the implantation of a permanent pacemaker for bradyarrhythmias, underwent MIBG scintigraphy. The patients were divided into VVI pacemaker and DDD pacemaker groups. The tomograms were divided into nine segments and the MIBG defect in each segment scored on a scale ranging from 0 (normal uptake) to 3 (no uptake). Total MIBG defect scores were generated by summing the scores for the nine segments in each patient. MIBG scintigraphic abnormalities were found in ten of the twelve patients. The six patients with the VVI pacemaker manifested MIBG scintigraphic abnormalities. These MIBG scintigraphic abnormalities were observed in all segments, particularly in the posterior segments. The mean total defect score of the VVI group was higher than that of the DDD group (14.8±9.8 vs 3.0±3.5, respectively p<0.05). Therefore, we conclude that despite several limitations of the study, MIBG scintigraphic abnormalities occur in patients with implanted permanent pacemakers, and that such abnormalities are more prominent with the VVI than DDD pacemaker. (author)