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61.
Electrical activity in the gamma frequency range is instrumental for temporal encoding on the millisecond scale in attentive vertebrate brains. Surprisingly, also circadian pacemaker neurons in the cockroach Rhyparobia maderae (Leucophaea maderae) employ fast spontaneous rhythmic activity in the gamma band frequency range (20–70 Hz) together with slow rhythmic activity. The ionic conductances controlling this fast spontaneous activity are still unknown. Here, Ca2+ imaging combined with pharmacology was employed to analyse ion channels underlying spontaneous activity in dispersed circadian pacemakers of the adult accessory medulla, which controls circadian locomotor activity rhythms. Fast spontaneous Ca2+ transients in circadian pacemakers accompany tetrodotoxin (TTX)‐blockable spontaneous action potentials. In contrast to vertebrate pacemakers, the spontaneous depolarisations from rest appear to be rarely initiated via TTX‐sensitive sustained Na+ channels. Instead, they are predominantly driven by mibefradil‐sensitive, low‐voltage‐activated Ca2+ channels and DK‐AH269‐sensitive hyperpolarisation‐activated, cyclic nucleotide‐gated cation channels. Rhythmic depolarisations activate voltage‐gated Na+ channels and nifedipine‐sensitive high‐voltage‐activated Ca2+ channels. Together with Ca2+ rises, the depolarisations open repolarising small‐conductance but not large‐conductance Ca2+‐dependent K+ channels. In contrast, we hypothesise that P/Q‐type Ca2+ channels coupled to large‐conductance Ca2+‐dependent K+ channels are involved in input‐dependent activity. 相似文献
62.
63.
Low overall mortality of Turkish residents in Germany persists and extends into a second generation: merely a healthy migrant effect?* 总被引:7,自引:0,他引:7
Oliver Razum Hajo Zeeb H. Seval Akgün & Selma Yilmaz 《Tropical medicine & international health : TM & IH》1998,3(4):297-303
Summary objective To test the hypothesis that as a minority with lower socio-economic status, Turkish residents in Germany might experience a higher mortality than Germans.
methods All-cause mortality rates by age group and sex of Turkish and German adults for the time period 1980–94 were calculated from death registry data and mid-year population estimates.
results The age-adjusted mortality rate (per 100000) of Turkish males aged 25–65 years resident in Germany was 299 in 1980 and 247 in 1990, consistently half that of German males. The mortality of Turkish females in Germany was 140 in 1990, half that of German females. Mortality of Turkish males/females in Ankara was 835 and 426 in 1990.
conclusion In view of the socio-economic status of Turkish residents in Germany the large mortality difference compared to Germans is unexpected. It cannot be fully explained by a selection at the time of hiring (healthy migrant effect) because it lasts over decades and extends into the second generation. A healthy worker effect is unlikely because Turkish residents have a lower employment rate than Germans. There is little evidence for movement of gravely ill persons back to Turkey. An 'unhealthy re-migration effect' in which socially successful migrants with a lower mortality risk stay in the host country while less successful ones return home even before becoming manifestly ill would partly explain our findings. 相似文献
methods All-cause mortality rates by age group and sex of Turkish and German adults for the time period 1980–94 were calculated from death registry data and mid-year population estimates.
results The age-adjusted mortality rate (per 100000) of Turkish males aged 25–65 years resident in Germany was 299 in 1980 and 247 in 1990, consistently half that of German males. The mortality of Turkish females in Germany was 140 in 1990, half that of German females. Mortality of Turkish males/females in Ankara was 835 and 426 in 1990.
conclusion In view of the socio-economic status of Turkish residents in Germany the large mortality difference compared to Germans is unexpected. It cannot be fully explained by a selection at the time of hiring (healthy migrant effect) because it lasts over decades and extends into the second generation. A healthy worker effect is unlikely because Turkish residents have a lower employment rate than Germans. There is little evidence for movement of gravely ill persons back to Turkey. An 'unhealthy re-migration effect' in which socially successful migrants with a lower mortality risk stay in the host country while less successful ones return home even before becoming manifestly ill would partly explain our findings. 相似文献
64.
65.
Functional and metabolic remodelling in GLUT4-deficient hearts confers hyper-responsiveness to substrate intervention 总被引:10,自引:0,他引:10
Huggins CE Domenighetti AA Ritchie ME Khalil N Favaloro JM Proietto J Smyth GK Pepe S Delbridge LM 《Journal of molecular and cellular cardiology》2008,45(2):270-280
Cardiovascular sequelae including diabetic cardiomyopathy constitute the major cause of death in diabetic patients. Although several factors may contribute to the development of this cardiomyopathy, the underlying molecular/cellular mechanisms leading to cardiac dysfunction are still partially understood. Recently, a novel paradigm for the role of the adipocytokine resistin in diabetes has emerged. Resistin has been proposed to be a link between obesity, insulin resistance and diabetes. Using microarray analysis, we have recently found that cardiomyocytes isolated from type 2 diabetic hearts express high levels of resistin. However, the function of resistin with respect to cardiac function is unknown. In this study we show that resistin is not only expressed in the heart, but also promotes cardiac hypertrophy. Adenovirus-mediated overexpression of resistin in cultured neonatal rat ventricular myocytes (NRVM) significantly increased sarcomere organization and cell size, increased protein synthesis and increased the expression of atrial natriuretic factor and β-myosin heavy chain. Overexpression of resistin in NRVM was also associated with activation of the mitogen-activated protein (MAP) kinases, ERK1/2 and p38, as well as increased Ser-636 phosphorylation of insulin receptor substrate-1 (IRS-1), indicating that IRS-1/MAPK pathway may be involved in the observed hypertrophic response. Overexpression of resistin in adult cultured cardiomyocytes significantly altered myocyte mechanics by depressing cell contractility as well as contraction and relaxation velocities. Intracellular Ca2+ measurements showed slower Ca2+ transients decay in resistin-transduced myocytes compared to controls, suggesting impaired cytoplasmic Ca2+ clearing or alterations in myofilament activation. We conclude that resistin overexpression alters cardiac contractility, confers to primary cardiomyocytes all the features of the hypertrophic phenotype and promotes cardiac hypertrophy possibly via the IRS-1/MAPK pathway. 相似文献
66.
Erik Teunissen Eric Van Bavel Francine Van Den Driessen Mareeuw Anne Macfarlane Evelyn Van Weel-Baumgarten Maria Van Den Muijsenbergh 《Scandinavian journal of primary health care》2015,33(2):82-90
Objective. To explore the views and experiences of general practitioners (GPs) in relation to recognition, recording, and treatment of mental health problems of undocumented migrants (UMs), and to gain insight in the reasons for under-registration of mental health problems in the electronic medical records. Design. Qualitative study design with semi-structured interviews using a topic guide. Subjects and setting. Sixteen GPs in the Netherlands with clinical expertise in the care of UMs. Results. GPs recognized many mental health problems in UMs. Barriers that prevented them from recording these problems and from delivering appropriate care were their low consultation rates, physical presentation of mental health problems, high number of other problems, the UM’s lack of trust towards health care professionals, and cultural differences in health beliefs and language barriers. Referrals to mental health care organizations were often seen as problematic by GPs. To overcome these barriers, GPs provided personalized care as far as possible, referred to other primary care professionals such as social workers or mental health care nurses in their practice, and were a little less restrictive in prescribing psychotropics than guidelines recommended. Conclusions. GPs experienced a variety of barriers in engaging with UMs when identifying or suspecting mental health problems. This explains why there is a gap between the high recognition of mental health problems and the low recording of these problems in general practice files. It is recommended that GPs address mental health problems more actively, strive for continuity of care in order to gain trust of the UMs, and look for opportunities to provide mental care that is accessible and acceptable for UMs. 相似文献
67.
β-Adrenergic Receptor Activation and Intracellular Ca2+. Introduction:β-Adrenergic receptor agonists have been shown to increase the voltage-dependent Ca2+ current in cardiac myocytes. Additionally, adrenergic receptor activation has been shown to increase intracellular Ca2+, to increase systolic Ca2+ transients and to enhance Ca2+ uptake into the sarcoplasmic reticulum, thereby accelerating relaxation. The present study was designed first to characterize the influences of β-adrenergic receptor activation on intracellular Ca2+ activity as well as membrane potential in ventricular myocytes characterized as normal based on rigorous morphologic and electrophysiologic criteria. The second objective was to assess whether the increase in intracellular Ca2+ activity elicited by β-adrenergic receptor activation could elicit afterdepolarizations and triggered activity. Methods and Results: Intracellular Ca2+ and whole-cell voltage recordings were measured in cells in which indo-1 free acid was delivered intracellularly through the recording pipette. Isoproterenol produced complex Ca2+ transients underlying both early and delayed afterdepolarizations during pacing as well as aftertransients underlying triggered action potentials and delayed afterdepolarizations in the absence of pacing. The coupling interval of Ca2+i aftertransients was frequency dependent and followed that of the delayed afterdepolarizations. Ca2+i after transient amplitudes, however, exhibited a biphasic response with frequency revealing that factors other than pacing frequency alone contribute to control of the amplitude of the aftertransients. Inhibition of sarcoplasmic reticular release of Ca2+ by ryanodine abolished Ca2+i aftertransients and afterdepolarizations otherwise elicited by isoproterenol. Conclusion: These data demonstrate that normal cells stimulated by β-adrenergic agonists exhibit marked changes in intracellular Ca2+ homeostasis that may serve as the substrate for abnormal ion fluxes that ultimately contribute to electrophysiologic derangements underlying arrhythmogenesis in the intact heart. (J Cardiovasc Electrophysiol, Vol. 3, pp. 209–224, June 1992) 相似文献
68.
Edmond A. Murphy Sonia Rhee Reed E. Pyeritz Kenneth R. Berger 《American journal of medical genetics. Part A》1991,41(3):362-370
We explore the pursuit in a plane of a target moving at constant slow speed in a straight line. Two models of the pursuit are given. In the continuous case, the pursuer is moving at constant speed and is subject to proportionate angular homeostasis with correction constant b. In the discrete version movement occurs at a constant speed in a sequence of straight line segments of constant length (called the step size, s) the end of the segments being called the vertices. The pattern considered is not the absolute position of the pursuer, but its distance and orientation relative to the target. Both the transients and the asymptotic orbit are addressed. A key quantity is r, the speed of the target expressed as a fraction of that of the pursuer. If the speed of the pursuer is defined as unity, r is also the ratio of the speeds. There exists a critical speed fraction, R(b, s), a function of b and s, that defines what the term slow designates. R(b,s), which has to be found numerically, has the following property. For r < R(b, s), the asymptotic path is a simple closed curve. In the discrete case the vertices converge to a simple closed curve. The larger r, the more the path (or in the discrete analogue its set of vertices) departs from a circle, and the more eccentric the target is with respect to it. Interest centers on two issues. First we address the transient patterns of the path, notably whether or not the sense of any particular path (clockwise or counterclockwise) is the same throughout, or changes at some stage. These studies have a bearing on ontogenetic lateralization of the viscera; its relationship to the classification of dextrocardia is addressed. Second, we considor the asymptotic form of the path and its relationship to the parameters. The critical values of R (b, s) are extensively explored. 相似文献
69.
Lina T Al Kury Vadym Sydorenko Manal MA Smail Muhammad A Qureshi Anatoly Shmygol Dimitrios Papandreou Jaipaul Singh Frank Christopher Howarth 《Journal of diabetes investigation.》2021,12(4):493-500
Aims/IntroductionAbnormalities in Ca2+ signaling have a key role in hemodynamic dysfunction in diabetic heart. The purpose of this study was to explore the effects of streptozotocin (STZ)‐induced diabetes on Ca2+ signaling in epicardial (EPI) and endocardial (ENDO) cells of the left ventricle after 5–6 months of STZ injection.Materials and MethodsWhole‐cell patch clamp was used to measure the L‐type Ca2+ channel (LTCC) and Na+/Ca2+ exchanger currents. Fluorescence photometry techniques were used to measure intracellular free Ca2+ concentration.ResultsAlthough the LTCC current was not significantly altered, the amplitude of Ca2+ transients increased significantly in EPI‐STZ and ENDO‐STZ compared with controls. Time to peak LTCC current, time to peak Ca2+ transient, time to half decay of LTCC current and time to half decay of Ca2+ transients were not significantly changed in EPI‐STZ and ENDO‐STZ myocytes compared with controls. The Na+/Ca2+ exchanger current was significantly smaller in EPI‐STZ and in ENDO‐STZ compared with controls.ConclusionsSTZ‐induced diabetes resulted in an increase in amplitude of Ca2+ transients in EPI and ENDO myocytes that was independent of the LTCC current. Such an effect can be attributed, at least in part, to the dysfunction of the Na+/Ca2+ exchanger. Additional studies are warranted to improve our understanding of the regional impact of diabetes on Ca2+ signaling, which will facilitate the discovery of new targeted treatments for diabetic cardiomyopathy. 相似文献
70.
Nichole M. McMullen Feixiong Zhang Adam Hotchkiss Frederic Bretzner Jennifer M. Wilson Hong Ma Karim Wafa Robert M. Brownstone Kishore B.S. Pasumarthi 《Developmental dynamics》2009,238(11):2787-2799
There is scant information on the fate of cardiac progenitor cells (CPC) in the embryonic heart after chamber specification. Here we simultaneously tracked three lineage‐specific markers (Nkx2.5, MLC2v, and ANF) and confirmed that CPCs with an Nkx2.5+MLC2v?ANF? phenotype are present in the embryonic (E) day 11.5 mouse ventricular myocardium. We demonstrated that these CPCs could give rise to working cardiomyocytes and conduction system cells. Using a two‐photon imaging analysis, we found that the majority of CPCs are not capable of developing Ca2+ transients in response to β‐adrenergic receptor stimulation. In contrast, Nkx2.5+ cells expressing MLC2v but not ANF are capable of developing functional Ca2+ transients. We showed that Ca2+ transients could be invoked in Nkx2.5+MLC2v+ANF+ cells only upon inhibition of Gi, muscarinic receptors, or nitric oxide synthase (NOS) signaling pathways. Our data suggest that these inhibitory pathways may delay functional specification in a subset of developing ventricular cells. Developmental Dynamics 238:2787–2799, 2009. © 2009 Wiley‐Liss, Inc. 相似文献