Fractalkine depresses cardiomyocyte contractility.

Directory of Open Access Journals (Sweden)

David Taube

Full Text Available Our laboratory reported that male mice with cardiomyocyte-selective knockout of the prostaglandin E2 EP4 receptor sub-type (EP4 KO exhibit reduced cardiac function. Gene array on left ventricles (LV showed increased fractalkine, a chemokine implicated in heart failure. We therefore hypothesized that fractalkine is regulated by PGE2 and contributes to depressed contractility via alterations in intracellular calcium.Fractalkine was measured in LV of 28-32 week old male EP4 KO and wild type controls (WT by ELISA and the effect of PGE2 on fractalkine secretion was measured in cultured neonatal cardiomyocytes and fibroblasts. The effect of fractalkine on contractility and intracellular calcium was determined in Fura-2 AM-loaded, electrical field-paced cardiomyocytes. Cardiomyocytes (AVM from male C57Bl/6 mice were treated with fractalkine and responses measured under basal conditions and after isoproterenol (Iso stimulation.LV fractalkine was increased in EP4 KO mice but surprisingly, PGE2 regulated fractalkine secretion only in fibroblasts. Fractalkine treatment of AVM decreased both the speed of contraction and relaxation under basal conditions and after Iso stimulation. Despite reducing contractility after Iso stimulation, fractalkine increased the Ca(2+ transient amplitude but decreased phosphorylation of cardiac troponin I, suggesting direct effects on the contractile machinery.Fractalkine depresses myocyte contractility by mechanisms downstream of intracellular calcium.

Detecting cardiac contractile activity in the early mouse embryo using multiple modalities

Directory of Open Access Journals (Sweden)

Chiann-mun eChen

2015-01-01

Full Text Available The heart is one of the first organs to develop during mammalian embryogenesis. In the mouse, it starts to form shortly after gastrulation, and is derived primarily from embryonic mesoderm. The embryonic heart is unique in having to perform a mechanical contractile function while undergoing complex morphogenetic remodelling. Approaches to imaging the morphogenesis and contractile activity of the developing heart are important in understanding not only how this remodelling is controlled but also the origin of congenital heart defects. Here, we describe approaches for visualising contractile activity in the developing mouse embryo, using brightfield time lapse microscopy and confocal microscopy of calcium transients. We describe an algorithm for enhancing this image data and quantifying contractile activity from it. Finally we describe how atomic force microscopy can be used to record contractile activity prior to it being microscopically visible.

Exposure to low mercury concentration in vivo impairs myocardial contractile function

International Nuclear Information System (INIS)

Furieri, Lorena Barros; Fioresi, Mirian; Junior, Rogerio Faustino Ribeiro; Bartolome, Maria Visitacion; Fernandes, Aurelia Araujo; Cachofeiro, Victoria; Lahera, Vicente; Salaices, Mercedes; Stefanon, Ivanita; Vassallo, Dalton Valentim

2011-01-01

Increased cardiovascular risk after mercury exposure has been described but cardiac effects resulting from controlled chronic treatment are not yet well explored. We analyzed the effects of chronic exposure to low mercury concentrations on hemodynamic and ventricular function of isolated hearts. Wistar rats were treated with HgCl 2 (1st dose 4.6 μg/kg, subsequent dose 0.07 μg/kg/day, im, 30 days) or vehicle. Mercury treatment did not affect blood pressure (BP) nor produced cardiac hypertrophy or changes of myocyte morphometry and collagen content. This treatment: 1) in vivo increased left ventricle end diastolic pressure (LVEDP) without changing left ventricular systolic pressure (LVSP) and heart rate; 2) in isolated hearts reduced LV isovolumic systolic pressure and time derivatives, and β-adrenergic response; 3) increased myosin ATPase activity; 4) reduced Na + -K + ATPase (NKA) activity; 5) reduced protein expression of SERCA and phosphorylated phospholamban on serine 16 while phospholamban expression increased; as a consequence SERCA/phospholamban ratio reduced; 6) reduced sodium/calcium exchanger (NCX) protein expression and α-1 isoform of NKA, whereas α-2 isoform of NKA did not change. Chronic exposure for 30 days to low concentrations of mercury does not change BP, heart rate or LVSP but produces small but significant increase of LVEDP. However, in isolated hearts mercury treatment promoted contractility dysfunction as a result of the decreased NKA activity, reduction of NCX and SERCA and increased PLB protein expression. These findings offer further evidence that mercury chronic exposure, even at small concentrations, is an environmental risk factor affecting heart function. - Highlights: → Unchanges blood pressure, heart rate, systolic pressure. → Increases end diastolic pressure. → Promotes cardiac contractility dysfunction. → Decreases NKA activity, NCX and SERCA, increases PLB protein expression. → Small concentrations constitutes

Structural comparison of contractile nanomachines

Directory of Open Access Journals (Sweden)

Sebastian Kube

2015-05-01

Full Text Available Contractile molecular machines are a common feature among bacteriophages and prokaryotes. Due to their stability and the large size, contractile-tailed bacteriophages are traditionally investigated by electron microscopic methods. Complemented by crystallographic studies, a molecular model of contraction for the T4 phage was developed. Lately, also related contractile structures like the Photorhabdus virulence cassette-like particles, the R-Type pyocins and the contractile tubule of the bacterial Type VI secretion system have been analyzed by cryo electron microscopy. Photorhabdus virulence cassette particles and R-Type pyocins are toxin complexes reminiscent of bacteriophage tails that are secreted by bacteria to kill their insect host or competing bacteria. In contrast, the Type VI secretion system is an intracellular apparatus for injection of effector proteins into bacterial and eukaryotic cells. Although it shares homology with other contractile systems, the Type VI secretion system is additionally equipped with a recycling function, which makes it suitable for multiple rounds of action. Starting from the 3D reconstructions, we compare these molecular machines structurally and functionally to their viral counterparts and summarize the current knowledge on their respective mode of action.

Effects of Using Tricaine Methanesulfonate and Metomidate before Euthanasia on the Contractile Properties of Rainbow Trout (Oncorhynchus mykiss) Myocardium.

Science.gov (United States)

Roberts, Jordan C; Syme, Douglas A

2016-01-01

Because many anesthetics work through depressing cell excitability, unanesthetized euthanasia has become common for research involving excitable tissues (for example muscle and nerve) to avoid these depressive effects. However, anesthetic use during euthanasia may be indicated for studies involving isolated tissues if the potential depressive effects of brief anesthetic exposure dissipate after subsequent tissue isolation, washout, and saline perfusion. We explore this here by measuring whether, when applied prior to euthanasia, standard immersion doses of 2 fish anesthetics, tricaine methanesulfonate (TMS; 100 mg/L, n = 6) and methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate (metomidate, 10 mg/L, n = 6), have residual effects on the contractile properties (force and work output) of isolated and saline-perfused ventricular compact myocardium from rainbow trout (Oncorhynchus mykiss). Results suggest that direct exposure of muscle to immersion doses of TMS-but not metomidate-impairs muscle contractile performance. However, brief exposure (2 to 3 min) to either anesthetic during euthanasia only-providing that the agent is washed out prior to tissue experimentation-does not have an effect on the contractile properties of the myocardium. Therefore, the use of TMS, metomidate, and perhaps other anesthetics that depress cell excitability during euthanasia may be indicated when conducting research on isolated and rinsed tissues.

Beta adrenergic overstimulation impaired vascular contractility via actin-cytoskeleton disorganization in rabbit cerebral artery.

Directory of Open Access Journals (Sweden)

Hyoung Kyu Kim

Full Text Available BACKGROUND AND PURPOSE: Beta adrenergic overstimulation may increase the vascular damage and stroke. However, the underlying mechanisms of beta adrenergic overstimulation in cerebrovascular dysfunctions are not well known. We investigated the possible cerebrovascular dysfunction response to isoproterenol induced beta-adrenergic overstimulation (ISO in rabbit cerebral arteries (CAs. METHODS: ISO was induced in six weeks aged male New Zealand white rabbit (0.8-1.0 kg by 7-days isoproterenol injection (300 μg/kg/day. We investigated the alteration of protein expression in ISO treated CAs using 2DE proteomics and western blot analysis. Systemic properties of 2DE proteomics result were analyzed using bioinformatics software. ROS generation and following DNA damage were assessed to evaluate deteriorative effect of ISO on CAs. Intracellular Ca(2+ level change and vascular contractile response to vasoactive drug, angiotensin II (Ang II, were assessed to evaluate functional alteration of ISO treated CAs. Ang II-induced ROS generation was assessed to evaluated involvement of ROS generation in CA contractility. RESULTS: Proteomic analysis revealed remarkably decreased expression of cytoskeleton organizing proteins (e.g. actin related protein 1A and 2, α-actin, capping protein Z beta, and vimentin and anti-oxidative stress proteins (e.g. heat shock protein 9A and stress-induced-phosphoprotein 1 in ISO-CAs. As a cause of dysregulation of actin-cytoskeleton organization, we found decreased level of RhoA and ROCK1, which are major regulators of actin-cytoskeleton organization. As functional consequences of proteomic alteration, we found the decreased transient Ca(2+ efflux and constriction response to angiotensin II and high K(+ in ISO-CAs. ISO also increased basal ROS generation and induced oxidative damage in CA; however, it decreased the Ang II-induced ROS generation rate. These results indicate that ISO disrupted actin cytoskeleton proteome network

Impaired right ventricular contractile function in childhood obesity and its association with right and left ventricular changes: a cine DENSE cardiac magnetic resonance study.

Science.gov (United States)

Jing, Linyuan; Pulenthiran, Arichanah; Nevius, Christopher D; Mejia-Spiegeler, Abba; Suever, Jonathan D; Wehner, Gregory J; Kirchner, H Lester; Haggerty, Christopher M; Fornwalt, Brandon K

2017-06-28

Pediatric obesity is a growing public health problem, which is associated with increased risk of cardiovascular disease and premature death. Left ventricular (LV) remodeling (increased myocardial mass and thickness) and contractile dysfunction (impaired longitudinal strain) have been documented in obese children, but little attention has been paid to the right ventricle (RV). We hypothesized that obese/overweight children would have evidence of RV remodeling and contractile dysfunction. One hundred and three children, ages 8-18 years, were prospectively recruited and underwent cardiovascular magnetic resonance (CMR), including both standard cine imaging and displacement encoding with stimulated echoes (DENSE) imaging, which allowed for quantification of RV geometry and function/mechanics. RV free wall longitudinal strain was quantified from the end-systolic four-chamber DENSE image. Linear regression was used to quantify correlations of RV strain with LV strain and measurements of body composition (adjusted for sex and height). Analysis of variance was used to study the relationship between RV strain and LV remodeling types (concentric remodeling, eccentric/concentric hypertrophy). The RV was sufficiently visualized with DENSE in 70 (68%) subjects, comprising 36 healthy weight (13.6 ± 2.7 years) and 34 (12.1 ± 2.9 years) obese/overweight children. Obese/overweight children had a 22% larger RV mass index (8.2 ± 0.9 vs 6.7 ± 1.1 g/m 2.7 , p right ventricles in obese/overweight children.

Effect of a Periodized Power Training Program on the Functional Performances and Contractile Properties of the Quadriceps in Sprinters

Science.gov (United States)

Kamandulis, Sigitas; Skurvydas, Albertas; Brazaitis, Marius; Stanislovaitis, Aleksas; Duchateau, Jacques; Stanislovaitiene, Jurate

2012-01-01

Our purpose was to compare the effect of a periodized preparation consisting of power endurance training and high-intensity power training on the contractile properties of the quadriceps muscle and functional performances in well trained male sprinters (n = 7). After 4 weeks of high-intensity power training, 60-m sprint running time improved by an…

The effects of RSR13 on microvascular Po2 kinetics and muscle contractile performance in the rat arterial ligation model of peripheral arterial disease.

Science.gov (United States)

Watanabe, Aiko; Poole, David C; Kano, Yutaka

2017-10-01

Exercise intolerance and claudication are symptomatic of peripheral arterial disease. There is a close relationship between muscle O 2 delivery, microvascular oxygen partial pressure (P mv O 2 ), and contractile performance. We therefore hypothesized that a reduction of hemoglobin-oxygen affinity via RSR13 would maintain a higher P mv O 2 and enhance blood-muscle O 2 transport and contractile function. In male Wistar rats (12 wk of age), we created hindlimb ischemia via right-side iliac artery ligation (AL). The contralateral (left) muscle served as control (CONT). Seven days after AL, phosphorescence-quenching techniques were used to measure P mv O 2 at rest and during contractions (electrical stimulation; 1 Hz, 300 s) in tibialis anterior muscle (TA) under saline ( n = 10) or RSR13 ( n = 10) conditions. RSR13 at rest increased TA P mv O 2 in CONT (13.9 ± 1.6 to 19.3 ± 1.9 Torr, P < 0.05) and AL (9.0 ± 0.5 to 9.9 ± 0.7 Torr, P < 0.05). Furthermore, RSR13 extended maintenance of the initial TA force (i.e., improved contractile performance) such that force was not decreased significantly until contraction 240 vs. 150 in CONT and 80 vs. 20 in AL. This improved muscle endurance with RSR13 was accompanied by a greater ΔP mv O 2 (P mv O 2 decrease from baseline) (CONT, 7.4 ± 1.0 to 11.2 ± 1.3; AL, 6.9 ± 0.5 to 8.6 ± 0.6 Torr, both P < 0.05). Whereas RSR13 did not alter the kinetics profile of P mv O 2 (i.e., mean response time) substantially during contractions, muscle force was elevated, and the ratio of muscle force to P mv O 2 increased. In conclusion, reduction of hemoglobin-oxygen affinity via RSR13 in AL increased P mv O 2 and improved muscle contractile performance most likely via enhanced blood-muscle O 2 diffusion. NEW & NOTEWORTHY This is the first investigation to examine the effect of RSR13 (erythrocyte allosteric effector) on skeletal muscle microvascular oxygen partial pressure kinetics and contractile function using an arterial ligation model of

Genome sequence of Haloplasma contractile, an unusual contractile bacterium from a deep-sea anoxic brine lake.

KAUST Repository

Antunes, Andre; Alam, Intikhab; El Dorry, Hamza; Siam, Rania; Robertson, Anthony J.; Bajic, Vladimir B.; Stingl, Ulrich

2011-01-01

We present the draft genome of Haloplasma contractile, isolated from a deep-sea brine and representing a new order between Firmicutes and Mollicutes. Its complex morphology with contractile protrusions might be strongly influenced by the presence of seven MreB/Mbl homologs, which appears to be the highest copy number ever reported.

Genome sequence of Haloplasma contractile, an unusual contractile bacterium from a deep-sea anoxic brine lake.

KAUST Repository

Antunes, Andre

2011-09-01

We present the draft genome of Haloplasma contractile, isolated from a deep-sea brine and representing a new order between Firmicutes and Mollicutes. Its complex morphology with contractile protrusions might be strongly influenced by the presence of seven MreB/Mbl homologs, which appears to be the highest copy number ever reported.

Peak torque and rate of torque development influence on repeated maximal exercise performance: contractile and neural contributions.

Science.gov (United States)

Morel, Baptiste; Rouffet, David M; Saboul, Damien; Rota, Samuel; Clémençon, Michel; Hautier, Christophe A

2015-01-01

Rapid force production is critical to improve performance and prevent injuries. However, changes in rate of force/torque development caused by the repetition of maximal contractions have received little attention. The aim of this study was to determine the relative influence of rate of torque development (RTD) and peak torque (T(peak)) on the overall performance (i.e. mean torque, T(mean)) decrease during repeated maximal contractions and to investigate the contribution of contractile and neural mechanisms to the alteration of the various mechanical variables. Eleven well-trained men performed 20 sets of 6-s isokinetic maximal knee extensions at 240° · s(-1), beginning every 30 seconds. RTD, T(peak) and T(mean) as well as the Rate of EMG Rise (RER), peak EMG (EMG(peak)) and mean EMG (EMG(mean)) of the vastus lateralis were monitored for each contraction. A wavelet transform was also performed on raw EMG signal for instant mean frequency (if(mean)) calculation. A neuromuscular testing procedure was carried out before and immediately after the fatiguing protocol including evoked RTD (eRTD) and maximal evoked torque (eT(peak)) induced by high frequency doublet (100 Hz). T(mean) decrease was correlated to RTD and T(peak) decrease (R(²) = 0.62; p<0.001; respectively β=0.62 and β=0.19). RER, eRTD and initial if(mean) (0-225 ms) decreased after 20 sets (respectively -21.1 ± 14.1, -25 ± 13%, and ~20%). RTD decrease was correlated to RER decrease (R(²) = 0.36; p<0.05). The eT(peak) decreased significantly after 20 sets (24 ± 5%; p<0.05) contrary to EMG(peak) (-3.2 ± 19.5 %; p=0.71). Our results show that reductions of RTD explained part of the alterations of the overall performance during repeated moderate velocity maximal exercise. The reductions of RTD were associated to an impairment of the ability of the central nervous system to maximally activate the muscle in the first milliseconds of the contraction.

Effect of cadmium on myocardial contractility and calcium fluxes

International Nuclear Information System (INIS)

Pilati, C.F.

1979-01-01

The effect of cadmium on myocardial mechanical performance and calcium fluxes was studied in kitten isometric papillary muscles and in isovolumic Langendorff-perfused rabbit hearts. Therefore, it is concluded that cadmium-induced decreases in contractility are not primarily the result of cadmium interference with ATP metabolic processes. Furthermore, these results imply that cadmium causes no structural alterations of the contractile proteins. These data suggest that cadmium may be competing with the calcium needed for excitation-contraction coupling. During experiments using radioisotopic calcium, a statistically significant cellular influx of calcium was observed following the onset of 100 μM Cd ++ perfusion of isolated, Langendorff-prepared rabbit hearts

Separate effects of ischemia, hypoxia, and contractility on thallium-201 kinetics in rabbit myocardium

International Nuclear Information System (INIS)

Leppo, J.A.; Macneil, P.B.; Moring, A.F.; Apstein, C.S.

1986-01-01

The effects of hypoxia and ischemia, as well as altered contractility, on thallium-201 ( 201 TI) kinetics were evaluated in 42 isolated isovolumetrically contracting rabbit hearts. In Group A, three subgroups (n = 7 each) were studied that had either normal flow and oxygenation, hypoxia and normal flow, or ischemic flow and normal perfusate oxygen content. In Group B, three subgroups (n = 7 each) were studied and all hearts had normal flow but the contractile state was either enhanced with isoproterenol or impaired by hypocalcemia. A hemoglobin-free buffer perfusate was used in all experiments and multiple timed collections of arterial and coronary sinus effluent were used to model myocardial isotope activity during 30 min of constant uptake followed by 30 min of tracer clearance. During ischemia, hypoxia and hypocalcemia peak developed pressure and peak positive and negative dP/dt were all significantly reduced when compared to normal hemodynamic parameters (p less than 0.01). As expected, isoproterenol significantly elevated these parameters (p less than 0.04). Myocardial 201 TI kinetics were adequately described utilizing a bi-exponential model having a fast and slow component. Only ischemic hearts had significantly lower rate constants for 201 TI uptake and clearance than normal hearts (p less than 0.001). The mean (+/- s.d.) myocardial uptake and clearance rates for 201 TI (%/min) varied between 4.86 +/- 0.87 and 7.18 +/- 1.45 for the remaining groups of hearts. Therefore, myocardial 201 TI kinetics appear to be dominated by coronary flow and may not reflect marked alterations in the metabolic and contractile state. These data suggest that normal 201 TI uptake in impaired or hypercontractile cells, receiving normal flow, may not represent normal cellular function

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

Science.gov (United States)

Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

2012-11-07

Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

Directory of Open Access Journals (Sweden)

Ana E. González Wusener

2016-01-01

Full Text Available Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO cells and PTP1B reconstituted (WT cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype. We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.

PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

Science.gov (United States)

González Wusener, Ana E.; González, Ángela; Nakamura, Fumihiko; Arregui, Carlos O.

2016-01-01

ABSTRACT Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype. We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration. PMID:26700725

Sex differences and the effects of ovariectomy on the β-adrenergic contractile response

Science.gov (United States)

McIntosh, Victoria J.; Chandrasekera, P. Charukeshi

2011-01-01

The presence of sex differences in myocardial β-adrenergic responsiveness is controversial, and limited studies have addressed the mechanism underlying these differences. Studies were performed using isolated perfused hearts from male, intact female and ovariectomized female mice to investigate sex differences and the effects of ovarian hormone withdrawal on β-adrenergic receptor function. Female hearts exhibited blunted contractile responses to the β-adrenergic receptor agonist isoproterenol (ISO) compared with males but not ovariectomized females. There were no sex differences in β1-adrenergic receptor gene or protein expression. To investigate the role of adenylyl cyclase, phosphodiesterase, and the cAMP-signaling cascade in generating sex differences in the β-adrenergic contractile response, dose-response studies were performed in isolated perfused male and female hearts using forskolin, 3-isobutyl-1-methylxanthine (IBMX), and 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate (CPT-cAMP). Males showed a modestly enhanced contractile response to forskolin at 300 nM and 5 μM compared with females, but there were no sex differences in the response to IBMX or CPT-cAMP. The role of the A1 adenosine receptor (A1AR) in antagonizing the β-adrenergic contractile response was investigated using both the A1AR agonist 2-chloro-N6-cyclopentyl-adenosine and A1AR knockout (KO) mice. Intact females showed an enhanced A1AR anti-adrenergic effect compared with males and ovariectomized females. The β-adrenergic contractile response was potentiated in both male and female A1ARKO hearts, with sex differences no longer present above 1 nM ISO. The β-adrenergic contractile response is greater in male hearts than females, and minor differences in the action of adenylyl cyclase or the A1AR may contribute to these sex differences. PMID:21685268

Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

Science.gov (United States)

Ianuzzo, C. D.; Chen, V.

1977-01-01

Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

Sleep Deprivation Impairs and Caffeine Enhances My Performance, but Not Always Our Performance.

Science.gov (United States)

Faber, Nadira S; Häusser, Jan A; Kerr, Norbert L

2017-02-01

What effects do factors that impair or enhance performance in individuals have when these individuals act in groups? We provide a framework, called the GIE ("Effects of Grouping on Impairments and Enhancements") framework, for investigating this question. As prominent examples for individual-level impairments and enhancements, we discuss sleep deprivation and caffeine. Based on previous research, we derive hypotheses on how they influence performance in groups, specifically process gains and losses in motivation, individual capability, and coordination. We conclude that the effect an impairment or enhancement has on individual-level performance is not necessarily mirrored in group performance: grouping can help or hurt. We provide recommendations on how to estimate empirically the effects individual-level performance impairments and enhancements have in groups. By comparing sleep deprivation to stress and caffeine to pharmacological cognitive enhancement, we illustrate that we cannot readily generalize from group results on one impairment or enhancement to another, even if they have similar effects on individual-level performance.

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

Directory of Open Access Journals (Sweden)

Kandadi Machender R

2012-11-01

Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

Cell stiffness, contractile stress and the role of extracellular matrix

International Nuclear Information System (INIS)

An, Steven S.; Kim, Jina; Ahn, Kwangmi; Trepat, Xavier; Drake, Kenneth J.; Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne; Fredberg, Jeffrey J.; Biswal, Shyam

2009-01-01

Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

Cell stiffness, contractile stress and the role of extracellular matrix

Energy Technology Data Exchange (ETDEWEB)

An, Steven S., E-mail: san@jhsph.edu [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Kim, Jina [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Ahn, Kwangmi [Division of Biostatistics, Penn State College of Medicine, Hershey, PA 17033 (United States); Trepat, Xavier [CIBER, Enfermedades Respiratorias, 07110 Bunyola (Spain); Drake, Kenneth J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Kumar, Sarvesh; Ling, Guoyu; Purington, Carolyn; Rangasamy, Tirumalai; Kensler, Thomas W.; Mitzner, Wayne [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Fredberg, Jeffrey J. [Division of Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 (United States); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E-7616, Baltimore, MD 21205 (United States); Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205 (United States)

2009-05-15

Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin. Regardless of ECM composition, upon adherence to increasingly rigid substrates, the ASM cell positively regulated expression of antioxidant genes in the glutathione pathway and heme oxygenase, and disruption of a redox-sensitive transcription factor, nuclear erythroid 2 p45-related factor (Nrf2), culminated in greater contractile scope. These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses.

Influence of intracellular acidosis on contractile function in the working rat heart

International Nuclear Information System (INIS)

Jeffrey, F.M.H.; Malloy, C.R.; Radda, G.K.

1987-01-01

The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. The authors developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and optimal O 2 delivery. Intracellular pH and high-energy phosphates were monitored by 31 P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH 4 Cl. Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. It was concluded that (1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular acidosis, and (2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation

Contractile injection systems of bacteriophages and related systems

DEFF Research Database (Denmark)

Taylor, Nicholas M I; van Raaij, Mark J; Leiman, Petr G

2018-01-01

Contractile tail bacteriophages, or myobacteriophages, use a sophisticated biomolecular structure to inject their genome into the bacterial host cell. This structure consists of a contractile sheath enveloping a rigid tube that is sharpened by a spike-shaped protein complex at its tip. The spike ...

Exercise reveals impairments in left ventricular systolic function in patients with metabolic syndrome.

Science.gov (United States)

Fournier, Sara B; Reger, Brian L; Donley, David A; Bonner, Daniel E; Warden, Bradford E; Gharib, Wissam; Failinger, Conard F; Olfert, Melissa D; Frisbee, Jefferson C; Olfert, I Mark; Chantler, Paul D

2014-01-01

Metabolic syndrome (MetS) is the manifestation of a cluster of cardiovascular risk factors and is associated with a threefold increase in the risk of cardiovascular morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to examine comprehensively the LV and arterial responses to exercise in individuals with MetS without diabetes and/or overt cardiovascular disease in comparison to a healthy control population. Cardiovascular function was characterized using Doppler echocardiography and gas exchange in individuals with MetS (n = 27) versus healthy control subjects (n = 20) at rest and during peak exercise. At rest, individuals with MetS displayed normal LV systolic function but reduced LV diastolic function compared with healthy control subjects. During peak exercise, individuals with MetS had impaired contractility, pump performance and vasodilator reserve capacity versus control subjects. A blunted contractile reserve response resulted in diminished arterial-ventricular coupling reserve and limited aerobic capacity in individuals with MetS versus control subjects. These findings are of clinical importance, because they provide insight into the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of cardiovascular morbidity and mortality.

Accessory left atrial diverticulae: contractile properties depicted with 64-slice cine-cardiac CT.

LENUS (Irish Health Repository)

Killeen, Ronan P

2012-02-01

To assess the contractility of accessory left atrial appendages (LAAs) using multiphasic cardiac CT. We retrospectively analyzed the presence, location, size and contractile properties of accessory LAAs using multiphasic cardiac 64-slice CT in 102 consecutive patients (63 males, 39 females, mean age 57). Multiplanar reformats were used to create image planes in axial oblique, sagittal oblique and coronal oblique planes. For all appendages with an orifice diameter >or= 10 mm, axial and sagittal diameters and appendage volumes were recorded in atrial diastole and systole. Regression analysis was performed to assess which imaging appearances best predicted accessory appendage contractility. Twenty-three (23%) patients demonstrated an accessory LAA, all identified along the anterior LA wall. Dimensions for axial oblique (AOD) and sagittal oblique (SOD) diameters and sagittal oblique length (SOL) were 6.3-19, 3.4-20 and 5-21 mm, respectively. All appendages (>or=10 mm) demonstrated significant contraction during atrial systole (greatest diameter reduction was AOD [3.8 mm, 27%]). Significant correlations were noted between AOD-contraction and AOD (R = 0.57, P < 0.05) and SOD-contraction and AOD, SOD and SOL (R = 0.6, P < 0.05). Mean diverticulum volume in atrial diastole was 468.4 +\\/- 493 mm(3) and in systole was 171.2 +\\/- 122 mm(3), indicating a mean change in volume of 297.2 +\\/- 390 mm(3), P < 0.0001. Stepwise multiple regression analysis revealed SOL to be the strongest independent predictor of appendage contractility (R(2) = 0.86, P < 0.0001) followed by SOD (R(2) = 0.91, P < 0.0001). Accessory LAAs show significant contractile properties on cardiac CT. Those accessory LAAs with a large sagittal height or depth should be evaluated for contractile properties, and if present should be examined for ectopic activity during electrophysiological studies.

Protein kinase Cα deletion causes hypotension and decreased vascular contractility.

Science.gov (United States)

Wynne, Brandi M; McCarthy, Cameron G; Szasz, Theodora; Molina, Patrick A; Chapman, Arlene B; Webb, R Clinton; Klein, Janet D; Hoover, Robert S

2018-03-01

Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated. In this study, we used a whole animal PKCα knock out (PKC KO) to test the hypothesis that global PKCα deficiency would reduce MAP, by a reduction in vascular contractility. Radiotelemetry measurements of ambulatory blood pressure (day/night) were obtained for 18 h/day during both normal chow and high-salt (4%) diet feedings. PKCα mice had a reduced MAP, as compared with control, which was not normalized with high-salt diet (14 days). Metabolic cage studies were performed to determine urinary sodium excretion. PKC KO mice had a significantly lower diastolic, systolic and MAP as compared with control. No significant differences in urinary sodium excretion were observed between the PKC KO and control mice, whether fed normal chow or high-salt diet. Western blot analysis showed a compensatory increase in renal sodium chloride cotransporter expression. Both aorta and mesenteric vessels were removed for vascular reactivity studies. Aorta and mesenteric arteries from PKC KO mice had a reduced receptor-independent relaxation response, as compared with vessels from control. Vessels from PKC KO mice exhibited a decrease in maximal contraction, compared with controls. Together, these data suggest that global deletion of PKCα results in reduced MAP due to decreased vascular contractility.

Measuring the Contractile Response of Isolated Tissue Using an Image Sensor

Directory of Open Access Journals (Sweden)

David Díaz-Martín

2015-04-01

Full Text Available Isometric or isotonic transducers have traditionally been used to study the contractile/relaxation effects of drugs on isolated tissues. However, these mechanical sensors are expensive and delicate, and they are associated with certain disadvantages when performing experiments in the laboratory. In this paper, a method that uses an image sensor to measure the contractile effect of drugs on blood vessel rings and other luminal organs is presented. The new method is based on an image-processing algorithm, and it provides a fast, easy and non-expensive way to analyze the effects of such drugs. In our tests, we have obtained dose-response curves from rat aorta rings that are equivalent to those achieved with classical mechanic sensors.

Facilitated ethanol metabolism promotes cardiomyocyte contractile dysfunction through autophagy in murine hearts.

Science.gov (United States)

Guo, Rui; Hu, Nan; Kandadi, Machender R; Ren, Jun

2012-04-01

Chronic drinking leads to myocardial contractile dysfunction where ethanol metabolism plays an essential role. Acetaldehyde, the main ethanol metabolite, mediates alcohol-induced cell injury although the underlying mechanism is still elusive. This study was designed to examine the mechanism involved in accelerated ethanol metabolism-induced cardiac defect with a focus on autophagy. Wild-type FVB and cardiac-specific overexpression of alcohol dehydrogenase mice were placed on a 4% nutrition-balanced alcohol diet for 8 weeks. Myocardial histology, immunohistochemistry, autophagy markers and signal molecules were examined. Expression of micro RNA miR-30a, a potential target of Beclin 1, was evaluated by real-time PCR. Chronic alcohol intake led to cardiac acetaldehyde accumulation, hypertrophy and overt autophagosome accumulation (LC3-II and Atg7), the effect of which was accentuated by ADH. Signaling molecules governing autophagy initiation including class III PtdIns3K, phosphorylation of mTOR and p70S6K were enhanced and dampened, respectively, following alcohol intake. These alcohol-induced signaling responses were augmented by ADH. ADH accentuated or unmasked alcohol-induced downregulation of Bcl-2, Bcl-xL and MiR-30a. Interestingly, ADH aggravated alcohol-induced p62 accumulation. Autophagy inhibition using 3-MA abolished alcohol-induced cardiomyocyte contractile anomalies. Moreover, acetaldehyde led to cardiomyocyte contractile dysfunction and autophagy induction, which was ablated by 3-MA. Ethanol or acetaldehyde increased GFP-LC3 puncta in H9c2 cells, the effect of which was ablated by 3-MA but unaffected by lysosomal inhibition using bafilomycin A(1), E64D and pepstatin A. In summary, these data suggested that facilitated acetaldehyde production via ADH following alcohol intake triggered cardiac autophagosome formation along with impaired lysosomal degradation, en route to myocardial defect.

Impact of tamsulosin and nifedipine on contractility of pregnant rat ureters in vitro.

Science.gov (United States)

Haddad, Lisette; Corriveau, Stéphanie; Rousseau, Eric; Blouin, Simon; Pasquier, Jean-Charles; Ponsot, Yves; Roy-Lacroix, Marie-Ève

2018-01-01

To evaluate the in vitro effect of tamsulosin and nifedipine on the contractility of pregnant rat ureters and to perform quantitative analysis of the pharmacological effects. Medical expulsive therapy (MET) is commonly used to treat urolithiasis. However, this treatment is seldom used in pregnant women since no studies support this practice. This was an in vitro study on animal tissue derived from pregnant Sprague-Dawley rats. A total of 124 ureteral segments were mounted in an organ bath system and contractile response to methacholine (MCh) was assessed. Tamsulosin or nifedipine were added at cumulative concentrations (0.001-1 μM). The area under the curve (AUC) from isometric tension measurements was calculated. The effect of pharmacological agents and the respective controls were assessed by calculating the AUC for each 5-min interval. Statistical analyses were performed using the Mann-Whitney-Wilcoxon nonparametric test. Both drugs displayed statistically significant inhibitory activity at concentrations of 0.1 and 1 μM for tamsulosin and 1 μM for nifedipine when calculated as the AUC as compared to DMSO controls. Tamsulosin and nifedipine directly inhibit MCh-induced contractility of pregnant rat ureters. Further work is needed to determine the clinical efficacy of these medications for MET in pregnancy.

Quantifying esophagogastric junction contractility with a novel HRM topographic metric, the EGJ-Contractile Integral: normative values and preliminary evaluation in PPI non-responders.

Science.gov (United States)

Nicodème, F; Pipa-Muniz, M; Khanna, K; Kahrilas, P J; Pandolfino, J E

2014-03-01

Despite its obvious pathophysiological relevance, the clinical utility of measures of esophagogastric junction (EGJ) contractility is unsubstantiated. High-resolution manometry (HRM) may improve upon this with its inherent ability to integrate the magnitude of contractility over time and length of the EGJ. This study aimed to develop a novel HRM metric summarizing EGJ contractility and test its ability distinguish among subgroups of proton pump inhibitor non-responders (PPI-NRs). 75 normal controls and 88 PPI-NRs were studied. All underwent HRM. PPI-NRs underwent pH-impedance monitoring on PPI therapy scored in terms of acid exposure, number of reflux events, and reflux-symptom correlation and grouped as meeting all criteria, some criteria, or no criteria of abnormality. Control HRM studies were used to establish normal values for candidate EGJ contractility metrics, which were then compared in their ability to differentiate among PPI-NR subgroups. The EGJ contractile integral (EGJ-CI), a metric integrating contractility across the EGJ for three respiratory cycles, best distinguished the All Criteria PPI-NR subgroup from controls and other PPI-NR subgroups. Normal values (median, [IQR]) for this measure were 39 mmHg-cm [25-55 mmHg-cm]. The correlation between the EGJ-CI and a previously proposed metric, the lower esophageal sphincter-pressure integral, that used a fixed 10 s time frame and an atmospheric as opposed to gastric pressure reference was weak. Among HRM metrics tested, the EGJ-CI was best in distinguishing PPI-NRs meeting all criteria of abnormality on pH-impedance testing. Future prospective studies are required to explore its utility in management of broader groups of gastroesophageal reflux disease patients. © 2013 John Wiley & Sons Ltd.

Mild Cognitive Impairment Status and Mobility Performance

DEFF Research Database (Denmark)

Pedersen, Mette; Holt, Nicole E; Grande, Laura

2014-01-01

: An analysis was conducted on baseline data from the Boston Rehabilitative Impairment Study in the Elderly study, a cohort study of 430 primary care patients aged 65 or older. Neuropsychological tests identified participants with MCI and further subclassified those with impairment in memory domains (a......BACKGROUND: The prevalence of mild cognitive impairment (MCI) and mobility limitations is high among older adults. The aim of this study was to investigate the association between MCI status and both performance-based and self-report measures of mobility in community-dwelling older adults. METHODS...

Validation of an in vitro contractility assay using canine ventricular myocytes

Energy Technology Data Exchange (ETDEWEB)

Harmer, A.R., E-mail: alex.harmer@astrazeneca.com; Abi-Gerges, N.; Morton, M.J.; Pullen, G.F.; Valentin, J.P.; Pollard, C.E.

2012-04-15

Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ∼ 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ► Cardiac contractility is an important physiological function of the heart. ► Assessment of contractility is a logical part of pre-clinical drug safety testing. ► There are limited validated assays that predict effects of compounds on contractility. ► Using dog myocytes, we have developed an in vitro cardiac contractility assay. ► The assay predicted the in vivo contractility with a good level of accuracy.

An anthelmintic drug, pyrvinium pamoate, thwarts fibrosis and ameliorates myocardial contractile dysfunction in a mouse model of myocardial infarction.

Directory of Open Access Journals (Sweden)

Motoaki Murakoshi

Full Text Available Metabolic adaptation to limited supplies of oxygen and nutrients plays a pivotal role in health and disease. Heart attack results from insufficient delivery of oxygen and nutrients to the heart, where cardiomyocytes die and cardiac fibroblasts proliferate--the latter causing scar formation, which impedes regeneration and impairs contractility of the heart. We postulated that cardiac fibroblasts survive metabolic stress by adapting their intracellular metabolism to low oxygen and nutrients, and impeding this metabolic adaptation would thwart their survival and facilitate the repair of scarred heart. Herein, we show that an anthelmintic drug, Pyrvinium pamoate, which has been previously shown to compromise cancer cell survival under glucose starvation condition, also disables cardiac fibroblast survival specifically under glucose deficient condition. Furthermore, Pyrvinium pamoate reduces scar formation and improves cardiac contractility in a mouse model of myocardial infarction. As Pyrvinium pamoate is an FDA-approved drug, our results suggest a therapeutic use of this or other related drugs to repair scarred heart and possibly other organs.

Blood pressure and the contractility of a human leg muscle.

Science.gov (United States)

Luu, Billy L; Fitzpatrick, Richard C

2013-11-01

These studies investigate the relationships between perfusion pressure, force output and pressor responses for the contracting human tibialis anterior muscle. Eight healthy adults were studied. Changing the height of tibialis anterior relative to the heart was used to control local perfusion pressure. Electrically stimulated tetanic force output was highly sensitive to physiological variations in perfusion pressure showing a proportionate change in force output of 6.5% per 10 mmHg. This perfusion-dependent change in contractility begins within seconds and is reversible with a 53 s time constant, demonstrating a steady-state equilibrium between contractility and perfusion pressure. These stimulated contractions did not produce significant cardiovascular responses, indicating that the muscle pressor response does not play a major role in cardiovascular regulation at these workloads. Voluntary contractions at forces that would require constant motor drive if perfusion pressure had remained constant generated a central pressor response when perfusion pressure was lowered. This is consistent with a larger cortical drive being required to compensate for the lost contractility with lower perfusion pressure. The relationship between contractility and perfusion for this large postural muscle was not different from that of a small hand muscle (adductor pollicis) and it responded similarly to passive peripheral and active central changes in arterial pressure, but extended over a wider operating range of pressures. If we consider that, in a goal-oriented motor task, muscle contractility determines central motor output and the central pressor response, these results indicate that muscle would fatigue twice as fast without a pressor response. From its extent, timing and reversibility we propose a testable hypothesis that this change in contractility arises through contraction- and perfusion-dependent changes in interstitial K(+) concentration.

Administration of imatinib mesylate in rats impairs the neonatal development of intramuscular interstitial cells in bladder and results in altered contractile properties.

Science.gov (United States)

Gevaert, Thomas; Hutchings, Graham; Everaerts, Wouter; Prenen, Hans; Roskams, Tania; Nilius, Bernd; De Ridder, Dirk

2014-04-01

The KIT receptor is considered as a reliable marker for a subpopulation of interstitial cells (IC), and by persistent neonatal inhibition of KIT we have investigated the role of this receptor in the development of IC-networks in bladder and we have observed the functional consequences of this inhibition. Newborn rat pups were treated daily with the KIT inhibitor imatinib mesylate (IM). After 7 days animals were sacrificed and bladder samples were dissected for morphological and functional studies. Morphological research consisted of immunohistochemistry with IC specific antigens (KIT and vimentin) and electron microscopy. The functional studies were based on isolated bladder strips in organ baths, in which spontaneous bladder contractility and the response to a non-subtype selective muscarinic agonist was evaluated. Suburothelial and intramuscular IC were found and characterized in neonatal rat bladder. IM-treatment induced a significant decrease in numbers of IC based on specific immunohistochemical markers, and electron microscopy revealed evidence of IC cell injury. These morphological alterations were observed on intramuscular IC only and not on IC in the suburothelium. Isolated muscle strips from IM-treated animals had a lower contractile frequency and an altered response to muscarinic agonists. The present study shows the presence of regional subpopulations of IC in neonatal rat bladder, provides evidence for a dependence on KIT of the development of intramuscular IC and supports the hypothesis that a poor development of networks of intramuscular IC might have repercussions on spontaneous and muscarinic-induced bladder contractility. © 2013 Wiley Periodicals, Inc.

Effects of hypoxia and hypercapnia on geniohyoid contractility and endurance.

Science.gov (United States)

Salmone, R J; Van Lunteren, E

1991-08-01

Sleep apnea and other respiratory diseases produce hypoxemia and hypercapnia, factors that adversely affect skeletal muscle performance. To examine the effects of these chemical alterations on force production by an upper airway dilator muscle, the contractile and endurance characteristics of the geniohyoid muscle were examined in situ during severe hypoxia (arterial PO2 less than 40 Torr), mild hypoxia (PO2 45-65 Torr), and hypercapnia (PCO2 55-80 Torr) and compared with hyperoxic-normocapnic conditions in anesthetized cats. Muscles were studied at optimal length, and contractile force was assessed in response to supramaximal electrical stimulation of the hypoglossal nerve (n = 7 cats) or geniohyoid muscle (n = 2 cats). There were no significant changes in the twitch kinetics or force-frequency curve of the geniohyoid muscle during hypoxia or hypercapnia. However, the endurance of the geniohyoid, as reflected in the fatigue index (ratio of force at 2 min to initial force in response to 40-Hz stimulation at a duty cycle 0.33), was significantly reduced by severe hypoxia but not by hypercapnia or mild hypoxia. In addition, the downward shift in the force-frequency curve after the repetitive stimulation protocol was greater during hypoxia than hyperoxia, especially at higher frequencies. In conclusion, the ability of the geniohyoid muscle to maintain force output during high levels of activation is adversely affected by severe hypoxia but not mild hypoxia or hypercapnia. However, none of these chemical perturbations affected muscle contractility acutely.

Comparison of contractile and extensile pneumatic artificial muscles

Science.gov (United States)

Pillsbury, Thomas E.; Wereley, Norman M.; Guan, Qinghua

2017-09-01

Pneumatic artificial muscles (PAMs) are used in robotic and prosthetic applications due to their high power to weight ratio, controllable compliance, and simple design. Contractile PAMs are typically used in traditional hard robotics in place of heavy electric motors. As the field of soft robotics grows, extensile PAMs are beginning to have increased usage. This work experimentally tests, models, and compares contractile and extensile PAMs to demonstrate the advantages and disadvantages of each type of PAM and applications for which they are best suited.

ALCOHOL AND DISTRACTION INTERACT TO IMPAIR DRIVING PERFORMANCE

Science.gov (United States)

Harrison, Emily L. R.; Fillmore, Mark T.

2011-01-01

Background Recognition of the risks associated with alcohol intoxication and driver distraction has led to a wealth of simulated driving research aimed at studying the adverse effects of each of these factors. Research on driving has moved beyond the individual, separate examination of these factors to the examination of potential interactions between alcohol intoxication and driver distraction. In many driving situations, distractions are commonplace and might have little or no disruptive influence on primary driving functions. Yet, such distractions might become disruptive to a driver who is intoxicated. Methods The present study examined the interactive impairing effects of alcohol intoxication and driver distraction on simulated driving performance in 40 young adult drivers using a divided attention task as a distracter activity. The interactive influence of alcohol and distraction was tested by having drivers perform the driving task under four different conditions: 0.65 g/kg alcohol; 0.65 g/kg alcohol + divided attention; placebo; and placebo + divided attention. Results As hypothesized, divided attention had no impairing effect on driving performance in sober drivers. However, under alcohol, divided attention exacerbated the impairing effects of alcohol on driving precision. Conclusions Alcohol and distraction continue to be appropriate targets for research into ways to reduce the rates of driving-related fatalities and injuries. Greater consideration of how alcohol and distraction interact to impair aspects of driving performance can further efforts to create prevention and intervention measures to protect drivers, particularly young adults. PMID:21277119

Alcohol and distraction interact to impair driving performance.

Science.gov (United States)

Harrison, Emily L R; Fillmore, Mark T

2011-08-01

Recognition of the risks associated with alcohol intoxication and driver distraction has led to a wealth of simulated driving research aimed at studying the adverse effects of each of these factors. Research on driving has moved beyond the individual, separate examination of these factors to the examination of potential interactions between alcohol intoxication and driver distraction. In many driving situations, distractions are commonplace and might have little or no disruptive influence on primary driving functions. Yet, such distractions might become disruptive to a driver who is intoxicated. The present study examined the interactive impairing effects of alcohol intoxication and driver distraction on simulated driving performance in 40 young adult drivers using a divided attention task as a distracter activity. The interactive influence of alcohol and distraction was tested by having drivers perform the driving task under four different conditions: 0.65 g/kg alcohol; 0.65 g/kg alcohol+divided attention; placebo; and placebo+divided attention. As hypothesized, divided attention had no impairing effect on driving performance in sober drivers. However, under alcohol, divided attention exacerbated the impairing effects of alcohol on driving precision. Alcohol and distraction continue to be appropriate targets for research into ways to reduce the rates of driving-related fatalities and injuries. Greater consideration of how alcohol and distraction interact to impair aspects of driving performance can further efforts to create prevention and intervention measures to protect drivers, particularly young adults. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The importance of myocardial contractile reserve in predicting response to cardiac resynchronization therapy

NARCIS (Netherlands)

Kloosterman, Mariëlle; Damman, Kevin; Van Veldhuisen, Dirk J; Rienstra, Michiel; Maass, Alexander H

AimTo perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure. Methods and resultsWe searched MEDLINE/PubMed and Cochrane for all papers published up

Stalk-length-dependence of the contractility of Vorticella convallaria

Science.gov (United States)

Gul Chung, Eun; Ryu, Sangjin

2017-12-01

Vorticella convallaria is a sessile protozoan of which the spasmoneme contracts on a millisecond timescale. Because this contraction is induced and powered by the binding of calcium ions (Ca2+), the spasmoneme showcases Ca2+-powered cellular motility. Because the isometric tension of V. convallaria increases linearly with its stalk length, it is hypothesized that the contractility of V. convallaria during unhindered contraction depends on the stalk length. In this study, the contractile force and energetics of V. convallaria cells of different stalk lengths were evaluated using a fluid dynamic drag model which accounts for the unsteadiness and finite Reynolds number of the water flow caused by contracting V. convallaria and the wall effect of the no-slip substrate. It was found that the contraction displacement, peak contraction speed, peak contractile force, total mechanical work, and peak power depended on the stalk length. The observed stalk-length-dependencies were simulated using a damped spring model, and the model estimated that the average spring constant of the contracting stalk was 1.34 nN µm-1. These observed length-dependencies of Vorticella’s key contractility parameters reflect the biophysical mechanism of the spasmonemal contraction, and thus they should be considered in developing a theoretical model of the Vorticella spasmoneme.

Inhibition of isolated human myometrium contractility by minoxidil and reversal by glibenclamide.

Science.gov (United States)

Prabhakaran, S S; Dhanasekar, K R; Thomas, E; Jose, R; Peedicayil, J; Samuel, P

2010-03-01

This study investigated the ability of the antihypertensive drug minoxidil to inhibit potassium chloride (KCl)-induced contractility of the isolated human myometrium. Twelve strips of myometrium obtained from 12 patients who underwent hysterectomy were triggered to contract with 55 mM KCl before and after incubation with 3 concentrations (1, 3 and 10 microM) of minoxidil. The percent inhibition by minoxidil on the extent of contraction, and the area under the contractile curve of KCl-induced contraction of the myometrial strips was determined. Furthermore, the effect of 10 microM glibenclamide on the inhibition generated by 3 microM minoxidil on KCl-induced contractility was studied. It was found that minoxidil produced a concentration-dependent inhibition of KCl-induced contractility of the myometrium and that glibenclamide reversed this inhibitory effect. These results suggest that the inhibitory effect of minoxidil on isolated human myometrium contractility may prove useful in clinical conditions requiring relaxation of the myometrium. 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

International Nuclear Information System (INIS)

Morton, M.J.; Armstrong, D.; Abi Gerges, N.; Bridgland-Taylor, M.; Pollard, C.E.; Bowes, J.; Valentin, J.-P.

2014-01-01

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

Energy Technology Data Exchange (ETDEWEB)

Morton, M.J., E-mail: michael.morton@astrazeneca.com [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Armstrong, D.; Abi Gerges, N. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Bridgland-Taylor, M. [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Pollard, C.E.; Bowes, J.; Valentin, J.-P. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom)

2014-09-01

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility.

Roles of calcium and IP3 in impaired colon contractility of rats following multiple organ dysfunction syndrome

Directory of Open Access Journals (Sweden)

C. Zheyu

2007-10-01

Full Text Available The purpose of the present study was to explore changes in rat colon motility, and determine the roles of calcium and inositol (1,4,5-triphosphate (IP3 in colon dysmotility induced by multiple organ dysfunction syndrome (MODS caused by bacteria peritonitis. The number of stools, the contractility of the muscle strips and the length of smooth muscle cells (SMC in the colon, the concentration of calcium and IP3 in SMC, and serum nitric oxide were measured. Number of stools, fecal weight, IP3 concentration in SMC and serum nitric oxide concentration were 0.77 ± 0.52 pellets, 2.51 ± 0.39 g, 4.14 ± 2.07 pmol/tube, and 113.95 ± 37.89 µmol/L, respectively, for the MODS group (N = 11 vs 1.54 ± 0.64 pellets, 4.32 ± 0.57 g, 8.19 ± 3.11 pmol/tube, and 37.42 ± 19.56 µmol/L for the control group (N = 20; P < 0.05. After treatment with 0.1 mM acetylcholine and 0.1 M potassium chloride, the maximum contraction stress of smooth muscle strips, the length of SMC and the changes of calcium concentration were 593 ± 81 and 458 ± 69 g/cm³, 48.1 ± 11.8 and 69.2 ± 15.7 µM, 250 ± 70 and 167 ± 48%, respectively, for the control group vs 321 ± 53 and 284 ± 56 g/cm³, 65.1 ± 18.5 and 87.2 ± 23.7 µM, 127 ± 35 and 112 ± 35% for the MODS group (P < 0.05. Thus, colon contractility was decreased in MODS, a result possibly related to reduced calcium concentration and IP3 in SMC.

Actomyosin contractility rotates the cell nucleus.

Science.gov (United States)

Kumar, Abhishek; Maitra, Ananyo; Sumit, Madhuresh; Ramaswamy, Sriram; Shivashankar, G V

2014-01-21

The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells.

Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra.

Science.gov (United States)

Cannon, Tracy W; Lee, Ji Youl; Somogyi, George; Pruchnic, Ryan; Smith, Christopher P; Huard, Johnny; Chancellor, Michael B

2003-11-01

To study the physiologic outcome of allogenic transplant of muscle-derived progenitor cells (MDPCs) in the denervated female rat urethra. MDPCs were isolated from muscle biopsies of normal 6-week-old Sprague-Dawley rats and purified using the preplate technique. Sciatic nerve-transected rats were used as a model of stress urinary incontinence. The experimental group was divided into three subgroups: control, denervated plus 20 microL saline injection, and denervated plus allogenic MDPCs (1 to 1.5 x 10(6) cells) injection. Two weeks after injection, urethral muscle strips were prepared and underwent electrical field stimulation. The pharmacologic effects of d-tubocurare, phentolamine, and tetrodotoxin on the urethral strips were assessed by contractions induced by electrical field stimulation. The urethral tissues also underwent immunohistochemical staining for fast myosin heavy chain and CD4-activated lymphocytes. Urethral denervation resulted in a significant decrease of the maximal fast-twitch muscle contraction amplitude to only 8.77% of the normal urethra and partial impairment of smooth muscle contractility. Injection of MDPCs into the denervated sphincter significantly improved the fast-twitch muscle contraction amplitude to 87.02% of normal animals. Immunohistochemistry revealed a large amount of new skeletal muscle fiber formation at the injection site of the urethra with minimal inflammation. CD4 staining showed minimal lymphocyte infiltration around the MDPC injection sites. Urethral denervation resulted in near-total abolishment of the skeletal muscle and partial impairment of smooth muscle contractility. Allogenic MDPCs survived 2 weeks in sciatic nerve-transected urethra with minimal inflammation. This is the first report of the restoration of deficient urethral sphincter function through muscle-derived progenitor cell tissue engineering. MDPC-mediated cellular urethral myoplasty warrants additional investigation as a new method to treat stress urinary

[Role of sialic acid loss in the myocardium in depressing the contractile function of the heart muscle during stress].

Science.gov (United States)

Meerson, F Z; Saulia, A I; Gudumak, V S

1985-01-01

Under conditions of stress a time-dependent decrease in content of sialic acids was found in adult rats; within 9 hrs of the animal immobilization the sialic acid content was decreased by 40% as compared with controls. At the same time, activities of trypsin and LDHI were increased in blood serum. The data obtained suggest that activation of proteases occurring during the stress led to increased hydrolysis of base components of glycocalyx and to impairment of the cardiomyocyte sarcolemma. These phenomena appear to be responsible for the post-stress deterioration of heart muscle contractile functions.

Skeletal muscle myofilament adaptations to aging, disease and disuse and their effects on whole muscle performance in older adult humans

Directory of Open Access Journals (Sweden)

Mark Stuart Miller

2014-09-01

Full Text Available Skeletal muscle contractile function declines with aging, disease and disuse. In vivo muscle contractile function depends on a variety of factors, but force, contractile velocity and power generating capacity ultimately derive from the summed contribution of single muscle fibers. The contractile performance of these fibers are, in turn, dependent upon the isoform and function of myofilament proteins they express, with myosin protein expression and its mechanical and kinetic characteristics playing a predominant role. Alterations in myofilament protein biology, therefore, may contribute to the development of functional limitations and disability in these conditions. Recent studies suggest that these conditions are associated with altered single fiber performance due to decreased expression of myofilament proteins and/or changes in myosin-actin cross-bridge interactions. Furthermore, cellular and myofilament-level adaptations are related to diminished whole muscle and whole body performance. Notably, the effect of these various conditions on myofilament and single fiber function tends to be larger in older women compared to older men, which may partially contribute to their higher rates of disability. To maintain functionality and provide the most appropriate and effective countermeasures to aging, disease and disuse in both sexes, a more thorough understanding is needed of the contribution of myofilament adaptations to functional disability in older men and women and their contribution to tissue level function and mobility impairment.

Slack length reduces the contractile phenotype of the Swine carotid artery.

Science.gov (United States)

Rembold, Christopher M; Garvey, Sean M; Tejani, Ankit D

2013-01-01

Contraction is the primary function of adult arterial smooth muscle. However, in response to vessel injury or inflammation, arterial smooth muscle is able to phenotypically modulate from the contractile state to several 'synthetic' states characterized by proliferation, migration and/or increased cytokine secretion. We examined the effect of tissue length (L) on the phenotype of intact, isometrically held, initially contractile swine carotid artery tissues. Tissues were studied (1) without prolonged incubation at the optimal length for force generation (1.0 Lo, control), (2) with prolonged incubation for 17 h at 1.0 Lo, or (3) with prolonged incubation at slack length (0.6 Lo) for 16 h and then restoration to 1.0 Lo for 1 h. Prolonged incubation at 1.0 Lo minimally reduced the contractile force without substantially altering the mediators of contraction (crossbridge phosphorylation, shortening velocity or stimulated actin polymerization). Prolonged incubation of tissues at slack length (0.6 Lo), despite return of length to 1.0 Lo, substantially reduced contractile force, reduced crossbridge phosphorylation, nearly abolished crossbridge cycling (shortening velocity) and abolished stimulated actin polymerization. These data suggest that (1) slack length treatment significantly alters the contractile phenotype of arterial tissue, and (2) slack length treatment is a model to study acute phenotypic modulation of intact arterial smooth muscle. Copyright © 2013 S. Karger AG, Basel.

Calcium-responsive contractility during fertilization in sea urchin eggs.

Science.gov (United States)

Stack, Christianna; Lucero, Amy J; Shuster, Charles B

2006-04-01

Fertilization triggers a reorganization of oocyte cytoskeleton, and in sea urchins, there is a dramatic increase in cortical F-actin. However, the role that myosin II plays during fertilization remains largely unexplored. Myosin II is localized to the cortical cytoskeleton both before and after fertilization and to examine myosin II contractility in living cells, Lytechinus pictus eggs were observed by time-lapse microscopy. Upon sperm binding, a cell surface deflection traversed the egg that was followed by and dependent on the calcium wave. The calcium-dependence of surface contractility could be reproduced in unfertilized eggs, where mobilization of intracellular calcium in unfertilized eggs under compression resulted in a marked contractile response. Lastly, inhibition of myosin II delayed absorption of the fertilization cone, suggesting that myosin II not only responds to the same signals that activate eggs but also participates in the remodeling of the cortical actomyosin cytoskeleton during the first zygotic cell cycle. (c) 2006 Wiley-Liss, Inc.

17 alpha-hydroxyprogesterone caproate vehicle, castor oil, enhances the contractile effect of oxytocin in human myometrium in pregnancy.

Science.gov (United States)

O'Sullivan, Michael D; Hehir, Mark P; O'Brien, Yvonne M; Morrison, John J

2010-05-01

The possibility exists that the vehicle for 17-alpha-hydroxyprogesterone caproate, castor oil, exerts an effect on human uterine contractility. The aim of this study was to evaluate its effects on contractility of myometrial preparations that were obtained during pregnancy. Myometrial strips were suspended under isometric conditions. Contractility was induced with oxytocin. Strips were incubated in castor oil or physiologic salt solution and suspended for a further oxytocin challenge. Contractile integrals were compared between both groups. Strips that were exposed to castor oil demonstrated increased contractile activity that was elicited by oxytocin (mean contractility value, 165.53%+/-17.03%; n=8; P=.004), compared with control strips (mean contractility value, 72.57%+/-7.48%; n=8; P=.003). There was a significant increase in contractile activity of the castor oil-exposed strips, compared with those that were exposed to physiologic salt solution (n=8; Pcastor oil results in enhanced oxytocin-induced contractility. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Dynamic MR cholangiography after fatty meal loading. Cystic contractility and dynamic evaluation of biliary stasis

International Nuclear Information System (INIS)

Omata, Takayuki; Saito, Kazuhiro; Kotake, Fumio; Mizokami, Yuji; Matsuoka, Takeshi; Abe, Kimihiko

2002-01-01

Dynamic MR cholangiography was conducted on patients with cholelithiasis or choledocholithiasis who had consumed a fatty test meal (Molyork) and the cystic contractility and dynamics of biliary stasis was evaluated. The subjects were 25 with intracystic cholelithiasis, 10 with choledocholithiasis and 10 normal controls. For an imaging sequence, the rapid acquisition with relaxation enhancement (RARE) method was employed and imaging was conducted for 40 min (every 30 s following Molyork administration) without breath-holding. The gallbladder contraction ratio was computed and the contractile ratio for the common bile duct was calculated. To determine the bile flow to the duodenum, the high-intensity signal, indicating the flow from the lower common bile duct, and perfusion of the duodenum were observed in dynamic mode on the monitor with the naked eye and interpreted as positive bile flow. The frequency of this flow was visually monitored. The gallbladder contractile ratio was significantly reduced in patients with cholelithiasis or choledocholithiasis compared with the controls. In a comparison with the normal controls, no sequential changes were noted in the mean contractile ratio of the common bile duct of the patients with cholelithiasis or choledocholithiasis. The mean frequency of bile flow observed for each 40 min period was 13±2.4, 6±2.2, and 4±1.3 times for the controls, those with intracystic cholelithiasis, and those with choledocholithiasis, respectively. Compared with the controls, the latter two patient groups showed evident reductions in the frequency of bile flow to the duodenum (p<0.001). Dynamic MRC combined with Molyork loading makes it possible to compute cystic contractile ratios and perform a dynamic examination of bile flow under non-invasive, near-physiological conditions. (author)

Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase.

NARCIS (Netherlands)

Heunks, L.M.A.; Machiels, H.A.; Abreu, R.A. de; Zhu, X.; Heijden, E. van der; Dekhuijzen, P.N.R.

2001-01-01

Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an

Contractility of the guinea pig bladder measured in situ and in vitro

NARCIS (Netherlands)

J.M. Groen (Jan); R. van Mastrigt (Ron); J.L.H.R. Bosch (Ruud)

1994-01-01

textabstractTo study the relative importance of neurogenic factors in detrusor contractility and to relate a total bladder in vitro contractility model to a previously described bladder wall strip model, active intravesical pressure values were compared in situ and in vitro in eight male guinea

Myocardial contractile function in survived neonatal piglets after cardiopulmonary bypass

Directory of Open Access Journals (Sweden)

Popov Aron-Frederik

2010-11-01

Full Text Available Abstract Background Hemodynamic function may be depressed in the early postoperative stages after cardiac surgery. The aim of this study was the analysis of the myocardial contractility in neonates after cardiopulmonary bypass (CPB and mild hypothermia. Methods Three indices of left ventricular myocardial contractile function (dP/dt, (dP/dt/P, and wall thickening were studied up to 6 hours after CPB in neonatal piglets (CPB group; n = 4. The contractility data were analysed and then compared to the data of newborn piglets who also underwent median thoracotomy and instrumentation for the same time intervals but without CPB (non-CPB group; n = 3. Results Left ventricular dP/dtmax and (dP/dtmax/P remained stable in CPB group, while dP/dtmax decreased in non-CPB group 5 hours postoperatively (1761 ± 205 mmHg/s at baseline vs. 1170 ± 205 mmHg/s after 5 h; p max and (dP/dtmax/P there were no statistically significant differences between the two groups. Comparably, although myocardial thickening decreased in the non-CPB group the differences between the two groups were not statistically significant. Conclusions The myocardial contractile function in survived neonatal piglets remained stable 6 hours after cardiopulmonary bypass and mild hypothermia probably due to regional hypercontractility.

Spontaneous actin dynamics in contractile rings

Science.gov (United States)

Kruse, Karsten; Wollrab, Viktoria; Thiagarajan, Raghavan; Wald, Anne; Riveline, Daniel

Networks of polymerizing actin filaments are known to be capable to self-organize into a variety of structures. For example, spontaneous actin polymerization waves have been observed in living cells in a number of circumstances, notably, in crawling neutrophils and slime molds. During later stages of cell division, they can also spontaneously form a contractile ring that will eventually cleave the cell into two daughter cells. We present a framework for describing networks of polymerizing actin filaments, where assembly is regulated by various proteins. It can also include the effects of molecular motors. We show that the molecular processes driven by these proteins can generate various structures that have been observed in contractile rings of fission yeast and mammalian cells. We discuss a possible functional role of each of these patterns. The work was supported by Agence Nationale de la Recherche, France, (ANR-10-LABX-0030-INRT) and by Deutsche Forschungsgemeinschaft through SFB1027.

Numerical investigation of perforated polymer microcantilever sensor for contractile behavior of cardiomyocytes

Science.gov (United States)

Khoa Nguyen, Trieu; Lee, Dong-Weon; Lee, Bong-Kee

2017-06-01

In this study, a numerical investigation of microcantilever sensors for detecting the contractile behavior of cardiomyocytes (CMs) was performed. Recently, a novel surface-patterned perforated SU-8 microcantilever sensor has been developed for the preliminary screening of cardiac toxicity. From the contractile motion of the CMs cultured on the microcantilever surface, a macroscopic bending of the microcantilever was obtained, which is considered to reflect a physiological change. As a continuation of the previous research, a novel numerical method based on a surface traction model was proposed and verified to further understand the bending behavior of the microcantilevers. Effects of various factors, including surface traction magnitude, focal area of CMs, and stiffness of microcantilever, on the bending displacement were investigated. From static and transient analyses, the focal area was found to be the most crucial factor. In addition, the current result can provide a design guideline for various micromechanical devices based on the same principle.

Thick filament length and isoform composition determine self-organized contractile units in actomyosin bundles.

Science.gov (United States)

Thoresen, Todd; Lenz, Martin; Gardel, Margaret L

2013-02-05

Diverse myosin II isoforms regulate contractility of actomyosin bundles in disparate physiological processes by variations in both motor mechanochemistry and the extent to which motors are clustered into thick filaments. Although the role of mechanochemistry is well appreciated, the extent to which thick filament length regulates actomyosin contractility is unknown. Here, we study the contractility of minimal actomyosin bundles formed in vitro by mixtures of F-actin and thick filaments of nonmuscle, smooth, and skeletal muscle myosin isoforms with varied length. Diverse myosin II isoforms guide the self-organization of distinct contractile units within in vitro bundles with shortening rates similar to those of in vivo myofibrils and stress fibers. The tendency to form contractile units increases with the thick filament length, resulting in a bundle shortening rate proportional to the length of constituent myosin thick filament. We develop a model that describes our data, providing a framework in which to understand how diverse myosin II isoforms regulate the contractile behaviors of disordered actomyosin bundles found in muscle and nonmuscle cells. These experiments provide insight into physiological processes that use dynamic regulation of thick filament length, such as smooth muscle contraction. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Low Proportion of Dietary Plant Protein among Athletes with Premenstrual Syndrome-Related Performance Impairment.

Science.gov (United States)

Yamada, Keiko; Takeda, Takashi

2018-02-01

Premenstrual syndrome (PMS) is psychosomatic disorder that are limited to the late luteal phase in the menstrual cycle. PMS could impair athletic performance. To investigate associations between proportions of dietary plant and animal protein and PMS-related impairment of athletic performance, we surveyed 135 female athletes aged 18-23 years attending Kindai University. Participants belonged to authorized university clubs, all of which have high rankings in Japanese university sports. Participants completed self-administered questionnaires on diet history, demographics, and PMS-related impairment of athletic performance. Total protein, animal protein, and plant protein intake were examined, and the proportion of dietary plant protein was calculated for each participant. We divided athletes into two groups: those without PMS-related impairment of athletic performance (n = 117) and those with PMS-related performance impairment (n = 18). A t-test was used to compare mean values and multivariable adjusted mean values between groups; adjustment variables were energy intake, body mass index, and daily training duration. Total protein intake was not significantly different between the groups. However, athletes whose performance was affected by PMS reported higher intake of animal protein (mean 50.6 g) than athletes whose performance was unaffected by PMS (mean 34.9 g). Plant protein intake was lower among athletes with PMS-related impairment (mean 25.4 g) than among athletes without impairment (mean 26.9 g). The proportion of dietary plant protein was lower among athletes with PMS-related impairment (39.3%) than those without impairment (45.9%). A low proportion of dietary plant protein may cause PMS-related athletic impairment among athletes.

A comparative study of contractility of the heart ventricle in some ectothermic vertebrates

Directory of Open Access Journals (Sweden)

Sergey Kharin

2009-07-01

Full Text Available The purpose of this study was to analyze contractility of the heart ventricle in selected reptilian and amphibian species having the same ventricular excitation pattern. Systolic time intervals and indices of contractility of the heart ventricle were measured in anaesthetized frogs, snakes, and tortoises by use of polycardiography. The electromechanical delay was significantly shorter in tortoises compared with the other two species. The isovolumetric contraction time in frogs was approximately twofold longer than in reptiles. The pre-ejection period was the longest in frogs and the shortest in tortoises, whereas snakes were intermediate. The ejection time was slightly longer in tortoises compared with the other two species. The greatest isovolumetric contraction index and the smallest myocardial tension index corresponded to the frog and tortoise heart ventricle, respectively. The intrasystolic index in tortoises was significantly greater than in frogs, whereas quite similar to that in snakes. The frog ventricle had lower contractility compared with the reptilian one. Although ventricular contractility tended to be lower in snakes compared with tortoises, this difference was not statistically significant. Possible causes for these differences are discussed. We suppose a large variety in ventricular contractility among amphibian and reptilian species having the same ventricular activation pattern. This variety may be conditioned by heart anatomy, intracardiac shunting, lifestyles, and habitats. It can only be hypothesized that on the average, ventricular contractility is higher in reptiles compared with amphibians and in chelonians compared with snakes.

Evidence that communication impairment in schizophrenia is associated with generalized poor task performance.

Science.gov (United States)

Merrill, Anne M; Karcher, Nicole R; Cicero, David C; Becker, Theresa M; Docherty, Anna R; Kerns, John G

2017-03-01

People with schizophrenia exhibit wide-ranging cognitive deficits, including slower processing speed and decreased cognitive control. Disorganized speech symptoms, such as communication impairment, have been associated with poor cognitive control task performance (e.g., goal maintenance and working memory). Whether communication impairment is associated with poorer performance on a broader range of non-cognitive control measures is unclear. In the current study, people with schizophrenia (n =51) and non-psychiatric controls (n =26) completed speech interviews allowing for reliable quantitative assessment of communication impairment. Participants also completed multiple goal maintenance and working memory tasks. In addition, we also examined (a) simple measures of processing speed involving highly automatic prepotent responses and (b) a non-cognitive control measure of general task performance. Schizophrenia communication impairment was significantly associated with poor performance in all cognitive domains, with the largest association found with processing speed (r s =-0.52). Further, communication impairment was also associated with the non-cognitive control measure of poor general task performance (r s =-0.43). In contrast, alogia, a negative speech symptom, and positive symptoms were less if at all related to cognitive task performance. Overall, this study suggests that communication impairment in schizophrenia may be associated with relatively generalized poor cognitive task performance. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Sarcopenia and impairment in cognitive and physical performance

Directory of Open Access Journals (Sweden)

Tolea MI

2015-03-01

Full Text Available Magdalena I Tolea,1 James E Galvin1–3 1Alzheimer’s Disease Center, Department of Neurology, 2Department of Psychiatry, 3Department of Population Health, New York University School of Medicine, New York, NY, USA Background: Whether older adults with sarcopenia who underperform controls on tests of physical performance and cognition also have a higher likelihood of combined cognitive-physical impairment is not clear. We assessed the impact of sarcopenia on impairment in both aspects of functionality and the relative contribution of its components, muscle mass and strength.Methods: Two hundred and twenty-three community-dwelling adults aged 40 years and older (mean age =68.1±10.6 years; 65% female were recruited and underwent physical functionality, anthropometry, and cognitive testing. Participants with low muscle mass were categorized as pre-sarcopenic; those with low muscle mass and muscle strength as sarcopenic; those with higher muscle mass and low muscle strength only were categorized as non-sarcopenic and were compared on risk of cognitive impairment (Montreal Cognitive Assessment <26; Ascertaining Dementia 8 ≥2, physical impairment (Mini Physical Performance Test <12, both, or neither by ordinal logistic regression. Results: Compared to controls, those with sarcopenia were six times more likely to have combined cognitive impairment/physical impairment with a fully adjusted model showing a three-fold increased odds ratio. The results were consistent across different measures of global cognition (odds ratio =3.46, 95% confidence interval =1.07–11.45 for the Montreal Cognitive Assessment; odds ratio =3.61, 95% confidence interval =1.11–11.72 for Ascertaining Dementia 8. Pre-sarcopenic participants were not different from controls. The effect of sarcopenia on cognition is related to low muscle strength rather than low muscle mass. Conclusion: Individuals with sarcopenia are not only more likely to have single but also to have dual

Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales.

Science.gov (United States)

Huebsch, Nathaniel; Loskill, Peter; Mandegar, Mohammad A; Marks, Natalie C; Sheehan, Alice S; Ma, Zhen; Mathur, Anurag; Nguyen, Trieu N; Yoo, Jennie C; Judge, Luke M; Spencer, C Ian; Chukka, Anand C; Russell, Caitlin R; So, Po-Lin; Conklin, Bruce R; Healy, Kevin E

2015-05-01

Contractile motion is the simplest metric of cardiomyocyte health in vitro, but unbiased quantification is challenging. We describe a rapid automated method, requiring only standard video microscopy, to analyze the contractility of human-induced pluripotent stem cell-derived cardiomyocytes (iPS-CM). New algorithms for generating and filtering motion vectors combined with a newly developed isogenic iPSC line harboring genetically encoded calcium indicator, GCaMP6f, allow simultaneous user-independent measurement and analysis of the coupling between calcium flux and contractility. The relative performance of these algorithms, in terms of improving signal to noise, was tested. Applying these algorithms allowed analysis of contractility in iPS-CM cultured over multiple spatial scales from single cells to three-dimensional constructs. This open source software was validated with analysis of isoproterenol response in these cells, and can be applied in future studies comparing the drug responsiveness of iPS-CM cultured in different microenvironments in the context of tissue engineering.

Clinical Relationship between Steatocholecystitis and Gallbladder Contractility Measured by Cholescintigraphy

Directory of Open Access Journals (Sweden)

Chang Seok Bang

2015-01-01

Full Text Available Objective. Contractility of gallbladder is known to be decreased in fatty gallbladder diseases. However, clinical estimation data about this relationship is still lacking. The aim of this study was to investigate the association between steatocholecystitis and contractility of gallbladder. Methods. Patients with cholecystitis (steatocholecystitis versus nonsteatocholecystitis who underwent cholescintigraphy before cholecystectomy were retrospectively evaluated in a single teaching hospital of Korea. The association of steatocholecystitis with contractility of gallbladder, measured by preoperative cholescintigraphy, was assessed by univariable and multivariable analysis. Results. A total of 432 patients were finally enrolled (steatocholecystitis versus nonsteatocholecystitis; 75 versus 357, calculous versus acalculous cholecystitis; 316 versus 116. In the multivariable analysis, age (OR: 0.94, 95% CI: 0.90–0.99, P=0.01 and total serum cholesterol (OR: 1.02, 95% CI: 1.01–1.04, P=0.04 were related to steatocholecystitis in patients with acalculous cholecystitis. Only age (OR: 0.97, 95% CI: 0.94–0.99, P=0.004 was significantly related to steatocholecystitis in patients with calculous cholecystitis. However, ejection fraction of gallbladder reflecting contractility measured by cholescintigraphy was not related to steatocholecystitis irrespective of presence of gallbladder stone in patients with cholecystitis. Conclusion. Ejection fraction of gallbladder measured by cholescintigraphy cannot be used for the detection or confirmation of steatocholecystitis.

The role of voltage-gated potassium channels in the regulation of mouse uterine contractility

Directory of Open Access Journals (Sweden)

Abel Peter W

2007-11-01

Full Text Available Abstract Background Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv channels and large-conductance, calcium-activated potassium (BK channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium. Methods Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots. Results The Kv channel blocker 4-aminopyridine (4-AP caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were

Effects of minoxidil and nitroprusside on reflex increases in myocardial contractility.

Science.gov (United States)

Robie, N W

1978-01-01

1 The effects of nitroprusside and minoxidil on increases in myocardial contractility resulting from carotid artery occlusion were investigated in anaesthetized dogs. The results were compared with those produced by intravenous influsion of noradrenaline. 2 Nitroprusside and minoxidil attenuated the pressor responses produced by carotid artery occlusion. 3 Nitroprusside, but not minoxidil, attenuated the maximal myocardial contractility resulting from carotid occlusion. 4 The pressor and contractility responses to noradrenaline infusion were unaffected by either agent. 5 Nitroprusside failed to alter the myocardial responses produced by dimethylphenylpiperazinium. 6 These results, in conjunction with those of other investigators who have demonstrated that nitroprusside does not affect the release of noradrenaline from adrenergic neurons, suggest that nitroprusside may inhibit sympathetic nervous system reflex activity via an afferent and/or central component. PMID:620094

Effects of Crocetin Esters and Crocetin from Crocus sativus L. on Aortic Contractility in Rat Genetic Hypertension

Directory of Open Access Journals (Sweden)

Silvia Llorens

2015-09-01

Full Text Available Background: Endothelial dysfunction, characterized by an enhancement in vasoconstriction, is clearly associated with hypertension. Saffron (Crocus sativus L. bioactive compounds have been recognized to have hypotensive properties. Recently, we have reported that crocetin exhibits potent vasodilator effects on isolated aortic rings from hypertensive rats. In this work, we have aimed to analyze the anticontractile ability of crocetin or crocetin esters pool (crocins isolated from saffron. Thus, we have studied the effects of saffron carotenoids on endothelium-dependent and -independent regulation of smooth muscle contractility in genetic hypertension. Methods: We have measured the isometric responses of aortic segments with or without endothelium obtained from spontaneously hypertensive rats. The effects of carotenoids were studied by assessing the endothelial modulation of phenylephrine-induced contractions (10−9–10−5 M in the presence or absence of crocetin or crocins. The role of nitric oxide and prostanoids was analyzed by performing the experiments with L-NAME (NG-nitro-l-arginine methyl ester or indomethacin (both 10−5 M, respectively. Results: Crocetin, and to a minor extent crocins, diminished the maximum contractility of phenylephrine in intact rings, while crocins, but not crocetin, increased this contractility in de-endothelizated vessels. In the intact vessels, the effect of crocetin on contractility was unaffected by indomethacin but was abolished by L-NAME. However, crocetin but not crocins, lowered the already increased contractility caused by L-NAME. Conclusions: Saffron compounds, but especially crocetin have endothelium-dependent prorelaxing actions. Crocins have procontractile actions that take place via smooth muscle cell mechanisms. These results suggest that crocetin and crocins activate different mechanisms involved in the vasoconstriction pathway in hypertension.

Visual-motor integration performance in children with severe specific language impairment.

Science.gov (United States)

Nicola, K; Watter, P

2016-09-01

This study investigated (1) the visual-motor integration (VMI) performance of children with severe specific language impairment (SLI), and any effect of age, gender, socio-economic status and concomitant speech impairment; and (2) the relationship between language and VMI performance. It is hypothesized that children with severe SLI would present with VMI problems irrespective of gender and socio-economic status; however, VMI deficits will be more pronounced in younger children and those with concomitant speech impairment. Furthermore, it is hypothesized that there will be a relationship between VMI and language performance, particularly in receptive scores. Children enrolled between 2000 and 2008 in a school dedicated to children with severe speech-language impairments were included, if they met the criteria for severe SLI with or without concomitant speech impairment which was verified by a government organization. Results from all initial standardized language and VMI assessments found during a retrospective review of chart files were included. The final study group included 100 children (males = 76), from 4 to 14 years of age with mean language scores at least 2SD below the mean. For VMI performance, 52% of the children scored below -1SD, with 25% of the total group scoring more than 1.5SD below the mean. Age, gender and the addition of a speech impairment did not impact on VMI performance; however, children living in disadvantaged suburbs scored significantly better than children residing in advantaged suburbs. Receptive language scores of the Clinical Evaluation of Language Fundamentals was the only score associated with and able to predict VMI performance. A small subgroup of children with severe SLI will also have poor VMI skills. The best predictor of poor VMI is receptive language scores on the Clinical Evaluation of Language Fundamentals. Children with poor receptive language performance may benefit from VMI assessment and multidisciplinary

Effect of heat stress on contractility of tissue-engineered artificial skeletal muscle.

Science.gov (United States)

Takagi, Shunya; Nakamura, Tomohiro; Fujisato, Toshia

2018-01-23

The effects of heat stress on tissue like skeletal muscle have been widely studied. However, the mechanism responsible for the effect of heat stress is still unclear. A useful experimental tissue model is necessary because muscle function in cell culture may differ from native muscle and measuring its contractility is difficult. We previously reported three-dimensional tissue-engineered artificial skeletal muscle (TEM) that can be easily set in a measurement apparatus for quantitative evaluation of contractility. We have now applied TEM to the investigation of heat stress. We analyzed contractility immediately after thermal exposure at 39 °C for 24 or 48 h to evaluate the acute effects and after thermal exposure followed by normal culture to evaluate the aftereffects. Peak twitch contractile force and time-to-peak twitch were used as contractile parameters. Heat stress increased the TCF in the early stage (1 week) after normal culture; the TCF decreased temporarily in the middle to late stages (2-3 weeks). These results suggest that heat stress may affect both myoblast fusion and myotube differentiation in the early stage of TEM culture, but not myotube maturation in the late stage. The TCF increase rate with thermal exposure was significantly higher than that without thermal exposure. Although detailed analysis at the molecular level is necessary for further investigation, our artificial skeletal muscle may be a promising tool for heat stress investigation.

Timing and gender determine if acute pain impairs working memory performance.

Science.gov (United States)

Hood, Anna; Pulvers, Kim; Spady, Thomas J

2013-11-01

The effects of pain on memory are complex, and little is known about the vulnerability of working memory (WM) performance when individuals complete a WM test while concurrently experiencing pain. Here, we subjected 78 healthy nonsmoking participants to either acute pain or a control condition while we administered a WM test. In this context, we also tested WM 20 minutes after pain in order to determine if timing of pain affected WM performance, and assessed objective and subjective measures of pain. We hypothesized that pain would impair WM performance during pain. Further, women's WM performance would be impaired more than men. Importantly, there was an interaction between gender and condition, with women exposed to pain experiencing impairments during but not after the cold pressor task. Our data imply that timing and gender are critically important in whether acute pain is costly to WM performance. Our findings have interesting clinical, professional, and educational implications, and understanding the influence of pain could help to improve the interpretation of WM tests in these diverse settings. Results of this study support the growing body of work that attests to the detrimental effect of pain on WM performance. Further, this study provides new evidence that concurrently experiencing cold pressor pain impairs WM in regularly menstruating women and women taking a contraceptive. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Effects of ageing on single muscle fibre contractile function following short-term immobilisation

DEFF Research Database (Denmark)

Hvid, Lars G; Ørtenblad, Niels; Aagaard, Per

2011-01-01

Very little attention has been given to the combined effect of healthy ageing and short-term disuse on the contractile function of human single muscle fibres. Therefore, the present study investigated the effects of 2 weeks of lower limb cast immobilisation (i.e. disuse) on selected contractile...

Effect of Propafenone on the Contractile Activity of Latissimus Dorsi Muscle Isolated in an Organ Chamber: Experimental Study in Rats

Directory of Open Access Journals (Sweden)

Ricardo Simões

2002-03-01

Full Text Available OBJECTIVE: To study the effect of propafenone on the contractile function of latissimus dorsi muscle isolated from rats in an organ chamber. METHODS: We studied 20 latissimus dorsi muscles of Wistar rats and divided them into 2 groups: group I (n=10, or control group - we studied the feasibility of muscle contractility; group II (n=10, in which the contralateral muscles were grouped - we analyzed the effect of propafenone on muscle contractility. After building a muscle ring, 8 periods of sequential 2-minute baths were performed, with intervals of preprogrammed electrical stimulation using a pacemaker of 50 stimuli/min. In group II, propafenone, at the concentration of 9.8 µg/mL, was added to the bath in period 2 and withdrawn in period 4. RESULTS: In group I, no significant depression in muscle contraction occurred up to period 5 (p>0.05. In group II, a significant depression occurred in all periods, except between the last 2 periods (p0.05. CONCLUSION: Propafenone had a depressing effect on the contractile function of latissimus dorsi muscle isolated from rats and studied in an organ chamber.

Simulated Evaluation of Drug-Impaired Psychomotor Performance

OpenAIRE

Richmond R

2014-01-01

The purpose of this placebo-controlled, randomized-crossover study was to evaluate a computer-based divided-attention task as a method for measure impaired human psychomotor performance. The ability of the divided-attention task to detect and differentiate was evaluated using single oral doses of placebo, caffeine and diphenhydramine. Ten healthy men were the subjects of the study. Subject performance on divided-attention was compared with tests of short-term memory and a set of visual analog...

Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis.

Science.gov (United States)

Clausen, Torben; Nielsen, Ole Bækgaard; Clausen, Johannes D; Pedersen, Thomas Holm; Hayward, Lawrence J

2011-07-01

In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K(+) ingestion or rest after exercise. Force can be restored by muscle work or treatment with β(2)-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na(+) channel (Na(v)1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K(+)](o). In resting mutant soleus, tetrodotoxin (TTX)-suppressible (22)Na uptake and [Na(+)](i) were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P Na(+),K(+) pump-mediated (86)Rb uptake was 83% larger than in WT. Salbutamol stimulated (86)Rb uptake and reduced [Na(+)](i) both in mutant and WT soleus. Stimulating Na(+),K(+) pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na(+)](i) with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na(+),K(+) pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na(+)](i) on the synthesis of Na(+),K(+) pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na(+) influx and show that contractility can be restored by acute stimulation of the Na(+),K(+) pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in (86)Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated

Gender differences in alcohol impairment of simulated driving performance and driving-related skills.

Science.gov (United States)

Miller, Melissa A; Weafer, Jessica; Fillmore, Mark T

2009-01-01

Considerable laboratory research indicates that moderate doses of alcohol impair a broad range of skilled activities related to driving performance in young adults. Although laboratory studies show that the intensity of impairment is generally dependent on the blood alcohol concentration, some reviews of this literature suggest that women might be more sensitive to the impairing effects of alcohol than men. The present study tested this hypothesis. Drawing on data from previous experiments in our laboratory, we compared men and women in terms of the degree to which a challenge dose of alcohol (0.65 g/kg) impaired their simulated driving performance and measures of three separate behavioral and cognitive functions important to driving performance: motor coordination, speed of information processing and information-processing capacity. Alcohol significantly impaired all aspects of performance. Moreover, women displayed greater impairment than men on all behavioral tests and also reported higher levels of subjective intoxication compared with men. Both biological and social-cultural factors have been implicated in gender differences in the behavioral responses to alcohol. The current evidence of heightened sensitivity to alcohol in women highlights the need for better understanding the biological and environmental factors underlying this gender difference.

Progesterone Metabolites Produced by Cytochrome P450 3A Modulate Uterine Contractility in a Murine Model

Science.gov (United States)

Patil, Avinash S.; Swamy, Geeta K.; Murtha, Amy P.; Heine, R. Phillips; Zheng, Xiaomei; Grotegut, Chad A.

2015-01-01

Objective: We seek to characterize the effect of progesterone metabolites on spontaneous and oxytocin-induced uterine contractility. Study Design: Spontaneous contractility was studied in mouse uterine horns after treatment with progesterone, 2α-hydroxyprogesterone, 6β-hydroxyprogesterone (6β-OHP), 16α-hydroxyprogesterone (16α-OHP), or 17-hydroxyprogesterone caproate (17-OHPC) at 10−9 to 10−6 mol/L. Uterine horns were exposed to progestins (10−6 mol/L), followed by increasing concentrations of oxytocin (1-100 nmol/L) to study oxytocin-induced contractility. Contraction parameters were compared for each progestin and matched vehicle control using repeated measures 2-way analysis of variance. In vitro metabolism of progesterone by recombinant cytochrome P450 3A (CYP3A) microsomes (3A5, 3A5, and 3A7) identified major metabolites. Results: Oxytocin-induced contractile frequency was decreased by 16α-OHP (P = .03) and increased by 6β-OHP (P = .05). Progesterone and 17-OHPC decreased oxytocin-induced contractile force (P = .02 and P = .04, respectively) and frequency (P = .02 and P = .03, respectively). Only progesterone decreased spontaneous contractile force (P = .02). Production of 16α-OHP and 6β-OHP metabolites were confirmed in all CYP3A isoforms tested. Conclusion: Progesterone metabolites produced by maternal or fetal CYP3A enzymes influence uterine contractility. PMID:26037300

Myosin phosphorylation potentiates steady-state work output without altering contractile economy of mouse fast skeletal muscles.

Science.gov (United States)

Gittings, William; Bunda, Jordan; Vandenboom, Rene

2018-01-30

Skeletal myosin light chain kinase (skMLCK)-catalyzed phosphorylation of the myosin regulatory light chain (RLC) increases (i.e. potentiates) mechanical work output of fast skeletal muscle. The influence of this event on contractile economy (i.e. energy cost/work performed) remains controversial, however. Our purpose was to quantify contractile economy of potentiated extensor digitorum longus (EDL) muscles from mouse skeletal muscles with (wild-type, WT) and without (skMLCK ablated, skMLCK -/- ) the ability to phosphorylate the RLC. Contractile economy was calculated as the ratio of total work performed to high-energy phosphate consumption (HEPC) during a period of repeated isovelocity contractions that followed a potentiating stimulus (PS). Consistent with genotype, the PS increased RLC phosphorylation measured during, before and after isovelocity contractions in WT but not in skMLCK -/- muscles (i.e. 0.65 and 0.05 mol phosphate mol -1 RLC, respectively). In addition, although the PS enhanced work during repeated isovelocity contractions in both genotypes, the increase was significantly greater in WT than in skMLCK -/- muscles (1.51±0.03 versus 1.10±0.05, respectively; all data P economy calculated for WT muscles was similar to that calculated for skMLCK -/- muscles (i.e. 5.74±0.67 and 4.61±0.71 J kg -1  μmol -1 P, respectively ( P economy. © 2018. Published by The Company of Biologists Ltd.

Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animal model.

Science.gov (United States)

Corriveau, Stéphanie; Blouin, Simon; Raiche, Évelyne; Nolin, Marc-Antoine; Rousseau, Éric; Pasquier, Jean-Charles

2015-12-01

Abnormal uterine contraction patterns were recently demonstrated in uterine strips from pregnant women treated with Levothyroxine (T4). These abnormalities were correlated with an increased risk of C-section delivery and associated surgical complications. To date, no study has investigated whether uterine contractility is modified by hypothyroidism or T4 treatment. Herein, we analyze the physiological role of T4 on uterine contractions. Female non-pregnant Sprague-Dawley rats ( N  = 22) were used and divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low T4 doses (20 μg/kg/day) and 4) with high T4 doses (100 μg/kg/day). Hypothyroidism was induced by an iodine-deficient diet. Isometric tension measurements were performed in vitro on myometrium tissues in isolated organ baths. Contractile activity parameters were quantified (amplitude, duration, frequency and area under the curve) using pharmacological tools to assess their effect. Screening of thyroid function confirmed a hypothyroid state for all rats under iodine-free diet to which T4 was subsequently administered to counterbalance hypothyroidism. Results demonstrate that hypothyroidism significantly decreased contractile duration (-17%) and increased contractile frequency (+26%), while high doses of T4 increased duration (+200%) and decreased frequency (-51%). These results thus mimic the pattern of abnormal contractions previously observed in uterine tissue from T4-treated hypothyroid pregnant women. Our data suggest that changes in myometrial reactivity are induced by T4 treatment. Thus, in conjunction with our previous observations on human myometrial strips, management of hypothyroidism should be improved to reduce the rate of C-sections in this group of patients.

[Gallbladder contractility in children with functional abdominal pain or irritable bowel syndrome].

Science.gov (United States)

Iwańczak, Franciszek; Siedlecka-Dawidko, Jolanta; Iwanczak, Barbara

2013-07-01

III Rome Criteria of functional gastrointestinal disorders in children, distinguished the disturbances with abdominal pain, to which irritable bowel syndrome, functional abdominal pains, functional dyspepsia and abdominal migraine were included. THE AIM OF THE STUDY was sonographic assessment of the gallbladder and its contractility in functional abdominal pain and irritable bowel syndrome in children. The study comprised 96 children aged 6 to 18 years, 59 girls and 37 boys. Depending on diagnosis, the children were divided into three groups. 38 children with functional abdominal pain constituted the first group, 26 children with irritable bowel syndrome were included to the second group, the third group consisted of 32 healthy children (control group). Diagnosis of functional abdominal pain and irritable bowel syndrome was made based on the III Rome Criteria. In irritable bowel syndrome both forms with diarrhea (13) and with constipation (13) were observed. Anatomy and contractility of the gallbladder were assessed by ultrasound examination. The presence of septum, wall thickness, thick bile, vesicle volume in fasting state and 30th and 60th minute after test meal were taken into consideration. Test meal comprised about 15% of caloric requirement of moderate metabolism. Children with bile stones and organic diseases were excluded from the study. Thickened vesicle wall and thick bile were present more frequently in children with irritable bowel syndrome and functional abdominal pain than in control group (p functional abdominal pain than in irritable bowel syndrome and control group (p = 0.003, p = 0.05). Vesicle contractility after test meal was greatest in children with functional abdominal pain. Evaluation of diminished (smaller than 30%) and enlarged (greater then 80%) gallbladder contractility at 30th and 60th minute after test meal demonstrated disturbances of contractility in children with irritable bowel syndrome and functional abdominal pain. In children

The communicative performance of a severely hearing-impaired adolescent

Directory of Open Access Journals (Sweden)

Ann Russel

1981-11-01

Full Text Available This study describes the communicative performance of a severely hearing-impaired adolescent.The experimenter taught the subject how to play Russian Backgammon. The subject conversed with, and afterwards taught his mother, speech therapist, and a peer how to play the game. Each dyad played the game once. Videotape recordings were made of each dyadic situation. The channels of communication, both verbal and nonverbal, used by each speaker, were determined. A relational communication coding scheme, involving the analysis of requests and subsequent responses, was applied to the data. Results indicate that the hearing-impaired adolescent, though not always able to hold a dominant position in a dyadic situation, was capable of expressing the same types of control as normal adults. Moreover, the types of control expressed varied as a function of each contextual setting. Whenever the subject did hold a dominant position, the combined verbal plus nonverbal channel was his predominant mode of  communication. These findings  suggest that a sociolinguistic approach provides important information regarding a hearing-impaired adolescent's communicative performance.

Effect of lead on cholinergic contractile function in the forestomach, ileum and colon of the male Wistar rat

International Nuclear Information System (INIS)

Ryden, E.B.

1986-01-01

Gastrointestinal symptoms, including colic, are signs of lead poisoning in man, but the mechanism of these effects has not been elucidated. In order to understand the effects of lead on acetylcholine (ACh)-mediated responses, studies were undertaken to determine the isometric contractile response to methacholine, KCl and electric field stimulation in rat forestomach, ileum and colon under conditions of in vitro and in vivo treatment with lead acetate. Rats were dosed with 4% lead acetate in their diet, NIH-07, for 7 weeks, which resulted in renal and hematologic toxicity and blood lead levels of 180-389 ug/dl (1.2 x 10 -5 M). Tissues from in vivo treated rats were exposed to 1.2 x 10 -5 M lead acetate during in vitro contractile studies. E/sub max/ or ED 50 methacholine was not affected by 1.2 x 10 -5 M lead acetate, administered in vitro to control tissue. In the forestomach, a 10-fold higher concentration of lead (16 x 10 -5 M), administered in vitro, increased baseline tension and inhibition response to methacholine. However, in vivo lead treatment potentiated response to methacholine in the forestomach and increased baseline tension in the presence of physostigmine. The EFS response, attributable to ACh release, was not affected in the forestomach or ileum by 1.2 x 10 -5 M in vitro lead treatment. These data indicate that lead, administered in vivo in concentrations which cause renal and hematologic toxicity, does not impair cholinergic contractile response in gastrointestinal smooth muscle. Instead, the response to methacholine may be potentiated in the forestomach. Possible mechanisms of lead-induced potentiation of baseline or evoked tension include increased levels of non-elicited ACh release, inhibition of acetylcholinesterase or sensitization of muscarinic receptors

Metabolic and cardiac changes in high cholesterol-fructose-fed rats

DEFF Research Database (Denmark)

Axelsen, Lene N; Pedersen, Henrik D; Petersen, Jørgen S

2010-01-01

Introduction: High cholesterol-fructose (HCF) fed rats have previously been described as an animal model of impaired cardiac insulin signaling and decreased contractile performance. In this study, we evaluated the metabolic and cardiac effects of a HCF diet in rats. Methods: Male Sprague-Dawley r......Introduction: High cholesterol-fructose (HCF) fed rats have previously been described as an animal model of impaired cardiac insulin signaling and decreased contractile performance. In this study, we evaluated the metabolic and cardiac effects of a HCF diet in rats. Methods: Male Sprague...

Influence of metabolism modifiers of cyclic nucleotides on contractility of right ventricle of rat heart with intact and removed endocardial endothelium

Directory of Open Access Journals (Sweden)

Savić Slađana

2010-01-01

Full Text Available Introduction. Endocardial endothelium, a natural biological barrier between circulating blood in heart ventricle and cells, creates a complex yet finely tuned balance of interactions with the immediate environment. Objective. We investigated the roles of theophylline, nonspecific phosphodiesterase inhibitor, and imidazole, an activator of phosphodiesterase on contractility of the right ventricle of rat heart, with intact and removed endocardial endothelium. Methods. Adult rats, of both sexes, type Wistar albino, were used in this experiment. All experiments were conducted on the preparations of the right ventricle using two experimental models. In the first experimental model, an endocardial endothelium (EE was preserved, and in the second model, an endocardial endothelium (-EE was removed using 1% solution Triton X-100. Results. Theophylline (1x10-2 mol/l expressed the positive inotropic effect on the heart, regardless of the presence of the endocardial endothelium. Inotropic response as multiple process can be induced by inhibition of phosphodiesterase, accumulation of cyclic nucleotides and activation of Ca2+ channels. Imidazole (2x10-3 mol/l increased the contractility of the right ventricle of the heart with EE. The modulator effect of endocardial endothelium on contractility of imidazole proved to be significant. As imidazole influenced the contractility of the right ventricle only in the presence of the endocardial endothelium, it is assumed that its effect is mediated via deliverance of endothelial mediators with positive inotropic effect. Conclusion. An intact endocardial endothelium is necessary for completion of contractile performance of the heart.

The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning

Science.gov (United States)

Baldwin, K. M.; Caiozzo, V. J.; Haddad, F.; Baker, M. J.; Herrick, R. E.

1994-01-01

Previous studies have shown that the unloading of skeletal muscle, as occurring during exposure to space flight, exerts a profound effect on both the mass (cross sectional area) of skeletal muscle fibers and the relative expression of protein isoforms comprising the contractile system. Available information suggests that slow (type I) fibers, comprising chiefly the antigravity muscles of experimental animals, in addition to atrophying, undergo alterations in the type of myosin heavy chain (MHC) expressed such that faster isoforms become concomitantly expressed in a sub-population of slow fibers when insufficient force-bearing activity is maintained on the muscle. Consequently, these transformations in both mass and myosin heavy chain phenotype could exert a significant impact on the functional properties of skeletal muscle as manifest in the strength, contractile speed, and endurance scope of the muscle. To further explore these issues, a study was performed in which young adult male rats were exposed to zero gravity for six days, following which, the antigravity soleus muscle was examined for a) contractile properties, determined in situ and b) isomyosin expression, as studied using biochemical, molecular biology, and histochemical/immunohistochemical techniques.

Gene transfer of heterologous G protein-coupled receptors to cardiomyocytes: differential effects on contractility.

Science.gov (United States)

Laugwitz, K L; Weig, H J; Moretti, A; Hoffmann, E; Ueblacker, P; Pragst, I; Rosport, K; Schömig, A; Ungerer, M

2001-04-13

In heart failure, reduced cardiac contractility is accompanied by blunted cAMP responses to beta-adrenergic stimulation. Parathyroid hormone (PTH)-related peptide and arginine vasopressin are released from the myocardium in response to increased wall stress but do not stimulate contractility or adenylyl cyclase at physiological concentrations. To bypass the defective beta-adrenergic signaling cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V(2) vasopressin receptors (rV(2)-Rs), which are normally not expressed in the myocardium and which are both strongly coupled to adenylyl cyclase, and recombinant beta(2)-adrenergic receptors (rbeta(2)-ARs) were overexpressed in cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to increase contractility via the heterologous, recombinant receptors was compared. Whereas V(2)-Rs are uniquely coupled to Gs, PTH1-Rs and beta(2)-ARs are also coupled to other G proteins. Gene transfer of rPTH1-Rs or rbeta(2)-ARs to adult cardiomyocytes resulted in maximally increased basal contractility, which could not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs induced increased cAMP formation and phospholipase C activity. In contrast, healthy or failing rV(2)-R-expressing cardiomyocytes showed unaltered basal contractility. Their contractility and cAMP formation increased only at agonist exposure, which did not activate phospholipase C. In summary, we found that gene transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the transgene, as does that of beta(2)-ARS: In the absence of receptor agonists, rPTH1-Rs and rbeta(2)-ARs increase basal contractility, coupling to 2 G proteins simultaneously. In contrast, rV(2)-Rs are uniquely coupled to Gs and are not constitutively active, retaining their property to be activated exclusively on agonist stimulation. Therefore, gene transfer of V(2)-Rs might be more suited to test the effects of c

Suppression of guinea pig ileum induced contractility by plasma albumin of hibernators

Science.gov (United States)

Bruce, David S.; Ambler, Douglas L.; Henschel, Timothy M.; Oeltgen, Peter R.; Nilekani, Sita P.; Amstrup, Steven C.

1992-01-01

Previous studies suggest that hibernation may be regulated by internal opioids and that the putative “hibernation induction trigger” (HIT) may itself be an opioid. This study examined the effect of plasma albumin (known to bind HIT) on induced contractility of the guinea pig ileum muscle strip. Morphine (400 nM) depressed contractility and 100 nM naloxone restored it. Ten milligrams of lyophilized plasma albumin fractions from hibernating ground squirrels, woodchucks, black bears, and polar bears produced similar inhibition, with partial reversal by naloxone. Five hundredths mg of d-Ala2-d-Leu5-enkephalin (DADLE) also inhibited contractility and naloxone reversed it. Conclusions are that hibernating individuals of these species contain an HIT substance that is opioid in nature and summer animals do not; an endogenous opioid similar to leu-enkephalin may be the HIT compound or give rise to it.

A global, myosin light chain kinase-dependent increase in myosin II contractility accompanies the metaphase-anaphase transition in sea urchin eggs.

Science.gov (United States)

Lucero, Amy; Stack, Christianna; Bresnick, Anne R; Shuster, Charles B

2006-09-01

Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase-anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase-anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus.

A Global, Myosin Light Chain Kinase-dependent Increase in Myosin II Contractility Accompanies the Metaphase–Anaphase Transition in Sea Urchin Eggs

Science.gov (United States)

Lucero, Amy; Stack, Christianna; Bresnick, Anne R.

2006-01-01

Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase–anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase–anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus. PMID:16837551

Reliability of contractile properties of the knee extensor muscles in individuals with post-polio syndrome.

Directory of Open Access Journals (Sweden)

Eric L Voorn

Full Text Available To assess the reliability of contractile properties of the knee extensor muscles in 23 individuals with post-polio syndrome (PPS and 18 age-matched healthy individuals.Contractile properties of the knee extensors were assessed from repeated electrically evoked contractions on 2 separate days, with the use of a fixed dynamometer. Reliability was determined for fatigue resistance, rate of torque development (MRTD, and early and late relaxation time (RT50 and RT25, using the intraclass correlation coefficient (ICC and standard error of measurement (SEM, expressed as % of the mean.In both groups, reliability for fatigue resistance was good, with high ICCs (>0.90 and small SEM values (PPS: 7.1%, healthy individuals: 7.0%. Reliability for contractile speed indices varied, with the best values found for RT50 (ICCs>0.82, SEM values <2.8%. We found no systematic differences between test and retest occasions, except for RT50 in healthy subjects (p = 0.016.In PPS and healthy individuals, the reliability of fatigue resistance, as obtained from electrically evoked contractions is high. The reliability of contractile speed is only moderate, except for RT50 in PPS, demonstrating high reliability.This was the first study to examine the reliability of electrically evoked contractile properties in individuals with PPS. Our results demonstrate its potential to study mechanisms underlying muscle fatigue in PPS and to evaluate changes in contractile properties over time in response to interventions or from natural course.

3,5-Diiodo-l-Thyronine Increases Glucose Consumption in Cardiomyoblasts Without Affecting the Contractile Performance in Rat Heart

Directory of Open Access Journals (Sweden)

Ginevra Sacripanti

2018-05-01

modulate cardiac energy metabolism by increasing glucose consumption. Some evidence of toxicity and a transient impairment of contractile performance are observed only at 10 µM concentration. These effects appear to be specific for T2, since they are not reproduced by T3 or T4.

Visual Search Performance in Patients with Vision Impairment: A Systematic Review.

Science.gov (United States)

Senger, Cassia; Margarido, Maria Rita Rodrigues Alves; De Moraes, Carlos Gustavo; De Fendi, Ligia Issa; Messias, André; Paula, Jayter Silva

2017-11-01

Patients with visual impairment are constantly facing challenges to achieve an independent and productive life, which depends upon both a good visual discrimination and search capacities. Given that visual search is a critical skill for several daily tasks and could be used as an index of the overall visual function, we investigated the relationship between vision impairment and visual search performance. A comprehensive search was undertaken using electronic PubMed, EMBASE, LILACS, and Cochrane databases from January 1980 to December 2016, applying the following terms: "visual search", "visual search performance", "visual impairment", "visual exploration", "visual field", "hemianopia", "search time", "vision lost", "visual loss", and "low vision". Two hundred seventy six studies from 12,059 electronic database files were selected, and 40 of them were included in this review. Studies included participants of all ages, both sexes, and the sample sizes ranged from 5 to 199 participants. Visual impairment was associated with worse visual search performance in several ophthalmologic conditions, which were either artificially induced, or related to specific eye and neurological diseases. This systematic review details all the described circumstances interfering with visual search tasks, highlights the need for developing technical standards, and outlines patterns for diagnosis and therapy using visual search capabilities.

PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

Science.gov (United States)

Yang, Jason H.; Polanowska-Grabowska, Renata K.; Smith, Jeffrey S.; Shields, Charles W.; Saucerman, Jeffrey J.

2014-01-01

β-adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca2+ handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50 = 10.60±0.68 min; EC50 = 89.00 nmol/L) than in the cytosol (t50 = 3.71±0.25 min; EC50 = 1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca2+ and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50 = 1.84 nmol/L) over cell hypertrophy (EC50 = 85.88 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses. PMID:24225179

The Functional Lumen Imaging Probe Detects Esophageal Contractility not Observed with Manometry in Patients with Achalasia

Science.gov (United States)

Carlson, Dustin A.; Lin, Zhiyue; Kahrilas, Peter J.; Sternbach, Joel; Donnan, Erica N.; Friesen, Laurel; Listernick, Zoe; Mogni, Benjamin; Pandolfino, John E.

2015-01-01

Background & Aims The functional lumen imaging probe (FLIP) could improve characterization of achalasia subtypes by detecting non-occlusive esophageal contractions not observed with standard manometry. We aimed to evaluate for esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. Methods Fifty one treatment-naïve patients with achalasia, defined and sub-classified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intra-bag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were further characterized by propagation direction, repetitiveness, and based on whether they were occluding or non-occluding. Results Esophageal contractility was detected in all 10 controls: 8/10 had repetitive, antegrade, contractions and 9/10 had occluding contractions. Contractility was detected in 27% (4/15) of patients with type I achalasia and 65% (18/26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility not observed in controls (repetitive, retrograde contractions). Conclusions Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of pan-esophageal pressurization in patients with type II achalasia. These findings could have implications for additional sub-classification to supplement prediction of the achalasia disease course. PMID:26278501

Association between vestibular function and motor performance in hearing-impaired children.

Science.gov (United States)

Maes, Leen; De Kegel, Alexandra; Van Waelvelde, Hilde; Dhooge, Ingeborg

2014-12-01

The clinical balance performance of normal-hearing (NH) children was compared with the balance performance of hearing-impaired (HI) children with and without vestibular dysfunction to identify an association between vestibular function and motor performance. Prospective study. Tertiary referral center. Thirty-six children (mean age, 7 yr 5 mo; range, 3 yr 8 mo-12 yr 11 mo) divided into three groups: NH children with normal vestibular responses, HI children with normal vestibular responses, and HI children with abnormal vestibular function. A vestibular test protocol (rotatory and collic vestibular evoked myogenic potential testing) in combination with three clinical balance tests (balance beam walking, one-leg hopping, one-leg stance). Clinical balance performance. HI children with abnormal vestibular test results obtained the lowest quotients of motor performance, which were significantly lower compared with the NH group (p beam walking and one-leg stance; p = 0.003 for one-leg hopping). The balance performance of the HI group with normal vestibular responses was better in comparison with the vestibular impaired group but still significantly lower compared with the NH group (p = 0.020 for balance beam walking; p = 0.001 for one-leg stance; not significant for one-leg hopping). These results indicate an association between vestibular function and motor performance in HI children, with a more distinct motor deterioration if a vestibular impairment is superimposed to the auditory dysfunction.

Clinical Characteristics and Associated Systemic Diseases in Patients With Esophageal "Absent Contractility"-A Clinical Algorithm.

Science.gov (United States)

Laique, Sobia; Singh, Tavankit; Dornblaser, David; Gadre, Abhishek; Rangan, Vikram; Fass, Ronnie; Kirby, Donald; Chatterjee, Soumya; Gabbard, Scott

2018-01-19

This study was carried out to assess the clinical characteristics and associated systemic diseases seen in patients diagnosed with absent contractility as per the Chicago Classification version 3.0, allowing us to propose a diagnostic algorithm for their etiologic testing. The Chicago Classification version 3.0 has redefined major and minor esophageal motility disorders using high-resolution esophageal manometry. There is a dearth of publications based on research on absent contractility, which historically has been associated with myopathic processes such as systemic sclerosis (SSc). We conducted a retrospective, multicenter study. Data of patients diagnosed with absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January 2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to July 2016) and included: age, gender, associated medical conditions, surgical history, medications, and specific antibody testing. A total of 207 patients, including 57 male individuals and 150 female individuals, with mean age of 56.1 and 60.0 years, respectively, were included. Disease distribution was as follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic lupus erythematosus17, Sjögren syndrome 4, polymyositis 3, and dermatomyositis 3. Various other etiologies including gastroesophageal reflux disease, postradiation esophagitis, neuromuscular disorders, and surgical complications were seen in the remaining cohort. Most practitioners use the term "absent contractility" interchangeably with "scleroderma esophagus"; however, only 63% of patients with absent contractility had SSc. Overall, 20% had another systemic autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for absent contractility. Therefore, alternate diagnosis must be sought in these patients. We propose an algorithm for their etiologic evaluation.

Inhalation of Budesonide/Formoterol Increases Diaphragm Muscle Contractility

Directory of Open Access Journals (Sweden)

Chiyohiko Shindoh

2012-01-01

Conclusions: BUD/FORM inhalation has an inotropic effect on diaphragm muscle, protects diaphragm muscle deterioration after endotoxin injection, and inhibits NO production. Increments in muscle contractility with BUD/FORM inhalation are induced through a synergistic effect of an anti-inflammatory agent and 02-agonist.

Myocardial contractility in the echo lab: molecular, cellular and pathophysiological basis

Directory of Open Access Journals (Sweden)

Bombardini Tonino

2005-09-01

Full Text Available Abstract In the standard accepted concept, contractility is the intrinsic ability of heart muscle to generate force and to shorten, independently of changes in the preload or afterload with fixed heart rates. At molecular level the crux of the contractile process lies in the changing concentrations of Ca2+ ions in the myocardial cytosol. Ca2+ ions enter through the calcium channel that opens in response to the wave of depolarization that travels along the sarcolemma. These Ca2+ ions "trigger" the release of more calcium from the sarcoplasmic reticulum (SR and thereby initiate a contraction-relaxation cycle. In the past, several attempts were made to transfer the pure physiological concept of contractility, expressed in the isolated myocardial fiber by the maximal velocity of contraction of unloaded muscle fiber (Vmax, to the in vivo beating heart. Suga and Sagawa achieved this aim by measuring pressure/volume loops in the intact heart: during a positive inotropic intervention, the pressure volume loop reflects a smaller end-systolic volume and a higher end-systolic pressure, so that the slope of the pressure volume relationship moves upward and to the left. The pressure volume relationship is the most reliable index for assessing myocardial contractility in the intact circulation and is almost insensitive to changes in preload and after load. This is widely used in animal studies and occasionally clinically. The limit of the pressure volume relationship is that it fails to take into account the frequency-dependent regulation of contractility: the frequency-dependent control of transmembrane Ca2+ entry via voltage-gated Ca2+ channels provides cardiac cells with a highly sophisticated short-term system for the regulation of intracellular Ca2+ homeostasis. An increased stimulation rate increases the force of contraction: the explanation is repetitive Ca2+ entry with each depolarization and, hence, an accumulation of cytosolic calcium. As the heart

Contractility Dispersion in Long QT Syndrome

Directory of Open Access Journals (Sweden)

MH Nikoo

2009-09-01

Full Text Available Background: Previous studies, using M mode echocardiography, provided unexpected evidence of a mechanical alteration in patients with long QT syndrome. The aim of this study was to evaluate entire left ventricular (LV wall motion characteristics in patients with long QT syndrome using tissue Doppler imaging. Methods: We enrolled 17 patients with congenital long QT syndrome [11 female and 6 male], aged 21 to 45 years. 10 subjects without cardiac disease were also selected as a control group. Two-dimensional tissue Doppler imaging (TDI recording of the LV was obtained from the basal and mid-segments from apical four-chamber, two-chamber, and long-axis views. ‘Myocardial Contraction Duration’ [MCD] was defined as the time from start of R wave on ECG to end of S wave on TDI. MCD was measured in the six LV wall positions: septal, anteroseptal, lateral, inferior, posterior and anterior positions.Results: LV contractility dispersion was significantly greater in long QT syndrome patients compared to control group [0.051 ± 0.011 vs. 0.016 ± 0.06; P < 0.001]. Conclusion: Our study evaluated left ventricular dispersion of contractility duration in patients with long QT syndrome. This mechanical dispersion may be a reflection of the inhomogeneity of repolarisation in the long QT syndrome.

Isolation and maintenance-free culture of contractile myotubes from Manduca sexta embryos.

Directory of Open Access Journals (Sweden)

Amanda L Baryshyan

Full Text Available Skeletal muscle tissue engineering has the potential to treat tissue loss and degenerative diseases. However, these systems are also applicable for a variety of devices where actuation is needed, such as microelectromechanical systems (MEMS and robotics. Most current efforts to generate muscle bioactuators are focused on using mammalian cells, which require exacting conditions for survival and function. In contrast, invertebrate cells are more environmentally robust, metabolically adaptable and relatively autonomous. Our hypothesis is that the use of invertebrate muscle cells will obviate many of the limitations encountered when mammalian cells are used for bioactuation. We focus on the tobacco hornworm, Manduca sexta, due to its easy availability, large size and well-characterized muscle contractile properties. Using isolated embryonic cells, we have developed culture conditions to grow and characterize contractile M. sexta muscles. The insect hormone 20-hydroxyecdysone was used to induce differentiation in the system, resulting in cells that stained positive for myosin, contract spontaneously for the duration of the culture, and do not require media changes over periods of more than a month. These cells proliferate under normal conditions, but the application of juvenile hormone induced further proliferation and inhibited differentiation. Cellular metabolism under normal and low glucose conditions was compared for C2C12 mouse and M. sexta myoblast cells. While differentiated C2C12 cells consumed glucose and produced lactate over one week as expected, M. sexta muscle did not consume significant glucose, and lactate production exceeded mammalian muscle production on a per cell basis. Contractile properties were evaluated using index of movement analysis, which demonstrated the potential of these cells to perform mechanical work. The ability of cultured M. sexta muscle to continuously function at ambient conditions without medium replenishment

Myofilament Remodeling and Function Is More Impaired in Peripartum Cardiomyopathy Compared with Dilated Cardiomyopathy and Ischemic Heart Disease.

Science.gov (United States)

Bollen, Ilse A E; Ehler, Elisabeth; Fleischanderl, Karin; Bouwman, Floor; Kempers, Lanette; Ricke-Hoch, Melanie; Hilfiker-Kleiner, Denise; Dos Remedios, Cristobal G; Krüger, Martina; Vink, Aryan; Asselbergs, Folkert W; van Spaendonck-Zwarts, Karin Y; Pinto, Yigal M; Kuster, Diederik W D; van der Velden, Jolanda

2017-12-01

Peripartum cardiomyopathy (PPCM) and dilated cardiomyopathy (DCM) show similarities in clinical presentation. However, although DCM patients do not recover and slowly deteriorate further, PPCM patients show either a fast cardiac deterioration or complete recovery. The aim of this study was to assess if underlying cellular changes can explain the clinical similarities and differences in the two diseases. We, therefore, assessed sarcomeric protein expression, modification, titin isoform shift, and contractile behavior of cardiomyocytes in heart tissue of PPCM and DCM patients and compared these with nonfailing controls. Heart samples from ischemic heart disease (ISHD) patients served as heart failure control samples. Passive force was only increased in PPCM samples compared with controls, whereas PPCM, DCM, and ISHD samples all showed increased myofilament Ca 2+ sensitivity. Length-dependent activation was significantly impaired in PPCM compared with controls, no impairment was observed in ISHD samples, and DCM samples showed an intermediate response. Contractile impairments were caused by impaired protein kinase A (PKA)-mediated phosphorylation because exogenous PKA restored all parameters to control levels. Although DCM samples showed reexpression of EH-myomesin, an isoform usually only expressed in the heart before birth, PPCM and ISHD did not. The lack of EH-myomesin, combined with low PKA-mediated phosphorylation of myofilament proteins and increased compliant titin isoform, may explain the increase in passive force and blunted length-dependent activation of myofilaments in PPCM samples. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Robust gap repair in the contractile ring ensures timely completion of cytokinesis.

Science.gov (United States)

Silva, Ana M; Osório, Daniel S; Pereira, Antonio J; Maiato, Helder; Pinto, Inês Mendes; Rubinstein, Boris; Gassmann, Reto; Telley, Ivo Andreas; Carvalho, Ana Xavier

2016-12-19

Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an actin polymerization-dependent manner. An open ring is able to constrict, and rings repair from successive cuts. After gap repair, an increase in constriction velocity allows cytokinesis to complete at the same time as controls. Our analysis demonstrates that tension in the ring increases while net cortical tension at the site of ingression decreases throughout constriction and suggests that cytokinesis is accomplished by contractile modules that assemble and contract autonomously, enabling local repair of the actomyosin network. Consequently, cytokinesis is a highly robust process impervious to discontinuities in contractile ring structure. © 2016 Silva et al.

How is goodwill impairment driven by relative firm performance? : evidence from Germany

OpenAIRE

Brandão, Sara Fontes Coutinho Mesquita

2014-01-01

Goodwill treatment has been facing considerable changes in terms of regulation. More recently, IAS 36 (2004) develops the subject of impairment of assets, stating that goodwill should be subject to impairment tests on an annual basis. In the IFRS context, the present research study aims at investigating how goodwill impairment is driven by relative firm performance in Europe, using Germany evidence. More precisely, the paper focuses on two distinct analyses: comparing differenc...

Retosiban Prevents Stretch-Induced Human Myometrial Contractility and Delays Labor in Cynomolgus Monkeys.

Science.gov (United States)

Aye, Irving L M H; Moraitis, Alexandros A; Stanislaus, Dinesh; Charnock-Jones, D Stephen; Smith, Gordon C S

2018-03-01

Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies. To determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (1) the contractility of human myometrial explants and (2) labor in nonhuman primates. Human myometrial biopsies were obtained at planned term cesarean, and explants were exposed to stretch in the presence and absence of a range of drugs, including retosiban. The in vivo effects of retosiban were determined in cynomolgus monkeys. Prolonged mechanical stretch promoted myometrial extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Moreover, stretch-induced stimulation of myometrial contractility was prevented by ERK1/2 inhibitors. Retosiban (10 nM) prevented stretch-induced stimulation of myometrial contractility and phosphorylation of ERK1/2. Moreover, the inhibitory effect of retosiban on stretch-induced ERK1/2 phosphorylation was prevented by coincubation with a 100-fold excess of a peptide OTR antagonist, atosiban. Compared with vehicle-treated cynomolgus monkeys, treatment with oral retosiban (100 to 150 days of gestational age) reduced the risk of spontaneous delivery (hazard ratio = 0.07, 95% confidence interval 0.01 to 0.60, P = 0.015). The OTR acts as a uterine mechanosensor, whereby stretch increases myometrial contractility through agonist-free activation of the OTR. Retosiban prevents this through inverse agonism of the OTR and, in vivo, reduced the likelihood of spontaneous labor in nonhuman primates. We hypothesize that retosiban may be an effective preventative treatment of preterm birth in high-risk multiple pregnancies, an area of unmet clinical need.

Regional gastrointestinal contractility parameters using the wireless motility capsule

DEFF Research Database (Denmark)

Farmer, A D; Wegeberg, A-M L; Brock, B

2018-01-01

BACKGROUND: The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. AIMS: To describe normative values for motility/contractility parameters across age, gender and testing centres. METHODS: Healthy participants underwent...

The effect of exercise hypertrophy and disuse atrophy on muscle contractile properties: a mechanomyographic analysis.

Science.gov (United States)

Than, Christian; Tosovic, Danijel; Seidl, Laura; Mark Brown, J

2016-12-01

To determine whether mechanomyographic (MMG) determined contractile properties of the biceps brachii change during exercise-induced hypertrophy and subsequent disuse atrophy. Healthy subjects (mean ± SD, 23.7 ± 2.6 years, BMI 21.8 ± 2.4, n = 19) performed unilateral biceps curls (9 sets × 12 repetitions, 5 sessions per week) for 8 weeks (hypertrophic phase) before ceasing exercise (atrophic phase) for the following 8 weeks (non-dominant limb; treatment, dominant limb; control). MMG measures of muscle contractile properties (contraction time; T c , maximum displacement; D max , contraction velocity; V c ), electromyographic (EMG) measures of muscle fatigue (median power frequency; MPF), strength measures (maximum voluntary contraction; MVC) and measures of muscle thickness (ultrasound) were obtained. Two-way repeated measures ANOVA showed significant differences (P muscle thickness was greater than control, reflecting gross hypertrophy. MMG variables Dmax (weeks 2, 7) and Vc (weeks 7, 8) declined. During the atrophic phase, MVC (weeks 9-12) and muscle thickness (weeks 9, 10) initially remained high before declining to control levels, reflecting gross atrophy. MMG variables D max (weeks 9, 14) and V c (weeks 9, 14, 15) also declined during the atrophic phase. No change in T c was found throughout the hypertrophic or atrophic phases. MMG detects changes in contractile properties during stages of exercise-induced hypertrophy and disuse atrophy suggesting its applicability as a clinical tool in musculoskeletal rehabilitation.

Improvement of cardiac contractile function by peptide-based inhibition of NF-κB in the utrophin/dystrophin-deficient murine model of muscular dystrophy

Directory of Open Access Journals (Sweden)

Guttridge Denis C

2011-05-01

Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an inherited and progressive disease causing striated muscle deterioration. Patients in their twenties generally die from either respiratory or cardiac failure. In order to improve the lifespan and quality of life of DMD patients, it is important to prevent or reverse the progressive loss of contractile function of the heart. Recent studies by our labs have shown that the peptide NBD (Nemo Binding Domain, targeted at blunting Nuclear Factor κB (NF-κB signaling, reduces inflammation, enhances myofiber regeneration, and improves contractile deficits in the diaphragm in dystrophin-deficient mdx mice. Methods To assess whether cardiac function in addition to diaphragm function can be improved, we investigated physiological and histological parameters of cardiac muscle in mice deficient for both dystrophin and its homolog utrophin (double knockout = dko mice treated with NBD peptide. These dko mice show classic pathophysiological hallmarks of heart failure, including myocyte degeneration, an impaired force-frequency response and a severely blunted β-adrenergic response. Cardiac contractile function at baseline and frequencies and pre-loads throughout the in vivo range as well as β-adrenergic reserve was measured in isolated cardiac muscle preparations. In addition, we studied histopathological and inflammatory markers in these mice. Results At baseline conditions, active force development in cardiac muscles from NBD treated dko mice was more than double that of vehicle-treated dko mice. NBD treatment also significantly improved frequency-dependent behavior of the muscles. The increase in force in NBD-treated dko muscles to β-adrenergic stimulation was robustly restored compared to vehicle-treated mice. However, histological features, including collagen content and inflammatory markers were not significantly different between NBD-treated and vehicle-treated dko mice. Conclusions We conclude

The Functional Lumen Imaging Probe Detects Esophageal Contractility Not Observed With Manometry in Patients With Achalasia.

Science.gov (United States)

Carlson, Dustin A; Lin, Zhiyue; Kahrilas, Peter J; Sternbach, Joel; Donnan, Erica N; Friesen, Laurel; Listernick, Zoe; Mogni, Benjamin; Pandolfino, John E

2015-12-01

The functional lumen imaging probe (FLIP) could improve the characterization of achalasia subtypes by detecting nonocclusive esophageal contractions not observed with standard manometry. We aimed to evaluate esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. Fifty-one treatment-naive patients with achalasia, defined and subclassified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intrabag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were characterized further by propagation direction, repetitiveness, and based on whether they were occluding or nonoccluding. Esophageal contractility was detected in all 10 controls: 8 of 10 had repetitive antegrade contractions and 9 of 10 had occluding contractions. Contractility was detected in 27% (4 of 15) of patients with type I achalasia and in 65% (18 of 26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility that was not observed in controls (repetitive retrograde contractions). Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II achalasia. These findings could have implications for additional subclassification to supplement prediction of the achalasia disease course. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights

Impact of Age and Hearing Impairment on Work Performance during Long Working Hours

Directory of Open Access Journals (Sweden)

Verena Wagner-Hartl

2018-01-01

Full Text Available Based on demographic prognoses, it must be assumed that a greater number of older workers will be found in the future labor market. How to deal with their possible age-related impairments of sensory functions, like hearing impairment and work performance during extended working time, has not been addressed explicitly until now. The study addresses this interplay. The study was performed on two consecutive days after normal working hours. The 55 participants had to “work” in the study at least three additional hours to simulate a situation of long working hours. The tested measures for (job performance were: general attention, long-term selective attention, concentration, and reaction time. All of the investigated variables were taken at both days of the study (2 × 2 × 2 repeated measurement design. The results show effects for age, the interaction of hearing impairment and time of measurement, and effects of the measurement time. Older participants reacted slower than younger participants did. Furthermore, younger participants reacted more frequently in a correct way. Hearing impairment seems to have a negative impact especially on measures of false reactions, and therefore especially on measurement time 1. The results can be interpreted in a way that hearing-impaired participants are able to compensate their deficits over time.

Impact of Age and Hearing Impairment on Work Performance during Long Working Hours.

Science.gov (United States)

Wagner-Hartl, Verena; Grossi, Nina R; Kallus, K Wolfgang

2018-01-09

Based on demographic prognoses, it must be assumed that a greater number of older workers will be found in the future labor market. How to deal with their possible age-related impairments of sensory functions, like hearing impairment and work performance during extended working time, has not been addressed explicitly until now. The study addresses this interplay. The study was performed on two consecutive days after normal working hours. The 55 participants had to "work" in the study at least three additional hours to simulate a situation of long working hours. The tested measures for (job) performance were: general attention, long-term selective attention, concentration, and reaction time. All of the investigated variables were taken at both days of the study (2 × 2 × 2 repeated measurement design). The results show effects for age, the interaction of hearing impairment and time of measurement, and effects of the measurement time. Older participants reacted slower than younger participants did. Furthermore, younger participants reacted more frequently in a correct way. Hearing impairment seems to have a negative impact especially on measures of false reactions, and therefore especially on measurement time 1. The results can be interpreted in a way that hearing-impaired participants are able to compensate their deficits over time.

Plasticity of TOM complex assembly in skeletal muscle mitochondria in response to chronic contractile activity.

Science.gov (United States)

Joseph, Anna-Maria; Hood, David A

2012-03-01

We investigated the assembly of the TOM complex within skeletal muscle under conditions of chronic contractile activity-induced mitochondrial biogenesis. Tom40 import into mitochondria was increased by chronic contractile activity, as was its time-dependent assembly into the TOM complex. These changes coincided with contractile activity-induced augmentations in the expression of key protein import machinery components Tim17, Tim23, and Tom22, as well as the cytosolic chaperone Hsp90. These data indicate the adaptability of the TOM protein import complex and suggest a regulatory role for the assembly of this complex in exercise-induced mitochondrial biogenesis. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.

Effects of endothelin, calcium channel blockade and EDRF inhibition on the contractility of human uteroplacental arteries.

Science.gov (United States)

Fried, G; Liu, Y A

1994-08-01

In order to examine the possibility that endothelin might be important in the regulation of placental blood flow, human uteroplacental vessels were superfused in vitro to study the contractile effect of endothelin as compared with a known strong contractor of placental blood vessels, serotonin (5-HT). The contractile responses were compared in the presence and absence of calcium channel blocking agents, as well as in the presence of L-NMA, an inhibitor of EDRF/nitric oxide. Endothelin (ET, 10(-10)-10(-6) M) and 5-HT (10(-8)-10(-4) M) induced contractions in the vessels. Maximal contractions in the presence of endothelin were elicited at 10(-7) M, whereas 5-HT elicited maximal contractions at 10(-5) M. At 10(-7) M, ET was more potent than 5-HT. The calcium-channel blocking agents nifedipine, diltiazem and NiCl2 relaxed the vessels by 5-15% from baseline. The contractile response to ET in the presence of nifedipine or diltiazem was reduced by 55 and 67%, respectively. The response of 5-HT in the presence of nifedipine was reduced by 58%. The contractile response to 5-HT as well as ET in the presence of both nifedipine and NiCl2 was not significantly lower than in the presence of nifedipine only. The EDRF-inhibiting agent L-NMA caused a small contractile response at concentrations of 10(-6)-10(-5) M. ET as well as 5-HT added after pretreatment with L-NMA produced a larger contractile response than ET or 5-HT alone. The results show that ET has a strong contractile effect on placental blood vessels at concentrations likely to occur during labor and delivery. The mechanism whereby ET as well as 5-HT contracts placental vessel smooth muscle appears to partly involve nifedipine- and diltiazem-sensitive calcium channels, but almost half of the response depends on mobilization of calcium through other means.

Physical Performance Is Associated with Working Memory in Older People with Mild to Severe Cognitive Impairment

Directory of Open Access Journals (Sweden)

K. M. Volkers

2014-01-01

Full Text Available Background. Physical performances and cognition are positively related in cognitively healthy people. The aim of this study was to examine whether physical performances are related to specific cognitive functioning in older people with mild to severe cognitive impairment. Methods. This cross-sectional study included 134 people with a mild to severe cognitive impairment (mean age 82 years. Multiple linear regression was performed, after controlling for covariates and the level of global cognition, with the performances on mobility, strength, aerobic fitness, and balance as predictors and working memory and episodic memory as dependent variables. Results. The full models explain 49–57% of the variance in working memory and 40–43% of episodic memory. Strength, aerobic fitness, and balance are significantly associated with working memory, explaining 3–7% of its variance, irrespective of the severity of the cognitive impairment. Physical performance is not related to episodic memory in older people with mild to severe cognitive impairment. Conclusions. Physical performance is associated with working memory in older people with cognitive impairment. Future studies should investigate whether physical exercise for increased physical performance can improve cognitive functioning. This trial is registered with ClinicalTrials.gov NTR1482.

Extended driving impairs nocturnal driving performances.

Directory of Open Access Journals (Sweden)

Patricia Sagaspe

Full Text Available Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3-5 am, 1-5 am and 9 pm-5 am on open highway. Fourteen young healthy men (mean age [+/-SD] = 23.4 [+/-1.7] years participated Inappropriate line crossings (ILC in the last hour of driving of each session, sleep variables, self-perceived fatigue and sleepiness were measured. Compared to the short (3-5 am driving session, the incidence rate ratio of inappropriate line crossings increased by 2.6 (95% CI, 1.1 to 6.0; P<.05 for the intermediate (1-5 am driving session and by 4.0 (CI, 1.7 to 9.4; P<.001 for the long (9 pm-5 am driving session. Compared to the reference session (9-10 pm, the incidence rate ratio of inappropriate line crossings were 6.0 (95% CI, 2.3 to 15.5; P<.001, 15.4 (CI, 4.6 to 51.5; P<.001 and 24.3 (CI, 7.4 to 79.5; P<.001, respectively, for the three different durations of driving. Self-rated fatigue and sleepiness scores were both positively correlated to driving impairment in the intermediate and long duration sessions (P<.05 and increased significantly during the nocturnal driving sessions compared to the reference session (P<.01. At night, extended driving impairs driving performances and therefore should be limited.

The Hypocretin/Orexin Antagonist Almorexant Promotes Sleep Without Impairment of Performance in Rats

Directory of Open Access Journals (Sweden)

Stephen R Morairty

2014-01-01

Full Text Available The hypocretin receptor (HcrtR antagonist almorexant (ALM has potent hypnotic actions but little is known about neurocognitive performance in the presence of ALM. HcrtR antagonists are hypothesized to induce sleep by disfacilitation of wake-promoting systems whereas GABAA receptor modulators such as zolpidem (ZOL induce sleep through general inhibition of neural activity. To test the hypothesis that less functional impairment results from HcrtR antagonist-induced sleep, we evaluated the performance of rats in the Morris Water Maze in the presence of ALM vs. ZOL. Performance in spatial reference memory (SRM and spatial working memory (SWM tasks were assessed during the dark period after equipotent sleep-promoting doses (100 mg/kg, po following undisturbed and sleep deprivation (SD conditions. ALM-treated rats were indistinguishable from vehicle (VEH-treated rats for all SRM performance measures (distance travelled, latency to enter, time within, and number of entries into, the target quadrant after both the undisturbed and 6 h SD conditions. In contrast, rats administered ZOL showed impairments in all parameters measured compared to VEH or ALM in the undisturbed conditions. Following SD, ZOL-treated rats also showed impairments in all measures. ALM-treated rats were similar to VEH-treated rats for all SWM measures (velocity, time to locate the platform and success rate at finding the platform within 60 s after both the undisturbed and SD conditions. In contrast, ZOL-treated rats showed impairments in velocity and in the time to locate the platform. Importantly, ZOL rats only completed the task 23-50% of the time while ALM and VEH rats completed the task 79-100% of the time. Thus, following equipotent sleep-promoting doses, ZOL impaired rats in both memory tasks while ALM rats performed at levels comparable to VEH rats. These results are consistent with the hypothesis that less impairment results from HcrtR antagonism than from GABAA

Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride

DEFF Research Database (Denmark)

Mohanakumar, Sheyanth; Majgaard, Jens; Telinius, Niklas

2018-01-01

- with the impermeant anion aspartate and inhibition of Cl- transport and channels with the clinical diuretics furosemide and bendroflumethiazide, as well as DIDS and NPPB. The molecular expression of calcium-activated chloride channels was investigated by RT-PCR and proteins localized using immunoreactivity....... Spontaneous and norepinephrine-induced contractility in human lymphatic vessels was highly abrogated after Cl- substitution with aspartate. 100‒300µM DIDS or NPPB inhibited spontaneous contractile behavior. Norepinephrine-stimulated tone was furthermore markedly abrogated by 200µM DIDS. Furosemide lowered...

Performance-based functional impairment and readmission and death: a prospective study.

Science.gov (United States)

Aubert, Carole E; Folly, Antoine; Mancinetti, Marco; Hayoz, Daniel; Donzé, Jacques D

2017-06-08

Readmission and death are frequent after a hospitalisation and difficult to predict. While many predictors have been identified, few studies have focused on functional status. We assessed whether performance-based functional impairment at discharge is associated with readmission and death after an acute medical hospitalisation. We prospectively included patients aged ≥50 years admitted to the Department of General Internal Medicine of a large community hospital. Functional status was assessed shortly before discharge using the Timed Up and Go test performed twice in a standard way by trained physiotherapists and was defined as a test duration ≥15 s. Sensitivity analyses using a cut-off at >10 and >20 s were performed. The primary and secondary outcome measures were unplanned readmission and death, respectively, within 6 months after discharge. Within 6 months after discharge, 107/338 (31.7%) patients had an unplanned readmission and 31/338 (9.2%) died. Functional impairment was associated with higher risk of death (OR 2.44, 95% CI 1.15 to 5.18), but not with unplanned readmission (OR 1.34, 95% CI 0.84 to 2.15). No significant association was found between functional impairment and the total number of unplanned readmissions (adjusted OR 1.59, 95% CI 0.95 to 2.67). Functional impairment at discharge of an acute medical hospitalisation was associated with higher risk of death, but not of unplanned readmission within 6 months after discharge. Simple performance-based assessment may represent a better prognostic measure for mortality than for readmission. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Category verbal fluency performance may be impaired in amnestic mild cognitive impairment

Directory of Open Access Journals (Sweden)

Márcio Luiz Figueredo Balthazar

Full Text Available Abstract To study category verbal fluency (VF for animals in patients with amnestic mild cognitive impairment (aMCI, mild Alzheimer disease (AD and normal controls. Method: Fifteen mild AD, 15 aMCI, and 15 normal control subjects were included. Diagnosis of AD was based on DSM-IV and NINCDS-ADRDA criteria, while aMCI was based on the criteria of the International Working Group on Mild Cognitive Impairment, using CDR 0.5 for aMCI and CDR 1 for mild AD. All subjects underwent testing of category VF for animals, lexical semantic function (Boston Naming-BNT, CAMCOG Similarities item, WAIS-R forward and backward digit span, Rey Auditory Verbal Learning (RAVLT, Mini-Mental Status Examination (MMSE, and other task relevant functions such as visual perception, attention, and mood state (with Cornell Scale for Depression in Dementia. Data analysis used ANOVA and a post-hoc Tukey test for intergroup comparisons, and Pearson's coefficient for correlations of memory and FV tests with other task relevant functions (statistical significance level was p<0.05. Results: aMCI patients had lower performance than controls on category VF for animals and on the backward digit span subtest of WAIS-R but higher scores compared with mild AD patients. Mild AD patients scored significantly worse than aMCI and controls across all tests. Conclusion: aMCI patients may have poor performance in some non-memory tests, specifically category VF for animals in our study, where this could be attributable to the influence of working memory.

Recently active contractile deformation in the forearc of southern Peru

Science.gov (United States)

Hall, S. R.; Farber, D.; Audin, L.; Finkel, R. C.

2010-12-01

In the Precordillera and Western Cordillera of southern Peru (14°-18°S), vast pediment surfaces have been abandoned through drainage diversion and river incision, with the major drainages carving deep canyons. Within this region, we have identified range-sub-parallel contractile structures that accommodate significant distributed crustal deformation. Young geomorphic features document both the presence and youthfulness of these contractile structures. Here, we determine exposure ages on geomorphic features such as pediment surfaces and fluvial terraces using in situ produced cosmogenic radionuclides, in conjunction with field and remote mapping. This chronologic data reveals that ancient surfaces have been preserved as a result of very low erosion rates. We measure this rate to be chronology and geomorphic mapping, we calculate a Pleistocene river incision rate of ~0.3mm/yr determined from data collected along exoreic rivers. This rate is consistent with longer-term incision rates measured in other localities along this margin. We suggest that, in this region of southern Peru, the steep western wedge of the Andean margin supports the high topography of the Altiplano through a combination of uplift along steeply dipping contractile west-vergent structures and isostatic responses to the focused removal of large amounts of crustal material through canyon incision. Further, that these range sub-parallel structures are related at depth to a thrust system that plays a role in not only the maintenance of the Andean margin, but potentially in its formation as well.

Functional impairment in patients with major depressive disorder: the 2-year PERFORM study.

Science.gov (United States)

Hammer-Helmich, Lene; Haro, Josep Maria; Jönsson, Bengt; Tanguy Melac, Audrey; Di Nicola, Sylvie; Chollet, Julien; Milea, Dominique; Rive, Benoît; Saragoussi, Delphine

2018-01-01

The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment. This was a 2-year observational study in 1,159 outpatients with MDD aged 18-65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined. The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up. These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice.

Determinants of gross motor skill performance in children with visual impairments.

Science.gov (United States)

Haibach, Pamela S; Wagner, Matthias O; Lieberman, Lauren J

2014-10-01

Children with visual impairments (CWVI) generally perform poorer in gross motor skills when compared with their sighted peers. This study examined the influence of age, sex, and severity of visual impairment upon locomotor and object control skills in CWVI. Participants included 100 CWVI from across the United States who completed the Test of Gross Motor Development II (TGMD-II). The TGMD-II consists of 12 gross motor skills including 6 object control skills (catching, kicking, striking, dribbling, throwing, and rolling) and 6 locomotor skills (running, sliding, galloping, leaping, jumping, and hopping). The full range of visual impairments according to United States Association for Blind Athletes (USABA; B3=20/200-20/599, legally blind; B2=20/600 and up, travel vision; B1=totally blind) were assessed. The B1 group performed significantly worse than the B2 (0.000 ≤ p ≤ 0.049) or B3 groups (0.000 ≤ p ≤ 0.005); however, there were no significant differences between B2 and B3 except for the run (p=0.006), catch (p=0.000), and throw (p=0.012). Age and sex did not play an important role in most of the skills, with the exception of boys outperforming girls striking (p=0.009), dribbling (p=0.013), and throwing (p=0.000), and older children outperforming younger children in dribbling (p=0.002). The significant impact of the severity of visual impairment is likely due to decreased experiences and opportunities for children with more severe visual impairments. In addition, it is likely that these reduced experiences explain the lack of age-related differences in the CWVI. The large disparities in performance between children who are blind and their partially sighted peers give direction for instruction and future research. In addition, there is a critical need for intentional and specific instruction on motor skills at a younger age to enable CWVI to develop their gross motor skills. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vitro contractile effects of agents used in the clinical management of postpartum haemorrhage.

Science.gov (United States)

Morrison, John J; Crosby, David A; Crankshaw, Denis J

2016-10-15

Uterine atony is a major cause of postpartum haemorrhage and maternal mortality. However, the comparative pharmacology of agents used to treat this condition is poorly understood. This study evaluates, using human pregnant myometrium in vitro, a range of contractile parameters for agents used in the clinical treatment of atonic postpartum haemorrhage. The effects of oxytocin, carbetocin, ergometrine, carboprost, syntometrine and misoprostol were investigated in 146 myometrial strips from 19 donors. The potency and maximal response values were obtained, and compared, using both maximal amplitude and mean contractile force as indices of contraction. Single, EC50 concentrations of the agents were administered and both force and contraction peak parameters were compared during a 15-min exposure. Differences were considered significant when Poxytocin and carbetocin being the most potent. The most important difference between the agents was in their ability to increase the mean contractile force, with oxytocin superior to all agents except syntometrine. In single dose experiments, mean contractile force was the parameter that separated the agents. In this respect, oxytocin was not statistically different from carboprost or syntometrine, but was superior to all other agents. These findings support a clear role for oxytocin as the first line agent for treatment of postpartum haemorrhage and raise doubts about the potential clinical usefulness of misoprostol. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic fuzzy system predicting contractile reactivity patterns of small arteries

DEFF Research Database (Denmark)

Tang, J; Sheykhzade, Majid; Clausen, B F

2014-01-01

strategies. Results show that optimized fuzzy systems (OFSs) predict contractile reactivity of arteries accurately. In addition, OFSs identified significant differences that were undetectable using conventional analysis in the responses of arteries between groups. We concluded that OFSs may be used...

Impact of low vision rehabilitation on functional vision performance of children with visual impairment.

Science.gov (United States)

Ganesh, Suma; Sethi, Sumita; Srivastav, Sonia; Chaudhary, Amrita; Arora, Priyanka

2013-09-01

To evaluate the impact of low vision rehabilitation on functional vision of children with visual impairment. The LV Prasad-Functional Vision Questionnaire, designed specifically to measure functional performance of visually impaired children of developing countries, was used to assess the level of difficulty in performing various tasks pre and post visual rehabilitation in children with documented visual impairment. Chi-square test was used to assess the impact of rehabilitation intervention on functional vision performance; a P visual acuity prior to the introduction of low vision devices (LVDs) was 0.90 ± 0.05 for distance and for near it was 0.61 ± 0.05. After the intervention, the acuities improved significantly for distance (0.2 ± 0.27; P visual rehabilitation was especially found in those activities related to their studying lifestyle like copying from the blackboard (P visual rehabilitation, especially with those activities which are related to their academic output. It is important for these children to have an early visual rehabilitation to decrease the impairment associated with these decreased visual output and to enhance their learning abilities.

2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy

OpenAIRE

Cheng, Yuanhua; Hogarth, Kaley A.; O'Sullivan, M. Lynne; Regnier, Michael; Pyle, W. Glen

2015-01-01

1) First report to characterize and define the contractile kinetics and defects associated with naturally occurring dilated cardiomyopathy (DCM) in dogs. 2) Novel findings that dATP is able to reverse the contractile defects associated with naturally occurring canine DCM.

Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration.

Science.gov (United States)

Gregorevic, Paul; Plant, David R; Stupka, Nicole; Lynch, Gordon S

2004-07-15

Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca(2+)- and Sr(2+)-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had approximately 10% of the maximal force producing capacity (P(o)) of control (uninjured) fibres, and an altered sensitivity to Ca(2+) and Sr(2+) at 7 days post-injury. Increased force production and a shift in Ca(2+) sensitivity consistent with fibre maturation were observed during regeneration such that P(o) was restored to 36-45% of that in control fibres by 21 days, and sensitivity to Ca(2+) and Sr(2+) was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed.

A contractile and counterbalancing adhesion system controls the 3D shape of crawling cells.

Science.gov (United States)

Burnette, Dylan T; Shao, Lin; Ott, Carolyn; Pasapera, Ana M; Fischer, Robert S; Baird, Michelle A; Der Loughian, Christelle; Delanoe-Ayari, Helene; Paszek, Matthew J; Davidson, Michael W; Betzig, Eric; Lippincott-Schwartz, Jennifer

2014-04-14

How adherent and contractile systems coordinate to promote cell shape changes is unclear. Here, we define a counterbalanced adhesion/contraction model for cell shape control. Live-cell microscopy data showed a crucial role for a contractile meshwork at the top of the cell, which is composed of actin arcs and myosin IIA filaments. The contractile actin meshwork is organized like muscle sarcomeres, with repeating myosin II filaments separated by the actin bundling protein α-actinin, and is mechanically coupled to noncontractile dorsal actin fibers that run from top to bottom in the cell. When the meshwork contracts, it pulls the dorsal fibers away from the substrate. This pulling force is counterbalanced by the dorsal fibers' attachment to focal adhesions, causing the fibers to bend downward and flattening the cell. This model is likely to be relevant for understanding how cells configure themselves to complex surfaces, protrude into tight spaces, and generate three-dimensional forces on the growth substrate under both healthy and diseased conditions.

Carboxyl-terminal-dependent recruitment of nonmuscle myosin II to megakaryocyte contractile ring during polyploidization.

Science.gov (United States)

Badirou, Idinath; Pan, Jiajia; Legrand, Céline; Wang, Aibing; Lordier, Larissa; Boukour, Siham; Roy, Anita; Vainchenker, William; Chang, Yunhua

2014-10-16

Endomitosis is a unique megakaryocyte (MK) differentiation process that is the consequence of a late cytokinesis failure associated with a contractile ring defect. Evidence from in vitro studies has revealed the distinct roles of 2 nonmuscle myosin IIs (NMIIs) on MK endomitosis: only NMII-B (MYH10), but not NMII-A (MYH9), is localized in the MK contractile ring and implicated in mitosis/endomitosis transition. Here, we studied 2 transgenic mouse models in which nonmuscle myosin heavy chain (NMHC) II-A was genetically replaced either by II-B or by a chimeric NMHCII that combined the head domain of II-A with the rod and tail domains of II-B. This study provides in vivo evidence on the specific role of NMII-B on MK polyploidization. It demonstrates that the carboxyl-terminal domain of the heavy chains determines myosin II localization to the MK contractile ring and is responsible for the specific role of NMII-B in MK polyploidization.

Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery

Science.gov (United States)

Py, G; Ramonatxo, C; Sirvent, P; Sanchez, A M J; Philippe, A G; Douillard, A; Galbès, O; Lionne, C; Bonnieu, A; Chopard, A; Cazorla, O; Lacampagne, A; Candau, R B

2015-01-01

Clenbuterol is a β2-adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg−1 day−1) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P muscle contraction and relaxation force kinetics indicated that clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P fast rate constant of relaxation in soleus muscle (P fibres (fast twitch fibres) from clenbuterol-treated animals demonstrated decreased amplitude after 14 days (−19%, P < 0.01) and 21 days (−25%, P < 0.01). In conclusion, we showed that chronic clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca2+ release during contraction could partially explain these deleterious effects. PMID:25656230

Myosin phosphorylation improves contractile economy of mouse fast skeletal muscle during staircase potentiation.

Science.gov (United States)

Bunda, Jordan; Gittings, William; Vandenboom, Rene

2018-01-30

Phosphorylation of the myosin regulatory light chain (RLC) by skeletal myosin light chain kinase (skMLCK) potentiates rodent fast twitch muscle but is an ATP-requiring process. Our objective was to investigate the effect of skMLCK-catalyzed RLC phosphorylation on the energetic cost of contraction and the contractile economy (ratio of mechanical output to metabolic input) of mouse fast twitch muscle in vitro (25°C). To this end, extensor digitorum longus (EDL) muscles from wild-type (WT) and from skMLCK-devoid (skMLCK -/- ) mice were subjected to repetitive low-frequency stimulation (10 Hz for 15 s) to produce staircase potentiation of isometric twitch force, after which muscles were quick frozen for determination of high-energy phosphate consumption (HEPC). During stimulation, WT muscles displayed significant potentiation of isometric twitch force while skMLCK -/- muscles did not (i.e. 23% versus 5% change, respectively). Consistent with this, RLC phosphorylation was increased ∼3.5-fold from the unstimulated control value in WT but not in skMLCK -/- muscles. Despite these differences, the HEPC of WT muscles was not greater than that of skMLCK -/- muscles. As a result of the increased contractile output relative to HEPC, the calculated contractile economy of WT muscles was greater than that of skMLCK -/- muscles. Thus, our results suggest that skMLCK-catalyzed phosphorylation of the myosin RLC increases the contractile economy of WT mouse EDL muscle compared with skMLCK -/- muscles without RLC phosphorylation. © 2018. Published by The Company of Biologists Ltd.

Modifying influence of incorporated 137Cs upon the mechanisms of adrenergic control over contractile myucard function

International Nuclear Information System (INIS)

Lobanok, L.M.; Bulanova, K.Ya.; Gerasimovich, N.V.; Sineleva, M.V.; Milyutin, A.A.

1994-01-01

Incorporated 137 Cs (absorbed dose of 0.26 Gy) causes decrease of myocard's contractile function and intropic response to β-adrenagonists effect, isoproterenol-stimulated adenylate cyclase activity and β-adrenoreceptors affinity. Adrenergic effects, mediated by α-adrenergic structures on heart contractile function, on the contrary, become stronger, that is due to the increase of the receptors' dencity on sarcolemma surface

Functions of nonmuscle myosin II in assembly of the cellular contractile system.

Directory of Open Access Journals (Sweden)

Maria Shutova

Full Text Available The contractile system of nonmuscle cells consists of interconnected actomyosin networks and bundles anchored to focal adhesions. The initiation of the contractile system assembly is poorly understood structurally and mechanistically, whereas system's maturation heavily depends on nonmuscle myosin II (NMII. Using platinum replica electron microscopy in combination with fluorescence microscopy, we characterized the structural mechanisms of the contractile system assembly and roles of NMII at early stages of this process. We show that inhibition of NMII by a specific inhibitor, blebbistatin, in addition to known effects, such as disassembly of stress fibers and mature focal adhesions, also causes transformation of lamellipodia into unattached ruffles, loss of immature focal complexes, loss of cytoskeleton-associated NMII filaments and peripheral accumulation of activated, but unpolymerized NMII. After blebbistatin washout, assembly of the contractile system begins with quick and coordinated recovery of lamellipodia and focal complexes that occurs before reappearance of NMII bipolar filaments. The initial formation of focal complexes and subsequent assembly of NMII filaments preferentially occurred in association with filopodial bundles and concave actin bundles formed by filopodial roots at the lamellipodial base. Over time, accumulating NMII filaments help to transform the precursor structures, focal complexes and associated thin bundles, into stress fibers and mature focal adhesions. However, semi-sarcomeric organization of stress fibers develops at much slower rate. Together, our data suggest that activation of NMII motor activity by light chain phosphorylation occurs at the cell edge and is uncoupled from NMII assembly into bipolar filaments. We propose that activated, but unpolymerized NMII initiates focal complexes, thus providing traction for lamellipodial protrusion. Subsequently, the mechanical resistance of focal complexes activates a

Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy

Science.gov (United States)

Koide, M.; Hamawaki, M.; Narishige, T.; Sato, H.; Nemoto, S.; DeFreyte, G.; Zile, M. R.; Cooper G, I. V.; Carabello, B. A.

2000-01-01

BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

Morning anaerobic performance is not altered by vigilance impairment.

Directory of Open Access Journals (Sweden)

Romain Lericollais

Full Text Available The aim of this study was to determine the role played by vigilance on the anaerobic performance recorded during a Wingate test performed at the bathyphase (nadir of the circadian rhythmicity. Twenty active male participants performed a 60-s Wingate test at 6 a.m. during 3 test sessions in counter-balanced order the day after either (i a normal reference night, (ii a total sleep deprivation night, or (iii a total sleep deprivation night associated with an extended simulated driving task from 9 p.m. to 5 a.m. During this task, the number of inappropriate line crossings (ILCs was used to control and quantify the effective decrease in the level of vigilance. The main findings show that (i vigilance of each participant was significantly altered (i.e., a drastic and progressive increase in ILCs is shown during the 7.5 hours of driving by the sleep deprivation night associated with an extended driving task; (ii the subjective evaluation of vigilance performed by self-rated scale revealed an increased impairment of the vigilance level between the normal reference night, the total sleep deprivation night and the total sleep deprivation night associated with an extended driving task; and (iii the morning following this last condition, during the Wingate test, the recorded cycling biomechanical parameters (peak power, mean power and fatigue index values, power decrease, and cycling kinetic and kinematic patterns were not significantly different from the two other conditions. Consequently, these results show that anaerobic performances recorded during a Wingate test performed at the bathyphase of the circadian rhythmicity are not altered by a drastic impairment in vigilance. These findings seem to indicate that vigilance is probably not a factor that contributes to circadian variations in anaerobic performance.

Simulated astigmatism impairs academic-related performance in children.

Science.gov (United States)

Narayanasamy, Sumithira; Vincent, Stephen J; Sampson, Geoff P; Wood, Joanne M

2015-01-01

Astigmatism is an important refractive condition in children. However, the functional impact of uncorrected astigmatism in this population is not well established, particularly with regard to academic performance. This study investigated the impact of simulated bilateral astigmatism on academic-related tasks before and after sustained near work in children. Twenty visually normal children (mean age: 10.8 ± 0.7 years; six males and 14 females) completed a range of standardised academic-related tests with and without 1.50 D of simulated bilateral astigmatism (with both academic-related tests and the visual condition administered in a randomised order). The simulated astigmatism was induced using a positive cylindrical lens while maintaining a plano spherical equivalent. Performance was assessed before and after 20 min of sustained near work, during two separate testing sessions. Academic-related measures included a standardised reading test (the Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (the Developmental Eye Movement test). Each participant was systematically assigned either with-the-rule (WTR, axis 180°) or against-the-rule (ATR, axis 90°) simulated astigmatism to evaluate the influence of axis orientation on any decrements in performance. Reading, visual information processing and reading-related eye movement performance were all significantly impaired by both simulated bilateral astigmatism (p  0.05). Simulated astigmatism led to a reduction of between 5% and 12% in performance across the academic-related outcome measures, but there was no significant effect of the axis (WTR or ATR) of astigmatism (p > 0.05). Simulated bilateral astigmatism impaired children's performance on a range of academic-related outcome measures irrespective of the orientation of the astigmatism. These findings have

Resolving the role of actoymyosin contractility in cell microrheology.

Directory of Open Access Journals (Sweden)

Christopher M Hale

2009-09-01

Full Text Available Einstein's original description of Brownian motion established a direct relationship between thermally-excited random forces and the transport properties of a submicron particle in a viscous liquid. Recent work based on reconstituted actin filament networks suggests that nonthermal forces driven by the motor protein myosin II can induce large non-equilibrium fluctuations that dominate the motion of particles in cytoskeletal networks. Here, using high-resolution particle tracking, we find that thermal forces, not myosin-induced fluctuating forces, drive the motion of submicron particles embedded in the cytoskeleton of living cells. These results resolve the roles of myosin II and contractile actomyosin structures in the motion of nanoparticles lodged in the cytoplasm, reveal the biphasic mechanical architecture of adherent cells-stiff contractile stress fibers interdigitating in a network at the cell cortex and a soft actin meshwork in the body of the cell, validate the method of particle tracking-microrheology, and reconcile seemingly disparate atomic force microscopy (AFM and particle-tracking microrheology measurements of living cells.

Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

Science.gov (United States)

Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

2010-09-01

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

Investigating Cardiac MRI Based Right Ventricular Contractility As A Novel Non-Invasive Metric of Pulmonary Arterial Pressure

Science.gov (United States)

Menon, Prahlad G; Adhypak, Srilakshmi M; Williams, Ronald B; Doyle, Mark; Biederman, Robert WW

2014-01-01

BACKGROUND We test the hypothesis that cardiac magnetic resonance (CMR) imaging-based indices of four-dimensional (4D) (three dimensions (3D) + time) right ventricle (RV) function have predictive values in ascertaining invasive pulmonary arterial systolic pressure (PASP) measurements from right heart catheterization (RHC) in patients with pulmonary arterial hypertension (PAH). METHODS We studied five patients with idiopathic PAH and two age and sex-matched controls for RV function using a novel contractility index (CI) for amplitude and phase to peak contraction established from analysis of regional shape variation in the RV endocardium over 20 cardiac phases, segmented from CMR images in multiple orientations. RESULTS The amplitude of RV contractility correlated inversely with RV ejection fraction (RVEF; R2 = 0.64, P = 0.03) and PASP (R2 = 0.71, P = 0.02). Phase of peak RV contractility also correlated inversely to RVEF (R2 = 0.499, P = 0.12) and PASP (R2 = 0.66, P = 0.04). CONCLUSIONS RV contractility analyzed from CMR offers promising non-invasive metrics for classification of PAH, which are congruent with invasive pressure measurements. PMID:25624777

Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I.

Science.gov (United States)

Løkken, Nicoline; Hedermann, Gitte; Thomsen, Carsten; Vissing, John

2016-09-01

We investigated whether a linear relationship between muscle strength and cross-sectional area (CSA) is preserved in calf muscles of patients with Becker muscular dystrophy (BMD, n = 14) and limb-girdle type 2I muscular dystrophy (LGMD2I, n = 11), before and after correcting for muscle fat infiltration. The Dixon magnetic resonance imaging technique was used to quantify fat and calculate a fat-free contractile CSA. Strength was assessed by dynamometry. Muscle strength/CSA relationships were significantly lower in patients versus controls. The strength/contractile-CSA relationship was still severely lowered in BMD, but was almost normalized in LGMD2I. Our findings suggest close to intact contractile properties in LGMD2I, which are severely disrupted in BMD. Ann Neurol 2016;80:466-471. © 2016 American Neurological Association.

Mechanobiological induction of long-range contractility by diffusing biomolecules and size scaling in cell assemblies

Science.gov (United States)

Dasbiswas, K.; Alster, E.; Safran, S. A.

2016-06-01

Mechanobiological studies of cell assemblies have generally focused on cells that are, in principle, identical. Here we predict theoretically the effect on cells in culture of locally introduced biochemical signals that diffuse and locally induce cytoskeletal contractility which is initially small. In steady-state, both the concentration profile of the signaling molecule as well as the contractility profile of the cell assembly are inhomogeneous, with a characteristic length that can be of the order of the system size. The long-range nature of this state originates in the elastic interactions of contractile cells (similar to long-range “macroscopic modes” in non-living elastic inclusions) and the non-linear diffusion of the signaling molecules, here termed mechanogens. We suggest model experiments on cell assemblies on substrates that can test the theory as a prelude to its applicability in embryo development where spatial gradients of morphogens initiate cellular development.

Increasing Optimism Protects Against Pain-Induced Impairment in Task-Shifting Performance.

Science.gov (United States)

Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

2017-04-01

Persistent pain can lead to difficulties in executive task performance. Three core executive functions that are often postulated are inhibition, updating, and shifting. Optimism, the tendency to expect that good things happen in the future, has been shown to protect against pain-induced performance deterioration in executive function updating. This study tested whether this protective effect of a temporary optimistic state by means of a writing and visualization exercise extended to executive function shifting. A 2 (optimism: optimism vs no optimism) × 2 (pain: pain vs no pain) mixed factorial design was conducted. Participants (N = 61) completed a shifting task once with and once without concurrent painful heat stimulation after an optimism or neutral manipulation. Results showed that shifting performance was impaired when experimental heat pain was applied during task execution, and that optimism counteracted pain-induced deterioration in task-shifting performance. Experimentally-induced heat pain impairs shifting task performance and manipulated optimism or induced optimism counteracted this pain-induced performance deterioration. Identifying psychological factors that may diminish the negative effect of persistent pain on the ability to function in daily life is imperative. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Excessive interatrial adiposity is associated with left atrial remodeling, augmented contractile performance in asymptomatic population

Directory of Open Access Journals (Sweden)

Yau-Huei Lai

2016-05-01

Full Text Available Purpose: Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA structural/functional remodeling, a clinical hallmark of early stage heart failure (HF and atrial fibrillation (AF incidence, in asymptomatic population remain largely unexplored. Methods: This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS, and left atrioventricular groove (AVG fat thickness were all measured by multidetector computed tomography (MDCT (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA. We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. Results: All four adiposity measures were positively associated with greater LA volumes (all P < 0.05, while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01. In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (β-coef: 0.17 & 0.15, both P < 0.05, and impaired LA reservoir and conduit function (β-coef: −0.20 & −0.12, both P < 0.05 after adjusting for clinical variables. Conclusion: Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population.

Effect of a Carbohydrate-Rich Diet on Rat Detrusor Smooth Muscle Contractility: An Experimental Study

Directory of Open Access Journals (Sweden)

Mustafa Suat Bolat

2017-01-01

Full Text Available Objectives. We aimed to investigate the effect of a carbohydrate-rich diet on detrusor contractility in rats. Materials and Methods. Sprague-Dawley rats were randomized into two groups. The control group received regular food and water. The study group received carbohydrate-rich diet for six weeks. The rats’ detrusor muscle was isolated for pharmacological and histopathological examinations. Results. In the control and study groups, mean body weights were 431.5 ± 27.6 g and 528.0 ± 36.2 g, respectively (p < 0.001. Electrical stimulation of the detrusor strips of the control group resulted in gradual contraction. A decreased contractile response was shown in the study group. Acetylcholine in 10-7-10-3 molar concentration produced a decreased contractile response in the study group, compared to the control group (p < 0.01. The study group showed marked subepithelial and intermuscular fibrosis in the bladder. Conclusion. Carbohydrate-rich diet causes marked subepithelial and extracellular fibrosis and changes in contractility in the detrusor within a six-week period. Changes have higher costs in therapeutic choices and correction of these changes remains difficult. Putting an end to carbohydrate-rich diet would seem to be more cost-effective than dealing with the effects of consuming it in high proportions which should be the national policy worldwide.

Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease.

NARCIS (Netherlands)

Verhoekx, J.S.; Mudera, V.; Walbeehm, E.T.; Hovius, S.E.

2013-01-01

BACKGROUND: In an attempt to provide minimally invasive treatment for Dupuytren's disease, percutaneous disruption of the affected tissue followed by lipografting is being tested. Contractile myofibroblasts drive this fibroproliferative disorder, whereas stem cells have recently been implicated in

The Level of Vision Necessary for Competitive Performance in Rifle Shooting: Setting the Standards for Paralympic Shooting With Vision Impairment

Directory of Open Access Journals (Sweden)

Peter M Allen

2016-11-01

Full Text Available The aim of this study was to investigate the level of vision impairment that would reduce performance in shooting; to guide development of entry criteria to visually impaired (VI shooting. Nineteen international-level shooters without vision impairment took part in the study. Participants shot an air rifle, while standing, towards a regulation target placed at the end of a 10m shooting range. Cambridge simulation glasses were used to simulate six different levels of vision impairment. Visual acuity (VA and contrast sensitivity (CS were assessed along with shooting performance in each of seven conditions of simulated impairment and compared to that with habitual vision. Shooting performance was evaluated by calculating each individual’s average score in every level of simulated vision impairment and normalising this score by expressing it as a percentage of the baseline performance achieved with habitual vision. Receiver Operating Characteristic (ROC curves were constructed to evaluate the ability of different VA and CS cut-off criteria to appropriately classify these athletes as achieving ‘expected’ or ‘below expected’ shooting results based on their performance with different levels of VA and CS. Shooting performance remained relatively unaffected by mild decreases in VA and CS, but quickly deteriorated with more moderate losses. The ability of visual function measurements to classify shooting performance was good, with 78% of performances appropriately classified using a cut-off of 0.53 logMAR and 74% appropriately classified using a cut-off of 0.83 logCS. The current inclusion criteria for VI shooting (1.0 logMAR is conservative, maximising the chance of including only those with an impairment that does impact performance, but potentially excluding some who do have a genuine impairment in the sport. A lower level of impairment would include more athletes who do have a genuine impairment but would potentially include those who do not

The Mitochondrial Calcium Uniporter Selectively Matches Metabolic Output to Acute Contractile Stress in the Heart

Directory of Open Access Journals (Sweden)

Jennifer Q. Kwong

2015-07-01

Full Text Available In the heart, augmented Ca2+ fluxing drives contractility and ATP generation through mitochondrial Ca2+ loading. Pathologic mitochondrial Ca2+ overload with ischemic injury triggers mitochondrial permeability transition pore (MPTP opening and cardiomyocyte death. Mitochondrial Ca2+ uptake is primarily mediated by the mitochondrial Ca2+ uniporter (MCU. Here, we generated mice with adult and cardiomyocyte-specific deletion of Mcu, which produced mitochondria refractory to acute Ca2+ uptake, with impaired ATP production, and inhibited MPTP opening upon acute Ca2+ challenge. Mice lacking Mcu in the adult heart were also protected from acute ischemia-reperfusion injury. However, resting/basal mitochondrial Ca2+ levels were normal in hearts of Mcu-deleted mice, and mitochondria lacking MCU eventually loaded with Ca2+ after stress stimulation. Indeed, Mcu-deleted mice were unable to immediately sprint on a treadmill unless warmed up for 30 min. Hence, MCU is a dedicated regulator of short-term mitochondrial Ca2+ loading underlying a “fight-or-flight” response that acutely matches cardiac workload with ATP production.

Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions

Science.gov (United States)

Doyle, Andrew D.; Carvajal, Nicole; Jin, Albert; Matsumoto, Kazue; Yamada, Kenneth M.

2015-11-01

The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils.

Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

Science.gov (United States)

Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

2012-01-01

Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

Changes of contractile responses due to simulated weightlessness in rat soleus muscle

Science.gov (United States)

Elkhammari, A.; Noireaud, J.; Léoty, C.

1994-08-01

Some contractile and electrophysiological properties of muscle fibers isolated from the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles of rats were compared with those measured in SOL muscles from suspended rats. In suspendede SOL (21 days of tail-suspension) membrane potential (Em), intracellular sodium activity (aiNa) and the slope of the relationship between Em and log [K]o were typical of fast-twitch muscles. The relation between the maximal amplitude of K-contractures vs Em was steeper for control SOL than for EDL and suspended SOL muscles. After suspension, in SOL muscles the contractile threshold and the inactivation curves for K-contractures were shifted to more positive Em. Repriming of K-contractures was unaffected by suspencion. The exposure of isolated fibers to perchlorate (ClO4-)-containing (6-40 mM) solutions resulted ina similar concentration-dependent shift to more negative Em of activation curves for EDL and suspended SOL muscles. On exposure to a Na-free TEA solution, SOL from control and suspended rats, in contrast to EDL muscles, generated slow contractile responses. Suspended SOL showed a reduced sensitivity to the contracture-producing effect of caffeine compared to control muscles. These results suggested that the modification observed due to suspension could be encounted by changes in the characteristics of muscle fibers from slow to fast-twitch type.

Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility.

Science.gov (United States)

Dickerson, L W; Rodak, D J; Fleming, T J; Gatti, P J; Massari, V J; McKenzie, J C; Gillis, R A

1998-05-28

We hypothesized that selective control of ventricular contractility might be mediated by postganglionic parasympathetic neurons in the cranial medial ventricular (CMV) ganglion plexus located in a fat pad at the base of the aorta. Sinus rate, atrioventricular (AV) conduction (ventricular rate during atrial pacing), and left ventricular contractile force (LV dP/dt during right ventricular pacing) were measured in eight chloralose-anesthetized dogs both before and during bilateral cervical vagus stimulation (20-30 V, 0.5 ms pulses, 15-20 Hz). Seven of these dogs were tested under beta-adrenergic blockade (propranolol, 0.8 mg kg(-1) i.v.). Control responses included sinus node bradycardia or arrest during spontaneous rhythm, high grade AV block or complete heart block, and a 30% decrease in contractility from 2118 +/- 186 to 1526 +/- 187 mm Hg s(-1) (P 0.05) decrease in contractility but still elicited the same degree of sinus bradycardia and AV block (N = 8, P < 0.05). Five dogs were re-tested 3 h after trimethaphan fat pad injection, at which time blockade of vagally-induced negative inotropy was partially reversed, as vagal stimulation decreased LV dP/dt by 19%. The same dose of trimethaphan given either locally into other fat pads (PVFP or IVC-ILA) or systemically (i.v.) had no effect on vagally-induced negative inotropy. Thus, parasympathetic ganglia located in the CMV fat pad mediated a decrease in ventricular contractility during vagal stimulation. Blockade of the CMV fat pad had no effect on vagally-mediated slowing of sinus rate or AV conduction.

Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox).

Science.gov (United States)

Fortuna, Rafael; Vaz, Marco Aurélio; Youssef, Aliaa Rehan; Longino, David; Herzog, Walter

2011-01-04

Botulinum toxin type A (BTX-A) is a frequently used therapeutic tool to denervate muscles in the treatment of neuromuscular disorders. Although considered safe by the US Food and Drug Administration, BTX-A can produce adverse effects in target and non-target muscles. With an increased use of BTX-A for neuromuscular disorders, the effects of repeat injections of BTX-A on strength, muscle mass and structure need to be known. Therefore, the purpose of this study was to investigate the changes in strength, muscle mass and contractile material in New Zealand White (NZW) rabbits. Twenty NZW rabbits were divided into 4 groups: control and 1, 3 and 6 months of unilateral, repeat injections of BTX-A into the quadriceps femoris. Outcome measures included knee extensor torque, muscle mass and the percentage of contractile material in the quadriceps muscles of the target and non-injected contralateral hindlimbs. Strength in the injected muscles was reduced by 88%, 89% and 95% in the 1, 3 and 6 months BTX-A injected hindlimbs compared to controls. Muscle mass was reduced by 50%, 42% and 31% for the vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM), respectively, at 1 month, by 68%, 51% and 50% at 3 months and by 76%, 44% and 13% at 6 months. The percentage of contractile material was reduced for the 3 and 6 months animals to 80-64%, respectively, and was replaced primarily by fat. Similar, but less pronounced results were also observed for the quadriceps muscles of the contralateral hindlimbs, suggesting that repeat BTX-A injections cause muscle atrophy and loss of contractile tissue in target muscles and also in non-target muscles that are far removed from the injection site. Copyright © 2010 Elsevier Ltd. All rights reserved.

Performance Measurement and Accommodation: Students with Visual Impairments on Pennsylvania's Alternate Assessment

Science.gov (United States)

Zebehazy, Kim T.; Zigmond, Naomi; Zimmerman, George J.

2012-01-01

Introduction: This study investigated the use of accommodations and the performance of students with visual impairments and severe cognitive disabilities on the Pennsylvania Alternate System of Assessment (PASA)yCoan alternate performance-based assessment. Methods: Differences in test scores on the most basic level (level A) of the PASA of 286…

Acute hypoxia limits endurance but does not affect muscle contractile properties.

NARCIS (Netherlands)

Degens, H.; Sanchez Horneros, J.M.; Hopman, M.T.E.

2006-01-01

Acute hypoxia causes skeletal muscle dysfunction in vitro, but little is known about its effect on muscle function in vivo. In 10 healthy male subjects, isometric contractile properties and fatigue resistance of the quadriceps muscle were determined during normoxia and hypoxia using electrically

Age and visual impairment decrease driving performance as measured on a closed-road circuit.

Science.gov (United States)

Wood, Joanne M

2002-01-01

In this study the effects of visual impairment and age on driving were investigated and related to visual function. Participants were 139 licensed drivers (young, middle-aged, and older participants with normal vision, and older participants with ocular disease). Driving performance was assessed during the daytime on a closed-road driving circuit. Visual performance was assessed using a vision testing battery. Age and visual impairment had a significant detrimental effect on recognition tasks (detection and recognition of signs and hazards), time to complete driving tasks (overall course time, reversing, and maneuvering), maneuvering ability, divided attention, and an overall driving performance index. All vision measures were significantly affected by group membership. A combination of motion sensitivity, useful field of view (UFOV), Pelli-Robson letter contrast sensitivity, and dynamic acuity could predict 50% of the variance in overall driving scores. These results indicate that older drivers with either normal vision or visual impairment had poorer driving performance compared with younger or middle-aged drivers with normal vision. The inclusion of tests such as motion sensitivity and the UFOV significantly improve the predictive power of vision tests for driving performance. Although such measures may not be practical for widespread screening, their application in selected cases should be considered.

Hydrogen ion changes and contractile behavior in the perfused rat heart

NARCIS (Netherlands)

Cingolani, H.E.; Maas, A.H.J.; Zimmerman, A.N.E.; Meijler, F.L.

1975-01-01

The effect of acid-base alterations was analyzed using isolated rat hearts perfused at constant coronary perfusion pressure, and stimulated to contract at constant rate. The amount of shortening in the major axis and its derivative were measured to assess myocardial contractility. Both the

The Level of Vision Necessary for Competitive Performance in Rifle Shooting: Setting the Standards for Paralympic Shooting with Vision Impairment.

Science.gov (United States)

Allen, Peter M; Latham, Keziah; Mann, David L; Ravensbergen, Rianne H J C; Myint, Joy

2016-01-01

The aim of this study was to investigate the level of vision impairment (VI) that would reduce performance in shooting; to guide development of entry criteria to visually impaired (VI) shooting. Nineteen international-level shooters without VI took part in the study. Participants shot an air rifle, while standing, toward a regulation target placed at the end of a 10 m shooting range. Cambridge simulation glasses were used to simulate six different levels of VI. Visual acuity (VA) and contrast sensitivity (CS) were assessed along with shooting performance in each of seven conditions of simulated impairment and compared to that with habitual vision. Shooting performance was evaluated by calculating each individual's average score in every level of simulated VI and normalizing this score by expressing it as a percentage of the baseline performance achieved with habitual vision. Receiver Operating Characteristic curves were constructed to evaluate the ability of different VA and CS cut-off criteria to appropriately classify these athletes as achieving 'expected' or 'below expected' shooting results based on their performance with different levels of VA and CS. Shooting performance remained relatively unaffected by mild decreases in VA and CS, but quickly deteriorated with more moderate losses. The ability of visual function measurements to classify shooting performance was good, with 78% of performances appropriately classified using a cut-off of 0.53 logMAR and 74% appropriately classified using a cut-off of 0.83 logCS. The current inclusion criteria for VI shooting (1.0 logMAR) is conservative, maximizing the chance of including only those with an impairment that does impact performance, but potentially excluding some who do have a genuine impairment in the sport. A lower level of impairment would include more athletes who do have a genuine impairment but would potentially include those who do not actually have an impairment that impacts performance in the sport. An

Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90

Directory of Open Access Journals (Sweden)

Alex Henke

2016-08-01

Full Text Available Background: Prostate cancer-associated fibroblasts (CAF can stimulate malignant progression and invasion of prostatic tumour cells via several mechanisms including those active in extracellular matrix; Methods: We isolated CAF from prostate cancer patients of Gleason Score 6–10 and confirmed their cancer-promoting activity using an in vivo tumour reconstitution assay comprised of CAF and BPH1 cells. We tested the effects of heat shock protein 90 (HSP90 inhibitors upon reconstituted tumour growth in vivo. Additionally, CAF contractility was measured in a 3D collagen contraction assay and migration was measured by scratch assay; Results: HSP90 inhibitors dipalmitoyl-radicicol and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG reduced tumour size and proliferation in CAF/BPH1 reconstituted tumours in vivo. We observed that the most contractile CAF were derived from patients with lower Gleason Score and of younger age compared with the least contractile CAF. HSP90 inhibitors radicicol and 17-DMAG inhibited contractility and reduced the migration of CAF in scratch assays. Intracellular levels of HSP70 and HSP90 were upregulated upon treatment with HSP90 inhibitors. Inhibition of HSP90 also led to a specific increase in transforming growth factor beta 2 (TGFβ2 levels in CAF; Conclusions: We suggest that HSP90 inhibitors act not only upon tumour cells, but also on CAF in the tumour microenvironment.

Blebbistain, a myosin II inhibitor, as a novel strategy to regulate detrusor contractility in a rat model of partial bladder outlet obstruction.

Directory of Open Access Journals (Sweden)

Xinhua Zhang

Full Text Available Partial bladder outlet obstruction (PBOO, a common urologic pathology mostly caused by benign prostatic hyperplasia, can coexist in 40-45% of patients with overactive bladder (OAB and is associated with detrusor overactivity (DO. PBOO that induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB is a myosin II inhibitor we recently demonstrated potently relaxed normal detrusor smooth muscle (SM and reports suggest varied BLEB efficacy for different SM myosin (SMM isoforms and/or SMM vs nonmuscle myosin (NMM. We hypothesize BLEB inhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model, organ bath contractility, competitive and Real-Time-RT-PCR were performed. It was found that obstructed-bladder weight significantly increased 2.74-fold while in vitro contractility of detrusor to various stimuli was impaired ∼50% along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitude but depressed frequency. PBOO switched bladder from a phasic-type to a more tonic-type SM. Expression of 5' myosin heavy chain (MHC alternatively spliced isoform SM-A (associated with tonic-type SM increased 3-fold while 3' MHC SM1 and essential light chain isoform MLC(17b also exhibited increased relative expression. Total SMMHC expression was decreased by 25% while the expression of NMM IIB (SMemb was greatly increased by 4.5-fold. BLEB was found to completely relax detrusor strips from both sham-operated and PBOO rats pre-contracted with KCl, carbachol or electrical field stimulation although sensitivity was slightly decreased (20% only at lower doses for PBOO. Thus we provide the first thorough characterization of the response of rat bladder myosin to PBOO and demonstrate complete BLEB-induced PBOO bladder SM relaxation. Furthermore, the present study provides valuable

Effect of serotonin on small intestinal contractility in healthy volunteers

DEFF Research Database (Denmark)

Hansen, M.B.; Arif, F.; Gregersen, H.

2008-01-01

The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contrac......The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro......-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy.

Science.gov (United States)

Turdi, Subat; Han, Xuefeng; Huff, Anna F; Roe, Nathan D; Hu, Nan; Gao, Feng; Ren, Jun

2012-09-15

Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O(2)(-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. Copyright © 2012 Elsevier Inc. All rights reserved.

HIV-associated cognitive performance and psychomotor impairment in a Thai cohort on long-term cART.

Science.gov (United States)

Do, Tanya C; Kerr, Stephen J; Avihingsanon, Anchalee; Suksawek, Saowaluk; Klungkang, Supalak; Channgam, Taweesak; Odermatt, Christoph C; Maek-A-Nantawat, Wirach; Ruxtungtham, Kiat; Ananworanich, Jintanat; Valcour, Victor; Reiss, Peter; Wit, Ferdinand W

2018-01-01

To assess cognitive performance and psychomotor impairment in an HIV-positive cohort, well-suppressed on combination antiretroviral therapy (cART), in an Asian resource-limited setting. Cross-sectional sociodemographic and cognitive data were collected in 329 HIV-positive and 510 HIV-negative participants. Cognitive performance was assessed using the International HIV Dementia Scale (IHDS), Montreal Cognitive Assessment (MoCA), WAIS-III Digit Symbol, Trail Making A, and Grooved Pegboard (both hands). Psychomotor test scores in the HIV-positive participants were converted to Z-scores using scores of the HIV-negative participants as normative data. Psychomotor impairment was defined as performance on two tests more than 1 standard deviation (SD) from controls or more than 2 SD on one test. Multivariate linear and logistic regression analyses were used to investigate associations between HIV and non-HIV-related covariates and poorer cognitive performance and psychomotor impairment. HIV-positive participants, mean age 45 (SD 7.69) years received cART for a median of 12.1 years (interquartile range [IQR] 9.1-14.4). Median CD4 cell count was 563 cells/mm 3 (IQR 435-725), and 92.77% had plasma HIV RNA performance (tests all P 90% on long-term cART, we found that inferior cognitive performance and psychomotor impairment were primarily associated with non-HIV-related factors.

Prevention of vision loss protects against age-related impairment in learning and memory performance in DBA/2J mice

Directory of Open Access Journals (Sweden)

Aimee eWong

2013-09-01

Full Text Available The DBA/2J mouse is a model of pigmentary glaucoma in humans as it shows age‐related increases in intraocular pressure, retinal ganglion cell death and visual impairment. Previously, we showed that visual ability declines from 9 ‐12 months of age and visual impairment is correlated with poor learning and memory performance in visuo‐spatial tasks but not in tasks that do not depend on visual cues. To test the sensory impairment hypothesis of aging, which postulates that sensory impaired individuals are disadvantaged in their performance on psychometric tests as a direct result of difficulties in sensory perception, we treated DBA/2J mice with a conventional glaucoma medication used in humans (Timoptic‐XE, 0.00, 0.25 or 0.50% daily from 9 weeks to 12 months of age to determine whether prevention of vision loss prevented the decline in visuo-spatial learning and memory performance. At all ages tested (3, 6, 9 and 12 months of age, mice treated with Timoptic-XE (0.25 and 0.50% maintained a high level of performance, while 12 month old control mice (0.00% exhibited impaired performance in visually‐dependent, but not non‐visual tasks. These results demonstrate that when sensory function is preserved, cognitive performance is normalized. Thus, as in many aging humans, DBA/2J mice show age-related decrements in performance on visually presented cognitive tests, not because of cognitive impairment but as a direct consequence of poor visual ability. Our results demonstrate that age-related impairment in performance in visuo-spatial tasks in DBA/2J mice can be prevented by the preservation of visual ability.

Prevention of vision loss protects against age-related impairment in learning and memory performance in DBA/2J mice.

Science.gov (United States)

Wong, Aimée A; Brown, Richard E

2013-01-01

The DBA/2J mouse is a model of pigmentary glaucoma in humans as it shows age-related increases in intraocular pressure (IOP), retinal ganglion cell death and visual impairment. Previously, we showed that visual ability declines from 9 to 12 months of age and visual impairment is correlated with poor learning and memory performance in visuo-spatial tasks but not in tasks that do not depend on visual cues. To test the "sensory impairment" hypothesis of aging, which postulates that sensory impaired individuals are disadvantaged in their performance on psychometric tests as a direct result of difficulties in sensory perception, we treated DBA/2J mice with a conventional glaucoma medication used in humans (Timoptic-XE, 0.00, 0.25, or 0.50%) daily from 9 weeks to 12 months of age to determine whether prevention of vision loss prevented the decline in visuo-spatial learning and memory performance. At all ages tested (3, 6, 9, and 12 months of age), mice treated with Timoptic-XE (0.25 and 0.50%) maintained a high level of performance, while 12 month old control mice (0.00%) exhibited impaired performance in visually-dependent, but not non-visual tasks. These results demonstrate that when sensory function is preserved, cognitive performance is normalized. Thus, as in many aging humans, DBA/2J mice show age-related decrements in performance on visually presented cognitive tests, not because of cognitive impairment but as a direct consequence of poor visual ability. Our results demonstrate that age-related impairment in performance in visuo-spatial tasks in DBA/2J mice can be prevented by the preservation of visual ability.

Palmitate diet-induced loss of cardiac caveolin-3: a novel mechanism for lipid-induced contractile dysfunction.

Directory of Open Access Journals (Sweden)

Catherine J Knowles

Full Text Available Obesity is associated with an increased risk of cardiomyopathy, and mechanisms linking the underlying risk and dietary factors are not well understood. We tested the hypothesis that dietary intake of saturated fat increases the levels of sphingolipids, namely ceramide and sphingomyelin in cardiac cell membranes that disrupt caveolae, specialized membrane micro-domains and important for cellular signaling. C57BL/6 mice were fed two high-fat diets: palmitate diet (21% total fat, 47% is palmitate, and MCT diet (21% medium-chain triglycerides, no palmitate. We established that high-palmitate feeding for 12 weeks leads to 40% and 50% increases in ceramide and sphingomyelin, respectively, in cellular membranes. Concomitant with sphingolipid accumulation, we observed a 40% reduction in systolic contractile performance. To explore the relationship of increased sphingolipids with caveolins, we analyzed caveolin protein levels and intracellular localization in isolated cardiomyocytes. In normal cardiomyocytes, caveolin-1 and caveolin-3 co-localize at the plasma membrane and the T-tubule system. However, mice maintained on palmitate lost 80% of caveolin-3, mainly from the T-tubule system. Mice maintained on MCT diet had a 90% reduction in caveolin-1. These data show that caveolin isoforms are sensitive to the lipid environment. These data are further supported by similar findings in human cardiac tissue samples from non-obese, obese, non-obese cardiomyopathic, and obese cardiomyopathic patients. To further elucidate the contractile dysfunction associated with the loss of caveolin-3, we determined the localization of the ryanodine receptor and found lower expression and loss of the striated appearance of this protein. We suggest that palmitate-induced loss of caveolin-3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release.

REVERSIBLE IMPAIRMENT OF ASSETS AND THE IMPACT ON ECONOMIC PERFORMANCE

Directory of Open Access Journals (Sweden)

MIRON VASILE-CRISTIAN-IOACHIM

2015-03-01

Full Text Available Economic performance is an essential objective of economic entities activating in the energy sector. The profit and loss account provides relevant information for performance analyzes, but evaluating the factors which determined the modification of the financial result demands detailed analyzes based on specific techniques. This paper develops and implements an econometric model that analyses the relation between gross profit and the reversible impairment of assets. The results of the analysis have shown that, in the energy sector, there is a significant connection between those two variables.

Cantonese tone production performance of mainstream school children with hearing impairment.

Science.gov (United States)

Cheung, Karen K L; Lau, Ada H Y; Lam, Joffee H S; Lee, Kathy Y S

2014-12-01

This study investigated the Cantonese tone production ability of children with hearing impairment studying in mainstream schools. The participants were 87 Cantonese-speaking children with mild-to-profound degrees of hearing loss aged 5.92-13.58 in Hong Kong. Most of the children were fitted with hearing aids (n = 65); 17 of them had profound hearing impairment, one who had severe hearing loss had cochlear implantation, and four who had mild hearing loss were without any hearing device. The Hong Kong Cantonese Articulation Test was administered, and the tones produced were rated by two of the authors and a speech-language pathologist. Group effects of tones, hearing loss level, and also an interaction of the two were found to be significant. The children with profound hearing impairment performed significantly worse than most of the other children. Tone 1 was produced most accurately, whereas tone 6 productions were the poorest. No relationship was found between the number of years of mainstreaming and tone production ability. Tone production error pattern revealed that confusion patterns in tone perception coincided with those in production. Tones having a similar fundamental frequency (F0) at the onset also posed difficulty in tone production for children with hearing impairment.

[A basis for application of cardiac contractility variability in the Evaluation and assessment of exercise and fitness].

Science.gov (United States)

Bu, Bin; Wang, Aihua; Han, Haijun; Xiao, Shouzhong

2010-06-01

Cardiac contractility variability (CCV) is a new concept which is introduced in the research field of cardiac contractility in recent years, that is to say, there are some disparities between cardiac contractilities when heart contracts. The changing signals of cardiac contractility contain a plenty of information on the cardiovascular function and disorder. In order to collect and analyze the message, we could quantitatively evaluate the tonicity and equilibrium of cardiac sympathetic nerve and parasympathetic nerve, and the effects of bio-molecular mechanism on the cardiovascular activities. By analyzing CCV, we could further understand the background of human being's heritage characteristics, nerve types, the adjusting mechanism, the molecular biology, and the adjustment of cardiac automatic nerve. With the development of the computing techniques, the digital signal processing method and its application in medical field, this analysis has been progressing greatly. By now, the assessment of CCV, just like the analysis of heart rate variability, is mainly via time domain and frequency domain analysis. CCV is one of the latest research fields in human cardiac signals being scarcely reported in the field of sports medicine; however, its research progresses are of important value for cardiac physiology and pathology in sports medicine and rehabilitation medicine.

Impaired exercise performance and skeletal muscle mitochondrial function in rats with secondary carnitine deficiency

Directory of Open Access Journals (Sweden)

Jamal BOUITBIR

2016-08-01

Full Text Available Purpose: The effects of carnitine depletion upon exercise performance and skeletal muscle mitochondrial function remain largely unexplored. We therefore investigated the effect of N-trimethyl-hydrazine-3-propionate (THP, a carnitine analogue inhibiting carnitine biosynthesis and renal carnitine reabsorption, on physical performance and skeletal muscle mitochondrial function in rats.Methods: Male Sprague Dawley rats were treated daily with water (control rats; n=12 or with 20 mg/100 g body weight THP (n=12 via oral gavage for 3 weeks. Following treatment, half of the animals of each group performed an exercise test until exhaustion.Results: Distance covered and exercise performance were lower in THP-treated compared to control rats. In the oxidative soleus muscle, carnitine depletion caused atrophy (-24% and impaired function of complex II and IV of the mitochondrial electron transport chain. The free radical leak (ROS production relative to oxygen consumption was increased and the cellular glutathione pool decreased. Moreover, mRNA expression of markers of mitochondrial biogenesis and mitochondrial DNA were decreased in THP-treated compared to control rats. In comparison, in the glycolytic gastrocnemius muscle, carnitine depletion was associated with impaired function of complex IV and increased free radical leak, whilst muscle weight and cellular glutathione pool were maintained. Markers of mitochondrial proliferation and mitochondrial DNA were unaffected.Conclusions: Carnitine deficiency is associated with impaired exercise capacity in rats treated with THP. THP-induced carnitine deficiency is associated with impaired function of the electron transport chain in oxidative and glycolytic muscle as well as with atrophy and decreased mitochondrial DNA in oxidative muscle.

Long-term vascular contractility assay using genipin-modified muscular thin films

International Nuclear Information System (INIS)

Hald, Eric S; Steucke, Kerianne E; Reeves, Jack A; Win, Zaw; Alford, Patrick W

2014-01-01

Vascular disease is a leading cause of death globally and typically manifests chronically due to long-term maladaptive arterial growth and remodeling. To date, there is no in vitro technique for studying vascular function over relevant disease time courses that both mimics in vivo-like tissue structure and provides a simple readout of tissue stress. We aimed to extend tissue viability in our muscular thin film contractility assay by modifying the polydimethylsiloxane (PDMS) substrate with micropatterned genipin, allowing extracellular matrix turnover without cell loss. To achieve this, we developed a microfluidic delivery system to pattern genipin and extracellular matrix proteins on PDMS prior to cell seeding. Tissues constructed using this method showed improved viability and maintenance of in vivo-like lamellar structure. Functional contractility of tissues fabricated on genipin-modified substrates remained consistent throughout two weeks in culture. These results suggest that muscular thin films with genipin-modified PDMS substrates are a viable method for conducting functional studies of arterial growth and remodeling in vascular diseases. (paper)

Passive heating following the prematch warm-up in soccer: examining the time-course of changes in muscle temperature and contractile function.

Science.gov (United States)

Marshall, Paul W M; Cross, Rebecca; Lovell, Ric

2015-12-01

This study examined changes in muscle temperature, electrically evoked muscle contractile properties, and voluntary power before and after a soccer specific active warm-up and subsequent rest period. Ten amateur soccer players performed two experimental sessions that involved performance of a modified FIFA 11+ soccer specific warm-up, followed by a 12.5-min rest period where participants were required to wear either normal clothing or a passive electrical heating garment was applied to the upper thigh muscles. Assessments around the warm-up and cool-down included measures of maximal torque, rate of torque development, muscle temperature (Tm), and electrically evoked measures of quadriceps contractile function. Tm was increased after the warm-up by 3.2 ± 0.7°C (P warm-up between 20% and 30% (P warm-up did not effect variables measured. While Tm was reduced by 1.4 ± 0.4°C after the rest period (P warm-up levels. Voluntary and evoked rate of torque development remained elevated from pre warm-up levels at the end of the cool-down (P warm-up elevated muscle temperature by 3.2°C and was associated with concomitant increases of between 20% and 30% in voluntary rate of torque development, which seems explained by elevations in rate-dependent measures of intrinsic muscle contractile function. Application of a passive heating garment did not attenuate declines in muscle temperature during a 12.5-min rest period. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Considerations for Contractile Electroactive Materials and Actuators

Energy Technology Data Exchange (ETDEWEB)

Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Carl; Bernasek, Stephen L.; Abelev, Esta

2010-02-19

Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

International Nuclear Information System (INIS)

Xu, Guang-Ni; Yang, Kai; Xu, Zu-Peng; Zhu, Liang; Hou, Li-Na; Qi, Hong; Chen, Hong-Zhuan; Cui, Yong-Yao

2012-01-01

Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation. -- Highlights: ► CSE induces tracheal cell proliferation, hyper-contractility and α-SMA expression. ► Anisodamine reverses CSE-induced tracheal hyper-contractility and cell proliferation. ► ERK, PI3K, and NF-κB pathways and cyclin D1 contribute to the reversal effect.

Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure.

Science.gov (United States)

Hanft, Laurin M; Emter, Craig A; McDonald, Kerry S

2017-07-01

Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously

The Study of Fetal Rat Model of Intra-Amniotic Isoproterenol Injection Induced Heart Dysfunction and Phenotypic Switch of Contractile Proteins

Directory of Open Access Journals (Sweden)

Yifei Li

2014-01-01

Full Text Available To establish a reliable isoproterenol induced heart dysfunction fetal rat model and understand the switches of contractile proteins, 45 pregnant rats were divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated twice, and control groups. And 18 adult rats were divided into isoproterenol-treated and control groups. H&E staining, Masson staining, and transmission electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults. Then echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks later, respectively. Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart dysfunction were opposite to adult procedure. The administration of intra-amniotic isoproterenol to fetal rats could induce heart dysfunction and the regulation of contractile proteins of fetuses was different from adult procedure.

Role of contractile prostaglandins and Rho-kinase in growth factor-induced airway smooth muscle contraction

Directory of Open Access Journals (Sweden)

Zaagsma Johan

2005-07-01

Full Text Available Abstract Background In addition to their proliferative and differentiating effects, several growth factors are capable of inducing a sustained airway smooth muscle (ASM contraction. These contractile effects were previously found to be dependent on Rho-kinase and have also been associated with the production of eicosanoids. However, the precise mechanisms underlying growth factor-induced contraction are still unknown. In this study we investigated the role of contractile prostaglandins and Rho-kinase in growth factor-induced ASM contraction. Methods Growth factor-induced contractions of guinea pig open-ring tracheal preparations were studied by isometric tension measurements. The contribution of Rho-kinase, mitogen-activated protein kinase (MAPK and cyclooxygenase (COX to these reponses was established, using the inhibitors Y-27632 (1 μM, U-0126 (3 μM and indomethacin (3 μM, respectively. The Rho-kinase dependency of contractions induced by exogenously applied prostaglandin F2α (PGF2α and prostaglandin E2 (PGE2 was also studied. In addition, the effects of the selective FP-receptor antagonist AL-8810 (10 μM and the selective EP1-antagonist AH-6809 (10 μM on growth factor-induced contractions were investigated, both in intact and epithelium-denuded preparations. Growth factor-induced PGF2α-and PGE2-release in the absence and presence of Y-27632, U-0126 and indomethacin, was assessed by an ELISA-assay. Results Epidermal growth factor (EGF-and platelet-derived growth factor (PDGF-induced contractions of guinea pig tracheal smooth muscle preparations were dependent on Rho-kinase, MAPK and COX. Interestingly, growth factor-induced PGF2α-and PGE2-release from tracheal rings was significantly reduced by U-0126 and indomethacin, but not by Y-27632. Also, PGF2α-and PGE2-induced ASM contractions were largely dependent on Rho-kinase, in contrast to other contractile agonists like histamine. The FP-receptor antagonist AL-8810 (10 μM significantly

Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK

International Nuclear Information System (INIS)

Sandhu, Hardip; Xu, Cang Bao; Edvinsson, Lars

2010-01-01

Cigarette smoke exposure increases the risk of stroke. However, the underlying molecular mechanisms are poorly understood. Endothelin system plays key roles in the pathogenesis of stroke. The present study was designed to examine if lipid-soluble (dimethyl sulfoxide-soluble) cigarette smoke particles (DSP) induces upregulation of contractile endothelin type B (ET B ) receptors in rat cerebral arteries and if activation of mitogen activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) mediate the upregulation of contractile endothelin receptors in the cerebral arteries. Rat middle cerebral arteries were isolated and organ cultured in serum free medium for 24 h in the presence of DSP with or without specific inhibitors: MEK specific (U0126), p38 specific (SB202190), JNK specific (SP600125), NF-κB specific (BMS-345541) or (IMD-0354), transcription inhibitor (actinomycin D), or translation blocker (cycloheximide). Contractile responses to the ET B receptor agonist sarafotoxin 6c were investigated by a sensitive myograph. The expression of the ET B receptors were studied at mRNA and protein levels using quantitative real time PCR and immunohistochemistry, respectively. Results show that organ culture per se induced transcriptional upregulation of contractile ET B receptors in the cerebral vascular smooth muscle cells. This upregulation was further increased at the translational level by addition of DSP to the organ culture, but this increase was not seen by addition of nicotine or water-soluble cigarette smoke particles to the organ culture. The increased upregulation of contractile ET B receptors by DSP was abrogated by U0126, SP600125, actinomycin D, and cycloheximide, suggesting that the underlying molecular mechanisms involved in this process include activation of MEK and JNK MAPK-mediated transcription and translation of new contractile ET B receptors. Thus, the MAPK-mediated upregulation of contractile ET B receptors in cerebral arteries might be a

The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats with streptozotocin-induced diabetes.

Science.gov (United States)

Cheng, Xing; Xia, Zhengyuan; Leo, Joyce M; Pang, Catherine C Y

2005-09-05

We examined if myocardial depression at the acute phase of diabetes (3 weeks after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of inducible nitric oxide synthase and production of peroxynitrite, and if treatment with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac function. Four groups of rats were used: control, N-acetylcysteine-treated control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital-anaesthetized diabetic rats, relative to the controls, had reduced left ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats also had increased myocardial levels of thiobarbituric acid reactive substances, immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the control rats; but increased cardiac contractility to dobutamine, reduced myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine and level of 15-F2t-isoprostane, and increased cardiac contractility to dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces oxidative stress and improves cardiac function.

Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function

Directory of Open Access Journals (Sweden)

Matthew J. Birket

2015-10-01

Full Text Available Maximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC model of hypertrophic cardiomyopathy (HCM. A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM.

Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates.

Science.gov (United States)

Chadderdon, Scott M; Belcik, J Todd; Smith, Elise; Pranger, Lindsay; Kievit, Paul; Grove, Kevin L; Lindner, Jonathan R

2012-09-01

Insulin produces capillary recruitment in skeletal muscle through a nitric oxide (NO)-dependent mechanism. Capillary recruitment is blunted in obese and diabetic subjects and contributes to impaired glucose uptake. This study's objective was to define whether inactivity, in the absence of obesity, leads to impaired capillary recruitment and contributes to insulin resistance (IR). A comprehensive metabolic and vascular assessment was performed on 19 adult male rhesus macaques (Macaca mulatta) after sedation with ketamine and during maintenance anesthesia with isoflurane. Thirteen normal-activity (NA) and six activity-restricted (AR) primates underwent contrast-enhanced ultrasound to determine skeletal muscle capillary blood volume (CBV) during an intravenous glucose tolerance test (IVGTT) and during contractile exercise. NO bioactivity was assessed by flow-mediated vasodilation. Although there were no differences in weight, basal glucose, basal insulin, or truncal fat, AR primates were insulin resistant compared with NA primates during an IVGTT (2,225 ± 734 vs. 5,171 ± 3,431 μg·ml⁻¹·min⁻¹, P < 0.05). Peak CBV was lower in AR compared with NA primates during IVGTT (0.06 ± 0.01 vs. 0.12 ± 0.02 ml/g, P < 0.01) and exercise (0.10 ± 0.02 vs. 0.20 ± 0.02 ml/g, P < 0.01), resulting in a lower peak skeletal muscle blood flow in both circumstances. The insulin-mediated changes in CBV correlated inversely with the degree of IR and directly with activity. Flow-mediated dilation was lower in the AR primates (4.6 ± 1.0 vs. 9.8 ± 2.3%, P = 0.01). Thus, activity restriction produces impaired skeletal muscle capillary recruitment during a carbohydrate challenge and contributes to IR in the absence of obesity. Reduced NO bioactivity may be a pathological link between inactivity and impaired capillary function.

Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve

OpenAIRE

Holmager, Pernille; Egstrup, Michael; Gustafsson, Ida; Schou, Morten; Dahl, Jordi S.; Rasmussen, Lars Melholt; M?ller, Jacob E.; Tuxen, Christian; Faber, Jens; Kistorp, Caroline

2017-01-01

Background: Heart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserv...

Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle.

Science.gov (United States)

Hernández, Andrés; Schiffer, Tomas A; Ivarsson, Niklas; Cheng, Arthur J; Bruton, Joseph D; Lundberg, Jon O; Weitzberg, Eddie; Westerblad, Håkan

2012-08-01

Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca(2+) handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca(2+)] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤ 50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca(2+) handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca(2+) handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness.

The impact of visual impairment on the ability to perform activities of daily living for persons with severe/profound intellectual disability.

Science.gov (United States)

Dijkhuizen, Annemarie; Hilgenkamp, Thessa I M; Krijnen, Wim P; van der Schans, Cees P; Waninge, Aly

2016-01-01

The ability to perform activities of daily living (ADL) as a component of participation is one of the factors that contribute to quality of life. The ability to perform ADL for persons experiencing severe/profound intellectual disability (ID) may be reduced due to their cognitive and physical capacities. However, until recently, the impact of the significantly prevalent visual impairments on the performance of activities of daily living has not yet been revealed within this group. The purpose of this prospective cross-sectional study was to investigate the impact of visual impairment on the performance of activities of daily living for persons with a severe/profound intellectual disability. The Barthel Index (BI) and Comfortable Walking Speed (CWS) were used to measure the ability of performing activities of daily living (ADL) in 240 persons with severe/profound ID and having Gross Motor Functioning Classification System (GMFCS) levels I, II or III; this included 120 persons with visual impairment. The impact of visual impairment on ADL was analyzed with linear regression. The results of the study demonstrated that visual impairment slightly affects the ability of performing activities of daily living (BI) for persons experiencing a severe/profound intellectual disability. GMFCS Levels II or III, profound ID level, and visual impairment each have the effect of lowering BI scores. GMFCS Levels II or III, and profound ID level each have the effect of increasing CWS scores, which indicates a lower walking speed. A main effect of visual impairment is present on CWS, but our results do show a substantive interaction effect between GMFCS level III and visual impairment on Comfortable Walking Speed in persons with a severe/profound intellectual disability. Visual impairment has a slight effect on ability to perform ADL in persons experiencing severe/profound ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute exposure to lead increases myocardial contractility independent of hypertension development

Energy Technology Data Exchange (ETDEWEB)

Fioresi, M. [Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Departamento de Enfermagem, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Furieri, L.B.; Simões, M.R.; Ribeiro, R.F. Junior; Meira, E.F.; Fernandes, A.A.; Stefanon, I. [Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Vassallo, D.V. [Programa de Pós-Graduação em Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro de Ciências da Saúde de Vitória, Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil)

2013-02-01

We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetate iv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na{sup +},K{sup +}-ATPase and myosin Ca{sup 2+}-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2 vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13 vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na{sup +},K{sup +}-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension.

Acute exposure to lead increases myocardial contractility independent of hypertension development

International Nuclear Information System (INIS)

Fioresi, M.; Furieri, L.B.; Simões, M.R.; Ribeiro, R.F. Junior; Meira, E.F.; Fernandes, A.A.; Stefanon, I.; Vassallo, D.V.

2013-01-01

We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetate iv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na + ,K + -ATPase and myosin Ca 2+ -ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2 vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13 vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na + ,K + -ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension

Work-related stress is associated with impaired neuropsychological test performance: a clinical cross-sectional study.

Science.gov (United States)

Eskildsen, Anita; Andersen, Lars Peter; Pedersen, Anders Degn; Vandborg, Sanne Kjær; Andersen, Johan Hviid

2015-01-01

Patients on sick leave due to work-related stress often complain about impaired concentration and memory. However, it is undetermined how widespread these impairments are, and which cognitive domains are most long-term stress sensitive. Previous studies show inconsistent results and are difficult to synthesize. The primary aim of this study was to examine whether patients with work-related stress complaints have cognitive impairments compared to a matched control group without stress. Our secondary aim was to examine whether the level of self-reported perceived stress is associated with neuropsychological test performance. We used a broad neuropsychological test battery to assess 59 outpatients with work-related stress complaints (without major depression) and 59 healthy controls. We matched the patients and controls pairwise by sex, age and educational level. Compared to controls, patients generally showed mildly reduced performance across all the measured domains of the neuropsychological test battery. However, only three comparisons reached statistical significance (p working memory. There were no statistical significant associations between self-reported perceived stress level and neuropsychological test performance. In conclusion, we recommend that cognitive functions should be considered when evaluating patients with work-related stress complaints, especially when given advice regarding return to work. Since this study had a cross-sectional design, it is still uncertain whether the impairments are permanent. Further study is required to establish causal links between work-related stress and cognitive deficits.

Differential Kolaviron Attenuated Contractile Responses to Agonists on Isolated Rabbit Aorta in Na+-K+ Pump Blockade.

Science.gov (United States)

Uche, O K; Ofeimun, J O

2017-12-30

The mechanism of kolaviron-induced vascular smooth muscles (VSMs) responses has not been fullycharacterised. The present study investigated the effect and mode of action of kolaviron a biflavanoid-complex and majorcomponent of Garcinia Kola-fraction on differential contractile responses to agonists-[phenylephrine (PHE) and histamine(HIST)] on VSMs of rabbit isolated aortic rings in K+-free physiological salt solution (KFPSS). Cumulative concentrationresponses to PHE and HIST were examined on 2 mm ring segments of the thoracic aortae which were suspended in 20 mlorgan baths containing physiological salt solution (PSS) for measurement of isometric contractions, at 370C and pH 7.4. Themedium was bubbled with 95% O2, 5% CO2, and rings were given an initial load of 1g. Cumulative contractile responses tothe agonists were studied in normal PSS (control) and following 30 minutes exposure to K+-free PSS and/or 800µg/mLkolaviron. Contractile responses were expressed as percentage of 80 mM K+ contractions in normal PSS. Maximalcontractions (Emax) induced by PHE and HIST compared with high K+ contraction in the various preparations weredifferentially altered following exposure to K+-free or 800µg/mL kolaviron in both intact (+E) and endotheliumdenuded (-E) rings. Based on the efficacy (Emax) and potency (EC50) values for the dose-response curves of the agonists, it isconcluded that enhanced differential contractile responses elicited by agonists in K+-free PSS were significantly attenuatedby kolaviron concentration-dependently. This observation probably suggests the existence of another pathway of kolavironmode of action in vascular smooth muscle reactivity.

Gallbladder contractility and mucus secretion after cholesterol feeding in the prairie dog

NARCIS (Netherlands)

Li, Y. F.; Moody, F. G.; Weisbrodt, N. W.; Zalewsky, C. A.; Coelho, J. C.; Senninger, N.; Gouma, D.

1986-01-01

The purpose of our study was to evaluate changes in gallbladder contractility and mucus secretion in vitro during the early stages of gallstone formation in prairie dogs. Thirty-two animals were divided into five groups. Control animals were fed a trace cholesterol diet. Experimental animals were

Impaired Upper Esophageal Sphincter Reflexes in Patients with Supra-Esophageal Reflux Disease

Science.gov (United States)

Babaei, Arash; Venu, Mukund; Naini, Sohrab Rahimi; Gonzaga, Jason; Lang, Ivan; Massey, Benson; Jadcherla, Sudarshan; Shaker, Reza

2015-01-01

Background & Aims Normal responses of the upper esophageal sphincter (UES) and esophageal body to liquid reflux events prevent esophagopharyngeal reflux and its complications, but abnormal responses have not been characterized. We investigated whether patients with supra-esophageal reflux disease (SERD) have impaired UES and esophageal body responses to simulated reflux events. Methods We performed a prospective study of 25 patients with SERD (19–82 y old, 13 female) and complaints of regurgitation and supra-esophageal manifestations of reflux. We also included 10 patients with gastroesophageal reflux disease (GERD; 32–60 y old, 7 female) without troublesome regurgitation and supra-esophageal symptoms and 24 healthy asymptomatic individuals (controls; 19–49 y old, 13 female). UES and esophageal body pressure responses, along with luminal distribution of infusate during esophageal rapid and slow infusion of air or liquid, were monitored by concurrent high-resolution manometry and intraluminal impedance. Results A significantly smaller proportion of patients with SERD had UES contractile reflexes in response to slow esophageal infusion of acid than controls or patients with GERD. Only patients with SERD had abnormal UES relaxation responses to rapid distension with saline. Diminished esophageal peristaltic contractions resulted in esophageal stasis in patients with GERD or SERD. Conclusions Patients with SERD and complaints of regurgitation have impaired UES and esophageal responses to simulated liquid reflux events. These patterns could predispose them to esophagopharyngeal reflux. PMID:26188682

Adaptive responses of mouse skeletal muscle to contractile activity: The effect of age.

Science.gov (United States)

Vasilaki, A; McArdle, F; Iwanejko, L M; McArdle, A

2006-11-01

This study has characterised the time course of two major transcriptional adaptive responses to exercise (changes in antioxidant defence enzyme activity and heat shock protein (HSP) content) in muscles of adult and old male mice following isometric contractions and has examined the mechanisms involved in the age-related reduction in transcription factor activation. Muscles of B6XSJL mice were subjected to isometric contractions and analysed for antioxidant defence enzyme activities, heat shock protein content and transcription factor DNA binding activity. Data demonstrated a significant increase in superoxide dismutase (SOD) and catalase activity and HSP content of muscles of adult mice following contractile activity which was associated with increased activation of the transcription factors, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and heat shock factor (HSF) following contractions. Significant increases in SOD and catalase activity and heat shock cognate (HSC70) content were seen in quiescent muscles of old mice. The increase in antioxidant defence enzyme activity following contractile activity seen in muscles of adult mice was not seen in muscles of old mice and this was associated with a failure to fully activate NF-kappaB and AP-1 following contractions. In contrast, although the production of HSPs was also reduced in muscles of old mice following contractile activity compared with muscles of adult mice following contractions, this was not due to a gross reduction in the DNA binding activity of HSF.

Mental Fatigue: Impairment of Technical Performance in Small-Sided Soccer Games.

Science.gov (United States)

Badin, Oliver O; Smith, Mitchell R; Conte, Daniele; Coutts, Aaron J

2016-11-01

To assess the effects of mental fatigue on physical and technical performance in small-sided soccer games. Twenty soccer players (age 17.8 ± 1.0 y, height 179 ± 5 cm, body mass 72.4 ± 6.8 kg, playing experience 8.3 ± 1.4 y) from an Australian National Premier League soccer club volunteered to participate in this randomized crossover investigation. Participants played 15-min 5-vs-5 small-sided games (SSGs) without goalkeepers on 2 occasions separated by 1 wk. Before the SSG, 1 team watched a 30-min emotionally neutral documentary (control), while the other performed 30 min of a computer-based Stroop task (mental fatigue). Subjective ratings of mental and physical fatigue were recorded before and after treatment and after the SSG. Motivation was assessed before treatment and SSG; mental effort was assessed after treatment and SSG. Player activity profiles and heart rate (HR) were measured throughout the SSG, whereas ratings of perceived exertion (RPEs) were recorded before the SSG and immediately after each half. Video recordings of the SSG allowed for notational analysis of technical variables. Subjective ratings of mental fatigue and effort were higher after the Stroop task, whereas motivation for the upcoming SSG was similar between conditions. HR during the SSG was possibly higher in the control condition, whereas RPE was likely higher in the mental-fatigue condition. Mental fatigue had an unclear effect on most physical-performance variables but impaired most technical-performance variables. Mental fatigue impairs technical but not physical performance in small-sided soccer games.

Performance of the Hack's Impairment Index Score: A Novel Tool to Assess Impairment from Alcohol in Emergency Department Patients.

Science.gov (United States)

Hack, Jason B; Goldlust, Eric J; Ferrante, Dennis; Zink, Brian J

2017-10-01

Over 35 million alcohol-impaired (AI) patients are cared for in emergency departments (EDs) annually. Emergency physicians are charged with ensuring AI patients' safety by identifying resolution of alcohol-induced impairment. The most common standard evaluation is an extemporized clinical examination, as ethanol levels are not reliable or predictive of clinical symptoms. There is no standard assessment of ED AI patients. The objective was to evaluate a novel standardized ED assessment of alcohol impairment, Hack's Impairment Index (HII score), in a busy urban ED. A retrospective chart review was performed for all AI patients seen in our busy urban ED over 24 months. Trained nurses evaluated AI patients with both "usual" and HII score every 2 hours. Patients were stratified by frequency of visits for AI during this time: high (≥ 6), medium (2-5), and low (1). Within each category, comparisons were made between HII scores, measured ethanol levels, and usual nursing assessment of AI. Changes in HII scores over time were also evaluated. A total of 8,074 visits from 3,219 unique patients were eligible for study, including 7,973 (98.7%) with ethanol levels, 5,061 (62.7%) with complete HII scores, and 3,646 (45.2%) with health care provider assessments. Correlations between HII scores and ethanol levels were poor (Pearson's R 2  = 0.09, 0.09, and 0.17 for high-, medium-, and low-frequency strata). HII scores were excellent at discriminating nursing assessment of AI, while ethanol levels were less effective. Omitting extrema, HII scores fell consistently an average 0.062 points per hour, throughout patients' visits. The HII score applied a quantitative, objective assessment of alcohol impairment. HII scores were superior to ethanol levels as an objective clinical measure of impairment. The HII declines in a reasonably predictable manner over time, with serial evaluations corresponding well with health care provider evaluations. © 2017 by the Society for Academic

Image Processing Techniques for Assessing Contractility in Isolated Adult Cardiac Myocytes

Directory of Open Access Journals (Sweden)

Carlos Bazan

2009-01-01

The physiologic application of the methodology is evaluated by assessing overall contraction in enzymatically dissociated adult rat cardiocytes. Our results demonstrate the effectiveness of the proposed approach in characterizing the true, two-dimensional, “shortening” in the contraction process of adult cardiocytes. We compare the performance of the proposed method to that of a popular edge detection system in the literature. The proposed method not only provides a more comprehensive assessment of the myocyte contraction process but also can potentially eliminate historical concerns and sources of errors caused by myocyte rotation or translation during contraction. Furthermore, the versatility of the image processing techniques makes the method suitable for determining myocyte shortening in cells that usually bend or move during contraction. The proposed method can be utilized to evaluate changes in contractile behavior resulting from drug intervention, disease modeling, transgeneity, or other common applications to mammalian cardiocytes.

TNFα G308A polymorphism is associated with resilience to sleep deprivation-induced psychomotor vigilance performance impairment in healthy young adults.

Science.gov (United States)

Satterfield, Brieann C; Wisor, Jonathan P; Field, Stephanie A; Schmidt, Michelle A; Van Dongen, Hans P A

2015-07-01

Cytokines such as TNFα play an integral role in sleep/wake regulation and have recently been hypothesized to be involved in cognitive impairment due to sleep deprivation. We examined the effect of a guanine to adenine substitution at position 308 in the TNFα gene (TNFα G308A) on psychomotor vigilance performance impairment during total sleep deprivation. A total of 88 healthy women and men (ages 22-40) participated in one of five laboratory total sleep deprivation experiments. Performance on a psychomotor vigilance test (PVT) was measured every 2-3h. The TNFα 308A allele, which is less common than the 308G allele, was associated with greater resilience to psychomotor vigilance performance impairment during total sleep deprivation (regardless of time of day), and also provided a small performance benefit at baseline. The effect of genotype on resilience persisted when controlling for between-subjects differences in age, gender, race/ethnicity, and baseline sleep duration. The TNFα G308A polymorphism predicted less than 10% of the overall between-subjects variance in performance impairment during sleep deprivation. Nonetheless, the differential effect of the polymorphism at the peak of performance impairment was more than 50% of median performance impairment at that time, which is sizeable compared to the effects of other genotypes reported in the literature. Our findings provided evidence for a role of TNFα in the effects of sleep deprivation on psychomotor vigilance performance. Furthermore, the TNFα G308A polymorphism may have predictive potential in a biomarker panel for the assessment of resilience to psychomotor vigilance performance impairment due to sleep deprivation. Copyright © 2014 Elsevier Inc. All rights reserved.

Negative Emotional Arousal Impairs Associative Memory Performance for Emotionally Neutral Content in Healthy Participants.

Directory of Open Access Journals (Sweden)

Jonathan Guez

Full Text Available The effect of emotional arousal on memory presents a complex pattern with previous studies reporting conflicting results of both improved and reduced memory performance following arousal manipulations. In this study we further tested the effect of negative emotional arousal (NEA on individual-item recognition and associative recognition of neutral stimuli in healthy participants, and hypothesized that NEA will particularly impair associative memory performance. The current study consists of two experiments; in both, participants studied a list of word-pairs and were then tested for items (items recognition test, and for associations (associative recognition test. In the first experiment, the arousal manipulation was induced by flashing emotionally-negative or neutral pictures between study-pairs while in the second experiment arousal was induced by presenting emotionally-negative or neutral pictures between lists. The results of the two experiments converged and supported an associative memory deficit observed under NEA conditions. We suggest that NEA is associated with an altered ability to bind one stimulus to another as a result of impaired recollection, resulting in poorer associative memory performance. The current study findings may contribute to the understanding of the mechanism underlying memory impairments reported in disorders associated with traumatic stress.

Alcohol effects on simulated driving performance and self-perceptions of impairment in DUI offenders.

Science.gov (United States)

Van Dyke, Nicholas; Fillmore, Mark T

2014-12-01

Drivers with a history of driving under the influence (DUI) of alcohol self-report heightened impulsivity and display reckless driving behaviors as indicated by increased rates of vehicle crashes, moving violations, and traffic tickets. Such poor behavioral self-regulation could also increase sensitivity to the disruptive effects of alcohol on driving performance. The present study examined the degree to which DUI drivers display an increased sensitivity to the acute impairing effects of alcohol on simulated driving performance and overestimate their driving fitness following alcohol consumption. Adult drivers with a history of DUI and a demographically matched group of drivers with no history of DUI (controls) were tested following a 0.65 g/kg alcohol and a placebo. Results indicated that alcohol impaired several measures of driving performance, and there was no difference between DUI offenders and controls in these impairments. However, following alcohol, DUI drivers self-reported a greater ability and willingness to drive compared with controls. These findings indicate that drivers with a history of DUI might perceive themselves as more fit to drive after drinking, which could play an important role in their decisions to drink and drive. PsycINFO Database Record (c) 2014 APA, all rights reserved.

The influence of unilateral saccular impairment on functional balance performance and self-report dizziness.

Science.gov (United States)

McCaslin, Devin L; Jacobson, Gary P; Grantham, Sarah L; Piker, Erin G; Verghese, Susha

2011-09-01

Postural stability in humans is largely maintained by vestibular, visual, and somatosensory inputs to the central nervous system. Recent clinical advances in the assessment of otolith function (e.g., cervical and ocular vestibular evoked myogenic potentials [cVEMPs and oVEMPs], subjective visual vertical [SVV] during eccentric rotation) have enabled investigators to identify patients with unilateral otolith impairments. This research has suggested that patients with unilateral otolith impairments perform worse than normal healthy controls on measures of postural stability. It is not yet known if patients with unilateral impairments of the saccule and/or inferior vestibular nerve (i.e., unilaterally abnormal cVEMP) perform differently on measures of postural stability than patients with unilateral impairments of the horizontal SCC (semicircular canal) and/or superior vestibular nerve (i.e., unilateral caloric weakness). Further, it is not known what relationship exists, if any, between otolith system impairment and self-report dizziness handicap. The purpose of this investigation was to determine the extent to which saccular impairments (defined by a unilaterally absent cVEMP) and impairments of the horizontal semicircular canal (as measured by the results of caloric testing) affect vestibulospinal function as measured through the Sensory Organization Test (SOT) of the computerized dynamic posturography (CDP). A secondary objective of this investigation was to measure the effects, if any, that saccular impairment has on a modality-specific measure of health-related quality of life. A retrospective cohort study. Subjects were assigned to one of four groups based on results from balance function testing: Group 1 (abnormal cVEMP response only), Group 2 (abnormal caloric response only), Group 3 (abnormal cVEMP and abnormal caloric response), and Group 4 (normal control group). Subjects were 92 adult patients: 62 were seen for balance function testing due to complaints

Effects of testosterone on contractile properties of sexually dimorphic forelimb muscles in male bullfrogs (Rana catesbeiana, Shaw 1802

Directory of Open Access Journals (Sweden)

Aaron R. Kampe

2013-07-01

This study examined the effects of testosterone (T on the contractile properties of two sexually dimorphic forelimb muscles and one non-dimorphic muscle in male bullfrogs (Rana catesbeiana, Shaw 1802. The dimorphic muscles in castrated males with testosterone replacement (T+ achieved higher forces and lower fatigability than did castrated males without replaced testosterone (T0 males, but the magnitude of the differences was low and many of the pair-wise comparisons of each muscle property were not statistically significant. However, when taken as a whole, the means of seven contractile properties varied in the directions expected of masculine values in T+ animals in the sexually dimorphic muscles. Moreover, these data, compared with previous data on male and female bullfrogs, show that values for T+ males are similar to normal males and are significantly different from females. The T0 males tended to be intermediate in character between T+ males and females, generally retaining masculine values. This suggests that the exposure of young males to T in their first breeding season produces a masculinizing effect on the sexually dimorphic muscles that is not reversed between breeding seasons when T levels are low. The relatively minor differences in contractile properties between T+ and T0 males may indicate that as circulating T levels rise during breeding season in normal males, contractile properties can be enhanced rapidly to maximal functional levels for breeding success.

Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists

Directory of Open Access Journals (Sweden)

Jill J. Leckey

2017-10-01

Full Text Available We investigated the effect of pre- “race” ingestion of a 1,3-butanediol acetoacetate diester on blood ketone concentration, substrate metabolism and performance of a cycling time trial (TT in professional cyclists. In a randomized cross-over design, 10 elite male cyclists completed a ~31 km laboratory-based TT on a cycling ergometer programmed to simulate the 2017 World Road Cycling Championships course. Cyclists consumed a standardized meal [2 g/kg body mass (BM carbohydrate (CHO] the evening prior to a trial day and a CHO breakfast (2 g/kg BM CHO with 200 mg caffeine on the morning of a trial day. Cyclists were randomized to consume either the ketone diester (2 × 250 mg/kg or a placebo drink, followed immediately by 200 mL diet cola, given ~ 30 min before and immediately prior to commencing a 20 min incremental warm-up. Blood samples were collected prior to and during the warm-up, pre- and post- TT and at regular intervals after the TT. Urine samples were collected pre- and post- warm-up, immediately post TT and 60 min post TT. Pre-exercise ingestion of the diester resulted in a 2 ± 1% impairment in TT performance that was associated with gut discomfort and higher perception of effort. Serum β-hydroxybutyrate, serum acetoacetate, and urine ketone concentrations increased from rest following ketone ingestion and were higher than placebo throughout the trial. Ketone ingestion induces hyperketonemia in elite professional cyclists when in a carbohydrate fed state, and impairs performance of a cycling TT lasting ~50 min.

Wechsler Memory Scale-III Faces test performance in patients with mild cognitive impairment and mild Alzheimer's disease.

Science.gov (United States)

Seelye, Adriana M; Howieson, Diane B; Wild, Katherine V; Moore, Mindy Milar; Kaye, Jeffrey A

2009-08-01

Little is known about the sensitivity of the Wechsler Memory Scale-Third Edition (WMS-III) Faces subtest to memory impairment associated with mild cognitive impairment (MCI). In this study, Faces performance was examined in 24 MCI patients, 46 mild Alzheimer's disease (AD) patients, and 98 elderly controls. We hypothesized that participants with diagnoses of MCI or AD would be impaired relative to controls on Faces. Analyses showed that AD participants performed significantly worse than MCI and intact participants, although there were no significant differences between MCI and intact participants. Data suggest that brain areas specialized for face recognition memory may be less affected by MCI and mild AD than regions specialized for verbal memory.

Gait and Cognition in Parkinson’s Disease: Cognitive Impairment Is Inadequately Reflected by Gait Performance during Dual Task

Directory of Open Access Journals (Sweden)

Heiko Gaßner

2017-10-01

Full Text Available IntroductionCognitive and gait deficits are common symptoms in Parkinson’s disease (PD. Motor-cognitive dual tasks (DTs are used to explore the interplay between gait and cognition. However, it is unclear if DT gait performance is indicative for cognitive impairment. Therefore, the aim of this study was to investigate if cognitive deficits are reflected by DT costs of spatiotemporal gait parameters.MethodsCognitive function, single task (ST and DT gait performance were investigated in 67 PD patients. Cognition was assessed by the Montreal Cognitive Assessment (MoCA followed by a standardized, sensor-based gait test and the identical gait test while subtracting serial 3’s. Cognitive impairment was defined by a MoCA score <26. DT costs in gait parameters [(DT − ST/ST × 100] were calculated as a measure of DT effect on gait. Correlation analysis was used to evaluate the association between MoCA performance and gait parameters. In a linear regression model, DT gait costs and clinical confounders (age, gender, disease duration, motor impairment, medication, and depression were correlated to cognitive performance. In a subgroup analysis, we compared matched groups of cognitively impaired and unimpaired PD patients regarding differences in ST, DT, and DT gait costs.ResultsCorrelation analysis revealed weak correlations between MoCA score and DT costs of gait parameters (r/rSp ≤ 0.3. DT costs of stride length, swing time variability, and maximum toe clearance (|r/rSp| > 0.2 were included in a regression analysis. The parameters only explain 8% of the cognitive variance. In combination with clinical confounders, regression analysis showed that these gait parameters explained 30% of MoCA performance. Group comparison revealed strong DT effects within both groups (large effect sizes, but significant between-group effects in DT gait costs were not observed.ConclusionThese findings suggest that DT gait performance is not indicative

Cognitive function affects trainability for physical performance in exercise intervention among older adults with mild cognitive impairment.

Science.gov (United States)

Uemura, Kazuki; Shimada, Hiroyuki; Makizako, Hyuma; Doi, Takehiko; Yoshida, Daisuke; Tsutsumimoto, Kota; Anan, Yuya; Suzuki, Takao

2013-01-01

Although much evidence supports the hypothesis that cognitive function and physical function are interrelated, it is unclear whether cognitive decline with mild cognitive impairment influences trainability of physical performance in exercise intervention. The purpose of this study was to examine the association between cognitive function at baseline and change in physical performance after exercise intervention in older adults with mild cognitive impairment. Forty-four older adults diagnosed with mild cognitive impairment based on the Peterson criteria (mean age 74.8 years) consented to and completed a 6-month twice weekly exercise intervention. The Timed Up and Go (TUG) test was used as a measure of physical performance. The Mini-Mental State Examination (MMSE), Trail Making Test Part B, Geriatric Depression Scale, baseline muscle strength of knee extension, and attendance rate of intervention, were measured as factors for predicting trainability. In the correlation analysis, the change in TUG showed modest correlations with attendance rate in the exercise program (r = -0.354, P = 0.027) and MMSE at baseline (r = -0.321, P = 0.034). A multiple regression analysis revealed that change in TUG was independently associated with attendance rate (β = -0.322, P = 0.026) and MMSE score (β = -0.295, P = 0.041), controlling for age and gender. General cognitive function was associated with improvements in physical performance after exercise intervention in subjects with mild cognitive impairment. Further research is needed to examine the effects of exercise programs designed to address cognitive obstacles in older adults with mild cognitive impairment.

Atomic Structure of Type VI Contractile Sheath from Pseudomonas aeruginosa.

Science.gov (United States)

Salih, Osman; He, Shaoda; Planamente, Sara; Stach, Lasse; MacDonald, James T; Manoli, Eleni; Scheres, Sjors H W; Filloux, Alain; Freemont, Paul S

2018-02-06

Pseudomonas aeruginosa has three type VI secretion systems (T6SSs), H1-, H2-, and H3-T6SS, each belonging to a distinct group. The two T6SS components, TssB/VipA and TssC/VipB, assemble to form tubules that conserve structural/functional homology with tail sheaths of contractile bacteriophages and pyocins. Here, we used cryoelectron microscopy to solve the structure of the H1-T6SS P. aeruginosa TssB1C1 sheath at 3.3 Å resolution. Our structure allowed us to resolve some features of the T6SS sheath that were not resolved in the Vibrio cholerae VipAB and Francisella tularensis IglAB structures. Comparison with sheath structures from other contractile machines, including T4 phage and R-type pyocins, provides a better understanding of how these systems have conserved similar functions/mechanisms despite evolution. We used the P. aeruginosa R2 pyocin as a structural template to build an atomic model of the TssB1C1 sheath in its extended conformation, allowing us to propose a coiled-spring-like mechanism for T6SS sheath contraction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impaired theta-gamma coupling during working memory performance in schizophrenia.

Science.gov (United States)

Barr, Mera S; Rajji, Tarek K; Zomorrodi, Reza; Radhu, Natasha; George, Tony P; Blumberger, Daniel M; Daskalakis, Zafiris J

2017-11-01

Working memory deficits represent a core feature of schizophrenia. These deficits have been associated with dysfunctional dorsolateral prefrontal cortex (DLPFC) cortical oscillations. Theta-gamma coupling describes the modulation of gamma oscillations by theta phasic activity that has been directly associated with the ordering of information during working memory performance. Evaluating theta-gamma coupling may provide greater insight into the neural mechanisms mediating working memory deficits in this disorder. Thirty-eight patients diagnosed with schizophrenia or schizoaffective disorder and 38 healthy controls performed the verbal N-Back task administered at 4 levels, while EEG was recorded. Theta (4-7Hz)-gamma (30-50Hz) coupling was calculated for target and non-target correct trials for each working memory load. The relationship between theta-gamma coupling and accuracy was determined. Theta-gamma coupling was significantly and selectively impaired during correct responses to target letters among schizophrenia patients compared to healthy controls. A significant and positive relationship was found between theta-gamma coupling and 3-Back accuracy in controls, while this relationship was not observed in patients. These findings suggest that impaired theta-gamma coupling contribute to working memory dysfunction in schizophrenia. Future work is needed to evaluate the predictive utility of theta-gamma coupling as a neurophysiological marker for functional outcomes in this disorder. Copyright © 2017. Published by Elsevier B.V.

Impaired financial capacity in late life depression is associated with cognitive performance on measures of executive functioning and attention.

Science.gov (United States)

Mackin, R Scott; Areán, Patricia A

2009-09-01

Few studies have evaluated the prevalence of impairments of financial capacity among individuals with psychiatric disorders. Late life depression (LLD) is a common psychiatric disorder associated with significant disability and cognitive impairment. The purpose of this investigation was to determine the prevalence and cognitive correlates of impairments of financial capacity among individuals with LLD. Participants included 65 LLD individuals and 32 comparison subjects. Assessments included measures of financial capacity, cognitive functioning, and depression symptom severity. Individuals with LLD exhibited a significantly higher rate of impaired financial capacity (22%) than the comparison group (6%). Results of a multiple regression analysis indicated that performance on measures of executive functioning and attention, but not depression severity, were most strongly associated with financial capacity performance in LLD. Our results suggest impairments of financial capacity in LLD are largely explained by cognitive functioning in these domains.

Contractility-afterload mismatch in patients with protein-losing enteropathy after the Fontan operation.

Science.gov (United States)

Ozawa, Hideto; Ueno, Takayoshi; Iwai, Shigemitsu; Kawata, Hiroaki; Nishigaki, Kyouichi; Kishimoto, Hidefumi; Sawa, Yoshiki

2014-10-01

This study aimed to clarify the relationship between onset of protein-losing enteropathy (PLE) and Fontan circulation, with special reference to the development of contractility-afterload mismatch. The PLE group comprised 9 patients who experienced PLE after undergoing the Fontan operation, and the control group consisted of 32 patients had did not experienced PLE more than 10 years after the Fontan operation. The study compared the pre- and postoperative values of arterial elastance (Ea), end-systolic elastance (Ees), and contractility-afterload mismatch (Ea/Ees). Furthermore, the variations in the values were examined during the preoperative, postoperative, and midterm postoperative periods in seven PLE patients who underwent cardiac catheterization at the onset of PLE and during the pre- and postintervention periods in three PLE patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE. Comparison of the values obtained before and after Fontan operations showed that the Ea values increased significantly in the PLE group. However, the pre- and postoperative Ees values did not differ in the two groups. During the postoperative period, Ea/Ees increased significantly, and the Ea and Ea/Ees values increased continuously until the onset of PLE in the PLE group. In the patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE, the Ea/Ees decreased significantly, and the serum albumin levels improved after the intervention. Contractility-afterload mismatch, mainly caused by the increase in the afterload of the systemic ventricle, may have an important role in the development of PLE after the Fontan operation.

Structure of the Elastin-Contractile Units in the Thoracic Aorta and How Genes That Cause Thoracic Aortic Aneurysms and Dissections Disrupt This Structure.

Science.gov (United States)

Karimi, Ashkan; Milewicz, Dianna M

2016-01-01

The medial layer of the aorta confers elasticity and strength to the aortic wall and is composed of alternating layers of smooth muscle cells (SMCs) and elastic fibres. The SMC elastin-contractile unit is a structural unit that links the elastin fibres to the SMCs and is characterized by the following: (1) layers of elastin fibres that are surrounded by microfibrils; (2) microfibrils that bind to the integrin receptors in focal adhesions on the cell surface of the SMCs; and (3) SMC contractile filaments that are linked to the focal adhesions on the inner side of the membrane. The genes that are altered to cause thoracic aortic aneurysms and aortic dissections encode proteins involved in the structure or function of the SMC elastin-contractile unit. Included in this gene list are the genes encoding protein that are structural components of elastin fibres and microfibrils, FBN1, MFAP5, ELN, and FBLN4. Also included are genes that encode structural proteins in the SMC contractile unit, including ACTA2, which encodes SMC-specific α-actin and MYH11, which encodes SMC-specific myosin heavy chain, along with MYLK and PRKG1, which encode kinases that control SMC contraction. Finally, mutations in the gene encoding the protein linking integrin receptors to the contractile filaments, FLNA, also predispose to thoracic aortic disease. Thus, these data suggest that functional SMC elastin-contractile units are important for maintaining the structural integrity of the aorta. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Considerations for Contractile Electroactive Polymeric Materials and Actuators

Energy Technology Data Exchange (ETDEWEB)

Rasmussen, Lenore; Erickson, Carl J.; Meixler, Lewis D.; Ascione, George; Gentile, Charles A.; Tilson, Charles; Bernasek, Stephen L.; Abelev, Esta

2009-06-16

Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface.

Considerations for Contractile Electroactive Polymeric Materials and Actuators

International Nuclear Information System (INIS)

Rasmussen, L.; Erickson, Carl J.; Meixler, Lewis D.; Ascione, G.; Gentile, Charles A.; Tilson, C.; Bernasek, Stephen L.; Abelev, E.

2009-01-01

Ras Labs produces electroactive polymer (EAP) based materials and actuators that bend, swell, ripple and now contract (new development) with low electric input. This is an important attribute because of the ability of contraction to produce life-like motion. The mechanism of contraction is not well understood. Radionuclide-labeled experiments were conducted to follow the movement of electrolytes and water in these EAPs when activated. Extreme temperature experiments were performed on the contractile EAPs with very favorable results. One of the biggest challenges in developing these actuators, however, is the electrode-EAP interface because of the pronounced movement of the EAP. Plasma treatments of metallic electrodes were investigated in order to improve the attachment of the embedded electrodes to the EAP material. Surface analysis, adhesive testing, and mechanical testing were conducted to test metal surfaces and metal-polymer interfaces. The nitrogen plasma treatment of titanium produced a strong metal-polymer interface; however, oxygen plasma treatment of both stainless steel and titanium produced even stronger metal-polymer interfaces. Plasma treatment of the electrodes allows for the embedded electrodes and the EAP material of the actuator to work and move as a unit, with no detachment, by significantly improving the metal-polymer interface

Impaired work performance among women with symptomatic uterine fibroids.

Science.gov (United States)

Lerner, Debra; Mirza, Fadi G; Mirza, Fadi; Chang, Hong; Renzulli, Karen; Perch, Katherine; Chelmow, David

2008-10-01

To assess the work impact of symptomatic uterine fibroids (UFs). A cohort study compared 58 employed women with symptomatic UFs to 56 healthy controls. Data sources included a self-administered mail questionnaire and medical charts. At-work performance limitations and productivity loss were measured with the Work Limitations Questionnaire. Univariate and multivariate case-control group differences were tested. Based on adjusted mean scores, the UF group had significantly more at-work limitations and productivity loss than controls, while absence rates were similar. The UF group's performance was impaired 18% of the time on average versus 8% for controls (P-values, 0.005-0.040). At-work limitations were explained by depression symptoms, Non-White race/ethnicity, and poorer health-related quality of life. Fibroids and related symptoms impose a burden on the working lives' of women, their employers, and the economy.

Stochastic Ratcheting on a Funneled Energy Landscape Is Necessary for Highly Efficient Contractility of Actomyosin Force Dipoles

Science.gov (United States)

Komianos, James E.; Papoian, Garegin A.

2018-04-01

Current understanding of how contractility emerges in disordered actomyosin networks of nonmuscle cells is still largely based on the intuition derived from earlier works on muscle contractility. In addition, in disordered networks, passive cross-linkers have been hypothesized to percolate force chains in the network, hence, establishing large-scale connectivity between local contractile clusters. This view, however, largely overlooks the free energy of cross-linker binding at the microscale, which, even in the absence of active fluctuations, provides a thermodynamic drive towards highly overlapping filamentous states. In this work, we use stochastic simulations and mean-field theory to shed light on the dynamics of a single actomyosin force dipole—a pair of antiparallel actin filaments interacting with active myosin II motors and passive cross-linkers. We first show that while passive cross-linking without motor activity can produce significant contraction between a pair of actin filaments, driven by thermodynamic favorability of cross-linker binding, a sharp onset of kinetic arrest exists at large cross-link binding energies, greatly diminishing the effectiveness of this contractility mechanism. Then, when considering an active force dipole containing nonmuscle myosin II, we find that cross-linkers can also serve as a structural ratchet when the motor dissociates stochastically from the actin filaments, resulting in significant force amplification when both molecules are present. Our results provide predictions of how actomyosin force dipoles behave at the molecular level with respect to filament boundary conditions, passive cross-linking, and motor activity, which can explicitly be tested using an optical trapping experiment.

Stochastic Ratcheting on a Funneled Energy Landscape Is Necessary for Highly Efficient Contractility of Actomyosin Force Dipoles

Directory of Open Access Journals (Sweden)

James E. Komianos

2018-04-01

Full Text Available Current understanding of how contractility emerges in disordered actomyosin networks of nonmuscle cells is still largely based on the intuition derived from earlier works on muscle contractility. In addition, in disordered networks, passive cross-linkers have been hypothesized to percolate force chains in the network, hence, establishing large-scale connectivity between local contractile clusters. This view, however, largely overlooks the free energy of cross-linker binding at the microscale, which, even in the absence of active fluctuations, provides a thermodynamic drive towards highly overlapping filamentous states. In this work, we use stochastic simulations and mean-field theory to shed light on the dynamics of a single actomyosin force dipole—a pair of antiparallel actin filaments interacting with active myosin II motors and passive cross-linkers. We first show that while passive cross-linking without motor activity can produce significant contraction between a pair of actin filaments, driven by thermodynamic favorability of cross-linker binding, a sharp onset of kinetic arrest exists at large cross-link binding energies, greatly diminishing the effectiveness of this contractility mechanism. Then, when considering an active force dipole containing nonmuscle myosin II, we find that cross-linkers can also serve as a structural ratchet when the motor dissociates stochastically from the actin filaments, resulting in significant force amplification when both molecules are present. Our results provide predictions of how actomyosin force dipoles behave at the molecular level with respect to filament boundary conditions, passive cross-linking, and motor activity, which can explicitly be tested using an optical trapping experiment.

Eye gaze performance for children with severe physical impairments using gaze-based assistive technology-A longitudinal study.

Science.gov (United States)

Borgestig, Maria; Sandqvist, Jan; Parsons, Richard; Falkmer, Torbjörn; Hemmingsson, Helena

2016-01-01

Gaze-based assistive technology (gaze-based AT) has the potential to provide children affected by severe physical impairments with opportunities for communication and activities. This study aimed to examine changes in eye gaze performance over time (time on task and accuracy) in children with severe physical impairments, without speaking ability, using gaze-based AT. A longitudinal study with a before and after design was conducted on 10 children (aged 1-15 years) with severe physical impairments, who were beginners to gaze-based AT at baseline. Thereafter, all children used the gaze-based AT in daily activities over the course of the study. Compass computer software was used to measure time on task and accuracy with eye selection of targets on screen, and tests were performed with the children at baseline, after 5 months, 9-11 months, and after 15-20 months. Findings showed that the children improved in time on task after 5 months and became more accurate in selecting targets after 15-20 months. This study indicates that these children with severe physical impairments, who were unable to speak, could improve in eye gaze performance. However, the children needed time to practice on a long-term basis to acquire skills needed to develop fast and accurate eye gaze performance.

Opportunities to Target Specific Contractile Abnormalities with Smooth Muscle Protein Kinase Inhibitors

Directory of Open Access Journals (Sweden)

Annegret Ulke-Lemée

2010-05-01

Full Text Available Smooth muscle is a major component of most hollow organ systems (e.g., airways, vasculature, bladder and gut/gastrointestine; therefore, the coordinated regulation of contraction is a key property of smooth muscle. When smooth muscle functions normally, it contributes to general health and wellness, but its dysfunction is associated with morbidity and mortality. Rho-associated protein kinase (ROCK is central to calcium-independent, actomyosin-mediated contractile force generation in the vasculature, thereby playing a role in smooth muscle contraction, cell motility and adhesion. Recent evidence supports an important role for ROCK in the increased vasoconstriction and remodeling observed in various models of hypertension. This review will provide a commentary on the development of specific ROCK inhibitors and their clinical application. Fasudil will be discussed as an example of bench-to-bedside development of a clinical therapeutic that is used to treat conditions of vascular hypercontractility. Due to the wide spectrum of biological processes regulated by ROCK, many additional clinical indications might also benefit from ROCK inhibition. Apart from the importance of ROCK in smooth muscle contraction, a variety of other protein kinases are known to play similar roles in regulating contractile force. The zipper-interacting protein kinase (ZIPK and integrin-linked kinase (ILK are two well-described regulators of contraction. The relative contribution of each kinase to contraction depends on the muscle bed as well as hormonal and neuronal stimulation. Unfortunately, specific inhibitors for ZIPK and ILK are still in the development phase, but the success of fasudil suggests that inhibitors for these other kinases may also have valuable clinical applications. Notably, the directed inhibition of ZIPK with a pseudosubstrate molecule shows unexpected effects on the contractility of gastrointestinal smooth muscle.

Correlation among personal, social performance and cognitive impairment in male schizophrenic patient

Science.gov (United States)

Damanik, R.; Effendy, E.; Camellia, V.

2018-03-01

Schizophrenia is a dramatic mental illness with tragic manifestation. The consequences of the illness are for the individual, affected his or her family and society. Schizophrenia is one of the twenty illness that causes Years Lost due to Disability. Treating only the symptom is insufficient. The aim of treatment must include the quality of life of aschizophrenic person. This study aims to examine the relationship between cognitive impairment and performance of the person with schizophrenia. Cognitive test is scaled with Indonesian version of Montreal Cognitive Assessment (MoCA-Ina), while personal and social performance isscaled with Personal and Social Performance scale. There are many studies that search the relationship between cognitive impairment and social functioning of schizophrenic patients, but this is the first study that uses PSP and MoCA-Ina. Both PSP and MoCA-Ina are easy to use but still have high sensitivity and specificity, and perhaps can build people’s interest to use it in clinical practice. Twenty-five male schizophrenic patients were assessed in Prof. M. Ildrem Mental Hospital of North Sumatera Province of Indonesia. Positive correlations between MoCA-Ina and PSP score were identified. Clinicians should pay attention to cognitive and might give some early intervention to it.

The Longitudinal Joint Effect of Obesity and Major Depression on Work Performance Impairment

NARCIS (Netherlands)

Nigatu, Yeshambel T.; Reijneveld, Sijmen A.; Penninx, Brenda W. J. H.; Schoevers, Robert A.; Bultmann, Ute

Objectives. We examined the longitudinal effect of obesity, major depression, and their combination on work performance impairment (WPI). Methods. We collected longitudinal data (2004-2013) on 1726 paid employees from the Netherlands Study of Depression and Anxiety at baseline and 2-, 4-, and 6-year

The longitudinal joint effect of obesity and major depression on work performance impairment

NARCIS (Netherlands)

Nigatu, Y.T.; Reijneveld, S.A.; Penninx, B.W.; Schoevers, R.A.; Bultmann, U.

2015-01-01

Objectives: We examined the longitudinal effect of obesity, major depression, and their combination on work performance impairment (WPI). Methods: We collected longitudinal data (2004-2013) on 1726 paid employees from the Netherlands Study of Depression and Anxiety at baseline and 2-, 4-, and 6-year

Effect of short-term outlet obstruction on rat bladder nerve density and contractility

NARCIS (Netherlands)

Barendrecht, M. M.; Chichester, P.; Michel, M. C.; Levin, R. M.

2007-01-01

1 The present study was designed to investigate the relationship between innervation density and contractile responses to field stimulation and exogenous agonists at early time points after induction of bladder outlet obstruction (BOO) in rats. 2 When compared with sham-operated animals, 1, 3 and 7

Contractile function and motor unit firing rates of the human hamstrings.

Science.gov (United States)

Kirk, Eric A; Rice, Charles L

2017-01-01

Neuromuscular properties of the lower limb in health, aging, and disease are well described for major lower limb muscles comprising the quadriceps, triceps surae, and dorsiflexors, with the notable exception of the posterior thigh (hamstrings). The purpose of this study was to further characterize major muscles of the lower limb by comprehensively exploring contractile properties in relation to spinal motor neuron output expressed as motor unit firing rates (MUFRs) in the hamstrings of 11 (26.5 ± 3.8) young men. Maximal isometric voluntary contraction (MVC), voluntary activation, stimulated contractile properties including a force-frequency relationship, and MUFRs from submaximal to maximal voluntary contractile intensities were assessed in the hamstrings. Strength and MUFRs were assessed at two presumably different muscle lengths by varying the knee joint angles (90° and 160°). Knee flexion MVCs were 60-70% greater in the extended position (160°). The frequency required to elicit 50% of maximum tetanic torque was 16-17 Hz. Mean MUFRs at 25-50% MVC were 9-31% less in the biceps femoris compared with the semimembranosus-semitendinosus group. Knee joint angle (muscle length) influenced MUFRs such that mean MUFRs were greater in the shortened (90°) position at 50% and 100% MVC. Compared with previous reports, mean maximal MUFRs in the hamstrings are greater than those in the quadriceps and triceps surae and somewhat less than those in the tibialis anterior. Mean maximal MUFRs in the hamstrings are influenced by changes in knee joint angle, with lower firing rates in the biceps femoris compared with the semimembranosus-semitendinosus muscle group. We studied motor unit firing rates (MUFRs) at various voluntary contraction intensities in the hamstrings, one of the only major lower limb muscles to have MUFRs affected by muscle length changes. Within the hamstrings muscle-specific differences have greater impact on MUFRs than length changes, with the biceps femoris

Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury

Directory of Open Access Journals (Sweden)

Han-Bin Lin

2014-01-01

Full Text Available Matrix metalloproteinases (MMPs significantly contribute to ischemia reperfusion (I/R injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2 in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury.

A thermodynamical model for stress-fiber organization in contractile cells

OpenAIRE

Foucard, Louis; Vernerey, Franck J.

2012-01-01

Cell mechanical adaptivity to external stimuli is vital to many of its biological functions. A critical question is therefore to understand the formation and organization of the stress fibers from which emerge the cell’s mechanical properties. By accounting for the mechanical aspects and the viscoelastic behavior of stress fibers, we here propose a thermodynamic model to predict the formation and orientation of stress fibers in contractile cells subjected to constant or cyclic stretch and dif...

Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

Science.gov (United States)

Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

2015-03-18

Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright �

Inhibition of CYP2E1 attenuates chronic alcohol intake-induced myocardial contractile dysfunction and apoptosis.

Science.gov (United States)

Zhang, Rong-Huai; Gao, Jian-Yuan; Guo, Hai-Tao; Scott, Glenda I; Eason, Anna R; Wang, Xiao-Ming; Ren, Jun

2013-01-01

Alcohol intake is associated with myocardial contractile dysfunction and apoptosis although the precise mechanism is unclear. This study was designed to examine the effect of the cytochrome P450 enzyme CYP2E1 inhibition on ethanol-induced cardiac dysfunction. Adult male mice were fed a 4% ethanol liquid or pair-fed control diet for 6weeks. Following 2weeks of diet feeding, a cohort of mice started to receive the CYP2E1 inhibitor diallyl sulfide (100mg/kg/d, i.p.) for the remaining feeding duration. Cardiac function was assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate CYP2E1, heme oxygenase-1 (HO-1), iNOS, the intracellular Ca(2+) regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase, Na(+)Ca(2+) exchanger and phospholamban, pro-apoptotic protein cleaved caspase-3, Bax, c-Jun-NH(2)-terminal kinase (JNK) and apoptosis signal-regulating kinase (ASK-1). Ethanol led to elevated levels of CYP2E1, iNOS and phospholamban, decreased levels of HO-1 and Na(+)Ca(2+) exchanger, cardiac contractile and intracellular Ca(2+) defects, cardiac fibrosis, overt O(2)(-) production, and apoptosis accompanied with increased phosphorylation of JNK and ASK-1, the effects were significantly attenuated or ablated by diallyl sulfide. Inhibitors of JNK and ASK-1 but not HO-1 inducer or iNOS inhibitor obliterated ethanol-induced cardiomyocyte contractile dysfunction, substantiating a role for JNK and ASK-1 signaling in ethanol-induced myocardial injury. Taken together, these findings suggest that ethanol metabolism through CYP2E1 may contribute to the pathogenesis of alcoholic cardiomyopathy including myocardial contractile dysfunction, oxidative stress and apoptosis, possibly through activation of JNK and ASK-1 signaling. Copyright © 2012 Elsevier B.V. All rights reserved.

Impairment of exercise performance following cold water immersion is not attenuated after 7 days of cold acclimation.

Science.gov (United States)

Jones, Douglas M; Roelands, Bart; Bailey, Stephen P; Buono, Michael J; Meeusen, Romain

2018-03-19

It is well-documented that severe cold stress impairs exercise performance. Repeated immersion in cold water induces an insulative type of cold acclimation, wherein enhanced vasoconstriction leads to greater body heat retention, which may attenuate cold-induced exercise impairments. The purpose of this study, therefore, was to investigate changes in exercise performance during a 7-day insulative type of cold acclimation. Twelve healthy participants consisting of eight males and four females (mean ± SD age: 25.6 ± 5.2 years, height: 174.0 ± 8.9 cm, weight: 75.6 ± 13.1 kg) performed a 20 min self-paced cycling test in 23 °C, 40% humidity without prior cold exposure. Twenty-four hours later they began a 7-day cold acclimation protocol (daily 90 min immersion in 10 °C water). On days one, four, and seven of cold acclimation, participants completed the same cycling test. Measurements of work completed, core and skin temperatures, heart rate, skin blood flow, perceived exertion, and thermal sensation were measured during each cycling test. Successful insulative cold acclimation was observed. Work produced during the baseline cycling test (220 ± 70 kJ) was greater (p immersions (195 ± 58, 197 ± 60, and 194 ± 62 kJ) despite similar ratings of perceived exertion during each test, suggesting that cold exposure impaired cycling performance. This impairment, however, was not attenuated over the cold acclimation period. Results suggest that insulative cold acclimation does not attenuate impairments in exercise performance that were observed following acute cold water immersion.

Caffeine administration at night during extended wakefulness effectively mitigates performance impairment but not subjective assessments of fatigue and sleepiness.

Science.gov (United States)

Paech, Gemma M; Banks, Siobhan; Pajcin, Maja; Grant, Crystal; Johnson, Kayla; Kamimori, Gary H; Vedova, Chris B Della

2016-06-01

The current study investigated the effects of repeated caffeine administration on performance and subjective reports of sleepiness and fatigue during 50h extended wakefulness. Twenty-four, non-smokers aged 22.5±2.9y (mean±SD) remained awake for two nights (50h) in a controlled laboratory environment. During this period, 200mg of caffeine or placebo gum was administered at 01:00, 03:00, 05:00 and 07:00 on both nights (total of 800mg/night). Neurobehavioral performance and subjective reports were assessed throughout the wake period. Caffeine improved performance compared to placebo, but did not affect overall ratings of subjective sleepiness and fatigue. Performance and sleepiness worsened with increasing time awake for both conditions. However, caffeine slowed performance impairments such that after 50h of wakefulness performance was better following caffeine administration compared to placebo. Caffeine also slowed the increase in subjective sleepiness and performance ratings, but only during the first night of wakefulness. After two nights of sleep deprivation, there was no difference in sleepiness ratings between the two conditions. These results demonstrate that strategic administration of caffeine effectively mitigates performance impairments associated with 50h wakefulness but does not improve overall subjective assessments of sleepiness, fatigue and performance. Results indicate that while performance impairment is alleviated, individuals may continue to report feelings of sleepiness. Individuals who use caffeine as a countermeasure in sustained operations may feel as though caffeine is not effective despite impairments in objective performance being largely mitigated. Copyright © 2016 Elsevier Inc. All rights reserved.

Validation of Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), a Performance- Based Measurement of Instrumental Activities of Daily Living for Patients with Vascular Cognitive Impairment.

Science.gov (United States)

Chen, Hui-Mei; Lin, Hsiu-Fen; Huang, Mei-Feng; Chang, Chun-Wei; Yeh, Yi-Chun; Lo, Yi-Ching; Yen, Cheng-Fang; Chen, Cheng-Sheng

2016-01-01

Patients with cerebrovascular diseases often presented both cognitive and physical impairment. Disability in everyday functioning involving cognitive impairment among patients may be hard to completely rely on informants' reports, as their reports may be confounded with physical impairment. The aim of this study was to validate a performance-based measure of functional assessment, the Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), for vascular cognitive impairment (VCI) by examining its psychometric properties and diagnostic accuracy. Ninety-seven patients with cerebrovascular diseases, including 30 with vascular dementia (VaD), 28 with mild cognitive impairment and 39 with no cognitive impairment, and 49 healthy control adults were recruited during study period. The TPIADL, as well as the Mini Mental State Examination (MMSE), Lawton-IADL and Barthel Index (BI), were performed. The internal consistency, convergent and criteria validity of the TPIADL were examined. Cronbach's alpha of the TPIADL test was 0.84. The TPIADL scores were significantly correlated with the Lawton IADL (r = -0.587, p cognitive domain of Lawton IADL (r = -0.663) than with physical domain of Lawton IADL (r = -0.541). The area under the relative operating characteristic curve was 0.888 (95% CI = 0.812-0.965) to differentiate VaD from other groups. The optimal cut-off point of the TPIADL for detecting VaD was 6/7, which gives a sensitivity of 73.3% and a specificity of 84.5%. The TPIADL is a brief and sensitive tool for the detection of IADL impairment in patients with VaD.

Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ETB, 5-HT1B and AT1 Receptor-Mediated Contractility Downstream of Occlusion

DEFF Research Database (Denmark)

Rasmussen, Marianne N P; Hornbak, Malene; Larsen, Stine S

2013-01-01

Background/Aims: In response to experimental stroke, a characteristic functional and expressional upregulation of contractile G-protein-coupled receptors has been uncovered in the affected cerebral vasculature; however, the mechanism initiating this phenomenon remains unknown. Methods: Using...... a model of permanent distal occlusion of rat middle cerebral arteries, we investigated whether there was a regional difference in receptor-mediated contractility of segments located upstream and downstream of the occlusion site. The contractile response to endothelin, angiotensin and 5-hydroxytryptamine...... receptor stimulation was studied by sensitive wire myograph. Results: Only downstream segments exhibited an augmented contractile response to stimulation with each of the three ligands, with the response towards sarafotoxin 6c being especially augmented compared to sham, upstream and contralateral controls...

Learning trajectories for speech motor performance in children with specific language impairment.

Science.gov (United States)

Richtsmeier, Peter T; Goffman, Lisa

2015-01-01

Children with specific language impairment (SLI) often perform below expected levels, including on tests of motor skill and in learning tasks, particularly procedural learning. In this experiment we examined the possibility that children with SLI might also have a motor learning deficit. Twelve children with SLI and thirteen children with typical development (TD) produced complex nonwords in an imitation task. Productions were collected across three blocks, with the first and second blocks on the same day and the third block one week later. Children's lip movements while producing the nonwords were recorded using an Optotrak camera system. Movements were then analyzed for production duration and stability. Movement analyses indicated that both groups of children produced shorter productions in later blocks (corroborated by an acoustic analysis), and the rate of change was comparable for the TD and SLI groups. A nonsignificant trend for more stable productions was also observed in both groups. SLI is regularly accompanied by a motor deficit, and this study does not dispute that. However, children with SLI learned to make more efficient productions at a rate similar to their peers with TD, revealing some modification of the motor deficit associated with SLI. The reader will learn about deficits commonly associated with specific language impairment (SLI) that often occur alongside the hallmark language deficit. The authors present an experiment showing that children with SLI improved speech motor performance at a similar rate compared to typically developing children. The implication is that speech motor learning is not impaired in children with SLI. Copyright © 2015 Elsevier Inc. All rights reserved.

Mental Fatigue Impairs Soccer-Specific Physical and Technical Performance.

Science.gov (United States)

Smith, Mitchell R; Coutts, Aaron J; Merlini, Michele; Deprez, Dieter; Lenoir, Matthieu; Marcora, Samuele M

2016-02-01

To investigate the effects of mental fatigue on soccer-specific physical and technical performance. This investigation consisted of two separate studies. Study 1 assessed the soccer-specific physical performance of 12 moderately trained soccer players using the Yo-Yo Intermittent Recovery Test, Level 1 (Yo-Yo IR1). Study 2 assessed the soccer-specific technical performance of 14 experienced soccer players using the Loughborough Soccer Passing and Shooting Tests (LSPT, LSST). Each test was performed on two occasions and preceded, in a randomized, counterbalanced order, by 30 min of the Stroop task (mentally fatiguing treatment) or 30 min of reading magazines (control treatment). Subjective ratings of mental fatigue were measured before and after treatment, and mental effort and motivation were measured after treatment. Distance run, heart rate, and ratings of perceived exertion were recorded during the Yo-Yo IR1. LSPT performance time was calculated as original time plus penalty time. LSST performance was assessed using shot speed, shot accuracy, and shot sequence time. Subjective ratings of mental fatigue and effort were higher after the Stroop task in both studies (P motivation was similar between conditions. This mental fatigue significantly reduced running distance in the Yo-Yo IR1 (P performance time were not different between conditions; however, penalty time significantly increased in the mental fatigue condition (P = 0.015). Mental fatigue also impaired shot speed (P = 0.024) and accuracy (P performance.

Matching of sarcoplasmic reticulum and contractile properties in rat fast- and slow-twitch muscle fibres.

Science.gov (United States)

Trinh, Huong H; Lamb, Graham D

2006-07-01

1. The twitch characteristics (fast-twitch or slow-twitch) of skeletal muscle fibres are determined not only by the contractile apparatus properties of the fibre, but also by the time-course of Ca2+ release and re-uptake by the sarcoplasmic reticulum (SR). The present study examined, in individual fibres from non-transforming muscle of the rat, whether particular SR properties are matched to the contractile apparatus properties of the fibre, in particular in the case of fibres with fast-twitch contractile apparatus located in a slow-twitch muscle, namely the soleus. 2. Force was recorded in single, mechanically skinned fibres from extensor digitorum longus (EDL), gastrocnemius, peroneus longus and soleus muscles. Using repeated cycles in which the SR was emptied of all releasable Ca2+ and then reloaded, it was possible to determine the relative amount of Ca2+ present in the SR endogenously, the maximum SR capacity and the rate of Ca2+ loading. The sensitivity of the contractile apparatus to Ca2+ and Sr2+ was used to classify the fibres as fast-twitch (FT), slow-twitch (ST) or mixed (fibres examined) and thereby identify the likely troponin C and myosin heavy chain types present. 3. There was no significant difference in SR properties between the groups of FT fibres obtained from the four different muscles, including soleus. Despite some overlap in the SR properties of individual fibres between the FT and ST groups, the properties of the FT fibres in all four muscles studied were significantly different from those of the ST and mixed fibres. 4. In general, in FT fibres the SR had a larger capacity and the endogenous Ca2+ content was a relatively lower percentage of maximum compared with ST fibres. Importantly, in terms of their SR properties, FT fibres from soleus muscle more closely resembled FT fibres from other muscles than they did ST fibres from soleus muscle.

Dynamic working memory performance in individuals with single-domain amnestic mild cognitive impairment.

Science.gov (United States)

Guild, Emma B; Vasquez, Brandon P; Maione, Andrea M; Mah, Linda; Ween, Jon; Anderson, Nicole D

2014-01-01

Previous studies have observed poorer working memory performance in individuals with amnestic mild cognitive impairment than in healthy older adults. It is unclear, however, whether these difficulties are true only of the multiple-domain clinical subtype in whom poorer executive functioning is common. The current study examined working memory, as measured by the self-ordered pointing task (SOPT) and an n-back task, in healthy older adults and adults with single-domain amnestic mild cognitive impairment (aMCI). Individuals with single-domain aMCI committed more errors and required longer to develop an organizational strategy on the SOPT. The single-domain aMCI group did not differ from healthy older adults on the 1-back or 2-back, but had poorer discrimination on the 3-back task. This is, to our knowledge, the first characterization of dynamic working memory performance in a single-domain aMCI group. These results lend support for the idea that clinical amnestic MCI subtypes may reflect different stages on a continuum of progression to dementia and question whether standardized measures of working memory (span tasks) are sensitive enough to capture subtle changes in performance.

Development and validation of an exercise performance support system for people with lower extremity impairment.

Science.gov (United States)

Minor, M A; Reid, J C; Griffin, J Z; Pittman, C B; Patrick, T B; Cutts, J H

1998-02-01

To identify innovative strategies to support appropriate, self-directed exercise that increase physical activity levels of people with arthritis. This article reports on one interactive, multimedia exercise performance support system (PSS) for people with lower extremity impairments in strength or flexibility. An interdisciplinary team developed the PSS using self-report of lower extremity musculoskeletal impairments (flexibility and strength) to produce an individualized exercise program with video and print educational materials. Initial evaluation has investigated the validity and reliability of program assessments and recommendations. PSS self-report and professional assessments were similar, with more impairments indicated by self-report. PSS exercise recommendations were similar to those made by 3 expert physical therapists using the same exercise data base. Results of PSS impairment assessments were stable over a 1-week period. PSS exercise recommendations appear to be reliable and a valid reflection of current exercise knowledge in rheumatology. Furthermore, users were able to complete the computer-based program with minimal assistance and reported it to be enjoyable and informative.

Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice

NARCIS (Netherlands)

Rensen, Sander S.; Niessen, Petra M.; van Deursen, Jan M.; Janssen, Ben J.; Heijman, Edwin; Hermeling, Evelien; Meens, Merlijn; Lie, Natascha; Gijbels, Marion J.; Strijkers, Gustav J.; Doevendans, Pieter A.; Hofker, Marten H.; de Mey, Jo G. R.; van Eys, Guillaume J.

2008-01-01

Smoothelins are actin-binding proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. Their expression is strongly associated with the contractile phenotype of smooth muscle cells. Analysis of mice lacking both smoothelins (Smtn-A/B(-/-)

Physical Performance Is Associated with Working Memory in Older People with Mild to Severe Cognitive Impairment

NARCIS (Netherlands)

Volkers, K. M.; Scherder, E. J. A.

2014-01-01

Background. Physical performances and cognition are positively related in cognitively healthy people. The aim of this study was to examine whether physical performances are related to specific cognitive functioning in older people with mild to severe cognitive impairment. Methods. This

New insights into roles of acidocalcisomes and contractile vacuole complex in osmoregulation in protists.

Science.gov (United States)

Docampo, Roberto; Jimenez, Veronica; Lander, Noelia; Li, Zhu-Hong; Niyogi, Sayantanee

2013-01-01

While free-living protists are usually subjected to hyposmotic environments, parasitic protists are also in contact with hyperosmotic habitats. Recent work in one of these parasites, Trypanosoma cruzi, has revealed that its contractile vacuole complex, which usually collects and expels excess water as a mechanism of regulatory volume decrease after hyposmotic stress, has also a role in cell shrinking when the cells are submitted to hyperosmotic stress. Trypanosomes also have an acidic calcium store rich in polyphosphate (polyP), named the acidocalcisome, which is involved in their response to osmotic stress. Here, we review newly emerging insights on the role of acidocalcisomes and the contractile vacuole complex in the cellular response to hyposmotic and hyperosmotic stresses. We also review the current state of knowledge on the composition of these organelles and their other roles in calcium homeostasis and protein trafficking. © 2013, Elsevier Inc. All Rights Reserved.

Validation of Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL, a Performance- Based Measurement of Instrumental Activities of Daily Living for Patients with Vascular Cognitive Impairment.

Directory of Open Access Journals (Sweden)

Hui-Mei Chen

Full Text Available Patients with cerebrovascular diseases often presented both cognitive and physical impairment. Disability in everyday functioning involving cognitive impairment among patients may be hard to completely rely on informants' reports, as their reports may be confounded with physical impairment. The aim of this study was to validate a performance-based measure of functional assessment, the Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL, for vascular cognitive impairment (VCI by examining its psychometric properties and diagnostic accuracy.Ninety-seven patients with cerebrovascular diseases, including 30 with vascular dementia (VaD, 28 with mild cognitive impairment and 39 with no cognitive impairment, and 49 healthy control adults were recruited during study period. The TPIADL, as well as the Mini Mental State Examination (MMSE, Lawton-IADL and Barthel Index (BI, were performed. The internal consistency, convergent and criteria validity of the TPIADL were examined.Cronbach's alpha of the TPIADL test was 0.84. The TPIADL scores were significantly correlated with the Lawton IADL (r = -0.587, p <0.01. Notably, the TPIADL had a higher correlation coefficient with the cognitive domain of Lawton IADL (r = -0.663 than with physical domain of Lawton IADL (r = -0.541. The area under the relative operating characteristic curve was 0.888 (95% CI = 0.812-0.965 to differentiate VaD from other groups. The optimal cut-off point of the TPIADL for detecting VaD was 6/7, which gives a sensitivity of 73.3% and a specificity of 84.5%.The TPIADL is a brief and sensitive tool for the detection of IADL impairment in patients with VaD.

Contractile profile of esophageal and gastric fundus strips in experimental doxorubicin-induced esophageal atresia

Directory of Open Access Journals (Sweden)

F.A. Capeto

2015-05-01

Full Text Available Esophageal atresia (EA is characterized by esophageal and gastric motility changes secondary to developmental and postsurgical damage. This study evaluated the in vitro contractile profile of the distal esophagus and gastric fundus in an experimental model of EA induced by doxorubicin (DOXO. Wistar pregnant rats received DOXO 2.2 mg/kg on the 8th and 9th gestational days. On day 21.5, fetuses were collected, sacrificed, and divided into groups: control, DOXO without EA (DOXO-EA, and DOXO with EA (DOXO+EA. Strips from the distal esophagus and gastric fundus were mounted on a wire myograph and isolated organ-bath system, respectively, and subjected to increasing concentrations of carbamylcholine chloride (carbachol, CCh. The isolated esophagus was also stimulated with increasing concentrations of KCl. In esophagus, the concentration-effect curves were reduced in response to CCh in the DOXO+EA and DOXO-EA groups compared to the control group (P0.05. In response to KCl, the distal esophagus samples in the three groups were not statistically different with regard to Emax or EC50 values (P>0.05. No significant difference was noted for EC50 or Emax values in fundic strips stimulated with CCh (P>0.05. In conclusion, exposure of dams to DOXO during gestation inhibited the contractile behavior of esophageal strips from offspring in response to CCh but not KCl, regardless of EA induction. The gastric fundus of DOXO-exposed offspring did not have altered contractile responsiveness to cholinergic stimulation.

Altered Ca fluxes and contractile state during pH changes in cultured heart cells

International Nuclear Information System (INIS)

Kim, D.; Smith, T.W.

1987-01-01

The authors studied mechanisms underlying changes in myocardial contractile state produced by intracellular (pH/sub i/) or extracellular (pH 0 ) changes in pH using cultured chick embryo ventricular cells. A change in pH 0 of HEPES-buffered medium from 7.4 to 6.0 or to 8.8 changed the amplitude of cell motion by -85 or +60%, and 45 Ca uptake at 10 s by -29 or +22%, respectively. The pH 0 induced change in Ca uptake was not sensitive to nifedipine but was Na gradient dependent. Changes in pH/sub i/ produced by NH 4 Cl or preincubation in media at pH values ranging from 6.0 to 8.8 failed to alter significantly 45 Ca uptake or efflux. However, larger changes in pH/sub i/ were associated with altered Ca uptake. Changes in pH 0 from 7.5 to 6.0 or to 8.8 were associated with initial changes in 45 Ca efflux by +17 or -18%, respectively, and these effects were not Na dependent. Exposure of cells to 20 mM NH 4 Cl produced intracellular alkalinization and a positive inotropic effect, whereas subsequent removal of NH 4 Cl caused intracellular acidification and a negative inotropic effect. There was, however, a lack of close temporal relationships between pH/sub i/ and contractile state. These results indicated that pH 0 -induced changes in contractile state in cultured heart cells are closely correlated with altered transarcolemmal Ca movements and presumably are due to these Ca flux changes

Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions

Directory of Open Access Journals (Sweden)

Cleci M. Moreira

2012-01-01

Full Text Available OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1 streptozotocin-induced diabetic and control Wistar rats; (2 N-nitro-L-arginine methyl ester (L-NAME hypertensive and untreated Wistar rats; (3 deoxycorticosterone acetate (DOCA salt-treated, nephrectomized and salt- and DOCA-treated rats; (4 spontaneous hypertensive rats (SHR and Wistar Kyoto (WKY rats; (5 rats with myocardial infarction and shamoperated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester-treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L-arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes, a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better

Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat

DEFF Research Database (Denmark)

Tfelt-Hansen, Peer; Nilsson, Elisabeth; Edvinsson, Lars

2007-01-01

mmHg and luminally perfused. All vessels used attained spontaneous contractile tone (34.9+/-1.8% of resting tone) and responded to luminal adenosine triphosphate (ATP) with dilatation (24.1+/-4.0%), which showed functioning endothelium. Luminally added ergotamine or DHE induced maximal contractions...

Performance of Multi-Carrier Access Schemes with Receiver Impairments in Down Link Indoor Environment

DEFF Research Database (Denmark)

Das, Suvra Sekhar; Rao, Raieshwar Kurapati; Prasad, Ramjee

2006-01-01

impairments, such as synchronization error and channel estimation errors. This work is targeted towards unified verification of performance of the schemes for different spreading gains, load conditions and sub carrier grouping schemes in quasi static realistic indoor channel environment in the presence...

Verifax: Biometric instruments measuring neuromuscular disorders/performance impairments

Science.gov (United States)

Morgenthaler, George W.; Shrairman, Ruth; Landau, Alexander

1998-01-01

VeriFax, founded in 1990 by Dr. Ruth Shrairman and Mr. Alex Landau, began operations with the aim of developing a biometric tool for the verification of signatures from a distance. In the course of developing this VeriFax Autograph technology, two other related applications for the technologies under development at VeriFax became apparent. The first application was in the use of biometric measurements as clinical monitoring tools for physicians investigating neuromuscular diseases (embodied in VeriFax's Neuroskill technology). The second application was to evaluate persons with critical skills (e.g., airline pilots, bus drivers) for physical and mental performance impairments caused by stress, physiological disorders, alcohol, drug abuse, etc. (represented by VeriFax's Impairoscope prototype instrument). This last application raised the possibility of using a space-qualified Impairoscope variant to evaluate astronaut performance with respect to the impacts of stress, fatigue, excessive workload, build-up of toxic chemicals within the space habitat, etc. The three applications of VeriFax's patented technology are accomplished by application-specific modifications of the customized VeriFax software. Strong commercial market potentials exist for all three VeriFax technology applications, and market progress will be presented in more detail below.

Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion.

Science.gov (United States)

Ronan, William; Deshpande, Vikram S; McMeeking, Robert M; McGarry, J Patrick

2014-04-01

Numerous experimental studies have established that cells can sense the stiffness of underlying substrates and have quantified the effect of substrate stiffness on stress fibre formation, focal adhesion area, cell traction, and cell shape. In order to capture such behaviour, the current study couples a mixed mode thermodynamic and mechanical framework that predicts focal adhesion formation and growth with a material model that predicts stress fibre formation, contractility, and dissociation in a fully 3D implementation. Simulations reveal that SF contractility plays a critical role in the substrate-dependent response of cells. Compliant substrates do not provide sufficient tension for stress fibre persistence, causing dissociation of stress fibres and lower focal adhesion formation. In contrast, cells on stiffer substrates are predicted to contain large amounts of dominant stress fibres. Different levels of cellular contractility representative of different cell phenotypes are found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the inter-dependent biomechanical processes regulating stress fibre and focal adhesion formation.

EFFECT OF HYDROGEN SULFIDE ON ATRIUM CONTRACTILITY IN CONTROL AND DIABETHIC MICE

Directory of Open Access Journals (Sweden)

A. S. Lifanova

2014-01-01

Full Text Available Hydrogen sulfide (H2S is endogenously synthesized gasotransmitter that has a regulatory effect in cardiovascular system. Diabetes mellitus leads to an increased risk of hypertension and cardiovascular diseases, so the purpose of the study was to analyze the contractility of the atria mice after application of L-cysteine and H2S. Contractile activity of the myocardium was investigated in the experiment on isolated mouse atria. Alloxan was used for modeling diabetes. Intraperitoneal injection of alloxan resulted in a significant increase of glucose concentration in blood, whereas the concentration of glucose didn’t change at the injection of physiological solution. In control, the addition of NaHS resulted in a significant dose-dependent decrease of the amplitude of contraction of the myocardium, whereas the negative inotropic effect of NaHS was significantly lower in terms of modeling diabetes compare to control conditions. In the control, L-cysteine reduced the amplitude contractions significantly, whereas L-cysteine did not lead to significant changes in the amplitude of contractions in terms of modeling diabetes. These data indicate that the sensitivity of mice’s atria reduced for H2S and L-cysteine in diabetes mellitus.

Impaired laparoscopic performance of novice surgeons due to phone call distraction: a single-centre, prospective study.

Science.gov (United States)

Yang, Cui; Heinze, Julia; Helmert, Jens; Weitz, Juergen; Reissfelder, Christoph; Mees, Soeren Torge

2017-12-01

Distractions such as phone calls during laparoscopic surgery play an important role in many operating rooms. The aim of this single-centre, prospective study was to assess if laparoscopic performance is impaired by intraoperative phone calls in novice surgeons. From October 2015 to June 2016, 30 novice surgeons (medical students) underwent a laparoscopic surgery training curriculum including two validated tasks (peg transfer, precision cutting) until achieving a defined level of proficiency. For testing, participants were required to perform these tasks under three conditions: no distraction (control) and two standardised distractions in terms of phone calls requiring response (mild and strong distraction). Task performance was evaluated by analysing time and accuracy of the tasks and response of the phone call. In peg transfer (easy task), mild distraction did not worsen the performance significantly, while strong distraction was linked to error and inefficiency with significantly deteriorated performance (P phone call distractions result in impaired laparoscopic performance under certain circumstances. To ensure patient safety, phone calls should be avoided as far as possible in operating rooms.

Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.

Science.gov (United States)

Mendias, Christopher L; Schwartz, Andrew J; Grekin, Jeremy A; Gumucio, Jonathan P; Sugg, Kristoffer B

2017-03-01

Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sF o ), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point. NEW & NOTEWORTHY This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic

Cell density and actomyosin contractility control the organization of migrating collectives within an epithelium

Science.gov (United States)

Loza, Andrew J.; Koride, Sarita; Schimizzi, Gregory V.; Li, Bo; Sun, Sean X.; Longmore, Gregory D.

2016-01-01

The mechanisms underlying collective migration are important for understanding development, wound healing, and tumor invasion. Here we focus on cell density to determine its role in collective migration. Our findings show that increasing cell density, as might be seen in cancer, transforms groups from broad collectives to small, narrow streams. Conversely, diminishing cell density, as might occur at a wound front, leads to large, broad collectives with a distinct leader–follower structure. Simulations identify force-sensitive contractility as a mediator of how density affects collectives, and guided by this prediction, we find that the baseline state of contractility can enhance or reduce organization. Finally, we test predictions from these data in an in vivo epithelium by using genetic manipulations to drive collective motion between predicted migratory phases. This work demonstrates how commonly altered cellular properties can prime groups of cells to adopt migration patterns that may be harnessed in health or exploited in disease. PMID:27605707

Perfusion-induced changes in cardiac contractility depend on capillary perfusion.

Science.gov (United States)

Dijkman, M A; Heslinga, J W; Sipkema, P; Westerhof, N

1998-02-01

The perfusion-induced increase in cardiac contractility (Gregg phenomenon) is especially found in heart preparations that lack adequate coronary autoregulation and thus protection of changes in capillary pressure. We determined in the isolated perfused papillary muscle of the rat whether cardiac muscle contractility is related to capillary perfusion. Oxygen availability of this muscle is independent of internal perfusion, and perfusion may be varied or even stopped without loss of function. Muscles contracted isometrically at 27 degrees C (n = 7). During the control state stepwise increases in perfusion pressure resulted in all muscles in a significant increase in active tension. Muscle diameter always increased with increased perfusion pressure, but muscle segment length was unaffected. Capillary perfusion was then obstructed by plastic microspheres (15 microns). Flow, at a perfusion pressure of 66.6 +/- 26.2 cmH2O, reduced from 17.6 +/- 5.4 microliters/min in the control state to 3.2 +/- 1.3 microliters/min after microspheres. Active tension developed by the muscle in the unperfused condition before microspheres and after microspheres did not differ significantly (-12.8 +/- 29.4% change). After microspheres similar perfusion pressure steps as in control never resulted in an increase in active tension. Even at the two highest perfusion pressures (89.1 +/- 28.4 and 106.5 +/- 31.7 cmH2O) that were applied a significant decrease in active tension was found. We conclude that the Gregg phenomenon is related to capillary perfusion.

Turn Off the Music! Music Impairs Visual Associative Memory Performance in Older Adults

Science.gov (United States)

Reaves, Sarah; Graham, Brittany; Grahn, Jessica; Rabannifard, Parissa; Duarte, Audrey

2016-01-01

Purpose of the Study: Whether we are explicitly listening to it or not, music is prevalent in our environment. Surprisingly, little is known about the effect of environmental music on concurrent cognitive functioning and whether young and older adults are differentially affected by music. Here, we investigated the impact of background music on a concurrent paired associate learning task in healthy young and older adults. Design and Methods: Young and older adults listened to music or to silence while simultaneously studying face–name pairs. Participants’ memory for the pairs was then tested while listening to either the same or different music. Participants also made subjective ratings about how distracting they found each song to be. Results: Despite the fact that all participants rated music as more distracting to their performance than silence, only older adults’ associative memory performance was impaired by music. These results are most consistent with the theory that older adults’ failure to inhibit processing of distracting task-irrelevant information, in this case background music, contributes to their memory impairments. Implications: These data have important practical implications for older adults’ ability to perform cognitively demanding tasks even in what many consider to be an unobtrusive environment. PMID:26035876

Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity.

Science.gov (United States)

Tang, Mingxin; Zhang, Xiaoying; Li, Yingxin; Guan, Yinzheng; Ai, Xiaojie; Szeto, Christopher; Nakayama, Hiroyuki; Zhang, Hongyu; Ge, Shuping; Molkentin, Jeffery D; Houser, Steven R; Chen, Xiongwen

2010-08-01

Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavbeta2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon beta-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found: 1) in DTG myocytes, L-type Ca(2+) current (I(Ca,L)) density, myocyte fractional shortening (FS), peak Ca(2+) transients, and sarcoplasmic reticulum (SR) Ca(2+) content (caffeine-induced Ca(2+) transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and 2) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/dt and -dP/dt) measurements were significantly greater in DTG mice than in control mice. However, 1) the cardiac contractility (EF, FS, dP/dt, and -dP/dt)-enhancing effect of the beta-adrenergic agonist isoproterenol (2 microg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of beta-adrenergic stimulation on contraction, Ca(2+) transients, I(Ca,L), and SR Ca(2+) content in DTG myocytes; and 2) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high-activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart.

Cognitive function affects trainability for physical performance in exercise intervention among older adults with mild cognitive impairment

Directory of Open Access Journals (Sweden)

Uemura K

2013-01-01

Full Text Available Kazuki Uemura,1,3 Hiroyuki Shimada,1 Hyuma Makizako,1,3 Takehiko Doi,1 Daisuke Yoshida,1 Kota Tsutsumimoto,1 Yuya Anan,1 Takao Suzuki21Section for Health Promotion, Department for Research and Development to Support Independent Life of Elderly, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, 2Research Institute, National Center for Geriatrics and Gerontology, Aichi, 3Japan Society for the Promotion of Science, Tokyo, JapanBackground: Although much evidence supports the hypothesis that cognitive function and physical function are interrelated, it is unclear whether cognitive decline with mild cognitive impairment influences trainability of physical performance in exercise intervention. The purpose of this study was to examine the association between cognitive function at baseline and change in physical performance after exercise intervention in older adults with mild cognitive impairment.Methods: Forty-four older adults diagnosed with mild cognitive impairment based on the Peterson criteria (mean age 74.8 years consented to and completed a 6-month twice weekly exercise intervention. The Timed Up and Go (TUG test was used as a measure of physical performance. The Mini-Mental State Examination (MMSE, Trail Making Test Part B, Geriatric Depression Scale, baseline muscle strength of knee extension, and attendance rate of intervention, were measured as factors for predicting trainability.Results: In the correlation analysis, the change in TUG showed modest correlations with attendance rate in the exercise program (r = -0.354, P = 0.027 and MMSE at baseline (r = -0.321, P = 0.034. A multiple regression analysis revealed that change in TUG was independently associated with attendance rate (ß = -0.322, P = 0.026 and MMSE score (ß = -0.295, P = 0.041, controlling for age and gender.Conclusion: General cognitive function was associated with improvements in physical performance after exercise intervention in

High-calorie food-cues impair working memory performance in high and low food cravers.

Science.gov (United States)

Meule, Adrian; Skirde, Ann Kathrin; Freund, Rebecca; Vögele, Claus; Kübler, Andrea

2012-10-01

The experience of food craving can lead to cognitive impairments. Experimentally induced chocolate craving exhausts cognitive resources and, therefore, impacts working memory, particularly in trait chocolate cravers. In the current study, we investigated the effects of exposure to food-cues on working memory task performance in a group with frequent and intense (high cravers, n=28) and less pronounced food cravings (low cravers, n=28). Participants performed an n-back task that contained either pictures of high-calorie sweets, high-calorie savory foods, or neutral objects. Current subjective food craving was assessed before and after the task. All participants showed slower reaction times and made more omission errors in response to food-cues, particularly savory foods. There were no differences in task performance between groups. State cravings did not differ between groups before the task, but increased more in high cravers compared to low cravers during the task. Results support findings about food cravings impairing visuo-spatial working memory performance independent of trait cravings. They further show that this influence is not restricted to chocolate, but also applies to high-calorie savory foods. Limiting working memory capacity may be especially crucial in persons who are more prone to high-calorie food-cues and experience such cravings habitually. Copyright © 2012 Elsevier Ltd. All rights reserved.

Contractile properties of motor units and expression of myosin heavy chain isoforms in rat fast-type muscle after volitional weight-lifting training.

Science.gov (United States)

Łochyński, Dawid; Kaczmarek, Dominik; Mrówczyński, Włodzimierz; Warchoł, Wojciech; Majerczak, Joanna; Karasiński, Janusz; Korostyński, Michał; Zoladz, Jerzy A; Celichowski, Jan

2016-10-01

Dynamic resistance training increases the force and speed of muscle contraction, but little is known about modifications to the contractile properties of the main physiological types of motor units (MUs) that contribute to these muscle adaptations. Although the contractile profile of MU muscle fibers is tightly coupled to myosin heavy chain (MyHC) protein expression, it is not well understood if MyHC transition is a prerequisite for modifications to the contractile characteristics of MUs. In this study, we examined MU contractile properties, the mRNA expression of MyHC, parvalbumin, and sarcoendoplasmic reticulum Ca 2+ pump isoforms, as well as the MyHC protein content after 5 wk of volitional progressive weight-lifting training in the medial gastrocnemius muscle in rats. The training had no effect on MyHC profiling or Ca 2+ -handling protein gene expression. Maximum force increased in slow (by 49%) and fast (by 21%) MUs. Within fast MUs, the maximum force increased in most fatigue-resistant and intermediate but not most fatigable MUs. Twitch contraction time was shortened in slow and fast fatigue-resistant MUs. Twitch half-relaxation was shortened in fast most fatigue-resistant and intermediate MUs. The force-frequency curve shifted rightward in fast fatigue-resistant MUs. Fast fatigable MUs fatigued less within the initial 15 s while fast fatigue-resistant units increased the ability to potentiate the force within the first minute of the standard fatigue test. In conclusion, at the early stage of resistance training, modifications to the contractile characteristics of MUs appear in the absence of MyHC transition and the upregulation of Ca 2+ -handling genes. Copyright © 2016 the American Physiological Society.

Effect of a crude sulfated polysaccharide from Halymenia floresia (Rhodophyta on gastrointestinal smooth muscle contractility

Directory of Open Access Journals (Sweden)

José Ronaldo Vasconcelos Graça

2011-10-01

Full Text Available The aim of this work was to study the effect of Halymenia floresia (Hf on duodenum contractility, and on experimental protocols of gastric compliance (GC in rats. Fraction Hf2s exhibited a concentration-dependent myocontractile effect (EC50 12.48 µg/ml, and an inhibitory effect after consecutive washing. The contractile response promoted by Hf2s in the duodenum strips was completely inhibited by verapamil, and the effects were prevented in the presence of Ca2+-free medium. The pretreatment with atropine prevented the Hf2s myocontractile effect. Hf2s was also capable to decrease the GC (from 3.8±0.06 to 3.4±0.13 ml, P<0.05, which did not return to basal levels after more 50 min of observation. These results indicated that the algal polysaccharide possessed in vitro and in vivo gastrointestinal effects.

An Estimating Method of Contractile State Changes Come From Continuous Isometric Contraction of Skeletal Muscle

Energy Technology Data Exchange (ETDEWEB)

Park, H.J.; Lee, S.J. [Wonkwang University, Iksan (Korea)

2003-01-01

In this study was proposed that a new estimating method for investigation of contractile state changes which generated from continuous isometric contraction of skeletal muscle. The physiological changes (EMG, ECG) and the psychological changes by CNS(central nervous system) were measured by experiments, while the muscle of subjects contracted continuously with isometric contraction in constant load. The psychological changes were represented as three-step-change named 'fatigue', 'pain' and 'sick(greatly pain)' from oral test, and the method which compared physiological change with psychological change on basis of these three steps was developed. The result of analyzing the physiological signals, EMG and ECG signal changes were observed at the vicinity of judging point in time of psychological changes. Namely, it is supposed that contractile states have three kind of states pattern (stable, fatigue, pain) instead of two states (stable, fatigue). (author). 24 refs., 7 figs.

Dynamics of myosin II organization into cortical contractile networks and fibers

Science.gov (United States)

Nie, Wei; Wei, Ming-Tzo; Ou-Yang, Daniel; Jedlicka, Sabrina; Vavylonis, Dimitrios

2014-03-01

The morphology of adhered cells critically depends on the formation of a contractile meshwork of parallel and cross-linked stress fibers along the contacting surface. The motor activity and mini-filament assembly of non-muscle myosin II is an important component of cell-level cytoskeletal remodeling during mechanosensing. To monitor the dynamics of myosin II, we used confocal microscopy to image cultured HeLa cells that stably express myosin regulatory light chain tagged with GFP (MRLC-GFP). MRLC-GFP was monitored in time-lapse movies at steady state and during the response of cells to varying concentrations of blebbistatin which disrupts actomyosin stress fibers. Using image correlation spectroscopy analysis, we quantified the kinetics of disassembly and reassembly of actomyosin networks and compared them to studies by other groups. This analysis suggested that the following processes contribute to the assembly of cortical actomyosin into fibers: random myosin mini-filament assembly and disassembly along the cortex; myosin mini-filament aligning and contraction; stabilization of cortical myosin upon increasing contractile tension. We developed simple numerical simulations that include those processes. The results of simulations of cells at steady state and in response to blebbistatin capture some of the main features observed in the experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness.

Effects of Silodosin and Tamsulosin on the Seminal Vesicle Contractile Response.

Science.gov (United States)

Hayashi, Tokumasa; Takeya, Mitsue; Nakamura, Kei-ichiro; Matsuoka, Kei

2016-01-01

To understand the mechanisms underlying ejaculation dysfunction caused by α1A-adrenocetor (AR) antagonists, the effects of α1A-AR antagonists on the contractile responses of the seminal vesicle were investigated. Isolated seminal vesicles from guinea pigs were cannulated and pressurized, and the changes in the intraluminal pressure were recorded. Periodic applications of electrical stimulation (ES) caused biphasic increase in the intraluminal pressure, that is, initial and subsequent contractions. The effects of silodosin and tamsulosin, α1A-AR antagonists, on the contractile responses were examined. The ES-induced biphasic contractions were blocked by tetrodotoxin (TTX). Silodosin and tamsulosin suppressed the initial contractions in a dose-dependent manner, while also exerting various inhibitory effects on the subsequent contractions. Increases in the intraluminal pressure facilitated spontaneous phasic contractions. The spontaneous contractions were not affected by TTX or α1A-AR antagonists, but were abolished by nifedipine. The initial contractions triggered by neuronal excitations were suppressed by silodosin and tamsulosin, suggesting that the ejaculation dysfunction may be attributed to the α1A-AR antagonist-mediated suppression of nerve-evoked contractions in the seminal vesicle. The subsequent contractions may be induced by mechanical stimulation associated with the initial, nerve-evoked contractions. Alternatively, other transmitters may be involved to various degrees in the neuromuscular transmission of the seminal vesicle. © 2014 Wiley Publishing Asia Pty Ltd.

Improving the Audio Game-Playing Performances of People with Visual Impairments through Multimodal Training

Science.gov (United States)

Balan, Oana; Moldoveanu, Alin; Moldoveanu, Florica; Nagy, Hunor; Wersenyi, Gyorgy; Unnporsson, Runar

2017-01-01

Introduction: As the number of people with visual impairments (that is, those who are blind or have low vision) is continuously increasing, rehabilitation and engineering researchers have identified the need to design sensory-substitution devices that would offer assistance and guidance to these people for performing navigational tasks. Auditory…

Left atrial function in heart failure with impaired and preserved ejection fraction.

Science.gov (United States)

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

Central hemodynamics and left-ventricural contractility in patients with chronic obstructive pulmonary diseases and stable pulmonary hypertension: a radionuclide study

International Nuclear Information System (INIS)

Paleev, N.R.; Malov, G.A.; Cherejskaya, N.K.; Oblovatskaya, O.G.; Tsar'kova, L.N.; Zil'berman, E.Eh.; Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Serdechno-Sosudistoj Khirurgii)

1987-01-01

Systemic, central and intracardiac hemodynamics and left-ventricular contractility were studied radiocardiographically and radioventriculographically in 22 patients with stable pulmanory hypertension, developing in the presence of chronic obstructive pulmanory diseases. A tendency to increased circulating blood volume, significantly elevated end diastolic and end systolic indices, reduced total ejection fraction, and a tendency to decreased segmental ejection fractions were demonstrated. A significant reduction of the speed and percetage of left-ventricular myocardial circular fibre contraction is another evedence of incompetent left-ventricular contractility, in addition to the reduced ejection fraction

Robust gap repair in the contractile ring ensures timely completion of cytokinesis.

OpenAIRE

Silva, AM; Osório, DS; Pereira, AJ; Maiato, H; Pinto, IM; Rubinstein, B; Gassmann, R; Telley, IA; Carvalho, AX

2016-01-01

Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an acti...

The role of apical contractility in determining cell morphology in multilayered epithelial sheets and tubes

Science.gov (United States)

Zhen Tan, Rui; Lai, Tanny; Chiam, K.-H.

2017-08-01

A multilayered epithelium is made up of individual cells that are stratified in an orderly fashion, layer by layer. In such tissues, individual cells can adopt a wide range of shapes ranging from columnar to squamous. From histological images, we observe that, in flat epithelia such as the skin, the cells in the top layer are squamous while those in the middle and bottom layers are columnar, whereas in tubular epithelia, the cells in all layers are columnar. We develop a computational model to understand how individual cell shape is governed by the mechanical forces within multilayered flat and curved epithelia. We derive the energy function for an epithelial sheet of cells considering intercellular adhesive and intracellular contractile forces. We determine computationally the cell morphologies that minimize the energy function for a wide range of cellular parameters. Depending on the dominant adhesive and contractile forces, we find four dominant cell morphologies for the multilayered-layered flat sheet and three dominant cell morphologies for the two-layered curved sheet. We study the transitions between the dominant cell morphologies for the two-layered flat sheet and find both continuous and discontinuous transitions and also the presence of multistable states. Matching our computational results with histological images, we conclude that apical contractile forces from the actomyosin belt in the epithelial cells is the dominant force determining cell shape in multilayered epithelia. Our computational model can guide tissue engineers in designing artificial multilayered epithelia, in terms of figuring out the cellular parameters needed to achieve realistic epithelial morphologies.

Low thermal dependence of the contractile properties of a wing muscle in the bat Carollia perspicillata.

Science.gov (United States)

Rummel, Andrea D; Swartz, Sharon M; Marsh, Richard L

2018-05-29

Temperature affects contractile rate properties in muscle, which may affect locomotor performance. Endotherms are known to maintain high core body temperatures, but temperatures in the periphery of the body can fluctuate. Such a phenomenon occurs in bats, whose wing musculature is relatively poorly insulated, resulting in substantially depressed temperatures in the distal wing. We examined a wing muscle in the small-bodied tropical bat Carollia perspicillata and a hindlimb muscle in the laboratory mouse at 5°C intervals from 22 to 42°C to determine the thermal dependence of the contractile properties of both muscles. We found that the bat ECRL had low thermal dependence from near body temperature to 10°C lower, with Q 10 values of less than 1.5 for relaxation from contraction and shortening velocities in that interval, and with no significant difference in some rate properties in the interval between 32 and 37°C. In contrast, for all temperature intervals below 37°C, Q 10 values for the mouse EDL were 1.5 or higher, and rate properties differed significantly across successive temperature intervals from 37 to 22°C. An ANCOVA analysis found that the thermal dependencies of all measured isometric and isotonic rate processes were significantly different between the bat and mouse muscles. The relatively low thermal dependence of the bat muscle likely represents a downward shift of its optimal temperature and may be functionally significant in light of the variable operating temperatures of bat wing muscles. © 2018. Published by The Company of Biologists Ltd.

Performance, fatigue and stress in open-plan offices: The effects of noise and restoration on hearing impaired and normal hearing individuals

Directory of Open Access Journals (Sweden)

Helena Jahncke

2012-01-01

Full Text Available Hearing impaired and normal hearing individuals were compared in two within-participant office noise conditions (high noise: 60 L Aeq and low noise: 30 L Aeq . Performance, subjective fatigue, and physiological stress were tested during working on a simulated open-plan office. We also tested two between-participants restoration conditions following the work period with high noise (nature movie or continued office noise. Participants with a hearing impairment (N = 20 were matched with normal hearing participants (N = 18 and undertook one practice session and two counterbalanced experimental sessions. In each experimental session they worked for two hours with basic memory and attention tasks. We also measured physiological stress indicators (cortisol and catecholamines and self-reports of mood and fatigue. The hearing impaired participants were more affected by high noise than the normal hearing participants, as shown by impaired performance for tasks that involve recall of semantic information. The hearing impaired participants were also more fatigued by high noise exposure than participants with normal hearing, and they tended to have higher stress hormone levels during the high noise compared to the low noise condition. Restoration with a movie increased performance and motivation for the normal hearing participants, while rest with continued noise did not. For the hearing impaired participants, continued noise during rest increased motivation and performance, while the movie did not. In summary, the impact of noise and restorative conditions varied with the hearing characteristics of the participants. The small sample size does however encourage caution when interpreting the results.

Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.

Directory of Open Access Journals (Sweden)

Daniel Biermann

Full Text Available The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12. Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3 revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.

Turn Off the Music! Music Impairs Visual Associative Memory Performance in Older Adults.

Science.gov (United States)

Reaves, Sarah; Graham, Brittany; Grahn, Jessica; Rabannifard, Parissa; Duarte, Audrey

2016-06-01

Whether we are explicitly listening to it or not, music is prevalent in our environment. Surprisingly, little is known about the effect of environmental music on concurrent cognitive functioning and whether young and older adults are differentially affected by music. Here, we investigated the impact of background music on a concurrent paired associate learning task in healthy young and older adults. Young and older adults listened to music or to silence while simultaneously studying face-name pairs. Participants' memory for the pairs was then tested while listening to either the same or different music. Participants also made subjective ratings about how distracting they found each song to be. Despite the fact that all participants rated music as more distracting to their performance than silence, only older adults' associative memory performance was impaired by music. These results are most consistent with the theory that older adults' failure to inhibit processing of distracting task-irrelevant information, in this case background music, contributes to their memory impairments. These data have important practical implications for older adults' ability to perform cognitively demanding tasks even in what many consider to be an unobtrusive environment. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

New Insights into the Roles of Acidocalcisomes and the Contractile Vacuole Complex in Osmoregulation in Protists

Science.gov (United States)

Docampo, Roberto; Jimenez, Veronica; Lander, Noelia; Li, Zhu-Hong; Niyogi, Sayantanee

2013-01-01

While free-living protists are usually subjected to hyposmotic environments, parasitic protists are also in contact with hyperosmotic habitats. Recent work in one of these parasites, Trypanosoma cruzi, has revealed that its contractile vacuole complex, which usually collects and expels excess water as a mechanism of regulatory volume decrease after hyposmotic stress, has also a role in cell shrinking when the cells are submitted to hyperosmotic stress. Trypanosomes also have an acidic calcium store rich in polyphosphate (polyP), named the acidocalcisome, which is involved in their response to osmotic stress. Here, we review newly emerging insights on the role of acidocalcisomes and the contractile vacuole complex in the cellular response to hyposmotic and hyperosmotic stresses. We also review the current state of knowledge on the composition of these organelles and their other roles in calcium homeostasis and protein trafficking. PMID:23890380

Matrix elasticity regulates the optimal cardiac myocyte shape for contractility

Science.gov (United States)

McCain, Megan L.; Yuan, Hongyan; Pasqualini, Francesco S.; Campbell, Patrick H.

2014-01-01

Concentric hypertrophy is characterized by ventricular wall thickening, fibrosis, and decreased myocyte length-to-width aspect ratio. Ventricular thickening is considered compensatory because it reduces wall stress, but the functional consequences of cell shape remodeling in this pathological setting are unknown. We hypothesized that decreases in myocyte aspect ratio allow myocytes to maximize contractility when the extracellular matrix becomes stiffer due to conditions such as fibrosis. To test this, we engineered neonatal rat ventricular myocytes into rectangles mimicking the 2-D profiles of healthy and hypertrophied myocytes on hydrogels with moderate (13 kPa) and high (90 kPa) elastic moduli. Actin alignment was unaffected by matrix elasticity, but sarcomere content was typically higher on stiff gels. Microtubule polymerization was higher on stiff gels, implying increased intracellular elastic modulus. On moderate gels, myocytes with moderate aspect ratios (∼7:1) generated the most peak systolic work compared with other cell shapes. However, on stiffer gels, low aspect ratios (∼2:1) generated the most peak systolic work. To compare the relative contributions of intracellular vs. extracellular elasticity to contractility, we developed an analytical model and used our experimental data to fit unknown parameters. Our model predicted that matrix elasticity dominates over intracellular elasticity, suggesting that the extracellular matrix may potentially be a more effective therapeutic target than microtubules. Our data and model suggest that myocytes with lower aspect ratios have a functional advantage when the elasticity of the extracellular matrix decreases due to conditions such as fibrosis, highlighting the role of the extracellular matrix in cardiac disease. PMID:24682394

Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility.

Directory of Open Access Journals (Sweden)

Sheeja Rajasingh

Full Text Available Human induced pluripotent stem cells (iPSCs derived cardiomyocytes (iCMCs would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF and human umbilical vein endothelial cells (HUVECs were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.

Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility.

Science.gov (United States)

Rajasingh, Sheeja; Thangavel, Jayakumar; Czirok, Andras; Samanta, Saheli; Roby, Katherine F; Dawn, Buddhadeb; Rajasingh, Johnson

2015-01-01

Human induced pluripotent stem cells (iPSCs) derived cardiomyocytes (iCMCs) would provide an unlimited cell source for regenerative medicine and drug discoveries. The objective of our study is to generate functional cardiomyocytes from human iPSCs and to develop a novel method of measuring contractility of CMCs. In a series of experiments, adult human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) were treated with a combination of pluripotent gene DNA and mRNA under specific conditions. The iPSC colonies were identified and differentiated into various cell lineages, including CMCs. The contractile activity of CMCs was measured by a novel method of frame-by-frame cross correlation (particle image velocimetry-PIV) analysis. Our treatment regimen transformed 4% of HSFs into iPSC colonies at passage 0, a significantly improved efficiency compared with use of either DNA or mRNA alone. The iPSCs were capable of differentiating both in vitro and in vivo into endodermal, ectodermal and mesodermal cells, including CMCs with >88% of cells being positive for troponin T (CTT) and Gata4 by flow cytometry. We report a highly efficient combination of DNA and mRNA to generate iPSCs and functional iCMCs from adult human cells. We also report a novel approach to measure contractility of iCMCs.

Scintigraphic measurement of the contractile activity of the gastric antrum using factor analysis

International Nuclear Information System (INIS)

Bergmann, H.; Hoebart, J.; Kugi, A.; Stacher, G.; Granser, G.V.

1990-01-01

The motor activity of the gastric antrum is difficult to record by manometric means and scintigraphic methods have proved unsatisfactory so far as no consistent relationship between antral contractile activity and gastric emptying rate could be detected. We investigated, using data recorded in 16 healthy human subjects after the ingestion of a semisolid standard meal, whether a newly developed method employing factor analysis would yield more meaningful and reproducible results. Factor analysis was applied to sequential scintigraphic images (3-s frame time) of gastric antrum. The computed factor images and the respective factor curves are representative of distinct dynamic structures of the antrum. From the more or less sinusoidal excursions of the factor curves, which exhibited the 3 cycles per minute frequency characteristic for the stomach, amplitude, frequency and propagation velocity of antral contractions can be calculated. The amplitudes of the factor curves were used to calculate a contraction index. This contraction index was found to be correlated significantly negatively with the gastric half-emptying time of the ingested meal. The employed factor analytical approach thus seems a promising tool to further investigate the role of antral contractility in the process of gastric emptying. (Authors)

A thermodynamical model for stress-fiber organization in contractile cells.

Science.gov (United States)

Foucard, Louis; Vernerey, Franck J

2012-01-02

Cell mechanical adaptivity to external stimuli is vital to many of its biological functions. A critical question is therefore to understand the formation and organization of the stress fibers from which emerge the cell's mechanical properties. By accounting for the mechanical aspects and the viscoelastic behavior of stress fibers, we here propose a thermodynamic model to predict the formation and orientation of stress fibers in contractile cells subjected to constant or cyclic stretch and different substrate stiffness. Our results demonstrate that the stress fibers viscoelastic behavior plays a crucial role in their formation and organization and shows good consistency with various experiments.

Endothelin-1 and endothelin-2 initiate and maintain contractile responses by different mechanisms in rat mesenteric and cerebral arteries

DEFF Research Database (Denmark)

Compeer, M. G.; Janssen, G. M. J.; De Mey, J. G. R.

2013-01-01

, but relaxed ET-1-induced contractions in MRA. A PLC inhibitor prevented contractile responses to ET-1 and ET-2 in MRA and BA, and relaxed ET-1- and ET-2-induced responses in MRA and ET-1 effects in BA. A Rho-kinase inhibitor did not modify sensitivity, maximum and maintenance of responses to both peptides...... in both arteries but relaxed ET-2, but not ET-1, effects in MRA and ET-1 effects in BA. Conclusions and ImplicationsPLC played a key role in arterial contractile responses to ETs, but ET-1 and ET-2 initiated and maintained vasoconstriction through different mechanisms, and these differed between MRA...

Olfactory evaluation in Mild Cognitive Impairment: correlation with neurocognitive performance and endothelial function.

Science.gov (United States)

Tonacci, Alessandro; Bruno, Rosa M; Ghiadoni, Lorenzo; Pratali, Lorenza; Berardi, Nicoletta; Tognoni, Gloria; Cintoli, Simona; Volpi, Leda; Bonuccelli, Ubaldo; Sicari, Rosa; Taddei, Stefano; Maffei, Lamberto; Picano, Eugenio

2017-05-01

Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, associated with an increased risk of progression into the latter within months or years. Olfactory impairment, a well-known biomarker for neurodegeneration, might be present in the condition early, possibly representing a signal for future pathological onset. Our study aimed at evaluating olfactory function in MCI and healthy controls in relation to neurocognitive performance and endothelial function. A total of 85 individuals with MCI and 41 healthy controls, matched for age and gender, were recruited. Olfactory function was assessed by Sniffin' Sticks Extended Test (Burghart, Medizintechnik, GmbH, Wedel, Germany). A comprehensive neurocognitive assessment was performed. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery by ultrasound. MCI individuals showed an impaired olfactory function compared to controls. The overall olfactory score is able to predict MCI with a good sensitivity and specificity (70.3 and 77.4% respectively). In MCI, olfactory identification score is correlated with a number of neurocognitive abilities, including overall cognitive status, dementia rating, immediate and delayed memory, visuospatial ability and verbal fluency. FMD was reduced in MCI (2.90 ± 2.15 vs. 3.66 ± 1.96%, P = 0.016) and was positively associated with olfactory identification score (ρ s =0.219, P = 0.025). The association remained significant after controlling for age, gender, and smoking. In conclusion, olfactory evaluation is able to discriminate between MCI and healthy individuals. Systemic vascular dysfunction might be involved, at least indirectly, in olfactory dysfunction in MCI. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Introduction of non-linear elasticity models for characterization of shape and deformation statistics: application to contractility assessment of isolated adult cardiocytes.

Science.gov (United States)

Bazan, Carlos; Hawkins, Trevor; Torres-Barba, David; Blomgren, Peter; Paolini, Paul

2011-08-22

We are exploring the viability of a novel approach to cardiocyte contractility assessment based on biomechanical properties of the cardiac cells, energy conservation principles, and information content measures. We define our measure of cell contraction as being the distance between the shapes of the contracting cell, assessed by the minimum total energy of the domain deformation (warping) of one cell shape into another. To guarantee a meaningful vis-à-vis correspondence between the two shapes, we employ both a data fidelity term and a regularization term. The data fidelity term is based on nonlinear features of the shapes while the regularization term enforces the compatibility between the shape deformations and that of a hyper-elastic material. We tested the proposed approach by assessing the contractile responses in isolated adult rat cardiocytes and contrasted these measurements against two different methods for contractility assessment in the literature. Our results show good qualitative and quantitative agreements with these methods as far as frequency, pacing, and overall behavior of the contractions are concerned. We hypothesize that the proposed methodology, once appropriately developed and customized, can provide a framework for computational cardiac cell biomechanics that can be used to integrate both theory and experiment. For example, besides giving a good assessment of contractile response of the cardiocyte, since the excitation process of the cell is a closed system, this methodology can be employed in an attempt to infer statistically significant model parameters for the constitutive equations of the cardiocytes.

Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart.

Science.gov (United States)

Farkas, A S; Acsai, K; Nagy, N; Tóth, A; Fülöp, F; Seprényi, G; Birinyi, P; Nánási, P P; Forster, T; Csanády, M; Papp, J G; Varró, A; Farkas, A

2008-05-01

The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts. The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry. SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities. NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.

Increased plasma concentration of serum amyloid P component in centenarians with impaired cognitive performance

DEFF Research Database (Denmark)

Nybo, M; Olsen, H; Jeune, B

1998-01-01

these to the cognitive performance evaluated by Mini Mental State Examination (MMSE). We observed a significantly (p gender-matched controls (32.8+/-11.4 microg/ml). Six severely demented centenarians had an even......Serum amyloid P component (SAP) binds to all amyloid fibrils including those in the plaques and tangles of Alzheimer patients. To investigate whether the plasma SAP concentration correlated to cognitive impairment, we measured SAP levels in blood samples from 41 centenarians and compared...... higher SAP concentration (60.2 microg/ml), while the subgroup of cognitive intact centenarians (MMSE score >24) showed a normal SAP concentration (38.4+/-9.3 microg/ml). No dehydration or hepatic dysfunction was demonstrable in the centenarians. We conclude that the centenarians with impaired cognitive...

The Level of Vision Necessary for Competitive Performance in Rifle Shooting: Setting the Standards for Paralympic Shooting with Vision Impairment

NARCIS (Netherlands)

Allen, P.M.; Latham, K.; Mann, D.L.; Ravensbergen, H.J.C.; Myint, J.

2016-01-01

The aim of this study was to investigate the level of vision impairment (VI) that would reduce performance in shooting; to guide development of entry criteria to visually impaired (VI) shooting. Nineteen international-level shooters without VI took part in the study. Participants shot an air rifle,

Training leads to increased auditory brain-computer interface performance of end-users with motor impairments.

Science.gov (United States)

Halder, S; Käthner, I; Kübler, A

2016-02-01

Auditory brain-computer interfaces are an assistive technology that can restore communication for motor impaired end-users. Such non-visual brain-computer interface paradigms are of particular importance for end-users that may lose or have lost gaze control. We attempted to show that motor impaired end-users can learn to control an auditory speller on the basis of event-related potentials. Five end-users with motor impairments, two of whom with additional visual impairments, participated in five sessions. We applied a newly developed auditory brain-computer interface paradigm with natural sounds and directional cues. Three of five end-users learned to select symbols using this method. Averaged over all five end-users the information transfer rate increased by more than 1800% from the first session (0.17 bits/min) to the last session (3.08 bits/min). The two best end-users achieved information transfer rates of 5.78 bits/min and accuracies of 92%. Our results show that an auditory BCI with a combination of natural sounds and directional cues, can be controlled by end-users with motor impairment. Training improves the performance of end-users to the level of healthy controls. To our knowledge, this is the first time end-users with motor impairments controlled an auditory brain-computer interface speller with such high accuracy and information transfer rates. Further, our results demonstrate that operating a BCI with event-related potentials benefits from training and specifically end-users may require more than one session to develop their full potential. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Oscillatory behaviors and hierarchical assembly of contractile structures in intercalating cells

International Nuclear Information System (INIS)

Fernandez-Gonzalez, Rodrigo; Zallen, Jennifer A

2011-01-01

Fluctuations in the size of the apical cell surface have been associated with apical constriction and tissue invagination. However, it is currently not known if apical oscillatory behaviors are a unique property of constricting cells or if they constitute a universal feature of the force balance between cells in multicellular tissues. Here, we set out to determine whether oscillatory cell behaviors occur in parallel with cell intercalation during the morphogenetic process of axis elongation in the Drosophila embryo. We applied multi-color, time-lapse imaging of living embryos and SIESTA, an integrated tool for automated and semi-automated cell segmentation, tracking, and analysis of image sequences. Using SIESTA, we identified cycles of contraction and expansion of the apical surface in intercalating cells and characterized them at the molecular, cellular, and tissue scales. We demonstrate that apical oscillations are anisotropic, and this anisotropy depends on the presence of intact cell–cell junctions and spatial cues provided by the anterior–posterior patterning system. Oscillatory cell behaviors during axis elongation are associated with the hierarchical assembly and disassembly of contractile actomyosin structures at the medial cortex of the cell, with actin localization preceding myosin II and with the localization of both proteins preceding changes in cell shape. We discuss models to explain how the architecture of cytoskeletal networks regulates their contractile behavior and the mechanisms that give rise to oscillatory cell behaviors in intercalating cells

Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy.

Science.gov (United States)

Lawlor, Michael W; Armstrong, Dustin; Viola, Marissa G; Widrick, Jeffrey J; Meng, Hui; Grange, Robert W; Childers, Martin K; Hsu, Cynthia P; O'Callaghan, Michael; Pierson, Christopher R; Buj-Bello, Anna; Beggs, Alan H

2013-04-15

No effective treatment exists for patients with X-linked myotubular myopathy (XLMTM), a fatal congenital muscle disease caused by deficiency of the lipid phosphatase, myotubularin. The Mtm1δ4 and Mtm1 p.R69C mice model severely and moderately symptomatic XLMTM, respectively, due to differences in the degree of myotubularin deficiency. Contractile function of intact extensor digitorum longus (EDL) and soleus muscles from Mtm1δ4 mice, which produce no myotubularin, is markedly impaired. Contractile forces generated by chemically skinned single fiber preparations from Mtm1δ4 muscle were largely preserved, indicating that weakness was largely due to impaired excitation contraction coupling. Mtm1 p.R69C mice, which produce small amounts of myotubularin, showed impaired contractile function only in EDL muscles. Short-term replacement of myotubularin with a prototypical targeted protein replacement agent (3E10Fv-MTM1) in Mtm1δ4 mice improved contractile function and muscle pathology. These promising findings suggest that even low levels of myotubularin protein replacement can improve the muscle weakness and reverse the pathology that characterizes XLMTM.

Locomotion Characteristics and Match-Induced Impairments in Physical Performance in Male Elite Team Handball Players

DEFF Research Database (Denmark)

Michalsik, L B; Aagaard, Per; Madsen, K

2013-01-01

The purpose of this study was to determine the physical demands and match-induced impairments in physical performance in male elite Team Handball (TH) players in relation to playing position. Male elite TH field players were closely observed during 6 competitive seasons. Each player (wing players...

In vitro study on the effects of some selected agonists and antagonists of alpha(1)-adrenergic receptors on the contractility of the aneurysmally-changed aortic smooth muscle in humans.

Science.gov (United States)

Gnus, J; Czerski, A; Ferenc, S; Zawadzki, W; Witkiewicz, W; Hauzer, W; Rusiecka, A; Bujok, J

2012-02-01

The study included 18 sections of the aneurysmally-changed abdominal aortas, obtained from patients of the Provincial Specialist Hospital in Wroclaw and 18 sections of normal abdominal aortas obtained from swine. The collected samples were placed horizontally in the incubation chamber. Changes in their transverse section area were registered. They were stretched to a tension of 5 mN. Krebs-Henseleit buffer was used as the incubatory environment. Incubation of the sections was performed at a temperature of 37°C, in the gaseous mixture of oxygen and carbon dioxide used in the following proportion: 95% of O(2) and 5% of CO(2). Contractions of the aorta were registered with isotonic transducers (Letica Scientific Instruments). In the studies, we examined the influence of α(1)-adrenergic receptors (and their subtypes α(1A), α(1B), α(1D)) on the contractility of the aortic muscle in humans and swine by their stimulation or inhibition with some selected agonists or antagonists. This time, it was shown that the stimulation of α(1)-adrenergic receptors leads to contractions of the human and swine aortic muscle; the observed increase in the muscle tone may follow from the stimulation of all subtypes of alpha-1 receptor (α(1A), α(1B), α(1D)). All three subtypes of 1-adrenergic receptor are engaged in vasoconstriction, especially of α(1A) and α(1D) subtypes; the α(1B) subtype is less significant for aortic contractility. The contractile response of the aneurysmally-changed abdominal aorta in humans to agonists of α-adrenergic receptors was significantly less intense than that of the normal porcine aorta. It can be concluded that aneurysms influence the contractile response of the aorta.

Considerations for Contractile Electroactive Materials and Actuators

Energy Technology Data Exchange (ETDEWEB)

Lenore Rasmussen, David Schramm, Paul Rasmussen, Kevin Mullaly, Ras Labs, LLC, Intelligent Materials for Prosthetics & Automation, Lewis D. Meixler, Daniel Pearlman and Alice Kirk

2011-05-23

Ras Labs produces contractile electroactive polymer (EAP) based materials and actuators that bend, swell, ripple, and contract (new development) with low electric input. In addition, Ras Labs produces EAP materials that quickly contract and expand, repeatedly, by reversing the polarity of the electric input, which can be cycled. This phenomenon was explored using molecular modeling, followed by experimentation. Applied voltage step functions were also investigated. High voltage steps followed by low voltage steps produced a larger contraction followed by a smaller contraction. Actuator control by simply adjusting the electric input is extremely useful for biomimetic applications. Muscles are able to partially contract. If muscles could only completely contract, nobody could hold an egg, for example, without breaking it. A combination of high and low voltage step functions could produce gross motor function and fine manipulation within the same actuator unit. Plasma treated electrodes with various geometries were investigated as a means of providing for more durable actuation.

Impaired response inhibition in the rat 5 choice continuous performance task during protracted abstinence from chronic alcohol consumption.

Directory of Open Access Journals (Sweden)

Cristina Irimia

Full Text Available Impaired cognitive processing is a hallmark of addiction. In particular, deficits in inhibitory control can propel continued drug use despite adverse consequences. Clinical evidence shows that detoxified alcoholics exhibit poor inhibitory control in the Continuous Performance Task (CPT and related tests of motor impulsivity. Animal models may provide important insight into the neural mechanisms underlying this consequence of chronic alcohol exposure though pre-clinical investigations of behavioral inhibition during alcohol abstinence are sparse. The present study employed the rat 5 Choice-Continuous Performance Task (5C-CPT, a novel pre-clinical variant of the CPT, to evaluate attentional capacity and impulse control over the course of protracted abstinence from chronic intermittent alcohol consumption. In tests conducted with familiar 5C-CPT conditions EtOH-exposed rats exhibited impaired attentional capacity during the first hours of abstinence and impaired behavioral restraint (increased false alarms during the first 5d of abstinence that dissipated thereafter. Subsequent tests employing visual distractors that increase the cognitive load of the task revealed significant increases in impulsive action (premature responses at 3 and 5 weeks of abstinence, and the emergence of impaired behavioral restraint (increased false alarms at 7 weeks of abstinence. Collectively, these findings demonstrate the emergence of increased impulsive action in alcohol-dependent rats during protracted alcohol abstinence and suggest the 5C-CPT with visual distractors may provide a viable behavioral platform for characterizing the neurobiological substrates underlying impaired behavioral inhibition resulting from chronic intermittent alcohol exposure.

Bladder contractility is modulated by Kv7 channels in pig detrusor

DEFF Research Database (Denmark)

Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja

2013-01-01

Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view...... relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P...

Usefulness of BMIPP SPECT to evaluate myocardial viability, contractile reserve and coronary stenotic progression after reperfusion in acute myocardial infarction

International Nuclear Information System (INIS)

Katsunuma, Eita; Kurokawa, Shingo; Takahashi, Motoi; Fukuda, Naoto; Kurosawa, Toshiro; Izumi, Tohru

2001-01-01

Using combined 123 I-BMIPP (BMIPP), 201 Tl (Tl) and 99m Tc-PYP (PYP) myocardial SPECT imaging, risk areas of acute myocardial infarction were documented in the acute stage, and then these images were evaluated for how well they reflected muscle viability, contractile reserve and coronary stenotic progression subsequent to reperfusion therapy. Patients who only experienced a first attack of myocardial infarction were enrolled. In total, 36 cases who had had the occluded artery successfully reperfused were examined during the past year. They had no significant vessel disease except for the culprit single artery. The patients were comprised of 32 men and 4 women. The mean age was 59.5 years. All patients underwent coronary angiography and left ventricular (LV) angiography in the emergency room. BMIPP/Tl and PYP myocardial SPECT were conducted in the acute stage and chronic stage. In the chronic stage LV angiography was repeated to assess the improvement of LV wall motion. The response to postextrasystolic potentiation (PESP) testing was performed to estimate myocardial contractile reserve. The risk area of acute myocardial infarction (AMI) was documented by reduced BMIPP accumulation. The size of reduced BMIPP accumulation was larger than that of PYP accumulation. A BMIPP/Tl discrepancy and PYP accumulation were documented to assess myocardial viability. Both improvement in LV wall motion and augmentation of PESP response were more closely related to a BMIPP/Tl discrepancy in the presence or absence of PYP accumulation. Therefore, it would be possible to evaluate myocardial viability and contractile reserve by the BMIPP/Tl discrepancy. In patients with good viability, it is important to predict whether there is coronary stenotic progression or not. In this study, we demonstrated that most patients with improved BMIPP images had no significant progression at the site of intervention. Serial observation of BMIPP images from the acute stage to the chronic stage might

Regulation of myofibrillar accumulation in chick muscle cultures - Evidence for the involvement of calcium and lysosomes in non-uniform turnover of contractile proteins

Science.gov (United States)

Silver, Geri; Etlinger, Joseph D.

1985-01-01

The effects of calcium on the synthesis and the degradation of individual myofibrillar proteins were investigated using primary chick-leg skeletal muscle cultures labeled with S-35-methionine (for protein accumulation experiments) or Ca(2+)-45 (for calcium efflux experiments). It was found that the turnover of individual contractile proteins is regulated nonuniformly by a calcium-dependent mechanism involving lysosomes. The results also indicate that contractile proteins are released from the myofibril before their breakdown to amino acids.

Neurobehavioral Performance Impairment in Insomnia: Relationships with Self-Reported Sleep and Daytime Functioning

Science.gov (United States)

Shekleton, Julia A.; Flynn-Evans, Erin E.; Miller, Belinda; Epstein, Lawrence J.; Kirsch, Douglas; Brogna, Lauren A.; Burke, Liza M.; Bremer, Erin; Murray, Jade M.; Gehrman, Philip; Lockley, Steven W.; Rajaratnam, Shantha M. W.

2014-01-01

Study Objectives: Despite the high prevalence of insomnia, daytime consequences of the disorder are poorly characterized. This study aimed to identify neurobehavioral impairments associated with insomnia, and to investigate relationships between these impairments and subjective ratings of sleep and daytime dysfunction. Design: Cross-sectional, multicenter study. Setting: Three sleep laboratories in the USA and Australia. Patients: Seventy-six individuals who met the Research Diagnostic Criteria (RDC) for Primary Insomnia, Psychophysiological Insomnia, Paradoxical Insomnia, and/or Idiopathic Childhood Insomnia (44F, 35.8 ± 12.0 years [mean ± SD]) and 20 healthy controls (14F, 34.8 ± 12.1 years). Interventions: N/A. Measurements and Results: Participants completed a 7-day sleep-wake diary, questionnaires assessing daytime dysfunction, and a neurobehavioral test battery every 60-180 minutes during an afternoon/evening sleep laboratory visit. Included were tasks assessing sustained and switching attention, working memory, subjective sleepiness, and effort. Switching attention and working memory were significantly worse in insomnia patients than controls, while no differences were found for simple or complex sustained attention tasks. Poorer sustained attention in the control, but not the insomnia group, was significantly associated with increased subjective sleepiness. In insomnia patients, poorer sustained attention performance was associated with reduced health-related quality of life and increased insomnia severity. Conclusions: We found that insomnia patients exhibit deficits in higher level neurobehavioral functioning, but not in basic attention. The findings indicate that neurobehavioral deficits in insomnia are due to neurobiological alterations, rather than sleepiness resulting from chronic sleep deficiency. Citation: Shekleton JA; Flynn-Evans EE; Miller B; Epstein LJ; Kirsch D; Brogna LA; Burke LM; Cremer E; Murray JM; Gehrman P; Lockley SW; Rajaratnam SMW

The longitudinal joint effect of obesity and major depression on work performance impairment.

Science.gov (United States)

Nigatu, Yeshambel T; Reijneveld, Sijmen A; Penninx, Brenda W J H; Schoevers, Robert A; Bültmann, Ute

2015-05-01

We examined the longitudinal effect of obesity, major depression, and their combination on work performance impairment (WPI). We collected longitudinal data (2004-2013) on 1726 paid employees from the Netherlands Study of Depression and Anxiety at baseline and 2-, 4-, and 6-year follow-up. We defined obesity with body mass index and waist circumference. We diagnosed major depression with the Composite International Diagnostic Interview 2.1. We assessed work performance impairment with a questionnaire for illness-associated costs. We used generalized estimating equations for modeling, and estimated interaction on the additive scale. Obesity, abdominal obesity, and major depression were longitudinally associated with increased risk of high WPI. The combinations of obesity and major depression, and of abdominal obesity and major depression were associated with increased risk of high WPI (odds ratios of 2.36 [95% confidence interval = 1.61, 3.44] and 1.88 [95% confidence interval = 1.40, 2.53], respectively), but the relative excess risks attributable to interaction were nonsignificant. The longitudinal joint effect of obesity and major depression on high WPI implies that obesity intervention may be more beneficial for individuals with major depression than those without regarding risk of high WPI, if confirmed in a large, representative sample.

Prior Mental Fatigue Impairs Marksmanship Decision Performance

Directory of Open Access Journals (Sweden)

James Head

2017-09-01

Full Text Available Purpose: Mental fatigue has been shown to impair subsequent physical performance in continuous and discontinuous exercise. However, its influence on subsequent fine-motor performance in an applied setting (e.g., marksmanship for trained soldiers is relatively unknown. The purpose of this study was to investigate whether prior mental fatigue influences subsequent marksmanship performance as measured by shooting accuracy and judgment of soldiers in a live-fire scenario.Methods: Twenty trained infantry soldiers engaged targets after completing either a mental fatigue or control intervention in a repeated measure design. Heart rate variability and the NASA-TLX were used to gauge physiological and subjective effects of the interventions. Target hit proportion, projectile group accuracy, and precision were used to measure marksmanship accuracy. Marksmanship accuracy was assessed by measuring bullet group accuracy (i.e., how close a group of shots are relative to center of mass and bullet group precision (i.e., how close are each individual shot to each other. Additionally, marksmanship decision accuracy (correctly shooting vs. correctly withholding shot when engaging targets was used to examine marksmanship performance.Results: Soldiers rated the mentally fatiguing task (59.88 ± 23.7 as having greater mental workload relative to the control intervention [31.29 ± 12.3, t(19 = 1.72, p < 0.001]. Additionally, soldiers completing the mental fatigue intervention (96.04 ± = 37.1 also had lower time-domain (standard deviation of normal to normal R-R intervals heart rate variability relative to the control [134.39 ± 47.4, t(18 = 3.59, p < 0.001]. Projectile group accuracy and group precision failed to show differences between interventions [t(19 = 0.98, p = 0.34, t(19 = 0.18, p = 0.87, respectively]. Marksmanship decision errors significantly increased after soldiers completed the mental fatigue intervention (48% ± 22.4 relative to the control

Pre-treatment with Toll-like receptor 4 antagonist inhibits lipopolysaccharide-induced preterm uterine contractility, cytokines, and prostaglandins in rhesus monkeys

Science.gov (United States)

Adams Waldorf, Kristina M.; Persing, David; Novy, Miles J.; Sadowsky, Drew W.; Gravett, Michael G.

2009-01-01

Intra-uterine infection, which occurs in the majority of early preterm births, triggers an immune response culminating in preterm labor. We hypothesized that blockade of lipopolysaccharide (LPS)-induced immune responses by a Toll-like receptor 4 antagonist (TLR4A) would prevent elevations in amniotic fluid (AF) cytokines, prostaglandins, and uterine contractility. Chronically catheterized rhesus monkeys at 128-147 days gestation received intra-amniotic infusions of either: 1) saline (n=6), 2) LPS (0.15-10μg; n=4), or 3) TLR4A pre-treatment with LPS (10 μg) one hour later (n=4). AF cytokines, prostaglandins, and uterine contractility were compared using oneway ANOVA with Bonferroni-adjusted pairwise comparisons. Compared to saline controls, LPS induced significant elevations in AF IL-8, TNF-α, PGE2, PGF2α, and uterine contractility (p<0.05). In contrast, TLR4A pre-treatment inhibited LPS-induced uterine activity and was associated with significantly lower AF IL-8, TNF-α, PGE2, and PGF2α versus LPS alone (p<0.05). Toll-like receptor antagonists, together with antibiotics, may delay or prevent infection-associated preterm birth. PMID:18187405

Reversal of impairment losses, firm performance and reporting incentives: Evidence from Malaysia

OpenAIRE

Shaari, Hasnah

2013-01-01

Malaysian Financial Reporting Standard (FRS) No. 136, Impairment of Assets, was issued in 2005. The standard requires public listed companies to report their non-current assets at no more than their recoverable amount. When the value of impaired assets is recovered, or partly recovered, FRS 136 requires the impairment charges to be reversed to its new recoverable amount. This study tests whether the reversal of impairment losses by Malaysian firms is more closely associated with economic reas...

Caffeine counteracts impairments in task-oriented psychomotor performance induced by chlorpheniramine: a double-blind placebo-controlled crossover study.

Science.gov (United States)

Kim, Sung-Wan; Bae, Kyung-Yeol; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Kim, Jong-Keun; Kang, Gaeun; Yoon, Jin-Sang

2013-01-01

This study aimed to evaluate the effects of chlorpheniramine on psychomotor performance and the counteracting effects of caffeine on those sedative antihistamine actions. Sixteen healthy young men participated in this study. Using a double-blind placebo-controlled crossover design, each subject was administered one of the following conditions in a random order with a one-week interval: 'placebo-placebo', '4 mg of chlorpheniramine-placebo', 'placebo-200 mg of caffeine' or '4 mg of chlorpheniramine-200 mg of caffeine'. Before and after the treatments, psychomotor functions were assessed using a battery of tests. Additionally, subjective responses were assessed using a visual analogue scale (VAS). Psychomotor performance changed over time in different ways according to the combination of study medications. In the 'chlorpheniramine-placebo' condition, reaction times of the compensatory tracking task were significantly impaired compared with the other three conditions. In addition, the number of omission errors of the continuous performance test were significantly greater compared with the 'placebo-caffeine' condition. However, the response pattern of the 'chlorpheniramine-caffeine' condition was not significantly different from that of the 'placebo-placebo' condition. Changes of VAS for sleepiness were significantly greater in the 'chlorpheniramine-placebo' condition compared with the other three conditions. In conclusion, chlorpheniramine significantly increases subjective sleepiness and objectively impairs psychomotor performance. However, caffeine counteracts these sedative effects and psychomotor impairments.

Does sleep deprivation impair orthopaedic surgeons' cognitive and psychomotor performance?

Science.gov (United States)

O'Brien, Michael J; O'Toole, Robert V; Newell, Mary Zadnik; Lydecker, Alison D; Nascone, Jason; Sciadini, Marcus; Pollak, Andrew; Turen, Clifford; Eglseder, W Andrew

2012-11-07

Sleep deprivation may slow reaction time, cloud judgment, and impair the ability to think. Our purpose was to study the cognitive and psychomotor performances of orthopaedic trauma surgeons on the basis of the amount of sleep that they obtained. We prospectively studied the performances of thirty-two orthopaedic trauma surgeons (residents, fellows, and attending surgeons) over two four-week periods at an urban academic trauma center. Testing sessions used handheld computers to administer validated cognitive and psychomotor function tests. We conducted a multivariate analysis to examine the independent association between test performance and multiple covariates, including the amount of sleep the night before testing. Our analysis demonstrated that orthopaedic surgeons who had slept four hours or less the night before the test had 1.43 times the odds (95% confidence interval, 1.04 to 1.95; p = 0.03) of committing at least one error on an individual test compared with orthopaedic surgeons who had slept more than four hours the previous night. The Running Memory test, which assesses sustained attention, concentration, and working memory, was most sensitive to deterioration in performance in participants who had had four hours of sleep or less; when controlling for other covariates, the test demonstrated a 72% increase in the odds of making at least one error (odds ratio, 1.72 [95% confidence interval, 1.02 to 2.90]; p = 0.04). No significant decrease in performance with sleep deprivation was shown with the other three tests. Orthopaedic trauma surgeons showed deterioration in performance on a validated cognitive task when they had slept four hours or less the previous night. It is unknown how performance on this test relates to surgical performance.

Cognitive flexibility: A distinct element of performance impairment due to sleep deprivation.

Science.gov (United States)

Honn, K A; Hinson, J M; Whitney, P; Van Dongen, H P A

2018-03-14

In around-the-clock operations, reduced alertness due to circadian misalignment and sleep loss causes performance impairment, which can lead to catastrophic errors and accidents. There is mounting evidence that performance on different tasks is differentially affected, but the general principles underlying this differentiation are not well understood. One factor that may be particularly relevant is the degree to which tasks require executive control, that is, control over the initiation, monitoring, and termination of actions in order to achieve goals. A key aspect of this is cognitive flexibility, i.e., the deployment of cognitive control resources to adapt to changes in events. Loss of cognitive flexibility due to sleep deprivation has been attributed to "feedback blunting," meaning that feedback on behavioral outcomes has reduced salience - and that feedback is therefore less effective at driving behavior modification under changing circumstances. The cognitive mechanisms underlying feedback blunting are as yet unknown. Here we present data from an experiment that investigated the effects of sleep deprivation on performance after an unexpected reversal of stimulus-response mappings, requiring cognitive flexibility to maintain good performance. Nineteen healthy young adults completed a 4-day in-laboratory study. Subjects were randomized to either a total sleep deprivation condition (n = 11) or a control condition (n = 8). Athree-phase reversal learning decision task was administered at baseline, and again after 30.5 h of sleep deprivation, or matching well-rested control. The task was based on a go/no go task paradigm, in which stimuli were assigned to either a go (response) set or a no go (no response) set. Each phase of the task included four stimuli (two in the go set and two in the no go set). After each stimulus presentation, subjects could make a response within 750 ms or withhold their response. They were then shown feedback on the accuracy of

The neuromechanical functional contractile properties of the thigh muscles measured using tensiomyography in male athletes and non-athletes

Directory of Open Access Journals (Sweden)

Toskić Lazar

2016-01-01

Full Text Available Involuntary neuromechanical muscle contractile properties, especially of the extensor muscles and knee joint flexors as the largest muscle groups of the caudal part of the body, play an important role in both everyday movement and sport. Based on these data we can obtain important information on the functional properties of muscles. The basic means of evaluation of the functional involuntary neuromechanical muscles contractile properties is the non-invasive tensiomyographic method (TMG. The aim of this study was to determine the differences between the involuntary neuromechanical contractile properties of the thigh muscles measured using the TMG method on a sample of male athletes and non-athletes. The sample of participants was made up of 17 athletes and 10 non-athletes. By applying the multivariate analysis of variance (MANOVA and the t-test, we achieved results which indicate that of the overall 30 variables, a difference was determined among 13 of them. Most of the differences were determined for the extensor muscles of the right knee, especially of the rectus femoris muscle. It was also shown that in addition to the main knee joint extensor muscle (rectus femoris the main knee joint flexor muscle (biceps femoris also takes part in the definition of the difference between athletes and non-athletes. The results have shown that the following variables: contraction time (Tc and delay contraction time (Td are the functional parameters for which the highest difference between athletes and non-athletes were determined (from t = -2.284, p < 0.05 for the vastus lateralis of the right leg to t = -4.018, p < 0.01 for the rectus femoris of the left leg. These results have shown that it is possible to determine the differences in the functional involuntary neuromechanical contractile properties of the thigh muscles among trained and untrained individuals using the tensiomyographic method, but at the same time indicated that these differences were very

Postactivation Potentiation of the Plantar Flexors Does Not Directly Translate to Jump Performance in Female Elite Young Soccer Players.

Science.gov (United States)

Prieske, Olaf; Maffiuletti, Nicola A; Granacher, Urs

2018-01-01

High-intensity muscle actions have the potential to temporarily improve muscle contractile properties (i.e., postactivation potentiation, PAP) thereby inducing acute performance enhancements. There is evidence that balance training can improve performance during strength exercises. Taking these findings together, the purpose of this study was to examine the acute effects of a combined balance and strength (B+S) exercise vs. a strength only (S) exercise on twitch contractile properties, maximum voluntary strength, and jump performance in young athletes. Female elite young soccer players ( N = 12) aged 14-15 years conducted three experimental conditions in randomized order: S included 3 sets of 8-10 dynamic leg extensions at 80% of the 1-repetition maximum, B+S consisted of 3 sets of 40 s double-leg stances on a balance board prior to leg extensions (same as S), and a resting control period. Before and 7 min after exercise, participants were tested for their electrically-evoked isometric twitches (i.e., twitch peak torque, twitch rate of torque development) and maximal voluntary contraction (MVC) torque of the plantar flexor muscles. Additionally, countermovement (CMJ) and drop jump (DJ) performances (i.e., CMJ/DJ height, DJ ground contact time) were assessed. Significant effects of condition on twitch contractile properties ( p jump performance outputs ( p jump performance. It is concluded that PAP effects in the plantar flexors may not directly translate to improved jump performance in female elite young soccer players. Therefore, the observed gains in jump performance following B+S are most likely related to neuromuscular changes (e.g., intramuscular coordination) rather than improved contractile properties.

A stepwise procedure to test contractility and susceptibility to injury for the rodent quadriceps muscle

Directory of Open Access Journals (Sweden)

Stephen J.P. Pratt

2014-07-01

Full Text Available In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies.  Biological markers can also be used in measuring muscle injury, such as increased creatine kinase levels in the blood, but these are not always correlated with loss in muscle function (i.e. loss of force production.  This is even true of histological findings from animals, which provide a “direct measure” of damage, but do not account for loss of function.  The most comprehensive measure of the overall health of the muscle is contractile force.  To date, animal models testing contractile force have been limited to the muscle groups moving the ankle.  Here we describe an in vivo animal model for the quadriceps, with abilities to measure torque, produce a reliable muscle injury, and follow muscle recovery within the same animal over time.  We also describe a second model used for direct measurement of force from an isolated quadriceps muscle in situ. 

Hypoxia-induced dysfunction of rat diaphragm: role of peroxynitrite.

NARCIS (Netherlands)

Zhu, X.; Heunks, L.M.A.; Versteeg, E.M.M.; Heijden, E. van der; Ennen, L.; Kuppevelt, A.H.M.S.M. van; Vina, J.; Dekhuijzen, P.N.R.

2005-01-01

Oxidants may play a role in hypoxia-induced respiratory muscle dysfunction. In the present study we hypothesized that hypoxia-induced impairment in diaphragm contractility is associated with elevated peroxynitrite generation. In addition, we hypothesized that strenuous contractility of the diaphragm

Neuropsychological Impairment in Prodromal, First-Episode, and Chronic Psychosis: Assessing RBANS Performance

Science.gov (United States)

Stone, William S.; Woodberry, Kristen A.; Seidman, Larry J.; Tang, YingYing; Guo, Qian; Zhuo, KaiMing; Qian, ZhenYing; Cui, HuiRu; Zhu, YiKang; Jiang, LiJuan; Chow, Annabelle; Tang, YunXiang; Li, ChunBo; Jiang, KaiDa; Yi, ZhengHui; Xiao, ZePing; Wang, JiJun

2015-01-01

Background Cognitive deficits are observed throughout all developmental phases of psychosis. However, prior studies have usually focused on a limited illness period and used a wide variety of cognitive instruments. Therefore, it has been difficult to characterize or highlight cognitive functioning in different stages of psychosis. Method We administered the RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) tests to 4 participant subgroups, including healthy volunteers (controls, HC, n = 28), subjects at high risk for clinical psychosis (prodrome, CHR, n = 27), first-episode schizophrenia patients (FE-Sz, n = 26), and mid-term and long-term chronic schizophrenia patients (Ch-Sz, n =147). Comparison, correlation, and regression analyses of RBANS index scores were assessed among groups. We examined clinical outcomes over 2 years between the CHR and HC subjects, and RBANS domains were used as possible predictors for conversion to psychosis. Results Performance on all RBANS domains was significantly impaired during a post-onset stage of psychosis (FE-Sz and Ch-Sz), and RBANS scores declined along with disease progression. Regression analyses showed that for CHR and HC subjects, baseline impairment in delayed memory (DM) significantly predicted conversion to psychosis. Additionally, partial correlations showed that for FE-Sz and Ch-Sz subjects, DM was the only correlate with a later stage of psychosis. Conclusions Cognitive deficits broadly emerged, and diminished functioning followed along with disease progression. Impairment in DM is perhaps one domain that helps us understand the development of psychosis. A critical need is to monitor and treat memory functioning for psychotic patients throughout all phases of the disease. PMID:25973925

Cognitive performance correlates with cerebrovascular impairments in multi-infarct dementia

International Nuclear Information System (INIS)

Judd, B.W.; Meyer, J.S.; Rogers, R.L.; Gandhi, S.; Tanahashi, N.; Mortel, K.F.; Tawaklna, T.

1986-01-01

Cerebral blood flow (CBF) was measured by the 133 Xe inhalation method in patients with multi-infarct dementia (MID, N = 26), Alzheimer's dementia (AD, N = 19), and among age-matched, neurologically normal, healthy volunteers (N = 26). Cognitive performance was assessed in all subjects using the Cognitive Capacity Screening Examination (CCSE). Cerebral vasomotor responses were calculated from differences in values of mean hemispheric gray matter blood flow (Delta CBF) measured during inhalation of 100% oxygen (hyperoxia) compared with CBF measured while breathing room air. Significant correlations were found between CCSE performance and vasomotor responsiveness in patients with MID (P less than .01), but not in patients with AD or in neurologically normal volunteers. Loss of vasomotor responsiveness is an indicator of cerebrovascular disease with rigidity and/or loss of reactivity of cerebral vessels, which impairs cerebrovascular responses to situational demands and predisposes to cerebral ischemia. Loss of cerebral vasomotor responsiveness among MID patients, which is a biologic marker of cerebrovascular disease, provides confirmatory evidence of the vascular etiology of MID and assists in separating MID from AD patients

Muscle contraction duration and fibre recruitment influence blood flow and oxygen consumption independent of contractile work during steady-state exercise in humans.

Science.gov (United States)

Richards, Jennifer C; Crecelius, Anne R; Kirby, Brett S; Larson, Dennis G; Dinenno, Frank A

2012-06-01

We tested the hypothesis that, among conditions of matched contractile work, shorter contraction durations and greater muscle fibre recruitment result in augmented skeletal muscle blood flow and oxygen consumption ( ) during steady-state exercise in humans. To do so, we measured forearm blood flow (FBF; Doppler ultrasound) during 4 min of rhythmic hand-grip exercise in 24 healthy young adults and calculated forearm oxygen consumption ( ) via blood samples obtained from a catheter placed in retrograde fashion into a deep vein draining the forearm muscle. In protocol 1 (n = 11), subjects performed rhythmic isometric hand-grip exercise at mild and moderate intensities during conditions in which time-tension index (isometric analogue of work) was held constant but contraction duration was manipulated. In this protocol, shorter contraction durations led to greater FBF (184 ± 25 versus 164 ± 25 ml min(-1)) and (23 ± 3 versus 17 ± 2 ml min(-1); both P flow. Our collective data indicate that, among matched workloads, shorter contraction duration and greater muscle fibre recruitment augment FBF and during mild-intensity forearm exercise, and that muscle blood flow is more closely related to metabolic cost ( ) rather than contractile work per se during steady-state exercise in humans.

Effects of different blood alcohol concentrations and post-alcohol impairment on driving behavior and task performance.

Science.gov (United States)

Liu, Yung-Ching; Ho, Chin Heng

2010-08-01

A study using simulator methodology was conducted to investigate the effects of (1) different blood alcohol concentrations (BAC) of 0, 0.05, 0.08, and 0.10 percent and (2) post-alcohol impairment (where BAC approximately 0%) on driving behavior and subsidiary cognitive task performance. Two driving sessions were investigated, that is, drunk driving and post-alcohol driving, with each requiring approximately 20 min of driving. In addition to driving safely, participants were instructed to perform the critical flicker fusion (CFF) test and completed the NASA-TLX mental workload questionnaire. Eight licensed drivers (6 males, 2 females) participated in this 2 (road complexities) x 2 (simulated driving sessions) x 4 (levels of BAC) within-subjects experiment. The study revealed that higher BAC levels were associated with lower performing driving behavior. The driver's mental workload reached the highest values in the post-alcohol session. In terms of tasks involving divided attention, the traffic sign distance estimation showed significant deterioration with increased BAC levels. The relationship between drunk-driving behavior and alcohol dosage was supported in this study. Noticeably, no significant difference was found between drunk driving and post-alcohol driving, indicating that even in the post-alcohol situation, the impairment still remained significant enough to jeopardize traffic safety as much as it does in the case of drunk driving. In real-life situations, adopting a rest-time strategy to avoid post-alcohol impairment effects may not be the most appropriate solution by drivers; rather, drivers should be given some tests to verify the probability of post-alcohol effects on driving.

Effect of acute and chronic simvastatin treatment on post-ischemic contractile dysfunction in isolated rat heart

Czech Academy of Sciences Publication Activity Database

Szárszoi, Ondrej; Malý, J.; Ošťádal, P.; Netuka, I.; Bešík, J.; Kolář, František; Ošťádal, Bohuslav

2008-01-01

Roč. 57, č. 5 (2008), s. 793-796 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : simvastatin * contractile dysfunction * protection Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.653, year: 2008

Na+/Ca2+ exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart

OpenAIRE

Farkas, A S; Acsai, K; Nagy, N; Tóth, A; Fülöp, F; Seprényi, G; Birinyi, P; Nánási, P P; Forster, T; Csanády, M; Papp, J G; Varró, A; Farkas, A

2008-01-01

Background and purpose: The Na+/Ca2+ exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na+ concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 μM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na+ concentrations in rabbit and rat hearts.

Action Potential Shortening and Impairment of Cardiac Function by Ablation of Slc26a6.

Science.gov (United States)

Sirish, Padmini; Ledford, Hannah A; Timofeyev, Valeriy; Thai, Phung N; Ren, Lu; Kim, Hyo Jeong; Park, Seojin; Lee, Jeong Han; Dai, Gu; Moshref, Maryam; Sihn, Choong-Ryoul; Chen, Wei Chun; Timofeyeva, Maria Valeryevna; Jian, Zhong; Shimkunas, Rafael; Izu, Leighton T; Chiamvimonvat, Nipavan; Chen-Izu, Ye; Yamoah, Ebenezer N; Zhang, Xiao-Dong

2017-10-01

Intracellular pH (pH i ) is critical to cardiac excitation and contraction; uncompensated changes in pH i impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH i regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl - /HCO 3 - exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH i , but also cardiac excitability. To test the mechanistic role of Slc26a6 in the heart, we took advantage of Slc26a6 knockout ( Slc26a6 -/ - ) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of Slc26a6 results in action potential shortening. There are reduced Ca 2+ transient and sarcoplasmic reticulum Ca 2+ load, together with decreased sarcomere shortening in Slc26a6 -/ - cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH i is elevated in Slc26a6 -/ - cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl - /HCO 3 - exchange activities of Slc26a6. Moreover, Slc26a6 -/ - mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system. Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl - /HCO 3 - transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH i , excitability, and contractility. pH i is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in Slc26a6 -/ - mice. © 2017 American Heart Association, Inc.

Lesions of reuniens and rhomboid thalamic nuclei impair radial maze win-shift performance.

Science.gov (United States)

Hembrook, Jacqueline R; Mair, Robert G

2011-08-01

The reuniens (Re) and rhomboid (Rh) nuclei are major sources of thalamic input to hippocampus and medial prefrontal cortex. We compared effects of lesions in ReRh and other parts of the midline-intralaminar complex on tasks affected by lesions in terminal fields innervated by these nuclei, including: visuospatial reaction time (VSRT), a measure of sensory guided responding; serial VSRT, a measure of action sequence learning; and win/shift radial arm maze (RAM) measures of spatial memory. ReRh lesions affected RAM, but not VSRT or serial VSRT performance. The effects of caudal intralaminar lesions were doubly dissociated from ReRh lesions, affecting VSRT, but not RAM or serial VSRT performance. Rostral intralaminar lesions did not produce significant impairments, other than a subgroup with larger lesions that were impaired performing a delayed RAM task. Combined lesions damaging all three sites produced RAM deficits comparable to ReRh lesions and VSRT deficits comparable to caudal intralaminar lesions. Thus there was no indication that deficits produced by lesions in one site were exacerbated significantly by the cumulative effect of damage in other parts of the midline-intralaminar complex. The effects of ReRh lesions provide evidence that these nuclei affect memory functions of hippocampus and medial prefrontal cortex. The double dissociation observed between the effects of ReRh and caudal intralaminar nuclei provides evidence that different nuclei within the midline-intralaminar complex affect distinct aspects of cognition consistent with the effects of lesions in the terminal fields they innervate. Copyright © 2010 Wiley-Liss, Inc.

The natural history of takotsubo syndrome: a two-year follow-up study with myocardial sympathetic and perfusion G-SPECT imaging

Energy Technology Data Exchange (ETDEWEB)

Sestini, Stelvio; Mazzeo, Christian; Castagnoli, Antonio [Nuclear Medicine Unit, N.O.P. - S. Stefano, U.S.L. Toscana Centro, Deptartment of Diagnostic Imaging, Prato (Italy); Pestelli, Francesco; Leoncini, Mario; Bellandi, Francesco [Cardiovascular Unit, N.O.P. - S. Stefano, U.S.L, Toscana Centro, Deptartment of Internal Medicine, Prato (Italy); Mansi, Luigi [Nuclear Medicine Unit, University II Naples, Deptartment of Diagnostic Imaging, Naples (Italy); Carrio, Ignasi [Hospital Sant Pau, Nuclear Medicine, Barcelona (Spain)

2017-02-15

To investigate changes in sympathetic activity, perfusion, and left ventricular (LV) functionality in takotsubo cardiomyopathy (TTC) patients from onset (T{sub 0}) to post-onset conditions at 1 month (T{sub 1}), 1-2 years (T{sub 2}, T{sub 3}). Twenty-two patients (70 ± 11 years) underwent serial gated single photon emission tomography (G-SPECT) studies with {sup 123}I-mIBG and {sup 99m}Tc-Sestamibi. Statistics were performed using ANOVA/Sheffe post-hoc, correlation test, and receiver operating characteristic (ROC) curve analysis (p < 0.05). Patients presented at T{sub 0} with LV ballooning and reduced early-late mIBG uptake (95%, 100%), left ventricular ejection fraction (LVEF){sub G-SPECT} (86%) and perfusion (77 %). Adrenergic dysfunction was greater in apex, it overlaps with contractile impairment, and both were more severe than perfusion defect. During follow-up, LVEF{sub G-SPECT}, contractility, and perfusion were normal, while 82% and 90% of patients at T{sub 1} and 50% at T{sub 2} and T{sub 3} continued to show a reduced apical early-late mIBG distribution. These patients presented at T{sub 0}-T{sub 1} with greater impairment of adrenergic function, contractility, and perfusion. A relationship was present within innervation and both perfusion and contractile parameters at T{sub 0} and T{sub 1}, and between the extent of adrenergic defect at T{sub 3} and both the defect extent and age at T{sub 0} (cut-off point 42.5%, 72 years). Outcome for TTC is not limited to a reversible contractile and perfusion abnormalities, but it includes residual adrenergic dysfunction, depending on the level of adrenergic impairment and age of patients at onset. The number of patients, as well as degree of perfusion abnormalities were found to be higher than those previously reported possibly depending on the time-interval between hospital admission and perfusion scan. (orig.)

Blocking muscarinic receptors in the olfactory bulb impairs performance on an olfactory short term memory task

Directory of Open Access Journals (Sweden)

Sasha eDevore

2012-09-01

Full Text Available Cholinergic inputs to cortical processing networks have long been associated with attentional and top-down processing. Experimental and theoretical studies suggest that cholinergic inputs to the main olfactory bulb (OB can modulate both neural and behavioral odor discrimination. Previous experiments from our laboratory and others demonstrate that blockade of nicotinic receptors directly impairs olfactory discrimination, whereas blockade of muscarinic receptors only measurably impairs olfactory perception when task demands are made more challenging, such as when very low-concentration odors are used or rats are required to maintain sensory memory over long durations. To further investigate the role of muscarinic signaling in the OB, we developed an olfactory delayed match-to-sample task using a digging-based behavioral paradigm. We find that rats are able to maintain robust short-term odor memory for tens to hundreds of seconds. To investigate the role of muscarinic signaling in task performance, we bilaterally infused scopolamine into the OB. We find that high dosages of scopolamine (38 mM impair performance on the task across all delays tested, including the baseline condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM had no measureable effects. These results indicate that general execution of the match-to-sample task, even with no delay, is at least partially dependent on muscarinic signaling in the OB.

Blocking muscarinic receptors in the olfactory bulb impairs performance on an olfactory short-term memory task.

Science.gov (United States)

Devore, Sasha; Manella, Laura C; Linster, Christiane

2012-01-01

Cholinergic inputs to cortical processing networks have long been associated with attentional and top-down processing. Experimental and theoretical studies suggest that cholinergic inputs to the main olfactory bulb (OB) can modulate both neural and behavioral odor discrimination. Previous experiments from our laboratory and others demonstrate that blockade of nicotinic receptors directly impairs olfactory discrimination, whereas blockade of muscarinic receptors only measurably impairs olfactory perception when task demands are made more challenging, such as when very low-concentration odors are used or rats are required to maintain sensory memory over long durations. To further investigate the role of muscarinic signaling in the OB, we developed an olfactory delayed match-to-sample task using a digging-based behavioral paradigm. We find that rats are able to maintain robust short-term odor memory for 10-100 s. To investigate the role of muscarinic signaling in task performance, we bilaterally infused scopolamine into the OB. We find that high dosages of scopolamine (38 mM) impair performance on the task across all delays tested, including the baseline condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM) had no measureable effects. These results indicate that general execution of the match-to-sample task, even with no delay, is at least partially dependent on muscarinic signaling in the OB.

Which impairments are most associated with high mobility performance in older adults? Implications for a rehabilitation prescription.

Science.gov (United States)

Bean, Jonathan F; Kiely, Dan K; LaRose, Sharon; Leveille, Suzanne G

2008-12-01

To test which rehabilitative impairments are associated with higher mobility performance among community-dwelling, mobility-limited older adults. Cross-sectional analysis of baseline data from participants within a randomized controlled trial. Outpatient rehabilitation research center. Community-dwelling older adults (N=138; mean age, 75.4 y) with mobility limitations as defined by the Short Physical Performance Battery (SPPB). Not applicable. Balance measured via the Berg Balance Scale, leg strength, leg velocity, submaximal aerobic capacity, body mass index (BMI), and mobility performance as measured by the SPPB. Each of the 5 physiologic attributes (unipedal balance, leg strength, leg velocity, submaximal aerobic capacity, BMI) was categorized into tertiles by using lower values as reference for impairment status. Within an adjusted model, measures associated with higher SPPB performance (>9) included a BBS score greater than or equal to 54 (odds ratio [OR]=4.54; 95% confidence interval [CI], 1.11-18.60), leg strength greater than or equal to 21.5 N/kg (OR=30.35; 95% CI, 5.48-168.09), leg velocity .0101 to .0129 m.s(-1).kg(-1) (OR=5.31; 95% CI, 1.25-22.57), and leg velocity greater than or equal to .0130 m.s(-1).kg(-1) (OR=22.86; 95% CI, 3.88-134.75). Our investigation highlights the importance of rehabilitative impairments in leg strength, leg velocity, and balance as being associated with mobility status as measured by the SPPB. In our sample of participants within an exercise trial, submaximal aerobic capacity and BMI status were not associated with mobility performance. These findings suggest that the augmentation of not only leg strength and balance but also leg velocity may be important in the rehabilitative care of mobility-limited older adults.

Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos

Directory of Open Access Journals (Sweden)

Maide Ö. Raeker

2011-01-01

Full Text Available During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that depletion of obscurin, a giant muscle protein, resulted in irregular cell morphology and disturbed extracellular matrix organization during skeletal muscle development. The resulting impairment of myocyte organization was associated with disturbance of the internal architecture of the myocyte suggesting that obscurin participates in organizing the internal structure of the myocyte and translating those structural cues to surrounding cells and tissues.

Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos

Science.gov (United States)

Raeker, Maide Ö.; Russell, Mark W.

2011-01-01

During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that depletion of obscurin, a giant muscle protein, resulted in irregular cell morphology and disturbed extracellular matrix organization during skeletal muscle development. The resulting impairment of myocyte organization was associated with disturbance of the internal architecture of the myocyte suggesting that obscurin participates in organizing the internal structure of the myocyte and translating those structural cues to surrounding cells and tissues. PMID:22190853

Preliminary evidence of improved cognitive performance following vestibular rehabilitation in children with combined ADHD (cADHD) and concurrent vestibular impairment.

Science.gov (United States)

Lotfi, Younes; Rezazadeh, Nima; Moossavi, Abdollah; Haghgoo, Hojjat Allah; Rostami, Reza; Bakhshi, Enayatollah; Badfar, Faride; Moghadam, Sedigheh Farokhi; Sadeghi-Firoozabadi, Vahid; Khodabandelou, Yousef

2017-12-01

Balance function has been reported to be worse in ADHD children than in their normal peers. The present study hypothesized that an improvement in balance could result in better cognitive performance in children with ADHD and concurrent vestibular impairment. This study was designed to evaluate the effects of comprehensive vestibular rehabilitation therapy on the cognitive performance of children with combined ADHD and concurrent vestibular impairment. Subject were 54 children with combined ADHD. Those with severe vestibular impairment (n=33) were randomly assigned to two groups that were matched for age. A rehabilitation program comprising overall balance and gate, postural stability, and eye movement exercises was assigned to the intervention group. Subjects in the control group received no intervention for the same time period. Intervention was administered twice weekly for 12 weeks. Choice reaction time (CRT) and spatial working memory (SWM) subtypes of the Cambridge Neuropsychological Test Automated Battery (CANTAB) were completed pre- and post-intervention to determine the effects of vestibular rehabilitation on the cognitive performance of the subjects with ADHD and concurrent vestibular impairment. ANCOVA was used to compare the test results of the intervention and control group post-test. The percentage of correct trial scores for the CRT achieved by the intervention group post-test increased significantly compared to those of the control group (p=0.029). The CRT mean latency scores were significantly prolonged in the intervention group following intervention (p=0.007) compared to the control group. No significant change was found in spatial functioning of the subjects with ADHD following 12 weeks of intervention (p>0.05). The study highlights the effect of vestibular rehabilitation on the cognitive performance of children with combined ADHD and concurrent vestibular disorder. The findings indicate that attention can be affected by early vestibular

Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

OpenAIRE

Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

2012-01-01

Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged ...

Influence of genotype on contractile protein differentiation in different bovine muscles during foetal life

OpenAIRE

Gagnière , Hélène; Ménissier , François; Geay , Yves; Picard , Brigitte

2000-01-01

International audience; The purpose of this work was to compare muscle fibre differentiation in two genetic types: "normal charolais" and double-muscled (DM) "INRA 95" cattles displaying muscle hypertrophy. Six muscles with different contractile and metabolic characteristics in adult animal: Masseter, Diaphragma (Di), Biceps femoris (BF), Longissimus thoracis, Semitendinosus and Cutaneus trunci (CT) were excised from 60 to 260-day-old fœtuses of both genotypes. These muscles present different...

Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes

Directory of Open Access Journals (Sweden)

Jan David Kijlstra

2015-12-01

Full Text Available The quantitative analysis of cardiomyocyte function is essential for stem cell-based approaches for the in vitro study of human cardiac physiology and pathophysiology. We present a method to comprehensively assess the function of single human pluripotent stem cell-derived cardiomyocyte (hPSC-CMs through simultaneous quantitative analysis of contraction kinetics, force generation, and electrical activity. We demonstrate that statistical analysis of movies of contracting hPSC-CMs can be used to quantify changes in cellular morphology over time and compute contractile kinetics. Using a biomechanical model that incorporates substrate stiffness, we calculate cardiomyocyte force generation at single-cell resolution and validate this approach with conventional traction force microscopy. The addition of fluorescent calcium indicators or membrane potential dyes allows the simultaneous analysis of contractility and calcium handling or action potential morphology. Accordingly, our approach has the potential for broad application in the study of cardiac disease, drug discovery, and cardiotoxicity screening.

Impaired Driving Performance as Evidence of a Magnocellular Deficit in Dyslexia and Visual Stress.

Science.gov (United States)

Fisher, Carri; Chekaluk, Eugene; Irwin, Julia

2015-11-01

High comorbidity and an overlap in symptomology have been demonstrated between dyslexia and visual stress. Several researchers have hypothesized an underlying or causal influence that may account for this relationship. The magnocellular theory of dyslexia proposes that a deficit in visuo-temporal processing can explain symptomology for both disorders. If the magnocellular theory holds true, individuals who experience symptomology for these disorders should show impairment on a visuo-temporal task, such as driving. Eighteen male participants formed the sample for this study. Self-report measures assessed dyslexia and visual stress symptomology as well as participant IQ. Participants completed a drive simulation in which errors in response to road signs were measured. Bivariate correlations revealed significant associations between scores on measures of dyslexia and visual stress. Results also demonstrated that self-reported symptomology predicts magnocellular impairment as measured by performance on a driving task. Results from this study suggest that a magnocellular deficit offers a likely explanation for individuals who report high symptomology across both conditions. While conclusions about the impact of these disorders on driving performance should not be derived from this research alone, this study provides a platform for the development of future research, utilizing a clinical population and on-road driving assessment techniques. Copyright © 2015 John Wiley & Sons, Ltd.

Cognitive impairment in methadone maintenance patients.

Science.gov (United States)

Mintzer, Miriam Z; Stitzer, Maxine L

2002-06-01

Few well-controlled studies have examined psychomotor and cognitive performance in methadone maintenance patients (MMP). In the present study, performance of 18 opioid-dependent MMP was evaluated relative to that of 21 control participants without substance abuse histories. The MMP and control groups were balanced with respect to gender, race, age, years of education, current employment status, current reading level, and estimated IQ score. Recent drug abstinence was verified by urine testing. Participants with a urine screen positive for benzodiazepines or a breathalyzer test positive for alcohol prior to performance testing were excluded. To avoid testing under conditions of acute heroin or cocaine intoxication, but without testing under conditions of acute withdrawal, participants with current use of heroin or cocaine were only required to abstain for 24 h prior to performance testing. MMP exhibited impairment relative to controls in psychomotor speed (digit symbol substitution and trail-making tests), working memory (two-back task), decision making (gambling task), and metamemory (confidence ratings on a recognition memory test); results also suggested possible impairment in inhibitory mechanisms (Stroop color-word paradigm). MMP did not exhibit impairment in time estimation, conceptual flexibility or long-term memory. The wide range of impaired functions is striking, and may have important implications for daily functioning in MMP. Further research is necessary to determine the clinical significance of the impairments in laboratory-based tests for daily performance in the natural environment, as well as to differentiate impairments due to acute methadone dosing, chronic methadone maintenance, chronic poly-drug abuse, and other factors. Copyright 2002 Elsevier Science Irealnd Ltd.

Enhancement of S1P-induced contractile response in detrusor smooth muscle of rats having cystitis.

Science.gov (United States)

Anjum, Irfan; Denizalti, Merve; Kandilci, Hilmi Burak; Durlu-Kandilci, Nezahat Tugba; Sahin-Erdemli, Inci

2017-11-05

Interstitial cystitis is a chronic disease characterized by lower abdominal pain and some nonspecific symptoms including an increase in urinary frequency and urgency. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that controls smooth muscle tone via G-protein coupled receptors (S1P 1-3 receptors). S1P production is known to take place both in physiological states and some pathological situations, such as in overactive bladder syndrome. The intracellular mechanism of S1P-induced contractile response was investigated in β-escin permeabilized detrusor smooth muscle of rats having cyclophosphamide-induced cystitis. The bladder was isolated from rats and detrusor smooth muscle strips were permeabilized with β-escin. S1P (50µM)-induced contraction and calcium sensitization response were significantly increased in cystitis. S1P-induced augmented contractile response was inhibited by S1P 2 receptor antagonist JTE-013 and S1P 3 receptor antagonist suramin. S1P 2 receptor protein expressions were increased in cystitis, where no change was observed in S1P 3 expressions between control and cystitis groups. S1P-induced contraction was reduced by Rho kinase (ROCK) inhibitor Y-27632 and protein kinase C (PKC) inhibitor GF-109203X in both control and cystitis group. S1P-induced increased calcium sensitization response was decreased by ROCK inhibitor and PKC inhibitor in cystitis. Our findings provide the first evidence that interstitial cystitis triggers S1P-induced increase in intracellular calcium in permeabilized detrusor smooth muscle of female rats. Both S1P 2 and S1P 3 receptors are involved in S1P mediated enhanced contractile response. The augmentation in S1P-induced contraction in interstitial cystitis involves both PKC and ROCK pathways of calcium sensitization. Copyright © 2017 Elsevier B.V. All rights reserved.

Dystypia: isolated typing impairment without aphasia, apraxia or visuospatial impairment.

Science.gov (United States)

Otsuki, Mika; Soma, Yoshiaki; Arihiro, Shoji; Watanabe, Yoshimasa; Moriwaki, Hiroshi; Naritomi, Hiroaki

2002-01-01

We report a 60-year-old right-handed Japanese man who showed an isolated persistent typing impairment without aphasia, agraphia, apraxia or any other neuropsychological deficit. We coined the term 'dystypia' for this peculiar neuropsychological manifestation. The symptom was caused by an infarction in the left frontal lobe involving the foot of the second frontal convolution and the frontal operculum. The patient's typing impairment was not attributable to a disturbance of the linguistic process, since he had no aphasia or agraphia. The impairment was not attributable to the impairment of the motor execution process either, since he had no apraxia. Thus, his typing impairment was deduced to be based on a disturbance of the intermediate process where the linguistic phonological information is converted into the corresponding performance. We hypothesized that there is a specific process for typing which branches from the motor programming process presented in neurolinguistic models. The foot of the left second frontal convolution and the operculum may play an important role in the manifestation of 'dystypia'. Copyright 2002 S. Karger AG, Basel

Self-perceived memory impairment and cognitive performance in an elderly independent population with age-related white matter changes

DEFF Research Database (Denmark)

Miranda, B.; Madureira, S.; Verdelho, A.

2008-01-01

OBJECTIVES: To determine whether self-perceived memory impairment is associated with the severity of white matter changes (WMC) and is related to cognitive impairment. METHODS: Data were drawn from the multinational Leukoaraiosis and Disability Study (LADIS), which investigates the impact of WMC....... A question about self-perceived memory impairment was used as a measure for presence of memory complaints. Cognitive performance was analysed test-by-test and in three main domains: memory, executive functions and speed/motor control. The Geriatric Depression Scale (GDS) was used as a measure of depressive...... symptoms. RESULTS: Six hundred and thirty-eight subjects were included in this study. No association was found between memory complaints and the severity of WMC. Subjects with memory complaints (n = 399) had a higher GDS score [t((637)) = -7.15; pcognitive tests...

Evolutionarily conserved sites in yeast tropomyosin function in cell polarity, transport and contractile ring formation

Directory of Open Access Journals (Sweden)

Susanne Cranz-Mileva

2015-08-01

Full Text Available Tropomyosin is a coiled-coil protein that binds and regulates actin filaments. The tropomyosin gene in Schizosaccharomyces pombe, cdc8, is required for formation of actin cables, contractile rings, and polar localization of actin patches. The roles of conserved residues were investigated in gene replacement mutants. The work validates an evolution-based approach to identify tropomyosin functions in living cells and sites of potential interactions with other proteins. A cdc8 mutant with near-normal actin affinity affects patch polarization and vacuole fusion, possibly by affecting Myo52p, a class V myosin, function. The presence of labile residual cell attachments suggests a delay in completion of cell division and redistribution of cell patches following cytokinesis. Another mutant with a mild phenotype is synthetic negative with GFP-fimbrin, inferring involvement of the mutated tropomyosin sites in interaction between the two proteins. Proteins that assemble in the contractile ring region before actin do so in a mutant cdc8 strain that cannot assemble condensed actin rings, yet some cells can divide. Of general significance, LifeAct-GFP negatively affects the actin cytoskeleton, indicating caution in its use as a biomarker for actin filaments.

Ankle taping does not impair performance in jump or balance tests.

Science.gov (United States)

Abián-Vicén, Javier; Alegre, Luis M; Fernández-Rodríguez, J Manuel; Lara, Amador J; Meana, Marta; Aguado, Xavier

2008-01-01

This study aimed to investigate the influence of prophylactic ankle taping on two balance tests (static and dynamic balance) and one jump test, in the push off and the landing phase. Fifteen active young subjects (age: 21.0 ± 4.4 years) without previous ankle injuries volunteered for the study. Each participant performed three tests in two different situations: with taping and without taping. The tests were a counter movement jump, static balance, and a dynamic posturography test. The tests and conditions were randomly performed. The path of the center of pressures was measured in the balance tests, and the vertical ground reaction forces were recorded during the push-off and landing phases of the counter movement jump. Ankle taping had no influence on balance performance or in the push off phase of the jump. However, the second peak vertical force value during the landing phase of the jump was 12% greater with ankle taping (0.66 BW, 95% CI -0.64 to 1.96). The use of prophylactic ankle taping had no influence on the balance or jump performance of healthy young subjects. In contrast, the taped ankle increased the second peak vertical force value, which could be related to a greater risk of injury produced by the accumulation of repeated impacts in sports where jumps are frequently performed. Key pointsAnkle taping has no influence on balance performance.Ankle taping does not impair performance during the push-off phase of the jump.Ankle taping could increase the risk of injury during landings by increasing peak forces.

Impaired exercise performance and muscle Na(+),K(+)-pump activity in renal transplantation and haemodialysis patients.

Science.gov (United States)

Petersen, Aaron C; Leikis, Murray J; McMahon, Lawrence P; Kent, Annette B; Murphy, Kate T; Gong, Xiaofei; McKenna, Michael J

2012-05-01

We examined whether abnormal skeletal muscle Na(+),K(+)-pumps underlie impaired exercise performance in haemodialysis patients (HDP) and whether these are improved in renal transplant recipients (RTx). Peak oxygen consumption ( O(2peak)) and plasma [K(+)] were measured during incremental exercise in 9RTx, 10 HDP and 10 healthy controls (CON). Quadriceps peak torque (PT), fatigability (decline in strength during thirty contractions), thigh muscle cross-sectional area (TMCSA) and vastus lateralis Na(+),K(+)-pump maximal activity, content and isoform (α(1)-α(3), β(1)-β(3)) abundance were measured. O(2peak) was 32 and 35% lower in RTx and HDP than CON, respectively (P Na(+),K(+)-pump activity was 28 and 31% lower in RTx and HDP, respectively than CON (P Na(+),K(+)-pump activity (r = 0.45, P = 0.02). O(2peak) and muscle Na(+),K(+)-pump activity were depressed and muscle fatigability increased in HDP, with no difference observed in RTx. These findings are consistent with the possibility that impaired exercise performance in HDP and RTx may be partially due to depressed muscle Na(+),K(+)-pump activity and relative TMCSA.

Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility

Energy Technology Data Exchange (ETDEWEB)

Kirby, R. Jason [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States); Qi, Feng [Sanford Burnham Prebys Medical Discovery Institute, Applied Bioinformatics Facility, 6400 Sanger Rd, Orlando, FL 32827 (United States); Phatak, Sharangdhar; Smith, Layton H. [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States); Malany, Siobhan, E-mail: smalany@sbpdiscovery.org [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States)

2016-08-15

Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. - Highlights: • Impedance-based monitoring of human iPSC-derived cardiomyocyte contractility • Limit cycle analysis of impedance data identifies aberrant oscillation patterns. • Nonlinear autocorrelation function quantifies beat irregularity. • Identification of hERG and non-hERG inhibitors with known risk of arrhythmia • Automated software processes limit cycle and autocorrelation analyses of 96w data.

Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility

International Nuclear Information System (INIS)

Kirby, R. Jason; Qi, Feng; Phatak, Sharangdhar; Smith, Layton H.; Malany, Siobhan

2016-01-01

Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. - Highlights: • Impedance-based monitoring of human iPSC-derived cardiomyocyte contractility • Limit cycle analysis of impedance data identifies aberrant oscillation patterns. • Nonlinear autocorrelation function quantifies beat irregularity. • Identification of hERG and non-hERG inhibitors with known risk of arrhythmia • Automated software processes limit cycle and autocorrelation analyses of 96w data

Cognitive Orientation to (Daily) Occupational Performance intervention leads to improvements in impairments, activity and participation in children with Developmental Coordination Disorder.

Science.gov (United States)

Thornton, Ashleigh; Licari, Melissa; Reid, Siobhan; Armstrong, Jodie; Fallows, Rachael; Elliott, Catherine

2016-01-01

Children diagnosed with Developmental Coordination Disorder (DCD) present with a variety of impairments in fine and gross motor function, which impact on their activity and participation in a variety of settings. This research aimed to determine if a 10-week group-based Cognitive Orientation to Daily Occupational Performance (CO-OP) intervention improved outcome measures across the impairment, activity and participation levels of the International Classification of Functioning, Disability and Health (ICF) framework. In this quasi-experimental, pre-post-test, 20 male children aged 8-10 years (x9y1m ± 9 m) with a confirmed diagnosis of DCD participated in either the 10 week group intervention based on the CO-OP framework (n = 10) or in a control period of regular activity for 10 weeks (n = 10). Outcome measures relating to impairment (MABC-2, motor overflow assessment), activity (Handwriting Speed Test) and participation [Canadian Occupational Performance Measure, (COPM) and Goal Attainment Scale) were measured at weeks 0 and 10 in the intervention group. Children who participated in the CO-OP intervention displayed improvements in outcome measures for impairment, activity and participation, particularly a reduction in severity of motor overflow. Parent and child performance and satisfaction ratings on the COPM improved from baseline to week 10 and all goals were achieved at or above the expected outcome. No significant changes were reported for the control group in impairment and activity (participation was not measured for this group). The strategies implemented by children in the CO-OP treatment group, targeted towards individualised goal attainment, show that CO-OP, when run in a group environment, can lead to improvements across all levels of the ICF. Development Coordination Disorder is a condition which has significant physical, academic and social impacts on a child and can lead to activity limitations and participation restrictions. Cognitive

Formation of contractile networks and fibers in the medial cell cortex through myosin-II turnover, contraction, and stress-stabilization.

Science.gov (United States)

Nie, Wei; Wei, Ming-Tzo; Ou-Yang, H Daniel; Jedlicka, Sabrina S; Vavylonis, Dimitrios

2015-01-01

The morphology of adhered cells depends crucially on the formation of a contractile meshwork of parallel and cross-linked fibers along the contacting surface. The motor activity and minifilament assembly of non-muscle myosin-II is an important component of cortical cytoskeletal remodeling during mechanosensing. We used experiments and computational modeling to study cortical myosin-II dynamics in adhered cells. Confocal microscopy was used to image the medial cell cortex of HeLa cells stably expressing myosin regulatory light chain tagged with GFP (MRLC-GFP). The distribution of MRLC-GFP fibers and focal adhesions was classified into three types of network morphologies. Time-lapse movies show: myosin foci appearance and disappearance; aligning and contraction; stabilization upon alignment. Addition of blebbistatin, which perturbs myosin motor activity, leads to a reorganization of the cortical networks and to a reduction of contractile motions. We quantified the kinetics of contraction, disassembly and reassembly of myosin networks using spatio-temporal image correlation spectroscopy (STICS). Coarse-grained numerical simulations include bipolar minifilaments that contract and align through specified interactions as basic elements. After assuming that minifilament turnover decreases with increasing contractile stress, the simulations reproduce stress-dependent fiber formation in between focal adhesions above a threshold myosin concentration. The STICS correlation function in simulations matches the function measured in experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness. © 2015 Wiley Periodicals, Inc.

High Intensity Exercise in Multiple Sclerosis: Effects on Muscle Contractile Characteristics and Exercise Capacity, a Randomised Controlled Trial.

Directory of Open Access Journals (Sweden)

Inez Wens

Full Text Available Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis (MS. The impact of high intensity exercise remains unknown.Thirty-four MS patients were randomized into a sedentary control group (SED, n = 11 and 2 exercise groups that performed 12 weeks of a high intensity interval (HITR, n = 12 or high intensity continuous cardiovascular training (HCTR, n = 11, both in combination with resistance training. M.vastus lateralis fiber cross sectional area (CSA and proportion, knee-flexor/extensor strength, body composition, maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks.Compared to SED, 12 weeks of high intensity exercise increased mean fiber CSA (HITR: +21 ± 7%, HCTR: +23 ± 5%. Furthermore, fiber type I CSA increased in HCTR (+29 ± 6%, whereas type II (+23 ± 7% and IIa (+23 ± 6%, CSA increased in HITR. Muscle strength improved in HITR and HCTR (between +13 ± 7% and +45 ± 20% and body fat percentage tended to decrease (HITR: -3.9 ± 2.0% and HCTR: -2.5 ± 1.2%. Furthermore, endurance capacity (Wmax +21 ± 4%, time to exhaustion +24 ± 5%, VO2max +17 ± 5% and lean tissue mass (+1.4 ± 0.5% only increased in HITR. Finally self-reported physical activity levels increased 73 ± 19% and 86 ± 27% in HCTR and HITR, respectively.High intensity cardiovascular exercise combined with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity in MS.ClinicalTrials.gov NCT01845896.

Personal Conflict Impairs Performance on an Unrelated Self-Control Task: Lingering Costs of Uncertainty and Conflict.

Science.gov (United States)

Alquist, Jessica L; Baumeister, Roy F; McGregor, Ian; Core, Tammy J; Benjamin, Ilil; Tice, Dianne M

2018-01-01

People have the ability to make important choices in their lives, but deliberating about these choices can have costs. The present study was designed to test the hypothesis that writing about conflicted personal goals and values (conflict condition) would impair self-control on an unrelated subsequent task as compared to writing about clear personal goals and values (clarity condition). Personal conflict activates the behavioral inhibition system (BIS; Hirsh, Mar, & Peterson, 2012), which may make it harder for participants to successfully execute self-control. In this large ( N =337), pre-registered study participants in the conflict condition performed worse on anagrams than participants in the clarity condition, and the effect of condition on anagram performance was mediated by a subjective uncertainty measure of BIS activation. This suggests that BIS activation leads to poor self-control. Moreover, given that conflict is inherent in the exercise of self-control, results point to BIS activation as a mechanism for why initial acts of self-control impair self-control on subsequent, unrelated tasks.

A matter of attention: Crossmodal congruence enhances and impairs performance in a novel trimodal matching paradigm.

Science.gov (United States)

Misselhorn, Jonas; Daume, Jonathan; Engel, Andreas K; Friese, Uwe

2016-07-29

A novel crossmodal matching paradigm including vision, audition, and somatosensation was developed in order to investigate the interaction between attention and crossmodal congruence in multisensory integration. To that end, all three modalities were stimulated concurrently while a bimodal focus was defined blockwise. Congruence between stimulus intensity changes in the attended modalities had to be evaluated. We found that crossmodal congruence improved performance if both, the attended modalities and the task-irrelevant distractor were congruent. If the attended modalities were incongruent, the distractor impaired performance due to its congruence relation to one of the attended modalities. Between attentional conditions, magnitudes of crossmodal enhancement or impairment differed. Largest crossmodal effects were seen in visual-tactile matching, intermediate effects for audio-visual and smallest effects for audio-tactile matching. We conclude that differences in crossmodal matching likely reflect characteristics of multisensory neural network architecture. We discuss our results with respect to the timing of perceptual processing and state hypotheses for future physiological studies. Finally, etiological questions are addressed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Muscle contractility decrement and correlated morphology during the pathogenesis of streptozotocin-diabetic mice.

Science.gov (United States)

Fahim, M A; el-Sabban, F; Davidson, N

1998-06-01

Peripheral neuropathy of both motor and sensory nerves has been well documented in diabetes mellitus, but the evidence for physiological and correlated morphological changes during the pathogenesis of myopathy is scarce. In the present report, we have chosen the dorsiflexor muscle of adult male mice as a model for studying in situ muscle contraction and neuromuscular ultrastructure during the pathogenesis of streptozotocin-induced diabetes. Thirty mice (30 g bodyweight) were injected once i.p. with streptozotocin solution (200 mg/Kg) to induce experimental diabetes mellitus. Comparative analyses of in situ muscle isometric contractile characteristics were studied (at 1 Hz, 5 Hz and 30 Hz nerve stimulation) in urethane-anesthetized (2 mg/g, i.p.) control and diabetic mice at three time points, 2 weeks, 4 weeks, and 8 weeks postinjection. Synaptic delay was also recorded in diabetic and age-matched control mice. There was a significant increase in synaptic delay in both 4-week and 8-week diabetic mice compared with control mice (8.9 +/- 1.2 msec and 7.6 +/- 0.6 msec, respectively, compared with 6.1 +/- 0.5 msec). At all three stimulation frequencies, diabetes did not affect muscle contractile speed but significantly reduced the twitch tension after 8 weeks, with no changes at 2 weeks or 4 weeks. The recorded single-twitch tension values were 2.6 +/- 0.3 g, 2.1 +/- 0.6 g, 2.2 +/- 0.7 g, and 1.2 +/- 0.1 g for control, 2 weeks, 4 weeks, and 8 weeks, respectively. At 30 Hz, the recorded tension values were 4.6 +/- 1.6 g, 3.1 +/- 1.2 g, 3.1 +/- 1.1 g, and 2.1 +/- 1.0 g for control, 2 weeks, 4 weeks, and 8 weeks, respectively. Ultrastructural changes in neuromuscular junctions were similar to those that have been described in disuse and aging. These changes were observed after 8 weeks and included serve loss of synaptic vesicles, electron-dense bodies, and myelin-like figures as well as degeneration of mitochondria. The results reveal that streptozotocin-induced diabetes

Performance changes and relationship between vertical jump measures and actual sprint performance in elite sprinters with visual impairment throughout a Parapan American games training season

Science.gov (United States)

Loturco, Irineu; Winckler, Ciro; Kobal, Ronaldo; Cal Abad, Cesar C.; Kitamura, Katia; Veríssimo, Amaury W.; Pereira, Lucas A.; Nakamura, Fábio Y.

2015-01-01

The aims of this study were to estimate the magnitude of variability and progression in actual competitive and field vertical jump test performances in elite Paralympic sprinters with visual impairment in the year leading up to the 2015 Parapan American Games, and to investigate the relationships between loaded and unloaded vertical jumping test results and actual competitive sprinting performance. Fifteen Brazilian Paralympic sprinters with visual impairment attended seven official competitions (four national, two international and the Parapan American Games 2015) between April 2014 and August 2015, in the 100- and 200-m dash. In addition, they were tested in five different periods using loaded (mean propulsive power [MPP] in jump squat [JS] exercise) and unloaded (squat jump [SJ] height) vertical jumps within the 3 weeks immediately prior to the main competitions. The smallest important effect on performances was calculated as half of the within-athlete race-to-race (or test-to-test) variability and a multiple regression analysis was performed to predict the 100- and 200-m dash performances using the vertical jump test results. Competitive performance was enhanced during the Parapan American Games in comparison to the previous competition averages, overcoming the smallest worthwhile enhancement in both the 100- (0.9%) and 200-m dash (1.43%). In addition, The SJ and JS explained 66% of the performance variance in the competitive results. This study showed that vertical jump tests, in loaded and unloaded conditions, could be good predictors of the athletes' sprinting performance, and that during the Parapan American Games the Brazilian team reached its peak competitive performance. PMID:26594181

Performance changes and relationship between vertical jump measures and actual sprint performance in elite sprinters with visual impairment throughout a Parapan American games training season

Directory of Open Access Journals (Sweden)

Irineu eLoturco

2015-11-01

Full Text Available The aims of this study were to estimate the magnitude of variability and progression in actual competitive and field vertical jump test performances in elite Paralympic sprinters with visual impairment in the year leading up to the 2015 Parapan American Games, and to investigate the relationships between loaded and unloaded vertical jumping test results and actual competitive sprinting performance. Fifteen Brazilian Paralympic sprinters with visual impairment attended seven official competitions (four national, two international and the Parapan American Games 2015 between April 2014 and August 2015, in the 100- and 200-m dash. In addition, they were tested in five different periods using loaded (mean propulsive power [MPP] in jump squat [JS] exercise and unloaded (squat jump [SJ] height vertical jumps within the 3 weeks immediately prior to the main competitions. The smallest important effect on performances was calculated as half of the within-athlete race-to-race (or test-to-test variability and a multiple regression analysis was performed to predict the 100- and 200-m dash performances using the vertical jump test results. Competitive performance was enhanced during the Parapan American Games in comparison to the previous competition averages, overcoming the smallest worthwhile enhancement in both the 100- (0.9% and 200-m dash (1.43%. In addition, The SJ and JS explained 66% of the performance variance in the competitive results. This study showed that vertical jump tests, in loaded and unloaded conditions, could be good predictors of the athletes’ sprinting performance, and that during the Parapan American Games the Brazilian team reached its peak competitive performance.

Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue

Science.gov (United States)

As part of a large 2-year study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate the effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and ser...

The influence of assistive technology devices on the performance of activities by visually impaired

Directory of Open Access Journals (Sweden)

Suzana Rabello

2014-04-01

Full Text Available Objective: To establish the influence of assistive technology devices (ATDs on the performance of activities by visually impaired schoolchildren in the resource room. Methods: A qualitative study that comprised observation and an educational intervention in the resource room. The study population comprised six visually impaired schoolchildren aged 12 to 14 years old. The participants were subjected to an eye examination, prescribed ATDs comprising optical and non-optical devices, and provided an orientation on the use of computers. The participants were assessed based on eye/object distance, font size, and time to read a computer screen and printed text. Results: The ophthalmological conditions included corneal opacity, retinochoroiditis, retinopathy of prematurity, aniridia, and congenital cataracts. Far visual acuity varied from 20/200 to 20/800 and near visual acuity from 0.8 to 6 M. Telescopes, spherical lenses, and support magnifying glasses were prescribed. Three out of five participants with low vision after intervention could decrease the font size on the screen computer, and most participants (83.3% reduced their reading time at the second observation session. Relative to the printed text, all the participants with low vision were able to read text written in smaller font sizes and reduced their reading time at the second observation session. Conclusion: Reading skills improved after the use of ATDs, which allowed the participants to perform their school tasks equally to their classmates.

Examining platelet-fibrin interactions during traumatic shock in a swine model using platelet contractile force and clot elastic modulus.

Science.gov (United States)

White, Nathan J; Martin, Erika J; Brophy, Donald F; Ward, Kevin R

2011-07-01

A significant proportion of severely injured patients develop early coagulopathy, characterized by abnormal clot formation, which impairs resuscitation and increases mortality. We have previously demonstrated an isolated decrease in clot strength by thrombelastography in a swine model of nonresuscitated traumatic shock. In order to more closely examine platelet-fibrin interactions in this setting, we define the observed decrease in clot strength in terms of platelet-induced clot contraction and clot elastic modulus using the Hemostasis Analysis System (HAS) (Hemodyne Inc., Richmond, Virginia, USA). Whole blood was sampled for HAS measurements, metabolic measurements, cell counts, and fibrinogen concentration at baseline prior to injury and again at a predetermined level of traumatic shock defined by oxygen debt. Male swine (N=17) received femur fracture and controlled arterial hemorrhage to achieve an oxygen debt of 80 ml/kg. Platelet counts were unchanged, but fibrinogen concentration was reduced significantly during shock (167.6 vs. 66.7 mg/dl, P=0.0007). Platelet contractile force generated during clot formation did not change during shock (11.7 vs. 10.4 kdynes, P=0.41), but clot elastic modulus was dynamically altered, resulting in a lower final value (22.9 vs. 17.3 kdynes/cm, Pshock, platelet function was preserved, whereas terminal clot elastic modulus was reduced during shock in a manner most consistent with early changes in the mechanical properties of the developing fibrin fiber network.

Creatine Loading, Resistance Exercise Performance, and Muscle Mechanics.

Science.gov (United States)

Stevenson, Scott W.; Dudley, Gary A.

2001-01-01

Examined whether creatine (CR) monohydrate loading would alter resistance exercise performance, isometric strength, or in vivo contractile properties of the quadriceps femoris muscle compared with placebo loading in resistance-trained athletes. Overall, CR loading did not provide an ergogenic benefit for the unilateral dynamic knee extension…

A single night of sleep loss impairs objective but not subjective working memory performance in a sex-dependent manner.

Science.gov (United States)

Rångtell, Frida H; Karamchedu, Swathy; Andersson, Peter; Liethof, Lisanne; Olaya Búcaro, Marcela; Lampola, Lauri; Schiöth, Helgi B; Cedernaes, Jonathan; Benedict, Christian

2018-01-31

Acute sleep deprivation can lead to judgement errors and thereby increases the risk of accidents, possibly due to an impaired working memory. However, whether the adverse effects of acute sleep loss on working memory are modulated by auditory distraction in women and men are not known. Additionally, it is unknown whether sleep loss alters the way in which men and women perceive their working memory performance. Thus, 24 young adults (12 women using oral contraceptives at the time of investigation) participated in two experimental conditions: nocturnal sleep (scheduled between 22:30 and 06:30 hours) versus one night of total sleep loss. Participants were administered a digital working memory test in which eight-digit sequences were learned and retrieved in the morning after each condition. Learning of digital sequences was accompanied by either silence or auditory distraction (equal distribution among trials). After sequence retrieval, each trial ended with a question regarding how certain participants were of the correctness of their response, as a self-estimate of working memory performance. We found that sleep loss impaired objective but not self-estimated working memory performance in women. In contrast, both measures remained unaffected by sleep loss in men. Auditory distraction impaired working memory performance, without modulation by sleep loss or sex. Being unaware of cognitive limitations when sleep-deprived, as seen in our study, could lead to undesirable consequences in, for example, an occupational context. Our findings suggest that sleep-deprived young women are at particular risk for overestimating their working memory performance. © 2018 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

α,β-Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress.

Science.gov (United States)

Wu, Zhenbiao; He, Emily Y; Scott, Glenda I; Ren, Jun

2015-01-01

Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism. © 2013 Wiley Periodicals, Inc.

Impact of low vision care on reading performance in children with multiple disabilities and visual impairment

Directory of Open Access Journals (Sweden)

Krishna Kumar Ramani

2014-01-01

Full Text Available Background: Lack of evidence in literature to show low vision care enhances the reading performance in children with Multiple Disabilities and Visual Impairment (MDVI. Aim: To evaluate the effectiveness of Low Vision Care intervention on the reading performance of children with MDVI. Materials and Methods: Three subjects who were diagnosed to have cerebral palsy and visual impairment, studying in a special school were recruited for the study. All of them underwent detailed eye examination and low vision care evaluation at a tertiary eye care hospital. A single subject multiple baseline (study design was adopted and the study period was 16 weeks. The reading performance (reading speed, reading accuracy, reading fluency was evaluated during the baseline phase and the intervention phase. The median of all the reading parameters for each week was noted. The trend of the reading performance was graphically represented in both the phases. Results: Reading speed increased by 37 Word per minute, 37 Letters per minute and 5 letters per minute for the subject 1, 2 and 3 respectively after the intervention. Reading accuracy was 84%, 91% and 86.4% at the end of the baseline period and 98.7%, 98.4% and 99% at the end of 16 weeks for subject 1, 2 and 3 respectively. Average reading fluency score was 8.3, 7.1 and 5.5 in the baseline period and 10.2, 10.2 and 8.7 in the intervention period. Conclusion: This study shows evidence of noticeable improvement in reading performance of children with MDVI using a novel study design.

Interleukin-6 downregulated vascular smooth muscle cell contractile proteins via ATG4B-mediated autophagy in thoracic aortic dissection.

Science.gov (United States)

An, Zhao; Qiao, Fan; Lu, Qijue; Ma, Ye; Liu, Yang; Lu, Fanglin; Xu, Zhiyun

2017-12-01

Interleukin-6 (IL-6) overexpression played an important role in the pathogenesis of thoracic aortic dissection (TAD). Our previous study found enhanced autophagy accompanying with contractile proteins α smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α) degradation in TAD aortic vascular smooth muscle cells (VSMCs). Autophagy is an important way for intracellular proteins degradation, while IL-6 has been found as a contributing factor of autophagy in some cancers. These indicated IL-6 might contribute to the occurrence of TAD by promoting autophagy-induced contractile proteins degradation, which has not been investigated. The aim of the present study is to verify this hypothesis and investigate the mechanism of it. We collected 10 TAD and 10 control aortic specimens from patients underwent TAD surgical repair and coronary artery bypass grafting, respectively. Quantitative real-time polymerase chain reaction was used to detect mRNA expression. Protein expression level was assessed by enzyme-linked immunosorbent assay, western blot, and immunohistochemistry. Microtubule-associated protein 1 light chain 3 beta overexpression adenovirus with green and red fluorescent protein tags and transmission electron microscopy were used to detect autophagy level in VSMCs. 3-Methyladenine (3-MA) and chloroquine were used to block autophagy in human VSMCs. Experiment results showed that the expression of IL-6 was significantly increased accompanying with up-regulated autophagy in TAD aortic wall compared with controls. In vitro results showed that IL-6 stimulation decreased the expression of VSMCs contractile proteins α-SMA and SM22α accompanying with up-regulated autophagy. Blocking autophagy with 3-MA or chloroquine inhibited IL-6 induced α-SMA and SM22α degradation. Further investigation showed that autophagy-related 4B cysteine peptidase (ATG4B) was significantly overexpressed in TAD aortic wall and played important role in IL-6 induced autophagy up

Striatal lesions produce distinctive impairments in reaction time performance in two different operant chambers.

Science.gov (United States)

Brasted, P J; Döbrössy, M D; Robbins, T W; Dunnett, S B

1998-08-01

The dorsal striatum plays a crucial role in mediating voluntary movement. Excitotoxic striatal lesions in rats have previously been shown to impair the initiation but not the execution of movement in a choice reaction time task in an automated lateralised nose-poke apparatus (the "nine-hole box"). Conversely, when a conceptually similar reaction time task has been applied in a conventional operant chamber (or "Skinner box"), striatal lesions have been seen to impair the execution rather than the initiation of the lateralised movement. The present study was undertaken to compare directly these two results by training the same group of rats to perform a choice reaction time task in the two chambers and then comparing the effects of a unilateral excitotoxic striatal lesion in both chambers in parallel. Particular attention was paid to adopting similar parameters and contingencies in the control of the task in the two test chambers. After striatal lesions, the rats showed predominantly contralateral impairments in both tasks. However, they showed a deficit in reaction time in the nine-hole box but an apparent deficit in response execution in the Skinner box. This finding confirms the previous studies and indicates that differences in outcome are not simply attributable to procedural differences in the lesions, training conditions or tasks parameters. Rather, the pattern of reaction time deficit after striatal lesions depends critically on the apparatus used and the precise response requirements for each task.

Positive stereotypes, negative outcomes: Reminders of the positive components of complementary gender stereotypes impair performance in counter-stereotypical tasks.

Science.gov (United States)

Kahalon, Rotem; Shnabel, Nurit; Becker, Julia C

2018-04-01

Gender stereotypes are complementary: Women are perceived to be communal but not agentic, whereas men are perceived to be agentic but not communal. The present research tested whether exposure to reminders of the positive components of these gender stereotypes can lead to stereotype threat and subsequent performance deficits on the complementary dimension. Study 1 (N = 116 female participants) revealed that compared to a control/no-stereotype condition, exposure to reminders of the stereotype about women's communality (but not to reminders of the stereotype about women's beauty) impaired women's math performance. In Study 2 (N = 86 male participants), reminders of the stereotype about men's agency (vs. a control/no-stereotype condition) impaired men's performance in a test of socio-emotional abilities. Consistent with previous research on stereotype threat, in both studies the effect was evident among participants with high domain identification. These findings extend our understanding of the potentially adverse implications of seemingly positive gender stereotypes. © 2018 The British Psychological Society.

Regulation of glycogen synthesis in rat skeletal muscle after glycogen-depleting contractile activity: effects of adrenaline on glycogen synthesis and activation of glycogen synthase and glycogen phosphorylase.

OpenAIRE

Franch, J; Aslesen, R; Jensen, J

1999-01-01

We investigated the effects of insulin and adrenaline on the rate of glycogen synthesis in skeletal muscles after electrical stimulation in vitro. The contractile activity decreased the glycogen concentration by 62%. After contractile activity, the glycogen stores were fully replenished at a constant and high rate for 3 h when 10 m-i.u./ml insulin was present. In the absence of insulin, only 65% of the initial glycogen stores was replenished. Adrenaline decreased insulin-stimulated glycogen s...

Dependence of intramyocardial pressure and coronary flow on ventricular loading and contractility: a model study.

Science.gov (United States)

Bovendeerd, Peter H M; Borsje, Petra; Arts, Theo; van De Vosse, Frans N

2006-12-01

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity.

Dynamics of myosin II organization into contractile networks and fibers at the medial cell cortex

Science.gov (United States)

Nie, Wei

The cellular morphology of adhered cells depends crucially on the formation of a contractile meshwork of parallel and cross-linked stress fibers along the contacting surface. The motor activity and mini-filament assembly of non-muscle myosin II is an important component of cell-level cytoskeletal remodeling during mechanosensing. To monitor the dynamics of non-muscle myosin II, we used confocal microscopy to image cultured HeLa cells that stably express myosin regulatory light chain tagged with GFP (MRLC-GFP). MRLC-GFP was monitored in time-lapse movies at steady state and during the response of cells to varying concentrations of blebbistatin (which disrupts actomyosin stress fibers). Using image correlation spectroscopy analysis, we quantified the kinetics of disassembly and reassembly of actomyosin networks and compared to studies by other groups. This analysis suggested the following processes: myosin minifilament assembly and disassembly; aligning and contraction; myosin filament stabilization upon increasing contractile tension. Numerical simulations that include those processes capture some of the main features observed in the experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness. We discuss methods to monitor myosin reorganization using non-linear imaging methods.

PPARγ Ligands Regulate Noncontractile and Contractile Functions of Airway Smooth Muscle: Implications for Asthma Therapy

Directory of Open Access Journals (Sweden)

Chantal Donovan

2012-01-01

Full Text Available In asthma, the increase in airway smooth muscle (ASM can contribute to inflammation, airway wall remodeling and airway hyperresponsiveness (AHR. Targetting peroxisome proliferator-activated receptor γ (PPARγ, a receptor upregulated in ASM in asthmatic airways, may provide a novel approach to regulate these contributions. This review summarises experimental evidence that PPARγ ligands, such as rosiglitazone (RGZ and pioglitazone (PGZ, inhibit proliferation and inflammatory cytokine production from ASM in vitro. In addition, inhaled administration of these ligands reduces inflammatory cell infiltration and airway remodelling in mouse models of allergen-induced airways disease. PPARγ ligands can also regulate ASM contractility, with acute treatment eliciting relaxation of mouse trachea in vitro through a PPARγ-independent mechanism. Chronic treatment can protect against the loss of bronchodilator sensitivity to β2-adrenoceptor agonists and inhibit the development of AHR associated with exposure to nicotine in utero or following allergen challenge. Of particular interest, a small clinical trial has shown that oral RGZ treatment improves lung function in smokers with asthma, a group that is generally unresponsive to conventional steroid treatment. These combined findings support further investigation of the potential for PPARγ agonists to target the noncontractile and contractile functions of ASM to improve outcomes for patients with poorly controlled asthma.

An EMMPRIN–γ-catenin–Nm23 complex drives ATP production and actomyosin contractility at endothelial junctions

Science.gov (United States)

Moreno, Vanessa; Gonzalo, Pilar; Gómez-Escudero, Jesús; Pollán, Ángela; Acín-Pérez, Rebeca; Breckenridge, Mark; Yáñez-Mó, María; Barreiro, Olga; Orsenigo, Fabrizio; Kadomatsu, Kenji; Chen, Christopher S.; Enríquez, José A.; Dejana, Elisabetta; Sánchez-Madrid, Francisco; Arroyo, Alicia G.

2014-01-01

ABSTRACT Cell–cell adhesions are important sites through which cells experience and resist forces. In endothelial cells, these forces regulate junction dynamics and determine endothelial barrier strength. We identify the Ig superfamily member EMMPRIN (also known as basigin) as a coordinator of forces at endothelial junctions. EMMPRIN localization at junctions correlates with endothelial junction strength in different mouse vascular beds. Accordingly, EMMPRIN-deficient mice show altered junctions and increased junction permeability. Lack of EMMPRIN alters the localization and function of VE-cadherin (also known as cadherin-5) by decreasing both actomyosin contractility and tugging forces at endothelial cell junctions. EMMPRIN ensures proper actomyosin-driven maturation of competent endothelial junctions by forming a molecular complex with γ-catenin (also known as junction plakoglobin) and Nm23 (also known as NME1), a nucleoside diphosphate kinase, thereby locally providing ATP to fuel the actomyosin machinery. These results provide a novel mechanism for the regulation of actomyosin contractility at endothelial junctions and might have broader implications in biological contexts such as angiogenesis, collective migration and tissue morphogenesis by coupling compartmentalized energy production to junction assembly. PMID:24994937

An EMMPRIN-γ-catenin-Nm23 complex drives ATP production and actomyosin contractility at endothelial junctions.

Science.gov (United States)

Moreno, Vanessa; Gonzalo, Pilar; Gómez-Escudero, Jesús; Pollán, Ángela; Acín-Pérez, Rebeca; Breckenridge, Mark; Yáñez-Mó, María; Barreiro, Olga; Orsenigo, Fabrizio; Kadomatsu, Kenji; Chen, Christopher S; Enríquez, José A; Dejana, Elisabetta; Sánchez-Madrid, Francisco; Arroyo, Alicia G

2014-09-01

Cell-cell adhesions are important sites through which cells experience and resist forces. In endothelial cells, these forces regulate junction dynamics and determine endothelial barrier strength. We identify the Ig superfamily member EMMPRIN (also known as basigin) as a coordinator of forces at endothelial junctions. EMMPRIN localization at junctions correlates with endothelial junction strength in different mouse vascular beds. Accordingly, EMMPRIN-deficient mice show altered junctions and increased junction permeability. Lack of EMMPRIN alters the localization and function of VE-cadherin (also known as cadherin-5) by decreasing both actomyosin contractility and tugging forces at endothelial cell junctions. EMMPRIN ensures proper actomyosin-driven maturation of competent endothelial junctions by forming a molecular complex with γ-catenin (also known as junction plakoglobin) and Nm23 (also known as NME1), a nucleoside diphosphate kinase, thereby locally providing ATP to fuel the actomyosin machinery. These results provide a novel mechanism for the regulation of actomyosin contractility at endothelial junctions and might have broader implications in biological contexts such as angiogenesis, collective migration and tissue morphogenesis by coupling compartmentalized energy production to junction assembly. © 2014. Published by The Company of Biologists Ltd.

Pretreatment with remifentanil protects against the reduced-intestinal contractility related to the ischemia and reperfusion injury in rat

Directory of Open Access Journals (Sweden)

Hale Sayan-Ozacmak

2015-12-01

Full Text Available BACKGROUND AND OBJECTIVES: Serious functional and structural alterations of gastrointestinal tract are observed in failure of blood supply, leading to gastrointestinal dismotility. Activation of opioid receptors provides cardioprotective effect against ischemia-reperfusion (I/R injury. The aim of the present study was to determine whether or not remifentanil could reduce I/R injury of small intestine. METHODS: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min followed by reperfusion (3 h. Four groups were designed: sham control; remifentanil alone; I/R control; and remifentanil + I/R. Animals in remifentanil + I/R group were subjected to infusion of remifentanil (2 ug kg-1 min-1 for 60 min, half of which started before inducing ischemia. Collecting the ileum tissues, evaluation of damage was based on contractile responses to carbachol, levels of lipid peroxidation and neutrophil infiltration, and observation of histopathological features in intestinal tissue. RESULTS: Following reperfusion, a significant decrease in carbachol-induced contractile response, a remarkable increase in both lipid peroxidation and neutrophil infiltration, and a significant injury in mucosa were observed. An average contractile response of remifentanil + I/R group was significantly different from that of the I/R group. Lipid peroxidation and neutrophil infiltration were also significantly suppressed by the treatment. The tissue samples of the I/R group were grade 4 in histopathological evaluation. In remifentanil + I/R group, on the other hand, the mucosal damage was moderate, staging as grade 1. CONCLUSIONS: The pretreatment with remifentanil can attenuate the intestinal I/R injury at a remarkable degree possibly by lowering lipid peroxidation and leukocyte infiltration.

Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

Science.gov (United States)

Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

2015-12-07

To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired

Pharmacological characterization and chemical fractionation of a liposterolic extract of saw palmetto (Serenoa repens): effects on rat prostate contractility.

Science.gov (United States)

Chua, Thiam; Eise, Nicole T; Simpson, Jamie S; Ventura, Sabatino

2014-03-14

Saw palmetto (Serenoa repens) was first used medicinally by native American Indians to treat urological disorders. Nowadays, saw palmetto extracts are widely used in Europe and North America to treat the urinary symptoms associated with benign prostatic hyperplasia even though its mechanisms of action are poorly understood. This study aimed to characterize the bioactive constituents of a lipid extract of saw palmetto that are able to affect contractility of the rat prostate gland. The mechanism of action will also be investigated. A commercially available lipid extract of saw palmetto was subjected to fractionation using normal phase column chromatography. Composition of fractions was assessed by proton nuclear magnetic resonance spectroscopy ((1)H NMR) and mass spectrometry (MS). Contractile activities of these fractions were evaluated pharmacologically using isolated preparations of rat prostate gland and compared to the activity of the crude extract. Saw palmetto extract inhibited contractions of the rat prostate gland which were consistent with smooth muscle relaxant activity. Only the ethyl acetate fraction resulting from chromatography inhibited contractions of isolated rat prostates similarly to the inhibition produced by the crude lipid extract. Comparison with authentic samples and analysis of NMR data revealed that this bioactivity was due to the fatty acid components present in the ethyl acetate fraction. Bioassay using various pharmacological tools identified multiple contractile mechanisms which were affected by the bioactive constituents. A fatty acid component of saw palmetto extract causes inhibition of prostatic smooth muscle contractions via a non-specific mechanism. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition.

Science.gov (United States)

Parikh, Victoria Nicole; Liu, Jing; Shang, Ching; Woods, Christopher; Chang, Alex Chia Yu; Zhao, Mingming; Charo, David N; Grunwald, Zachary; Huang, Yong; Seo, Kinya; Tsao, Philip S; Bernstein, Daniel; Ruiz-Lozano, Pilar; Quertermous, Thomas; Ashley, Euan A

2018-05-18

The G protein coupled receptor APJ is a promising therapeutic target for heart failure. Constitutive deletion of APJ in the mouse is protective against the hypertrophy-heart failure transition via elimination of ligand-independent, β-arrestin dependent stretch transduction. However, the cellular origin of this stretch transduction and the details of its interaction with apelin signaling remain unknown. We generated mice with conditional elimination of APJ in the endothelium (APJ endo-/- ) and myocardium (APJ myo-/- ). No baseline difference was observed in LV function in APJ endo-/- , APJ myo-/- or controls (APJ endo+/+ , APJ myo+/+ ). After exposure to transaortic constriction (TAC), APJ endo-/- animals developed left ventricular failure while APJ myo-/- were protected. At the cellular level, carbon fiber stretch of freshly isolated single cardiomyocytes demonstrated decreased contractile response to stretch in APJ -/- cardiomyocytes compared to APJ +/+ cardiomyocytes. Calcium transient did not change with stretch in either APJ -/- or APJ +/+ cardiomyocytes. Application of apelin to APJ +/+ cardiomyocytes resulted in decreased calcium transient. Further, hearts of mice treated with apelin exhibited decreased phosphorylation at Troponin I (cTnI) N-terminal residues (Ser 22,23), consistent with increased calcium sensitivity. These data establish that APJ stretch transduction is mediated specifically by myocardial APJ, that APJ is necessary for stretch-induced increases in contractility, and that apelin opposes APJ's stretch-mediated hypertrophy signaling by lowering calcium transient while maintaining contractility through myofilament calcium sensitization. These findings underscore apelin's unique potential as a therapeutic agent that can simultaneously support cardiac function and protect against the hypertrophy-heart failure transition.

The Neurocognitive Basis for Impaired Dual-Task Performance in Senior Fallers.

Science.gov (United States)

Nagamatsu, Lindsay S; Hsu, C Liang; Voss, Michelle W; Chan, Alison; Bolandzadeh, Niousha; Handy, Todd C; Graf, Peter; Beattie, B Lynn; Liu-Ambrose, Teresa

2016-01-01

Falls are a major health-care concern, and while dual-task performance is widely recognized as being impaired in those at-risk for falls, the underlying neurocognitive mechanisms remain unknown. A better understanding of the underlying mechanisms could lead to the refinement and development of behavioral, cognitive, or neuropharmacological interventions for falls prevention. Therefore, we conducted a cross-sectional study with community-dwelling older adults aged 70-80 years with a history of falls (i.e., two or more falls in the past 12 months) or no history of falls (i.e., zero falls in the past 12 months); n = 28 per group. We compared functional activation during cognitive-based dual-task performance between fallers and non-fallers using functional magnetic resonance imaging (fMRI). Executive cognitive functioning was assessed via Stroop, Trail Making, and Digit Span. Mobility was assessed via the Timed Up and Go test (TUG). We found that non-fallers exhibited significantly greater functional activation compared with fallers during dual-task performance in key regions responsible for resolving dual-task interference, including precentral, postcentral, and lingual gyri. Further, we report slower reaction times during dual-task performance in fallers and significant correlations between level of functional activation and independent measures of executive cognitive functioning and mobility. Our study is the first neuroimaging study to examine dual-task performance in fallers, and supports the notion that fallers have reduced functional brain activation compared with non-fallers. Given that dual-task performance-and the underlying neural concomitants-appears to be malleable with relevant training, our study serves as a launching point for promising strategies to reduce falls in the future.

AB286. SPR-13 Sex differences and participation of Toll-like receptor 4 to rat bladder contractile function

Science.gov (United States)

Szasz, Theodora; Burgess, Beth; Webb, R. Clinton

2016-01-01

Objective Innate immune mechanisms have been implicated in the pathophysiology of chronic sterile conditions such as hypertension and diabetes. We have recently demonstrated that Toll-like receptor 4 (TLR4) activation by endogenous molecules such as high mobility group box-1 (HMGB1) contributes to hypertrophy and hypercontractility in diabetic bladder dysfunction. It has been reported that women have a higher frequency of overactive bladder symptoms, while men have higher detrusor overactivity. We hypothesized that sex differences in the contribution of TLR4 to bladder contraction may underlie the sex differences observed clinically. Methods Female and male rat bladder contractile responses to carbacholine (CCh) and electrical field stimulation (EFS) were measured in the presence and absence of TLR4 inhibitor CLI-095 and in the presence and absence of urothelium. Results We observed that contractile responses to both CCh and EFS were higher in the male than the female bladder segments in both the presence and absence of urothelium [CCh Emax (mN): male + urothelium =84.3±1.2, male – urothelium =83.7±1.2, female + urothelium =49.8±0.8, female – urothelium =59.2±1.1; EFS 32 Hz (mN): male + urothelium= 84.9±7.1, male – urothelium =66.8±5.2, female + urothelium =57.8±5.9, female – urothelium =54.5±3.5]. Incubation of bladder segments with the TLR4 inhibitor CLI-095 significantly decreased contractile responses to both CCh and EFS in both sexes, irrespective of the presence of urothelium [CCh Emax (mN): male + urothelium =91.1±0.8, male – urothelium =75.4±1.8, female + urothelium =42.9±1.1, female – urothelium =52.5±1.1; EFS 32 Hz (mN): male + urothelium =80.8±7.9, male – urothelium =59.6±10.6, female + urothelium =43.3±2.6, female – urothelium =46.4±1.9]. Conclusions Our data suggest that although there are sex differences in the contractile function of the rat bladder in basal conditions, the participation of TLR4 to bladder contraction

The razor's edge: Australian rock music impairs men's performance when pretending to be a surgeon.

Science.gov (United States)

Fancourt, Daisy; Burton, Thomas Mw; Williamon, Aaron

2016-12-12

Over the past few decades there has been interest in the role of music in the operating theatre. However, despite many reported benefits, a number of potentially harmful effects of music have been identified. This study aimed to explore the effects of rock and classical music on surgical speed, accuracy and perceived distraction when performing multiorgan resection in the board game Operation. Single-blind, three-arm, randomised controlled trial. Imperial Festival, London, May 2016. Members of the public (n = 352) aged ≥ 16 years with no previous formal surgical training or hearing impairments. Participants were randomised to listen through noise-cancelling headphones to either the sound of an operating theatre, rock music or classical music. Participants were then invited to remove three organs from the board game patient, Cavity Sam, using surgical tweezers. Time taken (seconds) to remove three organs from Cavity Sam; the number of mistakes made in performing the surgery; and perceived distraction, rated on a five-point Likert-type scale from 1 (not at all distracting) to 5 (very distracting). Rock music impairs the performance of men but not women when undertaking complex surgical procedures in the board game Operation, increasing the time taken to operate and showing a trend towards more surgical mistakes. In addition, classical music was associated with lower perceived distraction during the game, but this effect was attenuated when factoring in how much people liked the music, with suggestions that only people who particularly liked the music of Mozart found it beneficial. Rock music (specifically Australian rock music) appears to have detrimental effects on surgical performance. Men are advised not to listen to rock music when either operating or playing board games.

5-HT4 receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study

NARCIS (Netherlands)

Prins, NH; van der Grijn, A; Lefebvre, RA; Akkermans, LMA; Schuurkes, JAJ

1 We aimed to study 5-HT4 receptors in canine stomach contractility both in vivo and in vitro. 2 In anaesthetized Beagle dogs, the selective 5-HT4 receptor agonist prucalopride (i.v.) induced dose-dependent tonic stomach contractions under isobaric conditions, an effect that was antagonized by the

Postactivation Potentiation of the Plantar Flexors Does Not Directly Translate to Jump Performance in Female Elite Young Soccer Players

Directory of Open Access Journals (Sweden)

Olaf Prieske

2018-03-01

Full Text Available High-intensity muscle actions have the potential to temporarily improve muscle contractile properties (i.e., postactivation potentiation, PAP thereby inducing acute performance enhancements. There is evidence that balance training can improve performance during strength exercises. Taking these findings together, the purpose of this study was to examine the acute effects of a combined balance and strength (B+S exercise vs. a strength only (S exercise on twitch contractile properties, maximum voluntary strength, and jump performance in young athletes. Female elite young soccer players (N = 12 aged 14–15 years conducted three experimental conditions in randomized order: S included 3 sets of 8–10 dynamic leg extensions at 80% of the 1-repetition maximum, B+S consisted of 3 sets of 40 s double-leg stances on a balance board prior to leg extensions (same as S, and a resting control period. Before and 7 min after exercise, participants were tested for their electrically-evoked isometric twitches (i.e., twitch peak torque, twitch rate of torque development and maximal voluntary contraction (MVC torque of the plantar flexor muscles. Additionally, countermovement (CMJ and drop jump (DJ performances (i.e., CMJ/DJ height, DJ ground contact time were assessed. Significant effects of condition on twitch contractile properties (p < 0.05, d = 1.1 and jump performance outputs (p < 0.05, 1.1 ≤ d ≤ 1.2 were found. Post-hoc tests revealed that S compared to control produced larger PAP for twitch peak torques by trend (p = 0.07, d = 1.8, 33 vs. 21% and significantly larger PAP for twitch rate of torque development (p < 0.05, d = 2.4, 55 vs. 43%. Following B+S compared to control, significant improvements in CMJ height (p < 0.01, d = 1.9, 3% and DJ contact time were found (p < 0.01, d = 2.0, 10%. This study revealed protocol-specific acute performance improvements. While S resulted in significant increases in twitch contractile properties, B+S produced

Inflammation induced by mast cell deficiency rather than the loss of interstitial cells of Cajal causes smooth muscle dysfunction in W/Wv mice

Science.gov (United States)

Winston, John H.; Chen, Jinghong; Shi, Xuan-Zheng; Sarna, Sushil K.

2014-01-01

The initial hypothesis suggested that the interstitial cells of Cajal (ICC) played an essential role in mediating enteric neuronal input to smooth muscle cells. Much information for this hypothesis came from studies in W/Wv mice lacking ICC. However, mast cells, which play critical roles in regulating inflammation in their microenvironment, are also absent in W/Wv mice. We tested the hypothesis that the depletion of mast cells in W/Wv mice generates inflammation in fundus muscularis externa (ME) that impairs smooth muscle reactivity to Ach, independent of the depletion of ICC. We performed experiments on the fundus ME from wild type (WT) and W/Wv mice before and after reconstitution of mast cells by bone marrow transplant. We found that mast cell deficiency in W/Wv mice significantly increased COX-2 and iNOS expression and decreased smooth muscle reactivity to Ach. Mast cell reconstitution or concurrent blockade of COX-2 and iNOS restored smooth muscle contractility without affecting the suppression of c-kit in W/Wv mice. The expression of nNOS and ChAT were suppressed in W/Wv mice; mast cell reconstitution did not restore them. We conclude that innate inflammation induced by mast cell deficiency in W/Wv mice impairs smooth muscle contractility independent of ICC deficiency. The impairment of smooth muscle contractility and the suppression of the enzymes regulating the synthesis of Ach and NO in W/Wv mice need to be considered in evaluating the role of ICC in regulating smooth muscle and enteric neuronal function in W/Wv mice. PMID:24550836

Gross motor skill performance in children with and without visual impairments--research to practice.

Science.gov (United States)

Wagner, Matthias O; Haibach, Pamela S; Lieberman, Lauren J

2013-10-01

The aim of this study was to provide an empirical basis for teaching gross motor skills in children with visual impairments. For this purpose, gross motor skill performance of 23, 6-12 year old, boys and girls who are blind (ICD-10 H54.0) and 28 sighted controls with comparable age and gender characteristics was compared on six locomotor and six object control tasks using the Test of Gross Motor Development-Second Edition. Results indicate that children who are blind perform significantly (pskills, whereby running, leaping, kicking and catching are the most affected skills, and corresponding differences are related to most running, leaping, kicking and catching component. Practical implications are provided. Copyright © 2013 Elsevier Ltd. All rights reserved.

Contractile Response of Bovine Lateral Saphenous Vein to Ergotamine Tartrate Exposed to Different Concentrations of Molecularly Imprinted Polymer

Directory of Open Access Journals (Sweden)

Manoj B. Kudupoje

2018-01-01

Full Text Available Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA. Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP comparison. Norepinephrine normalized percent contractile response to increasing ETA exhibited a sigmoidal dose response (max: 88.47 and log of the effective molar concentration (EC50 (−log [ETA] of 6.66 ± 0.17 M. Although sample preparation time affected contractile response (p < 0.001, pre-myograph incubation temperature (39 vs. 21 °C, 1 h had no effect (p > 0.05. Isothermal adsorption showed a maximum adsorption of 3.27E-008 moles·mg−1 and affinity between 0.51 and 0.57 mg (R2: 0.83–0.92 for both polymers, with no significant difference between polymers (p > 0.05. No significant differences in maximum inhibitory (p = 0.96 and IC50 responses (p = 0.163 between MIP and NIP were noticed. Normalized percent contraction could be predicted from the in vitro adsorption data (R2 = 0.87, p < 0.01, for both polymers. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity caused by ergot alkaloids, with little evidence of significant differences between MIP and NIP in aqueous media.

The Effect of Cleft Palate Repair on Contractile Properties of Single Permeabilized Muscle Fibers From Congenitally Cleft Goats Palates

Science.gov (United States)

A cleft palate goat model was used to study the contractile properties of the levator veli palatini (LVP) muscle which is responsible for the movement of the soft palate. In 15-25% of patients that undergo palatoplasty, residual velopharyngeal insufficiency (VPI) remains a problem and often require...

Triiodothyronine activates lactate oxidation without impairing fatty acid oxidation and improves weaning from extracorporeal membrane oxygenation.

Science.gov (United States)

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

2014-01-01

Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. It has previously been shown that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. METHODS AND RESULTS: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 h) and wean: normal circulation (Group-C); transient coronary occlusion (10 min) for ischemia-reperfusion (IR) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon ((13)C)-labeled lactate, medium-chain and long-chain FAs, was infused as oxidative substrates. Substrate fractional contribution (FC) to the citric acid cycle was analyzed by(13)C-nuclear magnetic resonance. ECMO depressed circulating T3 levels to 40% of the baseline at 4 h and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [adenosine triphosphate]/[adenosine diphosphate] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. T3 releases inhibition of lactate oxidation following IR injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.

Cardiac contractility, central haemodynamics and blood pressure regulation during semistarvation

DEFF Research Database (Denmark)

Stokholm, K H; Breum, L; Astrup, A

1991-01-01

pressure (BP) declined. The fall in BP was caused by the reduction in cardiac output as the total peripheral resistance was unchanged. Finally, the decline in total blood volume was not significant. These findings together with a reduction in heart rate indicated that a reduced sympathetic tone via......Eight obese patients were studied before and after 2 weeks of treatment by a very-low-calorie diet (VLCD). Cardiac output and central blood volume (pulmonary blood volume and left atrial volume) were determined by indicator dilution (125I-albumin) and radionuclide angiocardiography (first pass...... and equilibrium technique by [99Tcm]red blood cells). Cardiac output decreased concomitantly with the reduction in oxygen uptake as the calculated systemic arteriovenous difference of oxygen was unaltered. There were no significant decreases in left ventricular contractility indices, i.e. the ejection fraction...

Altered contractile responses of arteries from spontaneously hypertensive rat: The role of endogenous mediators and membrane depolarization

Czech Academy of Sciences Publication Activity Database

Bencze, Michal; Behuliak, Michal; Vavřínová, Anna; Zicha, Josef

2016-01-01

Roč. 166, Dec 1 (2016), s. 46-53 ISSN 0024-3205 R&D Projects: GA ČR(CZ) GAP304/12/0259; GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : femoral artery * SHR * vascular contractility * adrenergic contraction * tyramine * propranolol * neuropeptide Y Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.936, year: 2016

Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue.

Science.gov (United States)

Klotz, J L; Brown, K R; Xue, Y; Matthews, J C; Boling, J A; Burris, W R; Bush, L P; Strickland, J R

2012-02-01

As part of a 2-yr study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and serotonin receptors. Experiment 1 examined vasoconstrictive activities of 5-hydroxytryptamine (5HT), α-methylserotonin (ME5HT; a 5HT(2) receptor agonist), d-lysergic acid (LSA), and ergovaline (ERV) on lateral saphenous veins collected from steers immediately removed from a high-endophyte-infected tall fescue pasture (HE) or a low-endophyte-infected mixed-grass (LE) pasture. Using the same pastures, Exp. 2 evaluated effects of grazing 2 levels of toxic endophyte-infected tall fescue on vasoconstrictive activities of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), BW 723C86 (BW7), CGS-12066A (CGS), and 5-carboxamidotryptamine hemiethanolate maleate (5CT), agonists for 5HT(2A),( 2B), 5HT(1B), and 5HT(7) receptors, respectively. One-half of the steers in Exp. 2 were slaughtered immediately after removal from pasture, and the other one-half were fed finishing diets for >91 d before slaughter. For Exp. 1, maximal contractile intensities were greater (P 91 d. Experiment 1 demonstrated that grazing of HE pastures for 89 to 105 d induces functional alterations in blood vessels, as evidenced by reduced contractile capacity and altered serotonergic receptor activity. Experiment 2 demonstrated that grazing HE pastures alters vascular responses, which may be mediated through altered serotonin receptor activities, and these alterations may be ameliorated by the removal of ergot alkaloid exposure as demonstrated by the absence of differences in finished steers.

2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy.

Science.gov (United States)

Cheng, Yuanhua; Hogarth, Kaley A; O'Sullivan, M Lynne; Regnier, Michael; Pyle, W Glen

2016-01-01

Dilated cardiomyopathy (DCM) is a major type of heart failure resulting from loss of systolic function. Naturally occurring canine DCM is a widely accepted experimental paradigm for studying human DCM. 2-Deoxyadenosine triphosphate (dATP) can be used by myosin and is a superior energy substrate over ATP for cross-bridge formation and increased systolic function. The objective of this study was to evaluate the beneficial effect of dATP on contractile function of cardiac myofibrils from dogs with naturally occurring DCM. We measured actomyosin NTPase activity and contraction/relaxation properties of isolated myofibrils from nonfailing (NF) and DCM canine hearts. NTPase assays indicated replacement of ATP with dATP significantly increased myofilament activity in both NF and DCM samples. dATP significantly improved maximal tension of DCM myofibrils to the NF sample level. dATP also restored Ca(2+) sensitivity of tension that was reduced in DCM samples. Similarly, dATP increased the kinetics of contractile activation (kACT), with no impact on the rate of cross-bridge tension redevelopment (kTR). Thus, the activation kinetics (kACT/kTR) that were reduced in DCM samples were restored for dATP to NF sample levels. dATP had little effect on relaxation. The rate of early slow-phase relaxation was slightly reduced with dATP, but its duration was not, nor was the fast-phase relaxation or times to 50 and 90% relaxation. Our findings suggest that myosin utilization of dATP improves cardiac myofibril contractile properties of naturally occurring DCM canine samples, restoring them to NF levels, without compromising relaxation. This suggests elevation of cardiac dATP is a promising approach for the treatment of DCM. Copyright © 2016 the American Physiological Society.

The effects of glucose ingestion and glucose regulation on memory performance in older adults with mild cognitive impairment.

Science.gov (United States)

Riby, L M; Marriott, A; Bullock, R; Hancock, J; Smallwood, J; McLaughlin, J

2009-04-01

Previous research investigating the impact of glucose ingestion and/or improvements in glucose regulation has found selective cognitive facilitation on episodic memory tasks in successful ageing and dementia. The present study aimed to extend this research to mild cognitive impairment (MCI). In a repeated-measures design, 24 older adults with and 24 older adults without MCI performed a battery of memory and attention tasks after 25 g of glucose or a sweetness matched placebo. In addition, to assess the impact of individual differences in glucose regulation, blood glucose measurements were taken throughout the testing session. Consistent with previous research, cognitive facilitation was observed for episodic memory tasks only in both successful ageing and MCI. Older adults with MCI had a similar glucose regulatory response as controls but their fasting levels were elevated. Notably, higher levels of blood glucose were associated with impaired memory performance in both the glucose and placebo conditions. Importantly, both blood glucose and memory performance indices were significant predictors of MCI status. The utility of glucose supplementation and the use of glucose regulation as a biological marker are discussed in relation to these data.

Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility.

Science.gov (United States)

Yuan, Yuan; Tan, Yin-Feng; Xu, Peng; Li, Hailong; Li, Yong-Hui; Chen, Wen-Ya; Zhang, Jun-Qing; Chen, Feng; Huang, Guo-Jun

2014-01-01

Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its capsular fruit is commonly used in traditional Chinese medicine for the treatment of different urinary incontinence symptoms including frequency, urgency and nocturia. These symptoms are similar to the overactive bladder syndrome. In our lab, we found that the 95% ethanol extract of the capsular fruits exhibited significant anti-muscarinic activity. Some constituents in capsular fruits including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g., yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are regarded as representative chemicals with putative pharmacological activities. This study aimed to evaluate the in vitro antagonistic actions of izalpinin on carbachol-induced contraction of the rat detrusor muscle. In vitro inhibition of rat detrusor contractile response to carbachol was used to study the functional activity of izalpinin. The isolated detrusor strips of rats were mounted in organ baths containing oxygenated Krebs' solution. The cumulative consecutive concentration-response curves to carbachol-evoked contractions in strips of rat bladder were obtained. Carbachol induced concentration-dependent contractions of isolated rat bladder detrusor strips. The vehicle DMSO had no impact on the contraction response. The contraction effects were concentration-dependently antagonized by izalpinin, with a mean EC50 value of 0.35 µM. The corresponding cumulative agonist concentration-response curves shifted right-ward. Izalpinin exhibits inhibitory role of muscarinic receptor-related detrusor contractile activity, and it may be a promising lead compound to treat overactive bladder.

On the Optimal Detection and Error Performance Analysis of the Hardware Impaired Systems

KAUST Repository

Javed, Sidrah; Amin, Osama; Ikki, Salama S.; Alouini, Mohamed-Slim

2018-01-01

The conventional minimum Euclidean distance (MED) receiver design is based on the assumption of ideal hardware transceivers and proper Gaussian noise in communication systems. Throughout this study, an accurate statistical model of various hardware impairments (HWIs) is presented. Then, an optimal maximum likelihood (ML) receiver is derived considering the distinct characteristics of the HWIs comprised of additive improper Gaussian noise and signal distortion. Next, the average error probability performance of the proposed optimal ML receiver is analyzed and tight bounds are derived. Finally, different numerical and simulation results are presented to support the superiority of the proposed ML receiver over MED receiver and the tightness of the derived bounds.

On the Optimal Detection and Error Performance Analysis of the Hardware Impaired Systems

KAUST Repository

Javed, Sidrah

2018-01-15

The conventional minimum Euclidean distance (MED) receiver design is based on the assumption of ideal hardware transceivers and proper Gaussian noise in communication systems. Throughout this study, an accurate statistical model of various hardware impairments (HWIs) is presented. Then, an optimal maximum likelihood (ML) receiver is derived considering the distinct characteristics of the HWIs comprised of additive improper Gaussian noise and signal distortion. Next, the average error probability performance of the proposed optimal ML receiver is analyzed and tight bounds are derived. Finally, different numerical and simulation results are presented to support the superiority of the proposed ML receiver over MED receiver and the tightness of the derived bounds.

Abnormal glucose metabolism is associated with reduced left ventricular contractile reserve and exercise intolerance in patients with chronic heart failure

DEFF Research Database (Denmark)

Egstrup, M; Kistorp, C N; Schou, M

2013-01-01

AIMS: To investigate the associations between glucose metabolism, left ventricular (LV) contractile reserve, and exercise capacity in patients with chronic systolic heart failure (HF). METHODS AND RESULTS: From an outpatient HF clinic, 161 patients with systolic HF were included (mean age 70 ± 10...... or new DM. All patients completed low-dose dobutamine echocardiography (LDDE) and 154 patients a 6-min walking distance test (6MWD). Compared with patients with NGT, patients with known DM had lower resting LVEF (33.4 vs. 39.1%, P ... in LVEF could be observed in all glycemic groups (mean 8.2% absolute increase), but the contractile reserve was lower in patients with known DM (-5.4%, P = 0.001) and new DM (-3.5%, P = 0.035) compared to patients with NGT. 6MWD was lower in known DM (349 m) and new DM (379 m) compared with NGT (467 m) (P...

Extent and neural basis of semantic memory impairment in mild cognitive impairment.

Science.gov (United States)

Barbeau, Emmanuel J; Didic, Mira; Joubert, Sven; Guedj, Eric; Koric, Lejla; Felician, Olivier; Ranjeva, Jean-Philippe; Cozzone, Patrick; Ceccaldi, Mathieu

2012-01-01

An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.

LET-99 functions in the astral furrowing pathway, where it is required for myosin enrichment in the contractile ring.

Science.gov (United States)

Price, Kari L; Rose, Lesilee S

2017-09-01

The anaphase spindle determines the position of the cytokinesis furrow, such that the contractile ring assembles in an equatorial zone between the two spindle poles. Contractile ring formation is mediated by RhoA activation at the equator by the centralspindlin complex and midzone microtubules. Astral microtubules also inhibit RhoA accumulation at the poles. In the Caenorhabditis elegans one-cell embryo, the astral microtubule-dependent pathway requires anillin, NOP-1, and LET-99. LET-99 is well characterized for generating the asymmetric cortical localization of the Gα-dependent force-generating complex that positions the spindle during asymmetric division. However, whether the role of LET-99 in cytokinesis is specific to asymmetric division and whether it acts through Gα to promote furrowing are unclear. Here we show that LET-99 contributes to furrowing in both asymmetrically and symmetrically dividing cells, independent of its function in spindle positioning and Gα regulation. LET-99 acts in a pathway parallel to anillin and is required for myosin enrichment into the contractile ring. These and other results suggest a positive feedback model in which LET-99 localizes to the presumptive cleavage furrow in response to the spindle and myosin. Once positioned there, LET-99 enhances myosin accumulation to promote furrowing in both symmetrically and asymmetrically dividing cells. © 2017 Price and Rose. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Removal of urothelium affects bladder contractility and release of ATP but not release of NO in rat urinary bladder

Directory of Open Access Journals (Sweden)

Boone Timothy B

2010-05-01

Full Text Available Abstract Background The objective of our work was to investigate both the contractile function and the release of ATP and NO from strips of bladder tissue after removal of the urothelium. Methods The method of removal was a gentle swabbing motion rather than a sharp surgical cutting to separate the urothelium from the smooth muscle. The contractile response and ATP and NO release were measured in intact as well as on swabbed preparations. The removal of the urothelial layer was affirmed microscopically. Results After the swabbing, the smaller contractions were evoked by electrical as well as by chemical stimulation (50 μM carbachol or 50 μM α, β meATP. Electrical stimulation, carbachol and substance P (5 μM evoked lower release of ATP in the swabbed strips than in intact strips. Although release of NO evoked by electrical stimulation or substance P was not changed, release of NO evoked by carbachol was significantly less in the swabbed preparations. Conclusion Since swabbing removes only the urothelium, the presence of the suburothelial layer may explain the difference between our findings and those of others who found an increase in contractility. Evoked release of ATP is reduced in swabbed strips, indicating that ATP derives solely from the urothelium. On the other hand, electrical stimulation and substance P evoke identical degrees of NO release in both intact and swabbed preparations, suggesting that NO can be released from the suburothelium. Conversely, carbachol-induced release of NO is lower in swabbed strips, implying that the cholinergic receptors (muscarinic or nicotinic are located in the upper layer of the urothelium.

Low vitamin D status is associated with reduced muscle mass and impaired physical performance in frail elderly people.

Science.gov (United States)

Tieland, M; Brouwer-Brolsma, E M; Nienaber-Rousseau, C; van Loon, L J C; De Groot, L C P G M

2013-10-01

Serum 25-hydroxyvitamin D (25(OH)D) status has been associated with muscle mass, strength and physical performance in healthy elderly people. Yet, in pre-frail and frail elderly people this association has not been studied. The objective of this study was to explore the association between vitamin D intake and serum 25(OH)D status with muscle mass, strength and physical performance in a pre-frail and frail elderly population. This cross-sectional study included 127 pre-frail and frail elderly people in The Netherlands. Whole body and appendicular lean mass (ALM) (dual energy X-ray absorptiometry), leg strength (one repetition maximum), handgrip strength and physical performance (short physical performance battery) were measured, and blood samples were collected for the assessment of serum 25(OH)D status (liquid chromatography-tandem mass spectrometry). In addition, habitual dietary intake (3-day food records) and physical activity data (accelerometers) were collected. In total, 53% of the participants had a serum 25(OH)D level below 50  nmol/l. After adjustment for confounding factors, 25(OH)D status was associated with ALM (β=0.012, P=0.05) and with physical performance (β=0.020, PVitamin D intake was associated with physical performance (β=0.18, P0.05). In this frail elderly population, 25(OH)D status is low and suggests a modest association with reduced ALM and impaired physical performance. In addition, vitamin D intake tended to be associated with impaired physical performance. Our findings highlight the need for well-designed intervention trials to assess the impact of vitamin D supplementation on 25(OH)D status, muscle mass and physical performance in pre-frail and frail elderly people.

Controlled chaos: three-dimensional kinematics, fiber histochemistry, and muscle contractile dynamics of autotomized lizard tails.

Science.gov (United States)

Higham, Timothy E; Lipsett, Kathryn R; Syme, Douglas A; Russell, Anthony P

2013-01-01

greater resistance to fatigue, followed by the regenerate tail and then the fast iliofibularis fibers. These results suggest that the relatively slow and oxidative fibers found within the tail musculature have a significant impact on contractile function, which translates into a trade-off between longevity of performance and power after autotomy.

Explicit instructions facilitate performance of OCD participants but impair performance of non-OCD participants on a serial reaction time task.

Science.gov (United States)

Soref, Assaf; Liberman, Nira; Abramovitch, Amitai; Dar, Reuven

2018-04-01

Previous studies have shown that individuals diagnosed with OCD tend to rely on explicit processing while performing implicit learning tasks. We sought to investigate whether individuals with OCD are capable of implicit learning, but would demonstrate improved performance when explicit processing strategies are enhanced. Twenty-four participants with OCD and 24 non-psychiatric control (NPC) participants performed an implicit learning task in which they responded to a single target stimulus that successively appears at one of four locations according to an underlying sequence. We manipulated the learning strategy by informing half of the participants that the target stimulus location was determined by an underlying sequence, which they should identify (intentional learning). The other half of the participants was not informed of the existence of the underlying sequence, and was expected to learn the sequence implicitly (standard learning). We predicted that OCD participants will exhibit inferior performance compared to NPC participants in the standard learning condition, and that intentional learning instructions would impair the performance of NPC participants, but enhance the performance of OCD participants. The results supported these predictions and suggest that individuals with OCD prefer controlled to automatic processing. We discuss the implications of this conclusion to our understanding of OCD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multiple Antennas Systems and Full Duplex Relay Systems with Hardware Impairments: New Performance Limits

KAUST Repository

Javed, Sidrah

2016-12-01

Next generation of wireless communication mostly relies on multiple-input multipleoutput (MIMO) configuration and full-duplex relaying to improve data-rates, spectrale efficiency, spatial-multiplexing, quality-of-service and energy-efficiency etc. However, multiple radio frequency (RF) transceivers in MIMO system and multi-hops in relay networks, accumulate transceiver impairments, rendering an unacceptable system performance. Majority of the technical contributions either assume ideal hardware or inappropriately model hardware impairments which often induce misleading results especially for high data-rate communication systems. We propose statistical mathematical modeling of various hardware impairment (HWI) to characterize their deteriorating effects on the information signal. In addition, we model the aggregate HWI as improper Gaussian signaling (IGS), to fully characterize their asymmetric properties and the self-interfering signal attribute under I/Q imbalance. The proposed model encourages to adopt asymmetric transmission scheme, as opposed to traditional symmetric signaling. First, we present statistical baseband equivalent mathematical models for general MIMO system and two special scenarios of receive and transmit diversity systems under HWI. Then, we express their achievable rate under PGS and IGS transmit schemes. Moreover, we tune the IGS statistical characteristics to maximize the achievable rate. We also present optimal beam-forming/pre-coding and receive combiner vector for multiple-input single-output (MISO) and single-input multiple output (SIMO) systems, which lead to SDNR maximization. Moreover, we propose an adaptive scheme to switch between maximal IGS (MIGS) and PGS transmission based on the described conditions to reduce computational overhead. Subsequently, two case studies are presented. 1) Outage analysis has been carried out for SIMO, under transceiver distortion noise, for two diversity combining schemes 2) The benefits of employing IGS

Mechanism of action of ethanol on heart contractility

International Nuclear Information System (INIS)

Oquendo-Muriente, I.; De Mello, W.C.

1986-01-01

Ethanol depresses heart contractility. To investigate the mechanism of the negative inotropic action of ethanol, rat ventricular strips were dissected and mounted vertically in a transparent chamber. The preparation was superfused initially with normal oxygenated Tyrode solution (32.5 0 C) and electrically stimulated (1 Hz). After 1 hour of equilibration, contractures were elicited by exposing the muscle strips to high K + (100 mM) solution. Studies on the influence of (Ca 2+ ) 0 on K + contractures showed that the first rapid component of the contracture (58 mg/sec - S.E. +/- 8; n = 8) was greatly dependent upon (Ca 2+ ) 0 while the second slow component (20 mg/sec - S.E. +/- 5; n = 8) was slightly altered. The addition of ethanol (400 mg/100 ml) to high K solution abolished the fast component and reduced the amplitude of the second phase of K contractures. Similar results were obtained with verapamil (10 -5 M). These results, as well as studies on the effect of the drug on 45 Ca fluxes support the view that ethanol decreases the permeability of the heart cell membrane to Ca

Mechanism of action of ethanol on heart contractility

Energy Technology Data Exchange (ETDEWEB)

Oquendo-Muriente, I.; De Mello, W.C.

1986-03-05

Ethanol depresses heart contractility. To investigate the mechanism of the negative inotropic action of ethanol, rat ventricular strips were dissected and mounted vertically in a transparent chamber. The preparation was superfused initially with normal oxygenated Tyrode solution (32.5/sup 0/C) and electrically stimulated (1 Hz). After 1 hour of equilibration, contractures were elicited by exposing the muscle strips to high K/sup +/ (100 mM) solution. Studies on the influence of (Ca/sup 2 +/)/sub 0/ on K/sup +/ contractures showed that the first rapid component of the contracture (58 mg/sec - S.E. +/- 8; n = 8) was greatly dependent upon (Ca/sup 2 +/)/sub 0/ while the second slow component (20 mg/sec - S.E. +/- 5; n = 8) was slightly altered. The addition of ethanol (400 mg/100 ml) to high K solution abolished the fast component and reduced the amplitude of the second phase of K contractures. Similar results were obtained with verapamil (10/sup -5/ M). These results, as well as studies on the effect of the drug on /sup 45/Ca fluxes support the view that ethanol decreases the permeability of the heart cell membrane to Ca.

Postextrasystolic potentiation and contractile reserve: requirements and restrictions.

Science.gov (United States)

Lust, R M; Lutherer, L O; Gardner, M E; Cooper, M W

1982-12-01

These studies were conducted to examine the basic characteristics of postextrasystolic potentiation (PESP) and the relationship of loading effects to PESP. Measurements of left ventricular (LV) and aortic pressures, the rate of pressure rise, and echocardiographically determined LV dimensions were made in anesthetized open-chest dogs. The hearts were paced, and timed extrasystoles were introduced that were followed by postextrasystoles (PES). PES's were elicited after an interval equal to either a full compensatory pause or a time when the diastolic properties of the LV could not be distinguished from control (isolength). Potentiation of contraction for the PES's introduced after an isolength pause was dependent on both the heart rate and the extrasystolic interval, whereas the PES's that occurred after a full pause showed no dependence on either of these intervals. PESP elicited during the isolength period was not dependent on either preload and afterload. It is concluded that PESP depends on the combination of heart rate and extrasystolic and postextrasystolic intervals. Further, PESP may be inaccurate in assessing contractile reserve unless the heart rate and extrasystolic interval are known and the PES is introduced after an isolength pause.

Oesophageal motility disorders in patients with psychiatric disease

International Nuclear Information System (INIS)

Roland, J.; Dhaenen, H.; Ham, H.R.; Peters, O.; Piepsz, A.

1996-01-01

Clinical and experimental observations indicate that the motility of the oesophagus may be affected by emotional stimuli. The aim of this study was to evaluate the incidence of oesophageal contractility impairment in patients suffering from a psychiatric disorder. Fifty-one patients admitted to the psychiatric department were submitted to an oesophageal transit study by means of krypton-81m. All patients with an abnormal oesophageal transit underwent manometry and endoscopy. The level of depression and anxiety was evaluated by the treating psychiatrist, using the Hamilton Depression and Anxiety Rating Scales. The oesophageal transit was abnormal in 13 patients. Two of these 13 patients refused manometric investigation. In ten of the 11 remaining patients, the manometry revealed functional motor abnormalities. Endoscopy, performed in all these ten patients, was normal. In conclusion, a high percentage of oesophageal contractility disturbances was found in psychiatric patients complaining of anxiety and/or depression. These abnormalities were detected by scintigraphy as well as by manometry. Owing to the normal endoscopic findings, these contraction abnormalities are likely to reflect a functional motor impairment. (orig.). With 3 figs., 2 tabs

Oesophageal motility disorders in patients with psychiatric disease

Energy Technology Data Exchange (ETDEWEB)

Roland, J. [Department of Nuclear Medicine, Free University of Brussels, Brussels (Belgium); Dhaenen, H. [Department of Psychiatry, Free University of Brussels, Brussels (Belgium); Ham, H.R. [Department of Nuclear Medicine, Free University of Brussels, Brussels (Belgium); Peters, O. [Department of Gastro-enterology, Free University of Brussels, Brussels (Belgium); Piepsz, A. [Department of Nuclear Medicine, Free University of Brussels, Brussels (Belgium)

1996-12-01

Clinical and experimental observations indicate that the motility of the oesophagus may be affected by emotional stimuli. The aim of this study was to evaluate the incidence of oesophageal contractility impairment in patients suffering from a psychiatric disorder. Fifty-one patients admitted to the psychiatric department were submitted to an oesophageal transit study by means of krypton-81m. All patients with an abnormal oesophageal transit underwent manometry and endoscopy. The level of depression and anxiety was evaluated by the treating psychiatrist, using the Hamilton Depression and Anxiety Rating Scales. The oesophageal transit was abnormal in 13 patients. Two of these 13 patients refused manometric investigation. In ten of the 11 remaining patients, the manometry revealed functional motor abnormalities. Endoscopy, performed in all these ten patients, was normal. In conclusion, a high percentage of oesophageal contractility disturbances was found in psychiatric patients complaining of anxiety and/or depression. These abnormalities were detected by scintigraphy as well as by manometry. Owing to the normal endoscopic findings, these contraction abnormalities are likely to reflect a functional motor impairment. (orig.). With 3 figs., 2 tabs.

Does Impaired O2 Delivery During Exercise Accentuate Central and Peripheral Fatigue in Patients with Coexistent COPD-CHF?

Directory of Open Access Journals (Sweden)

Mayron F. Oliveira

2015-01-01

Full Text Available Impairment in oxygen (O2 delivery to the central nervous system (brain and skeletal locomotor muscle during exercise has been associated with central and peripheral neuromuscular fatigue in healthy humans. From a clinical perspective, impaired tissue O2 transport is a key pathophysiological mechanism shared by cardiopulmonary diseases, such as chronic obstructive pulmonary disease (COPD and chronic heart failure (CHF. In addition to arterial hypoxemic conditions in COPD, there is growing evidence that cerebral and muscle blood flow and oxygenation can be reduced during exercise in both isolated COPD and CHF. Compromised cardiac output due to impaired cardiopulmonary function/interactions and blood flow redistribution to the overloaded respiratory muscles (i.e., ↑work of breathing may underpin these abnormalities. Unfortunately, COPD and CHF coexist in almost a third of elderly patients making these mechanisms potentially more relevant to exercise intolerance. In this context, it remains unknown whether decreased O2 delivery accentuates neuromuscular manifestations of central and peripheral fatigue in coexistent COPD-CHF. If this holds true, it is conceivable that delivering a low-density gas mixture (heliox through non-invasive positive pressure ventilation could ameliorate cardiopulmonary function/interactions and reduce the work of breathing during exercise in these patients. The major consequence would be increased O2 delivery to the brain and active muscles with potential benefits to exercise capacity (i.e., ↓central and peripheral neuromuscular fatigue, respectively. We therefore hypothesize that patients with coexistent COPD-CHF stop exercising prematurely due to impaired central motor drive and muscle contractility as the cardiorespiratory system fails to deliver sufficient O2 to simultaneously attend the metabolic demands of the brain and the active limb muscles.

Performance of the EQ-5D and the EQ-5D+C in elderly patients with cognitive impairments

Directory of Open Access Journals (Sweden)

Verhey Frans RJ

2007-06-01

Full Text Available Abstract Background The EQ-5D is a reliable tool for measuring Health-Related Quality of Life (HRQoL. However, concern has been expressed that it may ignore elements of HRQoL, particularly cognition. In response to this concern, the EQ-5D has been extended with a cognitive dimension (EQ-5D+C. The aim of this study was to compare the performance of the EQ-5D and the EQ-5D+C in elderly patients with cognitive impairments by assessing their construct validity and responsiveness. Methods Data from the MEDICIE study (n = 196 were used, in which all questionnaires were rated by proxies. Results Regarding construct validity, we found similar correlations between the EQ-5D and the Mini Mental State Examination (MMSE and between the EQ-5D+C and the MMSE. Furthermore, both the EQ-5D and the EQ-5D+C were responsive to changes in the MMSE, with the EQ-5D performing slightly better. Conclusion We conclude that the EQ-5D performs well for evaluating HRQoL in a population with cognitive impairments. Based on the results of this explorative study, it does not seem necessary to adjust the current classification system by adding a cognitive dimension. However, in order to compare both instruments regarding utility values, it is necessary to develop a new scoring algorithm for the EQ-5D+C by conducting a general population study. Considering the explorative nature of this study, it is recommended that more aspects of the validity of both the EQ-5D and the EQ-5D+C are explored in patients with cognitive impairments using a more tailored study design.

Pharmacological radionuclide ventriculography for detection of myocardial contractile reserve in patients after myocardial infarction: head-to-head comparison of low dose dobutamine and low dose dypiridamole

International Nuclear Information System (INIS)

Petrasinovic, Z.; Ostojic, M.; Beleslin, B.; Stojkovic, S.; Nedeljkovic, M.; Stankovic, G.; Dikic, A.; Pavlovic, S.; Sobic, D.

2002-01-01

Background. Low dose pharmacological stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for recognition of myocardial viability. However, dependence on adequate acoustic window, observer experience, and the mild degree of wall motion changes make the viability assessment by stress echocardiography especially bothersome. The objective of the study was to evaluate the ability of low dose dobutamine and low dose dipyridamole radionuclide ventriculography to detect contractile reserve in patients after myocardial infarction and functional recovery after coronary angioplasty. Methods. The study group consisted of 20 consecutive patients (52±10 years, 17 male) with previous myocardial infarction and resting regional dyssynergy, in whom diagnostic cardiac catheterization revealed significant one-vessel coronary artery stenosis suitable for angioplasty. Each patient underwent equilibrium 99m-Tc radionuclide ventriculography which was performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes) and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global and regional ejection fractions were determined. Increase of regional ejection fraction for >5% (inferoapical and posterolateral regions) or >10% (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted regions, as well as in the follow up period, was considered as index of contractile reserve. After 8 weeks of successful angioplasty, resting radionuclide ventriculography was repeated in all patients in order to identify functional recovery of the infarct zone. Results. Out of the 180 analyzed segments (20x9), 90 regional ejection fractions have shown depressed contractility. The mean of the regional ejection fractions showing depressed contractility increased from the resting value of 34±12% to 42±14% in the follow-up period (p=0.06). Of the 90 with baseline dyssynergy, 46 were responders during low-dose dobutamine (51

Inhibition of hippocampal aromatization impairs spatial memory performance in a male songbird.

Science.gov (United States)

Bailey, David J; Ma, Chunqi; Soma, Kiran K; Saldanha, Colin J

2013-12-01

Recent studies have revealed the presence and regulation of aromatase at the vertebrate synapse, and identified a critical role played by presynaptic estradiol synthesis in the electrophysiological response to auditory and other social cues. However, if and how synaptic aromatization affects behavior remains to be directly tested. We have exploited 3 characteristics of the zebra finch hippocampus (HP) to test the role of synaptocrine estradiol provision on spatial memory function. Although the zebra finch HP contains abundant aromatase transcripts and enzyme activity, immunocytochemical studies reveal widespread pre- and postsynaptic, but sparse to undetectable somal, localization of this enzyme. Further, the superficial location of the avian HP makes possible the more exclusive manipulation of its neurochemical characteristics without perturbation of the neuropil and the resultant induction of astroglial aromatase. Last, as in other vertebrates, the HP is critical for spatial memory performance in this species. Here we report that local inhibition of hippocampal aromatization impairs spatial memory performance in an ecologically valid food-finding task. Local aromatase inhibition also resulted in lower levels of estradiol in the HP, but not in adjacent brain areas, and was achieved without the induction of astroglial aromatase. The observed decrement in acquisition and subsequent memory performance as a consequence of lowered aromatization was similar to that achieved by lesioning this locus. Thus, hippocampal aromatization, much of which is achieved at the synapse in this species, is critical for spatial memory performance.

Cellular Architecture Regulates Collective Calcium Signaling and Cell Contractility.

Directory of Open Access Journals (Sweden)

Jian Sun

2016-05-01

Full Text Available A key feature of multicellular systems is the ability of cells to function collectively in response to external stimuli. However, the mechanisms of intercellular cell signaling and their functional implications in diverse vascular structures are poorly understood. Using a combination of computational modeling and plasma lithography micropatterning, we investigate the roles of structural arrangement of endothelial cells in collective calcium signaling and cell contractility. Under histamine stimulation, endothelial cells in self-assembled and microengineered networks, but not individual cells and monolayers, exhibit calcium oscillations. Micropatterning, pharmacological inhibition, and computational modeling reveal that the calcium oscillation depends on the number of neighboring cells coupled via gap junctional intercellular communication, providing a mechanistic basis of the architecture-dependent calcium signaling. Furthermore, the calcium oscillation attenuates the histamine-induced cytoskeletal reorganization and cell contraction, resulting in differential cell responses in an architecture-dependent manner. Taken together, our results suggest that endothelial cells can sense and respond to chemical stimuli according to the vascular architecture via collective calcium signaling.

Reduced mismatch negativity in mild cognitive impairment: associations with neuropsychological performance.

Science.gov (United States)

Mowszowski, Loren; Hermens, Daniel F; Diamond, Keri; Norrie, Louisa; Hickie, Ian B; Lewis, Simon J G; Naismith, Sharon L

2012-01-01

Mild cognitive impairment (MCI) refers to a transitory state between healthy aging and dementia. Biomarkers are needed to facilitate early identification of MCI and predict progression to dementia. One potential neurophysiological biomarker, mismatch negativity (MMN), is an event-related potential reflecting fundamental, pre-attentive cognitive processes. MMN is reduced in normal aging and dementia and in neuropsychiatric samples and is associated with verbal memory deficits and poor executive functioning. This study aimed to investigate auditory MMN and its relationship to neuropsychological performance in MCI. Twenty-eight MCI participants and fourteen controls, aged ≥50 years, underwent neurophysiological and neuropsychological assessment, and completed questionnaires pertaining to disability. Relative to controls, the MCI group demonstrated reduced temporal MMN amplitude (p patients with MCI exhibit altered pre-attentive information processing, which in turn is associated with memory and psychosocial deficits. These findings overall suggest that MMN may be a viable neurophysiological biomarker of underlying disease in this 'at risk' group.

Effectiveness of braille and audio-tactile performance technique for improving oral hygiene status of visually impaired adolescents

Directory of Open Access Journals (Sweden)

Sushmita Deshpande

2017-01-01

Full Text Available Background: Visually impaired people encounter numerous challenges in their daily life which makes it a cumbersome task to pay special attention to oral health needs. Furthermore, there is little knowledge about oral health practices among caretakers and visually impaired individuals, due to which oral health is often neglected when compared to the general health. Hence, there was a need to educate visually challenged individuals about oral hygiene practices in a customized format so that the comprehension of brushing techniques could be conveyed at its best. Materials and Methods: The present study was a randomized control trial of sixty visually impaired adolescents who were divided into three groups of 20 each. In Group 1, Braille was used, whereas in Group 2, audio-tactile performance (ATP technique and in Group 3, a combination of both the methods were used to teach tooth brushing as a part of oral health education. Pre- and post-plaque index score using Silness and Loe (1967 after health education were calculated and tabulated for statistical analysis. Results: The postintervention mean plaque index score increased in Group 1 from 29.45 to 42.98, whereas the mean plaque score decreased in Groups 2 and 3 from 30.83–29.9 to 30.23–18.73, respectively. Intergroup comparison of postplaque index score using Kruskal–Wallis and ANOVA analysis showed significant difference among all three study groups. Conclusion: The combination of Braille and ATP technique of health education served as the most effective medium to teach oral hygiene methods to visually impaired adolescents.

Effectiveness of braille and audio-tactile performance technique for improving oral hygiene status of visually impaired adolescents.

Science.gov (United States)

Deshpande, Sushmita; Rajpurohit, Ladusingh; Kokka, Vivian Varghese

2017-01-01

Visually impaired people encounter numerous challenges in their daily life which makes it a cumbersome task to pay special attention to oral health needs. Furthermore, there is little knowledge about oral health practices among caretakers and visually impaired individuals, due to which oral health is often neglected when compared to the general health. Hence, there was a need to educate visually challenged individuals about oral hygiene practices in a customized format so that the comprehension of brushing techniques could be conveyed at its best. The present study was a randomized control trial of sixty visually impaired adolescents who were divided into three groups of 20 each. In Group 1, Braille was used, whereas in Group 2, audio-tactile performance (ATP) technique and in Group 3, a combination of both the methods were used to teach tooth brushing as a part of oral health education. Pre- and post-plaque index score using Silness and Loe (1967) after health education were calculated and tabulated for statistical analysis. The postintervention mean plaque index score increased in Group 1 from 29.45 to 42.98, whereas the mean plaque score decreased in Groups 2 and 3 from 30.83-29.9 to 30.23-18.73, respectively. Intergroup comparison of postplaque index score using Kruskal-Wallis and ANOVA analysis showed significant difference among all three study groups. The combination of Braille and ATP technique of health education served as the most effective medium to teach oral hygiene methods to visually impaired adolescents.

Performance in hippocampus- and PFC-dependent cognitive domains are not concomitantly impaired in rats exposed to 20 cGy of 1 GeV/n 56Fe particles

Science.gov (United States)

Britten, Richard A.; Miller, Vania D.; Hadley, Melissa M.; Jewell, Jessica S.; Macadat, Evangeline

2016-08-01

NASA is currently conducting ground based experiments to determine whether the radiation environment that astronauts will encounter on deep space missions will have an impact on their long-term health and their ability to complete the various tasks during the mission. Emerging data suggest that exposure of rodents to mission-relevant HZE radiation doses does result in the impairment of various neurocognitive processes. An essential part of mission planning is a probabilistic risk assessment process that takes into account the likely incidence and severity of a problem. To date few studies have reported the impact of space radiation in a format that is amenable to PRA, and those that have only reported data for a single cognitive process. This study has established the ability of individual male Wistar rats to conduct a hippocampus-dependent (spatial memory) task and a cortex-dependent (attentional set shifting task) 90 days after exposure to 20 cGy 1 GeV/n 56Fe particles. Radiation-induced impairment of performance in one cognitive domain was not consistently associated with impaired performance in the other domain. Thus sole reliance upon a single measure of cognitive performance may substantially under-estimate the risk of cognitive impairment, and ultimately it may be necessary to establish the likelihood that mission-relevant HZE doses will impair performance in the three or four cognitive domains that NASA considers to be most critical for mission success, and build a PRA using the composite data from such studies.

The retardation of myometrial infiltration, reduction of uterine contractility, and alleviation of generalized hyperalgesia in mice with induced adenomyosis by levo-tetrahydropalmatine (l-THP) and andrographolide.

Science.gov (United States)

Mao, Xiaoyan; Wang, Yuedong; Carter, Andrew V; Zhen, Xuechu; Guo, Sun-Wei

2011-10-01

Adenomyosis is a tough disease to manage nonsurgically. Levo-tetrahydropalmatine (l-THP), a known analgesic, and andrographolide, a nuclear factor kappa B (NF-κB) inhibitor, are both active ingredients extracted from Chinese medicinal herbs. We sought to determine whether treatment of l-THP, andrographolide, and valproic acid (VPA) would suppress the myometrial infiltration, improve pain behavior, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 55 female ICR mice neonatally dosed with tamoxifen, while another 8 (group C) were dosed with solvent only. Starting from 4 weeks after birth, hotplate test was administrated to all mice every 4 weeks. At the 16th week, all mice with induced adenomyosis were randomly divided into 6 groups, each receiving different treatment for 3 weeks: low- or high-dose l-THP, andrographolide, low-dose l-THP and andrographolide jointly, VPA, and untreated. Group C received no treatment. After treatment, the hotplate test was administered and all mice were killed. The depth of myometrial infiltration of ectopic endometrium and uterine contractility were measured and compared across groups. We found that induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and irregularity of uterine contractions. Treatment with either l-THP, andrographolide, VPA, or l-THP and andrographolide jointly suppressed myometrial infiltration, improved generalized hyperalgesia, and reduced the amplitude and irregularity of uterine contractions. These results suggest that increased uterine contractility, in the form of increased contractile amplitude and irregularity, may contribute to dysmenorrhea in women with adenomyosis. More importantly, l-THP, andrographolide, and VPA all seem to be promising compounds for treating adenomyosis.

Mental Fatigue Alters Cortical Activation and Psychological Responses, Impairing Performance in a Distance-Based Cycling Trial

Directory of Open Access Journals (Sweden)

Flávio O. Pires

2018-03-01

Full Text Available Purpose: We sought to verify if alterations in prefrontal cortex (PFC activation and psychological responses would play along with impairments in pacing and performance of mentally fatigued cyclists.Materials and Methods: Eight recreational cyclists performed two preliminary sessions to familiarize them with the rapid visual information processing (RVP test, psychological scales and 20 km cycling time trial (TT20km (session 1, as well as to perform a VO2MAX test (session 2. Thereafter, they performed a TT20km either after a RVP test (30 min or a time-matched rest control session (session 3 and 4 in counterbalanced order. Performance and psychological responses were obtained throughout the TT20km while PFC electroencephalography (EEG was obtained at 10 and 20 km of the TT20km and throughout the RVP test. Increases in EEG theta band power indicated a mental fatigue condition. Repeated-measures mixed models design and post-hoc effect size (ES were used in comparisons.Results: Cyclists completed the trial ~2.7% slower in mental fatigue (34.3 ± 1.3 min than in control (33.4 ± 1.1 min, p = 0.02, very large ES, with a lower WMEAN (224.5 ± 17.9 W vs. 240.2 ± 20.9 W, respectively; p = 0.03; extremely large ES. There was a higher EEG theta band power during RVP test (p = 0.03; extremely large ES, which remained during the TT20km (p = 0.01; extremely large ES. RPE increased steeper in mental fatigue than in control, together with isolated reductions in motivation at 2th km (p = 0.04; extremely large ES, felt arousal at the 2nd and 4th km (p = 0.01; extremely large ES, and associative thoughts to exercise at the 6th and 16th km (p = 0.02; extremely large ES of the TT20km.Conclusions: Mentally fatigued recreational cyclists showed impaired performance, altered PFC activation and faster increase in RPE during a TT20km.

The Relationship between Computer and Internet Use and Performance on Standardized Tests by Secondary School Students with Visual Impairments

Science.gov (United States)

Zhou, Li; Griffin-Shirley, Nora; Kelley, Pat; Banda, Devender R.; Lan, William Y.; Parker, Amy T.; Smith, Derrick W.

2012-01-01

Introduction: The study presented here explored the relationship between computer and Internet use and the performance on standardized tests by secondary school students with visual impairments. Methods: With data retrieved from the first three waves (2001-05) of the National Longitudinal Transition Study-2, the correlational study focused on…

Why does interactional justice promote organizational loyalty, job performance, and prevent mental impairment? The role of social support and social stressors.

Science.gov (United States)

Otto, Kathleen; Mamatoglu, Nihal

2015-01-01

Using social exchange theory as a conceptual framework, we investigated the relationship between interactional justice and the outcomes organizational loyalty (affective commitment, turnover intentions), perceived job performance (self-rated performance, personal accomplishment), and mental impairment (cognitive irritation, emotional exhaustion) in an online survey of 218 employees working in the field of computer technology. Specifically, we predicted that interactional justice would heighten the quality of social exchange relationships and therefore expected perceived social support (POS) and bullying to mediate the proposed relationships. We tested our hypotheses applying a latent structural equation model. Our findings revealed that POS mediated the relationship between interactional justice and organizational loyalty, whereas bullying mediated the relationship between interactional justice and mental impairment. Practical implications are discussed concerning how to foster interactional justice and POS and how to weaken bullying behavior.

Nonequilibrium phase transitions, fluctuations and correlations in an active contractile polar fluid.

Science.gov (United States)

Gowrishankar, Kripa; Rao, Madan

2016-02-21

We study the patterning, fluctuations and correlations of an active polar fluid consisting of contractile polar filaments on a two-dimensional substrate, using a hydrodynamic description. The steady states generically consist of arrays of inward pointing asters and show a continuous transition from a moving lamellar phase, a moving aster street, to a stationary aster lattice with no net polar order. We next study the effect of spatio-temporal athermal noise, parametrized by an active temperature TA, on the stability of the ordered phases. In contrast to its equilibrium counterpart, we find that the active crystal shows true long range order at low TA. On increasing TA, the asters dynamically remodel, concomitantly we find novel phase transitions characterized by bond-orientational and polar order upon "heating".

Action of ouabain and an amino-cardenolide on Na+-pump function and contractility of isolated canine heart cells

International Nuclear Information System (INIS)

Porterfield, L.M.; Songu-Mize, E.; Chryssanthis, T.; Caldwell, R.W.

1986-01-01

Viable, rod-shaped, Ca ++ -tolerant cells were isolated from the cardiac ventricle of adult mongrel dogs, a digitalis-sensitive species. These cells do not contract spontaneously but contractions were driven by electrical field stimulation. Changes in contractile amplitude were assessed by computer-assisted analysis of recorded phase contrast images. Addition of a polar aminocardenolide (AC), ASI-222, produced a dose-related increase in contractility with a concentration producing a 50% maximal response (RC 50 ) of 4 x 10 -8 M. For ouabain (OB) the RC 50 was 7 x 10 -7 M. Cellular Na + -pump (NaP) function was determined as digitalis-sensitive 86 Rb + -uptake. Addition of AC and OB to these cells produced a dose-related decrease in 86 Rb + -uptake; concentrations which produced a 50% inhibition (IC 50 ) of NaP function were of 6 x 10 -8 M and 1.2 x 10 -6 M for AC and OB, respectively. Their data indicates that in isolated dog heart cells AC is both a more potent inotropic agent and an inhibitor of NaP function by 15-20 fold than OB. The RC 50 and IC 50 for these processes correlate for each glycoside

Analysis on oscillating actuator frequency influence of the fluid flow characterization for 2D contractile water jet thruster

Science.gov (United States)

Shaari, M. F.; Abu Bakar, H.; Nordin, N.; Saw, S. K.; Samad, Z.

2013-12-01

Contractile body is an alternative mechanism instead of rotating blade propeller to generate water jet for locomotion. The oscillating motion of the actuator at different frequencies varies the pressure and volume of the pressure chamber in time to draw in and jet out the water at a certain mass flow rate. The aim of this research was to analyze the influence of the actuating frequency of the fluid flow in the pressure chamber of the thruster during this inflation-deflation process. A 70mm × 70mm × 18mm (L × W × T) 2D water jet thruster was fabricated for this purpose. The contractile function was driven using two lateral pneumatic actuators where the fluid flow analysis was focused on the X-Y plane vector. Observation was carried out using a video camera and Matlab image measurement technique to determine the volume of the flowing mass. The result demonstrated that the greater actuating frequency decreases the fluid flow rate and the Reynolds number. This observation shows that the higher frequency would give a higher mass flow rate during water jet generation.

The effectiveness of two novel techniques in establishing the mechanical and contractile responses of biceps femoris

International Nuclear Information System (INIS)

Ditroilo, Massimiliano; De Vito, Giuseppe; Hunter, Angus M; Haslam, Samuel

2011-01-01

Portable tensiomyography (TMG) and myotonometry (MMT) devices have been developed to measure mechanical and contractile properties of skeletal muscle. The aim of this study was to explore the sensitivity of the aforementioned techniques in detecting a change in passive mechanical properties of the biceps femoris (BF) muscle as a result of change in knee joint angle (i.e. muscle length). BF responses were assessed in 16 young participants (23.4 ± 4.9 years), at three knee joint angles (0°, 45° and 90°), for maximal isometric torque (MIT) along with myo-electrical activity. Contractile and mechanical properties were measured in a relaxed state. Inter-day reliability of the TMG and MMT was also assessed. MIT changed significantly (p < 0.01) across the three angles, so did stiffness and other parameters measured with MMT (p < 0.01). Conversely, TMG could detect changes only at two knee angles (0° and 45°, p < 0.01), when there is enough tension in the muscle. Reliability was overall insufficient for TMG whilst absolute reliability was excellent (coefficient of variation < 5%) for MMT. The ability of MMT more than TMG to detect an inherent change in stiffness can be conceivably exploited in a number of clinical/therapeutic applications that have to do with unnatural changes in passive muscle stiffness

Psycho acoustical Measures in Individuals with Congenital Visual Impairment.

Science.gov (United States)

Kumar, Kaushlendra; Thomas, Teenu; Bhat, Jayashree S; Ranjan, Rajesh

2017-12-01

In congenital visual impaired individuals one modality is impaired (visual modality) this impairment is compensated by other sensory modalities. There is evidence that visual impaired performed better in different auditory task like localization, auditory memory, verbal memory, auditory attention, and other behavioural tasks when compare to normal sighted individuals. The current study was aimed to compare the temporal resolution, frequency resolution and speech perception in noise ability in individuals with congenital visual impaired and normal sighted. Temporal resolution, frequency resolution, and speech perception in noise were measured using MDT, GDT, DDT, SRDT, and SNR50 respectively. Twelve congenital visual impaired participants with age range of 18 to 40 years were taken and equal in number with normal sighted participants. All the participants had normal hearing sensitivity with normal middle ear functioning. Individual with visual impairment showed superior threshold in MDT, SRDT and SNR50 as compared to normal sighted individuals. This may be due to complexity of the tasks; MDT, SRDT and SNR50 are complex tasks than GDT and DDT. Visual impairment showed superior performance in auditory processing and speech perception with complex auditory perceptual tasks.

Locomotion characteristics and match-induced impairments in physical performance in male elite team handball players.

Science.gov (United States)

Michalsik, L B; Aagaard, P; Madsen, K

2013-07-01

The purpose of this study was to determine the physical demands and match-induced impairments in physical performance in male elite Team Handball (TH) players in relation to playing position. Male elite TH field players were closely observed during 6 competitive seasons. Each player (wing players: WP, pivots: PV, backcourt players: BP) was evaluated during match-play using video recording and subsequently performing locomotion match analysis. A total distance of 3 627±568 m (group means±SD) was covered per match with a total effective playing time (TPT) of 53:51±5:52 min:s, while full-time players covered 3 945±538 m. The mean speed was 6.40±1.01 km · h - 1. High-intensity running constituted only 1.7±0.9% of TPT per match corresponding to 7.9±4.9% of the total distance covered. An average of 1 482.4±312.6 activity changes per player (n=82) with 53.2±14.1 high-intensity runs were observed per match. Total distance covered was greater in BP (3 765±532 m) and WP (3 641±501 m) than PV (3 295±495 m) (pteam sport that comprises several types of movement categories, which during match-play place moderate-to-high demands on intermittent endurance running capacity and where the amount of high-intensity running may be high during brief periods of the match. Signs of fatigue-related changes were observed in terms of temporary impaired physical performance, since the amount of high-intensity running was reduced in the second half. Notably, physical demands differed between playing positions, with WP demonstrating a more intensive activity pattern than BP and PV, respectively. © Georg Thieme Verlag KG Stuttgart · New York.

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

OpenAIRE

Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

2012-01-01

Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT) and cardiac-specific catalase overexpression mice were challenged...

Cognitive performance and informant reports in the diagnosis of cognitive impairment and dementia in African Americans and whites.

Science.gov (United States)

Potter, Guy G; Plassman, Brenda L; Burke, James R; Kabeto, Mohammed U; Langa, Kenneth M; Llewellyn, David J; Rogers, Mary A M; Steffens, David C

2009-11-01

The diagnosis of cognitive impairment and dementia must reflect an increasingly diverse and aging United States population. This study compared direct testing and informant reports of cognition with clinical diagnoses of cognitive impairment and dementia between African Americans and whites. Participants in the Aging, Demographics, and Memory Study completed in-person dementia evaluations, and were assigned clinical diagnoses (by a consensus panel of dementia experts) of normal; cognitive impairment, not demented (CIND); and dementia. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were used to assess cognitive performance and reported cognitive decline. A higher CERAD total score was associated with lower odds of CIND and dementia, at comparable ratios between African Americans and whites. Higher IQCODE scores were associated with increased odds of dementia in both African Americans and whites. Higher IQCODE scores were associated with increased odds of CIND among whites, but not among African Americans. Cultural differences may influence informant reports of prevalent CIND and dementia. Our findings also highlight the need for more comparative research to establish the cultural validity of measures used to diagnose these conditions.

Utero-tubal sperm transport and its impairment in endometriosis and adenomyosis.

Science.gov (United States)

Kissler, Stefan; Zangos, Stephan; Wiegratz, Inka; Kohl, Joachim; Rody, Achim; Gaetje, Regine; Doebert, Natascha; Wildt, Ludwig; Kunz, Georg; Leyendecker, Gerhard; Kaufmann, Manfred

2007-04-01

The uterus is composed of different smooth muscle layers that serve various functions. First, menstrual debris is expulsed at the time of the menses. Second, sperm is transported in the preovulatory phase to maximize fertility, and third, the human embryo is placed in an adequate setting during implantation. Endometriosis is a gynecologic disorder leading to severe pain symptoms such as severe pain during menstruation (dysmenorrhea), chronic pelvic pain, pain during sexual intercourse (dyspareunia), and abnormal uterine bleeding. Besides, endometriosis is often associated with female infertility and exhibits a massive impairment in the physiology of uterine contractility that can be documented by the in vivo examination method of hysterosalpingoscintigraphy (HSSG). In addition, endometriosis is associated in 80-90% of subjects with adenomyosis and our data clearly indicate that sperm transport is disturbed by hyperperistalsis when at least one focus of adenomyosis can be detected via magnetic resonance imaging (MRI) and turns into dysperistalsis (a complete failure in sperm transport capacity) when diffuse adenomyosis affecting all myometrial uterine muscle layers is detected. Hence, dysperistalsis is significantly associated with reduced spontaneous pregnancy rates. We therefore recommend MRI and HSSG in every sterility workup.

Medications and impaired driving.

Science.gov (United States)

Hetland, Amanda; Carr, David B

2014-04-01

To describe the association of specific medication classes with driving outcomes and provide clinical recommendations. The MEDLINE and EMBASE databases were searched for articles published from January 1973 to June 2013 on classes of medications associated with driving impairment. The search included outcome terms such as automobile driving, motor vehicle crash, driving simulator, and road tests. Only English-language articles that contained findings from observational or interventional designs with ≥ 10 participants were included in this review. Cross-sectional studies, case series, and case reports were excluded. Driving is an important task and activity for the majority of adults. Some commonly prescribed medications have been associated with driving impairment measured by road performance, driving simulation, and/or motor vehicle crashes. This review of 30 studies identified findings with barbiturates, benzodiazepines, hypnotics, antidepressants, opioid and nonsteroidal analgesics, anticonvulsants, antipsychotics, antiparkinsonian agents, skeletal muscle relaxants, antihistamines, anticholinergic medications, and hypoglycemic agents. Additional studies of medication impact on sedation, sleep latency, and psychomotor function, as well as the role of alcohol, are also discussed. Psychotropic agents and those with central nervous system side effects were associated with measures of impaired driving performance. It is difficult to determine if such associations are actually a result of medication use or the medical diagnosis itself. Regardless, clinicians should be aware of the increased risk of impaired driving with specific classes of medications, educate their patients, and/or consider safer alternatives.

Stereotype threat can both enhance and impair older adults' memory.

Science.gov (United States)

Barber, Sarah J; Mather, Mara

2013-12-01

Negative stereotypes about aging can impair older adults' memory via stereotype threat; however, the mechanisms underlying this phenomenon are unclear. In two experiments, we tested competing predictions derived from two theoretical accounts of stereotype threat: executive-control interference and regulatory fit. Older adults completed a working memory test either under stereotype threat about age-related memory declines or not under such threat. Monetary incentives were manipulated such that recall led to gains or forgetting led to losses. The executive-control-interference account predicts that stereotype threat decreases the availability of executive-control resources and hence should impair working memory performance. The regulatory-fit account predicts that threat induces a prevention focus, which should impair performance when gains are emphasized but improve performance when losses are emphasized. Results were consistent only with the regulatory-fit account. Although stereotype threat significantly impaired older adults' working memory performance when remembering led to gains, it significantly improved performance when forgetting led to losses.

Performance Evaluation of User Selection Protocols in Random Networks with Energy Harvesting and Hardware Impairments

Directory of Open Access Journals (Sweden)

Tan Nhat Nguyen

2016-01-01

Full Text Available In this paper, we evaluate performances of various user selection protocols under impact of hardware impairments. In the considered protocols, a Base Station (BS selects one of available Users (US to serve, while the remaining USs harvest the energy from the Radio Frequency (RF transmitted by the BS. We assume that all of the US randomly appear around the BS. In the Random Selection Protocol (RAN, the BS randomly selects a US to transmit the data. In the second proposed protocol, named Minimum Distance Protocol (MIND, the US that is nearest to the BS will be chosen. In the Optimal Selection Protocol (OPT, the US providing the highest channel gain between itself and the BS will be served. For performance evaluation, we derive exact and asymptotic closed-form expressions of average Outage Probability (OP over Rayleigh fading channels. We also consider average harvested energy per a US. Finally, Monte-Carlo simulations are then performed to verify the theoretical results.

The influence of age and mild cognitive impairment on associative memory performance and underlying brain networks.

Science.gov (United States)

Oedekoven, Christiane S H; Jansen, Andreas; Keidel, James L; Kircher, Tilo; Leube, Dirk

2015-12-01

Associative memory is essential to everyday activities, such as the binding of faces and corresponding names to form single bits of information. However, this ability often becomes impaired with increasing age. The most important neural substrate of associative memory is the hippocampus, a structure crucially implicated in the pathogenesis of Alzheimer's disease (AD). The main aim of this study was to compare neural correlates of associative memory in healthy aging and mild cognitive impairment (MCI), an at-risk state for AD. We used fMRI to investigate differences in brain activation and connectivity between young controls (n = 20), elderly controls (n = 32) and MCI patients (n = 21) during associative memory retrieval. We observed lower hippocampal activation in MCI patients than control groups during a face-name recognition task, and the magnitude of this decrement was correlated with lower associative memory performance. Further, increased activation in precentral regions in all older adults indicated a stronger involvement of the task positive network (TPN) with age. Finally, functional connectivity analysis revealed a stronger link of hippocampal and striatal components in older adults in comparison to young controls, regardless of memory impairment. In elderly controls, this went hand-in-hand with a stronger activation of striatal areas. Increased TPN activation may be linked to greater reliance on cognitive control in both older groups, while increased functional connectivity between the hippocampus and the striatum may suggest dedifferentiation, especially in elderly controls.

Correlates of impaired function in older women.

Science.gov (United States)

Ensrud, K E; Nevitt, M C; Yunis, C; Cauley, J A; Seeley, D G; Fox, K M; Cummings, S R

1994-05-01

To determine the factors associated with impaired function in older women. Cross-sectional analysis of baseline data collected for a multicenter, prospective study of risk factors for osteoporotic fractures. Four clinical centers in Portland, Oregon, Minneapolis, Minnesota, Baltimore, Maryland, and the Monongahela Valley, Pennsylvania. A total of 9,704 ambulatory, non-black women, aged 65 years and older, recruited from population-based listings. Independent variables, including demographic and historical information (medical conditions, health habits, and medications) and physiologic measures (anthropometry, blood pressure, mental status, vision, and neuromuscular performance) were obtained from a baseline questionnaire, interview, and examination. Measurement of function was assessed by self-reported ability to perform six physical and instrumental activities of daily living (ADL) and impaired function (dependent variable) was defined as difficulty performing three or more physical and instrumental ADLs. In order of decreasing strength of association, hip fracture, osteoarthritis, parkinsonism, slower walking speed, lower hip abduction force, back pain, greater Quetelet index, osteoporosis, former alcohol use, stroke, never drinking alcohol, lower mental status, use of anxiolytics and/or sleeping medications, inability to hold the tandem position, postural dizziness, cataracts, greater waist to hip ratio, lower physical activity in the past year, greater lifetime cigarette consumption, and lower grip strength were independently associated with impaired function in multivariate analyses. Age, low educational level, diabetes, current heavy alcohol use, postural hypotension, depth perception, and contrast sensitivity were not independent predictors. A combination of neuromuscular performance measures, including decreased muscle strength and impaired balance and gait, appeared to account for the effect of age on disability. A combination of many factors, including

L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

Science.gov (United States)

Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

2009-02-01

The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

Medicinal Δ(9) -tetrahydrocannabinol (dronabinol) impairs on-the-road driving performance of occasional and heavy cannabis users but is not detected in Standard Field Sobriety Tests.

Science.gov (United States)

Bosker, Wendy M; Kuypers, Kim P C; Theunissen, Eef L; Surinx, Anke; Blankespoor, Roos J; Skopp, Gisela; Jeffery, Wayne K; Walls, H Chip; van Leeuwen, Cees J; Ramaekers, Johannes G

2012-10-01

The acute and chronic effects of dronabinol [medicinal Δ(9) -tetrahydrocannabinol (THC)] on actual driving performance and the Standard Field Sobriety Test (SFST) were assessed. It was hypothesized that occasional users would be impaired on these tests and that heavy users would show less impairment due to tolerance. Double-blind, placebo-controlled, randomized, three-way cross-over study. Twelve occasional and 12 heavy cannabis users (14 males/10 females) received single doses of placebo, 10 and 20 mg dronabinol. Standard deviation of lateral position (SDLP; i.e. weaving) is the primary measure of road-tracking control. Time to speed adaptation (TSA) is the primary reaction-time measure in the car-following test. Percentage of impaired individuals on the SFST and subjective high on a visual analogue scale were secondary measures. Superiority tests showed that SDLP (P = 0.008) and TSA (P = 0.011) increased after dronabinol in occasional users. Equivalence tests demonstrated that dronabinol-induced increments in SDLP were bigger than impairment associated with BAC of 0.5 mg/ml in occasional and heavy users, although the magnitude of driving impairment was generally less in heavy users. The SFST did not discriminate between conditions. Levels of subjective high were comparable in occasional and heavy users. Dronabinol (medicinal tetrahydrocannabinol) impairs driving performance in occasional and heavy users in a dose-dependent way, but to a lesser degree in heavy users due possibly to tolerance. The Standard Field Sobriety Test is not sensitive to clinically relevant driving impairment caused by oral tetrahydrocannabinol. © 2012 The Authors. Addiction © 2012 Society for the Study of Addiction.

Neurobehavioral performance impairment in insomnia: relationships with self-reported sleep and daytime functioning.

Science.gov (United States)

Shekleton, Julia A; Flynn-Evans, Erin E; Miller, Belinda; Epstein, Lawrence J; Kirsch, Douglas; Brogna, Lauren A; Burke, Liza M; Bremer, Erin; Murray, Jade M; Gehrman, Philip; Lockley, Steven W; Rajaratnam, Shantha M W

2014-01-01

Despite the high prevalence of insomnia, daytime consequences of the disorder are poorly characterized. This study aimed to identify neurobehavioral impairments associated with insomnia, and to investigate relationships between these impairments and subjective ratings of sleep and daytime dysfunction. Cross-sectional, multicenter study. Three sleep laboratories in the USA and Australia. Seventy-six individuals who met the Research Diagnostic Criteria (RDC) for Primary Insomnia, Psychophysiological Insomnia, Paradoxical Insomnia, and/or Idiopathic Childhood Insomnia (44F, 35.8 ± 12.0 years [mean ± SD]) and 20 healthy controls (14F, 34.8 ± 12.1 years). N/A. Participants completed a 7-day sleep-wake diary, questionnaires assessing daytime dysfunction, and a neurobehavioral test battery every 60-180 minutes during an afternoon/evening sleep laboratory visit. Included were tasks assessing sustained and switching attention, working memory, subjective sleepiness, and effort. Switching attention and working memory were significantly worse in insomnia patients than controls, while no differences were found for simple or complex sustained attention tasks. Poorer sustained attention in the control, but not the insomnia group, was significantly associated with increased subjective sleepiness. In insomnia patients, poorer sustained attention performance was associated with reduced health-related quality of life and increased insomnia severity. We found that insomnia patients exhibit deficits in higher level neurobehavioral functioning, but not in basic attention. The findings indicate that neurobehavioral deficits in insomnia are due to neurobiological alterations, rather than sleepiness resulting from chronic sleep deficiency.

Cognitive impairment and driving safety.

Science.gov (United States)

Eby, David W; Molnar, Lisa J

2012-11-01

As the populations of many countries continue to age, cognitive impairment will likely become more common. Individuals with cognitive impairment pose special challenges for families, health professionals, driving safety professionals, and the larger community, particularly if these older adults depend on driving as their primary means of community mobility. It is vital that we continue to extend our knowledge about the driving behavior of individuals' with cognitive impairment, as well as try to develop effective means of screening and assessing these individuals for fitness to drive and help facilitate their transition to non-driving when appropriate. This special issue is intended to provide researchers and practitioners an opportunity to present the most recent research findings on driving-related issues among older adults with cognitive impairment. The issue contains 11 original contributions from seven countries. The topics covered by these papers are: crash risks; screening, assessment, and fitness to drive; driving performance using a driving simulator; and driving behaviors and driving-related decisions of people with cognitive impairments. Copyright © 2012. Published by Elsevier Ltd.

Insulin-Like Growth Factor I (IGF-1) Deficiency Ameliorates Sex Difference in Cardiac Contractile Function and Intracellular Ca2+ Homeostasis

Science.gov (United States)

Ceylan-Isik, Asli F.; Li, Qun; Ren, Jun

2011-01-01

Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (± dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR90), fura-fluorescence intensity (FFI) and intracellular Ca2+ clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ± dL/dt, longer TPS, TR90 and intracellular Ca2+ clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na+-Ca2+ exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca2+ regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca2+ regulation. PMID:21763763

Insulin-like growth factor I (IGF-1) deficiency ameliorates sex difference in cardiac contractile function and intracellular Ca(2+) homeostasis.

Science.gov (United States)

Ceylan-Isik, Asli F; Li, Qun; Ren, Jun

2011-10-10

Sex difference in cardiac contractile function exists which may contribute to the different prevalence in cardiovascular diseases between genders. However, the precise mechanisms of action behind sex difference in cardiac function are still elusive. Given that sex difference exists in insulin-like growth factor I (IGF-1) cascade, this study is designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on sex difference in cardiac function. Echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated including ventricular geometry, fractional shortening, peak shortening, maximal velocity of shortening/relengthening (±dL/dt), time-to-peak shortening (TPS), time-to-90% relengthening (TR(90)), fura-fluorescence intensity (FFI) and intracellular Ca(2+) clearance. Female C57 mice exhibited significantly higher plasma IGF-1 levels than their male counterpart. LID mice possessed comparably low IGF-1 levels in both sexes. Female C57 and LID mice displayed lower body, heart and liver weights compared to male counterparts. Echocardiographic analysis revealed larger LV mass in female C57 but not LID mice without sex difference in other cardiac geometric indices. Myocytes from female C57 mice exhibited reduced peak shortening, ±dL/dt, longer TPS, TR(90) and intracellular Ca(2+) clearance compared with males. Interestingly, this sex difference was greatly attenuated or abolished by IGF-1 deficiency. Female C57 mice displayed significantly decreased mRNA and protein levels of Na(+)-Ca(2+) exchanger, SERCA2a and phosphorylated phospholamban as well as SERCA activity compared with male C57 mice. These sex differences in Ca(2+) regulatory proteins were abolished or overtly attenuated by IGF-1 deficiency. In summary, our data suggested that IGF-1 deficiency may significantly attenuated or mitigate the sex difference in cardiomyocyte contractile function associated with intracellular Ca(2+) regulation. Copyright © 2011 Elsevier Ireland

Impairments of Motor Function While Multitasking in HIV.

Science.gov (United States)

Kronemer, Sharif I; Mandel, Jordan A; Sacktor, Ned C; Marvel, Cherie L

2017-01-01

Human immunodeficiency virus (HIV) became a treatable illness with the introduction of combination antiretroviral therapy (CART). As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND). The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing). Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction

Directory of Open Access Journals (Sweden)

Mouli Chakraborty

2015-12-01

Full Text Available Up to 80% of individuals with myotonic dystrophy type 1 (DM1 will develop cardiac abnormalities at some point during the progression of their disease, the most common of which is heart blockage of varying degrees. Such blockage is characterized by conduction defects and supraventricular and ventricular tachycardia, and carries a high risk of sudden cardiac death. Despite its importance, very few animal model studies have focused on the heart dysfunction in DM1. Here, we describe the characterization of the heart phenotype in a Drosophila model expressing pure expanded CUG repeats under the control of the cardiomyocyte-specific driver GMH5-Gal4. Morphologically, expression of 250 CUG repeats caused abnormalities in the parallel alignment of the spiral myofibrils in dissected fly hearts, as revealed by phalloidin staining. Moreover, combined immunofluorescence and in situ hybridization of Muscleblind and CUG repeats, respectively, confirmed detectable ribonuclear foci and Muscleblind sequestration, characteristic features of DM1, exclusively in flies expressing the expanded CTG repeats. Similarly to what has been reported in humans with DM1, heart-specific expression of toxic RNA resulted in reduced survival, increased arrhythmia, altered diastolic and systolic function, reduced heart tube diameters and reduced contractility in the model flies. As a proof of concept that the fly heart model can be used for in vivo testing of promising therapeutic compounds, we fed flies with pentamidine, a compound previously described to improve DM1 phenotypes. Pentamidine not only released Muscleblind from the CUG RNA repeats and reduced ribonuclear formation in the Drosophila heart, but also rescued heart arrhythmicity and contractility, and improved fly survival in animals expressing 250 CUG repeats.

Differences in Contractile Function of Myofibrils within Human Embryonic Stem Cell-Derived Cardiomyocytes vs. Adult Ventricular Myofibrils Are Related to Distinct Sarcomeric Protein Isoforms

Directory of Open Access Journals (Sweden)

Bogdan Iorga

2018-01-01

Full Text Available Characterizing the contractile function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs is key for advancing their utility for cellular disease models, promoting cell based heart repair, or developing novel pharmacological interventions targeting cardiac diseases. The aim of the present study was to understand whether steady-state and kinetic force parameters of β-myosin heavy chain (βMyHC isoform-expressing myofibrils within human embryonic stem cell-derived cardiomyocytes (hESC-CMs differentiated in vitro resemble those of human ventricular myofibrils (hvMFs isolated from adult donor hearts. Contractile parameters were determined using the same micromechanical method and experimental conditions for both types of myofibrils. We identified isoforms and phosphorylation of main sarcomeric proteins involved in the modulation of force generation of both, chemically demembranated hESC-CMs (d-hESC-CMs and hvMFs. Our results indicate that at saturating Ca2+ concentration, both human-derived contractile systems developed forces with similar rate constants (0.66 and 0.68 s−1, reaching maximum isometric force that was significantly smaller for d-hESC-CMs (42 kPa than for hvMFs (94 kPa. At submaximal Ca2+-activation, where intact cardiomyocytes normally operate, contractile parameters of d-hESC-CMs and hvMFs exhibited differences. Ca2+ sensitivity of force was higher for d-hESC-CMs (pCa50 = 6.04 than for hvMFs (pCa50 = 5.80. At half-maximum activation, the rate constant for force redevelopment was significantly faster for d-hESC-CMs (0.51 s−1 than for hvMFs (0.28 s−1. During myofibril relaxation, kinetics of the slow force decay phase were significantly faster for d-hESC-CMs (0.26 s−1 than for hvMFs (0.21 s−1, while kinetics of the fast force decay were similar and ~20x faster. Protein analysis revealed that hESC-CMs had essentially no cardiac troponin-I, and partially non-ventricular isoforms of some other sarcomeric proteins

Facial Recognition of Happiness Is Impaired in Musicians with High Music Performance Anxiety.

Science.gov (United States)

Sabino, Alini Daniéli Viana; Camargo, Cristielli M; Chagas, Marcos Hortes N; Osório, Flávia L

2018-01-01

Music performance anxiety (MPA) can be defined as a lasting and intense apprehension connected with musical performance in public. Studies suggest that MPA can be regarded as a subtype of social anxiety. Since individuals with social anxiety have deficits in the recognition of facial emotion, we hypothesized that musicians with high levels of MPA would share similar impairments. The aim of this study was to compare parameters of facial emotion recognition (FER) between musicians with high and low MPA. 150 amateur and professional musicians with different musical backgrounds were assessed in respect to their level of MPA and completed a dynamic FER task. The outcomes investigated were accuracy, response time, emotional intensity, and response bias. Musicians with high MPA were less accurate in the recognition of happiness ( p  = 0.04; d  = 0.34), had increased response bias toward fear ( p  = 0.03), and increased response time to facial emotions as a whole ( p  = 0.02; d  = 0.39). Musicians with high MPA displayed FER deficits that were independent of general anxiety levels and possibly of general cognitive capacity. These deficits may favor the maintenance and exacerbation of experiences of anxiety during public performance, since cues of approval, satisfaction, and encouragement are not adequately recognized.

Glucagon-like peptide-1 reduces contractile function and fails to boost glucose utilization in normal hearts in the presence of fatty acids.

Science.gov (United States)

Nguyen, T Dung; Shingu, Yasushige; Amorim, Paulo A; Schwarzer, Michael; Doenst, Torsten

2013-10-09

GLP-1 and exendin-4, which are used as insulin sensitizers or weight reducing drugs, were shown to improve glucose uptake in the heart. However, the direct effects of GLP-1 or exendin-4 on normal hearts in the presence of fatty acids, the main cardiac substrates, have never been investigated. We therefore assessed the effects of GLP-1 or exendin-4 on myocardial glucose uptake (GU), glucose oxidation (GO) and cardiac performance (CP) under conditions of fatty acid utilization. Rat hearts were perfused with only glucose (5 mM) or glucose (5 mM) plus oleate (0.4 mM) as substrates for 60 min. After 30 min, GLP-1 or exendin-4 (0.5 nM or 5 nM) was added. In the absence of oleate, GLP-1 increased both GU and GO. Exendin-4 increased GO but showed no effect on GU. Neither GLP-1 nor exendin-4 affected CP. However, when oleate was present, GLP-1 failed to stimulate glucose utilization and exendin-4 even decreased GU. Furthermore, now GLP-1 reduced CP. In contrast to prior reports, this negative inotropic effect could not be blocked by the protein kinase A inhibitor H-89. We then measured myocardial GO and CP in rats receiving a 4-week GLP-1 infusion. Interestingly, this chronic treatment resulted in a significant reduction in both GO and CP. Under the influence of oleate, GLP-1 reduces contractile function and fails to stimulate glucose utilization in normal hearts. Exendin-4 may acutely reduce cardiac glucose uptake but not contractility. We suggest advanced investigation of heart function and metabolism in patients treating with these peptides. © 2013.

Differential impairments underlying decision making in anorexia nervosa and bulimia nervosa: a cognitive modeling analysis.

Science.gov (United States)

Chan, Trista Wai Sze; Ahn, Woo-Young; Bates, John E; Busemeyer, Jerome R; Guillaume, Sebastien; Redgrave, Graham W; Danner, Unna N; Courtet, Philippe

2014-03-01

This study examined the underlying processes of decision-making impairments in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). We deconstructed their performance on the widely used decision task, the Iowa Gambling Task (IGT) into cognitive, motivational, and response processes using cognitive modeling analysis. We hypothesized that IGT performance would be characterized by impaired memory functions and heightened punishment sensitivity in AN, and by elevated sensitivity to reward as opposed to punishment in BN. We analyzed trial-by-trial data of IGT obtained from 224 individuals: 94 individuals with AN, 63 with BN, and 67 healthy comparison individuals (HC). The prospect valence learning model was used to assess cognitive, motivational, and response processes underlying IGT performance. Individuals with AN showed marginally impaired IGT performance compared to HC. Their performance was characterized by impairments in memory functions. Individuals with BN showed significantly impaired IGT performance compared to HC. They showed greater relative sensitivity to gains as opposed to losses than HC. Memory functions in AN were positively correlated with body mass index. This study identified differential impairments underlying IGT performance in AN and BN. Findings suggest that impaired decision making in AN might involve impaired memory functions. Impaired decision making in BN might involve altered reward and punishment sensitivity. Copyright © 2013 Wiley Periodicals, Inc.

Mechanisms Explaining Muscle Fatigue and Muscle Pain in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a Review of Recent Findings.

Science.gov (United States)

Gerwyn, Morris; Maes, Michael

2017-01-01

Here, we review potential causes of muscle dysfunction seen in many patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) such as the effects of oxidative and nitrosative stress (O&NS) and mitochondrial impairments together with reduced heat shock protein production and a range of metabolic abnormalities. Several studies published in the last few years have highlighted the existence of chronic O&NS, inflammation, impaired mitochondrial function and reduced heat shock protein production in many patients with ME/CFS. These studies have also highlighted the detrimental effects of chronically elevated O&NS on muscle functions such as reducing the time to muscle fatigue during exercise and impairing muscle contractility. Mechanisms have also been revealed by which chronic O&NS and or impaired heat shock production may impair muscle repair following exercise and indeed the adaptive responses in the striated muscle to acute and chronic increases in physical activity. The presence of chronic O&NS, low-grade inflammation and impaired heat shock protein production may well explain the objective findings of increased muscle fatigue, impaired contractility and multiple dimensions of exercise intolerance in many patients with ME/CFS.

Homocyst(e)ine impairs endocardial endothelial function.

Science.gov (United States)

Tyagi, S C; Smiley, L M; Mujumdar, V S

1999-12-01

Homocyst(e)ine injured vascular endothelium and modulated endothelial-dependent vascular function. Endothelium plays an analogous role in both the vessel and the endocardium. Therefore, we hypothesized that homocyst(e)ine modulated endocardial endothelium (EE) dependent cardiac function. The ex vivo cardiac rings from normal male Wistar-Kyoto rats were prepared. The contractile responses of left and right ventricular rings were measured in an isometric myobath, using different concentrations of CaCl2. The response was higher in the left ventricle than right ventricle and was elevated in endocardium without endothelium. The half effective concentration (EC50) and maximum tension generated by homocyst(e)ine were 10(6) and 5-fold lower than endothelin (ET) and angiotensin II (AII), respectively. However, in endothelial-denuded endocardium, homocyst(e)ine response was significantly increased (pine, and endothelial nitric oxide in EE function, cardiac rings were pretreated with AII (10(-10) M) or ET (10(-13) M) and then treated with homocyst(e)ine (10(-8) M). Results suggested that at these concentrations AII, ET, or homocyst(e)ine alone had no effect on cardiac contraction. However, in the presence of 10(-10) M AII or 10(-13) M ET, the cardiac contraction to homocyst(e)ine (10(-8) M) was significantly enhanced (pine. These results suggested that homocyst(e)ine impaired EE-dependent cardiac function and acted synergistically with AII and ET in enhancing the cardiac contraction.

S-glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans.

Science.gov (United States)

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-03-15

-glutathionylation of TnI(f) (latter examined only in toad). Following 40 min of cycling exercise in human subjects (at ∼60% peak oxygen consumption), TnI(f) in vastus lateralis muscle displayed a marked increase in S-glutathionylation (∼4-fold). These findings show that S-glutathionylation of TnI(f), most probably at Cys133, increases the Ca2+ sensitivity of the contractile apparatus, and that this occurs in exercising humans, with likely beneficial effects on performance.

Contractile Force of Human Extraocular Muscle: A Theoretical Analysis

Directory of Open Access Journals (Sweden)

Hongmei Guo

2016-01-01

Full Text Available Aim. The length-contractile force relationships of six human extraocular muscles (EOMs in primary innervations should be determined during eye movement modeling and surgery of clinical EOMs. This study aims to investigate these relationships. Method. The proposal is based on the assumption that six EOMs have similar constitutive relationships, with the eye suspended in the primary position. The constitutive relationships of EOMs are obtained by optimizing from previous experimental data and the theory of mechanical equilibrium using traditional model. Further, simulate the existing experiment of resistance force, and then compare the simulated results with the existing experimental results. Finally, the mechanical constitutive relationships of EOMs are obtained. Results. The results show that the simulated resistance forces from the other four EOMs except for the horizontal recti well agree with previous experimental results. Conclusion. The mechanical constitutive relationships of six EOMs in primary innervations are obtained, and the rationality of the constitutive relationships is verified. Whereafter, the active stress-strain relationships of the six EOMs in the primary innervations are obtained. The research results can improve the eye movement model to predict the surgical amounts of EOMs before EOM surgery more precisely.

Effects of lighting illuminance levels on stair negotiation performance in individuals with visual impairment.

Science.gov (United States)

Shaheen, Aliah F; Sourlas, Alexandros; Horton, Khim; McLean, Christopher; Ewins, David; Gould, David; Ghoussayni, Salim

2018-04-01

Stair-related falls of older people cause a substantial financial and social burden. Deterioration of the visual system amongst other factors put older people at a high risk of falling. Improved lighting is often recommended. The aim of this study was to investigate the effect of lighting illuminance on stair negotiation performance in older individuals with visual impairment. Eleven participants aged 60 or over with a vision of 6/18 or worse ascended and descended a staircase under: 50 lx, 100 lx, 200 lx, 300 lx and distributed 200 lx lighting. A motion capture system was used to measure movements of the lower limb. Clearance, clearance variability, temporal and spatial parameters and joint/segment kinematics were computed. There was no effect on clearance or clearance variability. Participants had lower speed, cadence, increased cycle time and stance time in the 50 lx compared to 300 lx and distributed 200 lx lighting in descent. The minimum hip angle in ascent was increased in the 200 lx lighting. Clearance was found to be moderately correlated with balance scores. Individuals with visual impairment adopt precautionary gait in dim lighting conditions. This does not always result in improvements in the parameters associated with risk of falling (e.g. clearance). Copyright © 2018 Elsevier Ltd. All rights reserved.

Motor Imagery Impairment in Postacute Stroke Patients

Directory of Open Access Journals (Sweden)

Niclas Braun

2017-01-01

Full Text Available Not much is known about how well stroke patients are able to perform motor imagery (MI and which MI abilities are preserved after stroke. We therefore applied three different MI tasks (one mental chronometry task, one mental rotation task, and one EEG-based neurofeedback task to a sample of postacute stroke patients (n=20 and age-matched healthy controls (n=20 for addressing the following questions: First, which of the MI tasks indicate impairment in stroke patients and are impairments restricted to the paretic side? Second, is there a relationship between MI impairment and sensory loss or paresis severity? And third, do the results of the different MI tasks converge? Significant differences between the stroke and control groups were found in all three MI tasks. However, only the mental chronometry task and EEG analysis revealed paresis side-specific effects. Moreover, sensitivity loss contributed to a performance drop in the mental rotation task. The findings indicate that although MI abilities may be impaired after stroke, most patients retain their ability for MI EEG-based neurofeedback. Interestingly, performance in the different MI measures did not strongly correlate, neither in stroke patients nor in healthy controls. We conclude that one MI measure is not sufficient to fully assess an individual’s MI abilities.

Effectiveness of Interventions to Address Visual and Visual-Perceptual Impairments to Improve Occupational Performance in Adults With Traumatic Brain Injury: A Systematic Review.

Science.gov (United States)

Berger, Sue; Kaldenberg, Jennifer; Selmane, Romeissa; Carlo, Stephanie

2016-01-01

Visual and visual-perceptual impairments occur frequently with traumatic brain injury (TBI) and influence occupational performance. This systematic review examined the effectiveness of interventions within the scope of occupational therapy to improve occupational performance for adults with visual and visual-perceptual impairments as a result of TBI. Medline, PsycINFO, CINAHL, OTseeker, and the Cochrane Database of Systematic Reviews were searched, and 66 full text articles were reviewed. Sixteen articles were included in the review. Strong evidence supports the use of scanning, limited evidence supports the use of adaptive strategies, and mixed evidence supports the use of cognitive interventions to improve occupational performance for adults with TBI. Evidence related to vision therapy varies on the basis of the specific intervention implemented. Although the strength of the research varied, implications are discussed for practice, education, and research. Copyright © 2016 by the American Occupational Therapy Association, Inc.

Valuing goodwill: not-for-profits prepare for annual impairment testing.

Science.gov (United States)

Heuer, Christian; Travers, Mary Ann K

2011-02-01

Accounting standards for valuing goodwill and intangible assets are becoming more rigorous for not-for-profit organizations: Not-for-profit healthcare organizations need to test for goodwill impairment at least annually. Impairment testing is a two-stage process: initial analysis to determine whether impairment exists and subsequent calculation of the magnitude of impairment. Certain "triggering" events compel all organizations--whether for-profit or not-for-profit--to perform an impairment test for goodwill or intangible assets.

Exercise-induced pulmonary haemorrhage impairs racing performance in Thoroughbred racehorses.

Science.gov (United States)

Morley, P S; Bromberek, J L; Saulez, M N; Hinchcliff, K W; Guthrie, A J

2015-05-01

Exercise-induced pulmonary haemorrhage (EIPH) occurs commonly in Thoroughbred racehorses worldwide. While EIPH is believed to be an important cause of impaired performance in these horses, there is limited evidence from sufficiently powered studies to evaluate this association. To evaluate whether EIPH is associated with finishing position, distance finished behind race winners and differences in race earning among Thoroughbred horses racing in South Africa. Prospective cross-sectional study. One thousand Thoroughbred horses racing in South Africa were enrolled prior to a single race and underwent tracheobronchoscopic examination within 2 h of racing. Three observers, blinded to the horses' identity and race performance, independently evaluated EIPH occurrence and severity using video recordings of the examination. Data were analysed using multivariable logistic and linear regression while controlling for important horse and race factors as potential confounding variables. Overall, 68% of horses had evidence of EIPH (grade ≥1). Horses without evidence of EIPH (severity grade 0), when compared with horses with any evidence of EIPH (grade ≥1), were >2 times more likely to win races (odds ratio = 2.3; 95% confidence interval 1.4-3.7; P = 0.001), finished an average of one length ahead of horses with EIPH (P = 0.03), and were 2.5 times more likely to be in the highest decile in race earnings (odds ratio = 2.5, 95% CI 1.5-4.1, PThoroughbred racehorses not medicated with furosemide and not using nasal dilator strips. These findings provide strong corroboration of previous research indicating that the occurrence of EIPH has a major impact on the ability of Thoroughbred racehorses to compete successfully as elite athletes. © 2014 EVJ Ltd.

Temperature effects on aerobic scope and cardiac performance of European perch (Perca fluviatilis).

Science.gov (United States)

Jensen, Denise Lyager; Overgaard, Johannes; Wang, Tobias; Gesser, Hans; Malte, Hans

2017-08-01

Several recent studies have highlighted how impaired cardiac performance at high temperatures and in hypoxia may compromise the capacity for oxygen transport. Thus, at high temperatures impaired cardiac capacity is proposed to reduce oxygen transport to a degree that lowers aerobic scope and compromises thermal tolerance (the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis). To investigate this hypothesis, we measured aerobic and cardiac performance of a eurythermal freshwater teleost, the European perch (Perca fluviatilis). Rates of oxygen consumption were measured during rest and activity at temperatures between 5°C and 27°C, and we evaluated cardiac function by in vivo measurements of heart rate and in vitro studies to determine contractility of myocardial strips. Aerobic scope increased progressively from 5°C to 21°C, after which it levelled off. Heart rate showed a similar response. We found little difference between resting and active heart rate at high temperature suggesting that increased cardiac scope during activity is primarily related to changes in stroke volume. To examine the effects of temperature on cardiac capacity, we measured isometric force development in electrically paced myocardial preparations during different combinations of temperature, pacing frequency, oxygenation and adrenergic stimulation. The force-frequency product increased markedly upon adrenergic stimulation at 21 and 27°C (with higher effects at 21°C) and the cardiac preparations were highly sensitive to hypoxia. These findings suggest that at (critically) high temperatures, cardiac output may diminish due to a decreased effect of adrenergic stimulation and that this effect may be further exacerbated if the heart becomes hypoxic. Hence cardiac limitations may contribute to the inability to increase aerobic scope at high temperatures in the European perch (Perca fluviatilis). Copyright © 2017 Elsevier Ltd. All rights reserved.

Intact and impaired conceptual memory processes in amnesia.

Science.gov (United States)

Keane, M M; Gabrieli, J D; Monti, L A; Fleischman, D A; Cantor, J M; Noland, J S

1997-01-01

To examine the status of conceptual memory processes in amnesia, a conceptual memory task with implicit or explicit task instructions was given to amnesic and control groups. After studying a list of category exemplars, participants saw category labels and were asked to generate as many exemplars as possible (an implicit memory task) or to generate exemplars that had been in the prior study list (an explicit memory task). After incidental deep or shallow encoding of exemplars, amnesic patients showed normal implicit memory performance (priming), a normal levels-of-processing effect on priming, and impaired explicit memory performance. After intentional encoding of exemplars, amnesic patients showed impaired implicit and explicit memory performance. Results suggest that although amnesic patients can show impairments on implicit and explicit conceptual memory tasks, their deficit does not generalize to all conceptual memory tasks.

Impaired visuospatial transformation but intact sequence processing in Parkinson disease.

Science.gov (United States)

Leek, E Charles; Kerai, Julie H; Johnston, Stephen J; Hindle, John V; Bracewell, R Martyn

2014-09-01

We examined whether visuospatial deficits in Parkinson disease (PD) can be explained by a domain-general, nonspatial impairment in the sequencing or serial chaining of mental operations. PD has been shown to be associated with impaired visuospatial processing, but the mechanisms of this impairment remain unclear. Thirteen patients with PD and 20 age-matched, neurologically normal controls performed a visuospatial grid navigation task requiring sequential spatial transformations. The participants also performed a control task of serial number subtraction designed to assess their nonvisuospatial sequencing. The tasks were matched in structure and difficulty. The patients were impaired on the visuospatial task but not in serial number subtraction. This finding suggests that visuospatial processing impairments in PD do not derive from a general impairment affecting sequencing or serial chaining. We argue that visuospatial deficits in PD result from impairments to spatial transformation routines involved in the computation of mappings between spatial locations. These routines are mediated by dopaminergic pathways linking the basal ganglia, prefrontal cortex, supplementary motor area, and parietal cortex.

Impairments of Motor Function While Multitasking in HIV

Directory of Open Access Journals (Sweden)

Cherie L. Marvel

2017-04-01

Full Text Available Human immunodeficiency virus (HIV became a treatable illness with the introduction of combination antiretroviral therapy (CART. As a result, patients with regular access to CART are expected to live decades with HIV. Long-term HIV infection presents unique challenges, including neurocognitive impairments defined by three major stages of HIV-associated neurocognitive disorders (HAND. The current investigation aimed to study cognitive and motor impairments in HIV using a novel multitasking paradigm. Unlike current standard measures of cognitive and motor performance in HIV, multitasking increases real-world validity by mimicking the dual motor and cognitive demands that are part of daily professional and personal settings (e.g., driving, typing and writing. Moreover, multitask assessments can unmask compensatory mechanisms, normally used under single task conditions, to maintain performance. This investigation revealed that HIV+ participants were impaired on the motor component of the multitask, while cognitive performance was spared. A patient-specific positive interaction between motor performance and working memory recall was driven by poor HIV+ multitaskers. Surprisingly, HAND stage did not correspond with multitask performance and a variety of commonly used assessments indicated normal motor function among HIV+ participants with poor motor performance during the experimental task. These results support the use of multitasks to reveal otherwise hidden impairment in chronic HIV by expanding the sensitivity of clinical assessments used to determine HAND stage. Future studies should examine the capability of multitasks to predict performance in personal, professional and health-related behaviors and prognosis of patients living with chronic HIV.

Localization of Impaired Kinesthetic Processing Post-stroke.

Science.gov (United States)

Kenzie, Jeffrey M; Semrau, Jennifer A; Findlater, Sonja E; Yu, Amy Y; Desai, Jamsheed A; Herter, Troy M; Hill, Michael D; Scott, Stephen H; Dukelow, Sean P

2016-01-01

Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects ( N = 142) and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke). The robotic exoskeleton measured subjects' ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects' mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common association with

Localization of impaired kinesthetic processing post-stroke

Directory of Open Access Journals (Sweden)

Jeffrey Michael Kenzie

2016-10-01

Full Text Available Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects (N=142 and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke. The robotic exoskeleton measured subjects’ ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects’ mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common

Cognitive impairment in COPD: a systematic review.

Science.gov (United States)

Torres-Sánchez, Irene; Rodríguez-Alzueta, Elisabeth; Cabrera-Martos, Irene; López-Torres, Isabel; Moreno-Ramírez, Maria Paz; Valenza, Marie Carmen

2015-01-01

The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD.

Cognitive impairment in COPD: a systematic review

Directory of Open Access Journals (Sweden)

Irene Torres-Sánchez

2015-04-01

Full Text Available The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD.

Acute lesions that impair affective empathy

Science.gov (United States)

Oishi, Kenichi; Hsu, John; Lindquist, Martin; Gottesman, Rebecca F.; Jarso, Samson; Crainiceanu, Ciprian; Mori, Susumu

2013-01-01

Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy—making inferences about how another person feels—engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy. PMID:23824490

Adaptation of motor unit contractile properties in rat medial gastrocnemius to treadmill endurance training: Relationship to muscle mitochondrial biogenesis.

Science.gov (United States)

Kryściak, Katarzyna; Majerczak, Joanna; Kryściak, Jakub; Łochyński, Dawid; Kaczmarek, Dominik; Drzymała-Celichowska, Hanna; Krutki, Piotr; Gawedzka, Anna; Guzik, Magdalena; Korostynski, Michał; Szkutnik, Zbigniew; Pyza, Elżbieta; Jarmuszkiewicz, Wiesława; Zoladz, Jerzy A; Celichowski, Jan

2018-01-01

This study aimed at investigating the effects of 2, 4 and 8 weeks of endurance training on the contractile properties of slow (S), fast fatigue resistant (FR) and fast fatigable (FF) motor units (MUs) in rat medial gastrocnemius (MG) in relation to the changes in muscle mitochondrial biogenesis. The properties of functionally isolated MUs were examined in vivo. Mitochondrial biogenesis was judged based on the changes in mitochondrial DNA copy number (mtDNA), the content of the electron transport chain (ETC) proteins and PGC-1α in the MG. Moreover, the markers of mitochondria remodeling mitofusins (Mfn1, Mfn2) and dynamin-like protein (Opa1) were studied using qPCR. A proportion of FR MUs increased from 37.9% to 50.8% and a proportion of FF units decreased from 44.7% to 26.6% after 8 weeks of training. The increased fatigue resistance, shortened twitch duration, and increased ability to potentiate force were found as early as after 2 weeks of endurance training, predominantly in FR MUs. Moreover, just after 2 weeks of the training an enhancement of the mitochondrial network remodeling was present as judged by an increase in expression of Mfn1, Opa1 and an increase in PGC-1α in the slow part of MG. Interestingly, no signs of intensification of mitochondrial biogenesis assessed by ETC proteins content and mtDNA in slow and fast parts of gastrocnemius were found at this stage of the training. Nevertheless, after 8 weeks of training an increase in the ETC protein content was observed, but mainly in the slow part of gastrocnemius. Concluding, the functional changes in MUs' contractile properties leading to the enhancement of muscle performance accompanied by an activation of signalling that controls the muscle mitochondrial network reorganisation and mitochondrial biogenesis belong to an early muscle adaptive responses that precede an increase in mitochondrial ETC protein content.

Sound localization in noise in hearing-impaired listeners.

Science.gov (United States)

Lorenzi, C; Gatehouse, S; Lever, C

1999-06-01

The present study assesses the ability of four listeners with high-frequency, bilateral symmetrical sensorineural hearing loss to localize and detect a broadband click train in the frontal-horizontal plane, in quiet and in the presence of a white noise. The speaker array and stimuli are identical to those described by Lorenzi et al. (in press). The results show that: (1) localization performance is only slightly poorer in hearing-impaired listeners than in normal-hearing listeners when noise is at 0 deg azimuth, (2) localization performance begins to decrease at higher signal-to-noise ratios for hearing-impaired listeners than for normal-hearing listeners when noise is at +/- 90 deg azimuth, and (3) the performance of hearing-impaired listeners is less consistent when noise is at +/- 90 deg azimuth than at 0 deg azimuth. The effects of a high-frequency hearing loss were also studied by measuring the ability of normal-hearing listeners to localize the low-pass filtered version of the clicks. The data reproduce the effects of noise on three out of the four hearing-impaired listeners when noise is at 0 deg azimuth. They reproduce the effects of noise on only two out of the four hearing-impaired listeners when noise is at +/- 90 deg azimuth. The additional effects of a low-frequency hearing loss were investigated by attenuating the low-pass filtered clicks and the noise by 20 dB. The results show that attenuation does not strongly affect localization accuracy for normal-hearing listeners. Measurements of the clicks' detectability indicate that the hearing-impaired listeners who show the poorest localization accuracy also show the poorest ability to detect the clicks. The inaudibility of high frequencies, "distortions," and reduced detectability of the signal are assumed to have caused the poorer-than-normal localization accuracy for hearing-impaired listeners.

Screening of Visually Impaired Children for Health Problems

Directory of Open Access Journals (Sweden)