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Sample records for human baroreflex responsiveness

  1. Human vagal baroreflex mechanisms in space.

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    Eckberg, Dwain L; Halliwill, John R; Beightol, Larry A; Brown, Troy E; Taylor, J Andrew; Goble, Ross

    2010-04-01

    Although astronauts' cardiovascular function is normal while they are in space, many have altered haemodynamic responses to standing after they return to Earth, including inordinate tachycardia, orthostatic hypotension, and uncommonly, syncope. Simulated microgravity impairs vagal baroreceptor-cardiac reflex function and causes orthostatic hypotension. Actual microgravity, however, has been shown to either increase, or not change vagal baroreflex gain. In this study, we tested the null hypothesis that spaceflight does not impair human baroreflex mechanisms. We studied 11 American and two German astronauts before, during (flight days 2-8), and after two, 9- and 10-day space shuttle missions, with graded neck pressure and suction, to elicit sigmoid, vagally mediated carotid baroreflex R-R interval responses. Baseline systolic pressures tended to be higher in space than on Earth (P = 0.015, repeated measures analysis of variance), and baseline R-R intervals tended to be lower (P = 0.049). Baroreceptor-cardiac reflex relations were displaced downward on the R-R interval axis in space. The average range of R-R interval responses to neck pressure changes declined from preflight levels by 37% on flight day 8 (P = 0.051), maximum R-R intervals declined by 14% (P = 0.003), and vagal baroreflex gain by 9% (P = 0.009). These measures returned to preflight levels by 7-10 days after astronauts returned to Earth. This study documents significant increases of arterial pressure and impairment of vagal baroreflex function in space. These results and results published earlier indicate that microgravity exposure augments sympathetic, and diminishes vagal cardiovascular influences.

  2. Effects of heat stress on baroreflex function in humans

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    Crandall, Craig G.; Cui, Jian; Wilson, Thad E.

    2003-01-01

    INTRODUCTION: Heat stress significantly reduces orthostatic tolerance in humans. The mechanism(s) causing this response remain unknown. The purpose of this review article is to present data pertaining to the hypothesis that reduced orthostatic tolerance in heat stressed individuals is a result of heat stress induced alterations in baroflex function. METHODS: In both normothermic and heat stressed conditions baroreflex responsiveness was assessed via pharmacological and non-pharmacological methods. In addition, the effects of heat stress on post-synaptic vasoconstrictor responsiveness were assessed. RESULTS: Generally, whole body heating did not alter baroreflex sensitivity defined as the gain of the linear portion of the baroreflex curve around the operating point. However, whole body heating shifted the baroreflex curve to the prevailing (i.e. elevated) heart rate and muscle sympathetic nerve activity. Finally, the heat stress impaired vasoconstrictor responses to exogenous administration of adrenergic agonists. CONCLUSION: Current data do not support the hypothesis that reduced orthostatic tolerance associated with heat stress in humans is due to impaired baroreflex responsiveness. This phenomenon may be partially due to the effects of heat stress on reducing vasoconstrictor responsiveness.

  3. System identification of baroreflex response to mild lower body negative pressure.

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    Aletti, Federico; Ferrario, Manuela; Xu, Da; Greaves, Danielle K; Shoemaker, Kevin J; Arbeille, Philippe; Cerutti, Sergio; Hughson, Richard L; Baselli, Giuseppe

    2011-01-01

    The effect of mild lower body negative pressure (LBNP) on baroreflex control of arterial blood pressure (ABP) has long been thought to affect cardiopulmonary baroreflex only, although recent studies have pointed out that arterial baroreceptors may be transiently unloaded too after the rapid onset of mild LBNP. This paper presents a spectral decomposition method for the black box identification of the contribution of arterial and cardiopulmonary baroreflexes to beat-by-beat variability of ABP in response to mild LBNP levels. The significant decrease of mean and diastolic arterial pressure and of the arterial baroreflex mediated contribution to overall variability of ABP which was found, suggested that the unloading of arterial baroreceptors may be reflected by an altered dynamic response of arterial baroreflex, too. In addition, arterial baroreflex mediated modulations were found to be the main player in the modulation of beat-by-beat fluctuations of ABP, while the role of cardiopulmonary baroreflex mediated responses appeared to contribute very little.

  4. Arterial baroreflex control of muscle sympathetic nerve activity under orthostatic stress in humans

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    Masashi eIchinose

    2012-08-01

    Full Text Available The mechanisms by which blood pressure is maintained against the orthostatic stress caused by gravity’s effect on the fluid distribution within the body are important issues in physiology, especially in humans who usually adopt an upright posture. Peripheral vasoconstriction and increased heart rate are major cardiovascular adjustments to orthostatic stress and comprise part of the reflex response elicited via the carotid sinus and aortic baroreceptors (arterial baroreflex: ABR and cardiopulmonary stretch receptors (cardiopulmonary baroreflex. In a series of studies, we have been characterizing the ABR-mediated regulation of cardiovascular hemodynamics and muscle sympathetic nerve activity (MSNA while applying orthostatic stress in humans. We have found that under orthostatic stress, dynamic carotid baroreflex responses are modulated as exemplified by the increases in the MSNA, blood pressure and heart rate responses elicited by carotid baroreflex unloading and the shorter period of MSNA suppression, comparable reduction and faster recovery of MAP and greater heart rate response to carotid baroreflex stimulation. Our results also show that ABR-mediated beat-to-beat control over burst incidence, burst strength and total MSNA is progressively modulated as orthostatic stress is increased until induction of syncope, and that the sensitivity of ABR control over the aforementioned MSNA variables is substantially reduced during the development of syncope. We suggest that in humans, the modulation of ABR function under orthostatic stress may be one of the mechanisms by which blood pressure is maintained and orthostatic hypotension limited, and impairment of ABR control over sympathetic vasomotor activity leads to the severe hypotension associated with orthostatic syncope.

  5. Neuronal modelling of baroreflex response to orthostatic stress

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    Samin, Azfar

    The accelerations experienced in aerial combat can cause pilot loss of consciousness (GLOC) due to a critical reduction in cerebral blood circulation. The development of smart protective equipment requires understanding of how the brain processes blood pressure (BP) information in response to acceleration. We present a biologically plausible model of the Baroreflex to investigate the neural correlates of short-term BP control under acceleration or orthostatic stress. The neuronal network model, which employs an integrate-and-fire representation of a biological neuron, comprises the sensory, motor, and the central neural processing areas that form the Baroreflex. Our modelling strategy is to test hypotheses relating to the encoding mechanisms of multiple sensory inputs to the nucleus tractus solitarius (NTS), the site of central neural processing. The goal is to run simulations and reproduce model responses that are consistent with the variety of available experimental data. Model construction and connectivity are inspired by the available anatomical and neurophysiological evidence that points to a barotopic organization in the NTS, and the presence of frequency-dependent synaptic depression, which provides a mechanism for generating non-linear local responses in NTS neurons that result in quantifiable dynamic global baroreflex responses. The entire physiological range of BP and rate of change of BP variables is encoded in a palisade of NTS neurons in that the spike responses approximate Gaussian 'tuning' curves. An adapting weighted-average decoding scheme computes the motor responses and a compensatory signal regulates the heart rate (HR). Model simulations suggest that: (1) the NTS neurons can encode the hydrostatic pressure difference between two vertically separated sensory receptor regions at +Gz, and use changes in that difference for the regulation of HR; (2) even though NTS neurons do not fire with a cardiac rhythm seen in the afferents, pulse

  6. 1/f Noise Outperforms White Noise in Sensitizing Baroreflex Function in the Human Brain

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    Soma, Rika; Nozaki, Daichi; Kwak, Shin; Yamamoto, Yoshiharu

    2003-08-01

    We show that externally added 1/f noise more effectively sensitizes the baroreflex centers in the human brain than white noise. We examined the compensatory heart rate response to a weak periodic signal introduced via venous blood pressure receptors while adding 1/f or white noise with the same variance to the brain stem through bilateral cutaneous stimulation of the vestibular afferents. In both cases, this noisy galvanic vestibular stimulation optimized covariance between the weak input signals and the heart rate responses. However, the optimal level with 1/f noise was significantly lower than with white noise, suggesting a functional benefit of 1/f noise for neuronal information transfer in the brain.

  7. Effects of repeated Valsalva maneuver straining on cardiac and vasoconstrictive baroreflex responses.

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    Convertino, Victor A; Ratliff, Duane A; Doerr, Donald F; Ludwig, David A; Muniz, Gary W; Benedetti, Erik; Chavarria, Jose; Koreen, Susan; Nguyen, Claude; Wang, Jeff

    2003-03-01

    We hypothesized that repeated respiratory straining maneuvers (repeated SM) designed to elevate arterial BPs (arterial baroreceptor loading) would acutely increase baroreflex responses. We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures), and changes in heart rate and diastolic BP after reductions in BP induced by a 15-s Valsalva maneuver in 10 female and 10 male subjects at 1, 3, 6, and 24 h after performing repeated SM. Baroreflex responses were also measured in each subject at 1, 3, 6, and 24 h at the same time on a separate day without repeated SM (control) in a randomized, counter-balanced cross-over experimental design. There was no statistical difference in carotid-cardiac and peripheral vascular baroreflex responses measured across time following repeated SM compared with the control condition. Integrated cardiac baroreflex response (deltaHR/ deltaSBP) measured during performance of a Valsalva maneuver was increased by approximately 50% to 1.1 +/- 0.2 bpm x mm Hg(-1) at 1 h and 1.0 +/- 0.1 bpm x mm Hg(-1) at 3 h following repeated SM compared with the control condition (0.7 +/- 0.1 bpm x mm Hg(-1) at both 1 and 3 h, respectively). However, integrated cardiac baroreflex response after repeated SM returned to control levels at 6 and 24 h after training. These responses did not differ between men and women. Our results are consistent with the notion that arterial baroreceptor loading induced by repeated SM increased aortic, but not carotid, cardiac baroreflex responses for as long as 3 h after repeated SM. We conclude that repeated SM increases cardiac baroreflex responsiveness which may provide patients, astronauts, and high-performance aircraft pilots with protection from development of orthostatic hypotension.

  8. Estrogen receptor-alpha mediates estrogen facilitation of baroreflex heart rate responses in conscious mice.

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    Pamidimukkala, Jaya; Xue, Baojian; Newton, Leslie G; Lubahn, Dennis B; Hay, Meredith

    2005-03-01

    Estrogen facilitates baroreflex heart rate responses evoked by intravenous infusion of ANG II and phenylephrine (PE) in ovariectomized female mice. The present study aims to identify the estrogen receptor subtype involved in mediating these effects of estrogen. Baroreflex responses to PE, ANG II, and sodium nitroprusside (SNP) were tested in intact and ovariectomized estrogen receptor-alpha knockout (ERalphaKO) with (OvxE+) or without (OvxE-) estrogen replacement. Wild-type (WT) females homozygous for the ERalpha(+/+) were used as controls. Basal mean arterial pressures (MAP) and heart rates were comparable in all the groups except the ERalphaKO-OvxE+ mice. This group had significantly smaller resting MAP, suggesting an effect of estrogen on resting vascular tone possibly mediated by the ERbeta subtype. Unlike the WT females, estrogen did not facilitate baroreflex heart rate responses to either PE or ANG II in the ERalphaKO-OvxE+ mice. The slope of the line relating baroreflex heart rate decreases with increases in MAP evoked by PE was comparable in ERalphaKO-OvxE- (-6.97 +/- 1.4 beats.min(-1).mmHg(-1)) and ERalphaKO-OvxE+ (-6.18 +/- 1.3) mice. Likewise, the slope of the baroreflex bradycardic responses to ANG II was similar in ERalphaKO-OvxE- (-3.87 +/- 0.5) and ERalphaKO-OvxE+(-2.60 +/- 0.5) females. Data suggest that estrogen facilitation of baroreflex responses to PE and ANG II is predominantly mediated by ERalpha subtype. A second important observation in the present study is that the slope of ANG II-induced baroreflex bradycardia is significantly blunted compared with PE in the intact as well as the ERalphaKO-OvxE+ females. We have previously reported that this ANG II-mediated blunting of cardiac baroreflexes is observed only in WT males and not in ovariectomized WT females independent of their estrogen replacement status. The present data suggest that in females lacking ERalpha, ANG II causes blunting of cardiac baroreflexes similar to males and may be

  9. Functional stochastic resonance in human baroreflex induced by 1/f-type noisy galvanic vestibular stimulation

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    Soma, Rika; Kwak, Shin; Yamamoto, Yoshiharu

    2003-05-01

    We hypothesized that 1/f noise is more beneficial than the conventional white noise in optimizing the brain's response to a weak input signal, and showed that externally added 1/f noise outperforms white noise in sensitizing human baroreflex centers in the brain. We examined the compensatory heart rate response to weak periodic signal introduced at the venous blood pressure receptor, while adding either 1/f or white noise with the same variance to the brain stem by electrically stimulating the bilateral vestibular afferents cutaneously. This stochastic galvanic vestibular stimulation, activating the vestibulo-sympathetic pathway in the brain stem, optimized covariance between weak input signals and the heart rate responses both with 1/f and white noise. Further, the optimal noise level with 1/f noise was significantly lower than that with white noise, suggesting the functional benefit of 1/f noise for the neuronal information transfer in the brain.

  10. The carotid baroreflex is reset following prolonged exercise in humans

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    Hart, E. C.; Rasmussen, P.; Secher, N. H.

    2010-01-01

    Alterations in the carotid baroreflex (CBR) control of arterial pressure may explain the reduction in arterial pressure and left ventricular (LV) function after prolonged exercise. We examined the CBR control of heart rate (HR) and mean arterial pressure (MAP), in addition to changes in LV function......, pre- to post-exercise....

  11. Baroreflex-mediated heart rate and vascular resistance responses 24 h after maximal exercise

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    Convertino, Victor A.

    2003-01-01

    INTRODUCTION: Plasma volume, heart rate (HR) variability, and stimulus-response relationships for baroreflex control of forearm vascular resistance (FVR) and HR were studied in eight healthy men after and without performing a bout of maximal exercise to test the hypotheses that acute expansion of plasma volume is associated with 1) reduction in baroreflex-mediated HR response, and 2) altered operational range for central venous pressure (CVP). METHODS: The relationship between stimulus (DeltaCVP) and vasoconstrictive reflex response (DeltaFVR) during unloading of cardiopulmonary baroreceptors was assessed with lower-body negative pressure (LBNP, 0, -5, -10, -15, -20 mm Hg). The relationship between stimulus (Deltamean arterial pressure (MAP)) and cardiac reflex response (DeltaHR) during loading of arterial baroreceptors was assessed with steady-state infusion of phenylephrine (PE) designed to increase MAP by 15 mm Hg alone and during application of LBNP (PE+LBNP) and neck pressure (PE+LBNP+NP). Measurements of vascular volume and autonomic baroreflex responses were conducted on two different test days, each separated by at least 1 wk. On one day, baroreflex response was tested 24 h after graded cycle exercise to volitional exhaustion. On another day, measurement of baroreflex response was repeated with no exercise (control). The order of exercise and control treatments was counterbalanced. RESULTS: Baseline CVP was elevated (P = 0.04) from a control value of 10.5 +/- 0.4 to 12.3 +/- 0.4 mm Hg 24 h after exercise. Average DeltaFVR/DeltaCVP during LBNP was not different (P = 0.942) between the exercise (-1.35 +/- 0.32 pru x mm Hg-1) and control (-1.32 +/- 0.36 pru x mm Hg-1) conditions. However, maximal exercise caused a shift along the reflex response relationship to a higher CVP and lower FVR. HR baroreflex response (DeltaHR/DeltaMAP) to PE+LBNP+NP was lower (P = 0.015) after maximal exercise (-0.43 +/- 0.15 beats x min-1 x mm Hg-1) compared with the control

  12. Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

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    Crandall, C. G.; Zhang, R.; Levine, B. D.

    2000-01-01

    The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.

  13. Protein malnutrition modifies medullary neuronal recruitment in response to intermittent stimulation of the baroreflex.

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    Rodrigues-Barbosa, Míriam Carmo; Carneiro, Cláudia Martins; de Oliveira, Lisandra Brandino; Silva, Fernanda Cacilda Santos; Xavier, Carlos Henrique; Gonçalves Fernandes, Luciano; Chianca, Deoclécio Alves

    2012-11-05

    Protein malnutrition after weaning changes the neurotransmission in neural pathways that organize cardiovascular reflexes in rats. The present study evaluates whether protein malnutrition alters the expression of c-fos protein (immediate-early gene expression) in central areas involved in the control of cardiovascular reflexes after intermittent stimulation of the baroreflex. The main nuclei we focused were paraventricular hypothalamus (PVH); nucleus tract solitarii (NTS); rostral ventromedial medulla (RVMM); rostral (RVLM) and caudal ventrolateral medulla (CVLM). Male Fisher rats at 28 days were submitted to two different isocaloric diets during the subsequent 35 days: control (CT) (15% protein) and malnourished (MN) (6% protein). thirtymin of intermittent (every 3 min) baroreflex stimulation was performed by infusing phenylephrine (Phe-0.25 mM) or, as control, 0.9% NaCl (Sal). Following ninety minutes, animals were anesthetized and perfused. The removed brains were sectioned (35 μm) and used for c-fos immunohistochemistry. Images were analyzed using the software Leica Q Win. Despite not altering the baseline MAP, malnutrition increased baseline HR and expression of c-fos in RVMM. Increases in c-fos expression after intermittent stimulation of baroreflex were evident in the PVH, medial NTS and CVLM in both dietary protocols. Current data further revealed a differential neuronal recruitment to stimulation of baroreflex in the caudal commissural and rostral NTS and RVLM of MN. We conclude that protein malnutrition modifies the cardiovascular control and the pattern of central response to baroreflex stimulation. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Baroreflex sensitivity as a determinant of responses to hydralazine in dogs.

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    Vidrio, H

    1983-01-01

    In order to evaluate the relation between hypotension induced by hydralazine and the resultant reflex tachycardia, as well as the role of baroreflex sensitivity in determining the magnitude of these responses, the drug was administered orally at a dose of 1 mg/kg to a group of trained conscious normotensive and renal hypertensive dogs. Responses were assessed by measuring blood pressure and heart rate for 8 hr after dosing and integrating the changes observed over time in order to obtain a mean value. Baroreflex gain was calculated as the ratio of heart rate to blood pressure responses. Hypotension was greater in hypertensives, whereas tachycardia was not different between groups. Gain was therefore smaller in hypertensives, but not uniformly so, a portion of these animals having values within the normotensive range. This high gain group responded with less hypotension and more tachycardia than did the low gain group. Differences in pressure and rate responses to repeated administration of hydralazine between the two groups were minimal. It is suggested that baroreflex gain, an innate individual characteristic, is an important determinant of acute pressure responses to hydralazine in dogs, hypertensive animals having less gain than normotensives and showing increased hypotensive responses. Gain appears not to be as important in determining the chronic effects of the drug.

  15. Baroreflex mechanisms and response to exercise in patients with heart disease.

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    Fukuma, Nagaharu; Kato, Kazuyo; Munakata, Kazuo; Hayashi, Hiroko; Kato, Yuko; Aisu, Noriko; Takahashi, Hiroshi; Mabuchi, Kousuke; Mizuno, Kyoichi

    2012-07-01

    Past reports showed that the baroreflex continuously regulates hemodynamics during exercise. However, it is still clinically unclear. If baroreflex mechanism is able to influence actually exercise cardiovascular control, baroreflex sympathetic and/or parasympathetic function relates to response to exercise. Therefore, we examined the relationship of heat rate changes to both blood pressure increment and decrement with tolerance and chronotropic response to peak exercise in patients with heart disease. In 25 male heart disease patients (60 ± 9 years) without decompensated heart failure, baroreceptor reflex sensitivity (BRS ms mmHg(-1) ) was measured by reflex heart rate responses to changes in blood pressure after phenylephrine (P-BRS) and nitroglycerin (N-BRS) injection, respectively. Symptom-limited treadmill exercise test was performed according to Bruce's protocol. (i) The absolute values of blood pressure change after the administrations were similar between the agents because the dosages of nitroglycerin and phenylephrine were set to equalize absolute changes in blood pressure. (ii) In this study population, the ratio of N-BRS to P-BRS was not significantly correlated with hypertension and diabetes mellitus. (iii) Exercise capacity (METs) (r= -0.626) and heart rate response to exercise per METs (r=0.670) was significantly related to N-BRS but not to P-BRS. We found that the abnormality of baroreflex function in the presence of blood pressure decrements can lead to insufficient capacity and easy sympathetic activation during exercise. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  16. A new non-invasive statistical method to assess the spontaneous cardiac baroreflex in humans.

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    Ducher, M; Fauvel, J P; Gustin, M P; Cerutti, C; Najem, R; Cuisinaud, G; Laville, M; Pozet, N; Paultre, C Z

    1995-06-01

    1. A new method was developed to evaluate cardiac baroreflex sensitivity. The association of a high systolic blood pressure with a low heart rate or the converse is considered to be under the influence of cardiac baroreflex activity. This method is based on the determination of the statistical dependence between systolic blood pressure and heart rate values obtained non-invasively by a Finapres device. Our computerized analysis selects the associations with the highest statistical dependence. A 'Z-coefficient' quantifies the strength of the statistical dependence. The slope of the linear regression, computed on these selected associations, is used to estimate baroreflex sensitivity. 2. The present study was carried out in 11 healthy resting male subjects. The results obtained by the 'Z-coefficient' method were compared with those obtained by cross-spectrum analysis, which has already been validated in humans. Furthermore, the reproducibility of both methods was checked after 1 week. 3. The results obtained by the two methods were significantly correlated (r = 0.78 for the first and r = 0.76 for the second experiment, P < 0.01). When repeated after 1 week, the average results were not significantly different. Considering individual results, test-retest correlation coefficients were higher with the Z-analysis (r = 0.79, P < 0.01) than with the cross-spectrum analysis (r = 0.61, P < 0.05). 4. In conclusion, as the Z-method gives results similar to but more reproducible than the cross-spectrum method, it might be a powerful and reliable tool to assess baroreflex sensitivity in humans.

  17. A quantitative method for studying human arterial baroreflexes

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    Eckberg, Dwain L.; Fritsch, Janice M.; Goble, Ross L.

    1991-01-01

    A new system is described that delivers precise, stereotyped pressure changes to the human neck and elicits neurally-mediated heart rate changes. The centerpiece of this system is a Silastic chamber that is strapped to the anterior neck. This chamber is connected to a stepping-motor-controlled bellows assembly. A strain-gauge transducer measures the intensity of pressure changes. The entire system is controlled by microprocessors, and both stimuli and responses are displayed on a digital oscilloscope. The end-product of this system is a reproducible baroreceptor stimulus-cardiac response relation that can be recorded rapidly and safely in astronauts in space.

  18. Development of artificial bionic baroreflex system.

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    Sunagawa, Kenji; Sugimachi, Masaru

    2010-01-01

    The baroreflex system is the fastest mechanism in the body to regulate arterial pressure. Because the neural system (i.e., autonomic nervous system) mediates the baroreflex and the system operates under the closed-loop condition, the quantitative dynamic characteristics of the baroreflex system remained unknown until recently despite the fact that a countless number of observational and qualitative studies had been conducted. In order to develop the artificial baroreflex system, i.e., the bionic baroreflex system, we first anatomically isolated the carotid sinuses to open the baroreflex loop and identified the open-loop transfer function of the baroreflex system using white noise pressure perturbations. We found that the baroreflex system is basically a lowpass filter and remarkably linear. As an actuator to implement the bionic baroreflex system, we then stimulated the sympathetic efferent nerves at various parts of the baroreflex loop and identified the transfer functions from the stimulation sites to systemic arterial pressure. We found that the actuator responses can be described remarkably well with linear transfer functions. Since transfer functions of the native baroreflex and of the actuator were identified, the controller that is required to reproduce the native baroreflex transfer function can be easily derived from those transfer functions. To examine the performance of bionic baroreflex system, we implemented it animal models of baroreflex failure. The bionic baroreflex system restored normal arterial pressure regulation against orthostatic stresses that is indistinguishable from the native baroreflex system.

  19. Impairment of the baroreflex control of human respiratory resistance with age

    Directory of Open Access Journals (Sweden)

    Tafil-Klawe M

    2009-12-01

    Full Text Available Abstract Background The mechanism responsible for the central baroreflex resetting with age are an area of limited knowledge. We previously demonstrated that in subjects aged above 50 the airway resistance did not change in response to baroreceptor activation, whereas in younger volunteers the airway resistance significantly decreased. Objective The aim of the present study was to evaluate the effect of carotid baroreceptor inactivation on the reflex change of respiratory resistance, in the course of aging. Materials and methods 80 healthy men, divided in four groups: aged 20-30 (Group I, 31-40 (Group II, 41-50 (Group III, and 51-60 (Group IV were included in the study. The selective inactivation of carotid baroreceptors was induced by generating a positive pressure of 40 mmHg for 5 s in two capsules placed bilaterally on the neck over the bifurcation of the carotid arteries. The oscillatory method (Siregnost FD5, Siemens was used to measure continuously respiratory resistance. Results Inactivation of carotid baroreceptors produced a short increase in respiratory resistance by 0.38 ± 0.01SE mbar/l/s, i.e., 21.7% above the resting level in Group I and by 0.25 ± 0.01 mbar/l/s in Group II. In the two older groups (III and IV respiratory resistance did not change in response to baroreceptors inactivation. Conclusions In humans aged above 40, carotid baroreceptors do not contribute to bronchodilator tone, which causes imbalance between the activities of upper airway and chest wall inspiratory muscles leading to a collapsing effect on the upper airway.

  20. Categorization of the hemodynamic response to hemodialysis: the importance of baroreflex sensitivity.

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    Chesterton, Lindsay J; Selby, Nicholas M; Burton, James O; Fialova, Jana; Chan, Cian; McIntyre, Chris W

    2010-01-01

    Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in hemodialysis (HD) patients. The baroreflex arc is under autonomic control and regulates blood pressure. This study aimed to investigate the contribution of impaired baroreflex sensitivity (BRS) to the pathophysiology of IDH. Thirty-four chronic HD (12 IDH-prone, 22 IDH-resistant) patients underwent BRS measurement during HD with relative blood volume monitoring. During analysis, patients were separated into four age-matched groups according to resting BRS>or=4.5 ms/mmHg and hemodynamic stability. Resting BRS was extremely heterogenous (geometric mean BRS 5.78+/-1.41 [range 1.76-41.41] ms/mmHg). Relative blood volume reduction was well matched in all groups (mean reduction in relative blood volume for all patients -6.74%+/-0.86%, P>0.05). Thirty-seven episodes of IDH occurred in the IDH prone, reduced BRS group. Patients with impaired resting BRS and prone to IDH had markedly different responses to HD as compared to the preserved BRS group, but the total peripheral resistance response was significantly lower than in the IDH-resistant patients (15.9%+/-2.1% vs. 42.4%+/-3.0%, respectively, P<0.001). In those patients prone to IDH and with impaired resting BRS, percentage reduction in cardiac output at the end of HD highly correlated with reduction in relative blood volume (r=0.94, P=0.006). Hypotension during dialysis may be an important source of recurrent cardiac injury and early recognition of those patients prone to relative symptomatic and asymptomatic hypotension remains important. Impaired resting BRS and recognition of a suboptimal peripheral pressor response, appear to predict those patients most likely to undergo hemodynamic instability and may assist in the pursuit of this elusive goal.

  1. Left ventricular, systemic arterial, and baroreflex responses to ketamine and TEE in chronically instrumented monkeys

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    Koenig, S. C.; Ludwig, D. A.; Reister, C.; Fanton, J. W.; Ewert, D.; Convertino, V. A.

    2001-01-01

    Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

  2. Renal responses to long-term carotid baroreflex activation therapy in patients with drug-resistant hypertension.

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    Alnima, Teba; de Leeuw, Peter W; Tan, Frans E S; Kroon, Abraham A

    2013-06-01

    Carotid baroreflex activation has been demonstrated to provide enduring reductions in arterial blood pressure. The aim of this study was to investigate the effect of long-term therapy on renal function. A total of 322 patients were enrolled in the Rheos Pivotal Trial. Group 1 consisted of 236 patients who started baroreflex activation therapy 1 month after device implantation, whereas in the 86 patients from group 2 the device was activated 6 months later. Serum creatinine and urine albumin/creatinine ratio were collected at screening (before device activation), and at months 6 and 12. Multilevel statistical analyses were adjusted for various covariables. Serum creatinine increased from 78 to 84 μmol/L, and glomerular filtration rate decreased from 92 to 87 mL/min per 1.73 m(2) in group 1 at month 6 (Pblood pressure reduction seemed to be significantly related to the change in glomerular filtration rate in both groups. Albumin/creatinine ratio did not change in both groups during follow-up. In conclusion, baroreflex activation therapy in hypertensive patients is associated with an initial mild decrease in glomerular filtration rate, which may be considered as a normal hemodynamic response to the drop in blood pressure. Long-term treatment does not result in further decrease in renal function, indicating baroreflex activation as a safe and effective therapy.

  3. Baroreflexes of the rat. IV. ADN-evoked responses at the NTS.

    Science.gov (United States)

    Tang, Xiaorui; Dworkin, Barry R

    2007-12-01

    In a long-term (7-21 days) neuromuscular blocked (NMB) rat preparation, using precise single-pulse aortic depressor nerve (ADN) stimulation and stable chronic evoked response (ER) recordings from the dorsal-medial solitary nucleus (dmNTS), two different response patterns were observed: continuous and discrete. For the continuous pattern, activity began approximately 3 ms after the stimulus and persisted for 45 ms; for the discrete pattern, two complexes were separated by a gap from approximately 17 to 25 ms. The early complex was probably transmitted via A-fibers: it had a low stimulus current threshold and an average conduction velocity (CV) of 0.58-5.5 m/s; the high threshold late (HTL) complex had a CV = 0.26-0.58 m/s. The average stimulus amplitude-ER magnitude transduction curves for the A and HTL complexes were sigmoidal. For individual rats, in the linear range, mean r2 = 0.96 +/- 0.03 for both complexes. The average stimulus amplitude vs. the systolic blood pressure change (delta sBP) transduction curve was also approximately linear; however, for individual rats, the relationship was not consistently reliable: mean r2 = 0.48 +/- 0.19. Approximately 90% of recording sites had respiratory, and 50% had cardiac synchronism. The NMB preparation is useful for studying central baroreflex mechanisms that operate on time scales of days or weeks, such as adaptation and other kinds of neural plasticity.

  4. Baroreflex Function in Rats after Simulated Microgravity

    Science.gov (United States)

    Hasser, Eileen M.

    1997-01-01

    Prolonged exposure of humans to decreased gravitational forces during spaceflight results in a number of adverse cardiovascular consequences, often referred to as cardiovascular deconditioning. Prominent among these negative cardiovascular effects are orthostatic intolerance and decreased exercise capacity. Rat hindlimb unweighting is an animal model which simulates weightlessness, and results in similar cardiovascular consequences. Cardiovascular reflexes, including arterial and cardiopulmonary baroreflexes, are required for normal adjustment to both orthostatic challenges and exercise. Therefore, the orthostatic intolerance and decreased exercise capacity associated with exposure to microgravity may be due to cardiovascular reflex dysfunction. The proposed studies will test the general hypothesis that hindlimb unweighting in rats results in impaired autonomic reflex control of the sympathetic nervous system. Specifically, we hypothesize that the ability to reflexly increase sympathetic nerve activity in response to decreases in arterial pressure or blood volume will be blunted due to hindlimb unweighting. There are 3 specific aims: (1) To evaluate arterial and cardiopulmonary baroreflex control of renal and lumbar sympathetic nerve activity in conscious rats subjected to 14 days of hindlimb unweighting; (2) To examine the interaction between arterial and cardiopulmonary baroreflex control of sympathetic nerve activity in conscious hindlimb unweighted rats; (3) to evaluate changes in afferent and/or central nervous system mechanisms in baroreflex regulation of the sympathetic nervous system. These experiments will provide information related to potential mechanisms for orthostatic and exercise intolerance due to microgravity.

  5. The role of the cholinergic system of the bed nucleus of the stria terminalis on the cardiovascular responses and the baroreflex modulation in rats.

    Science.gov (United States)

    Nasimi, Ali; Hatam, Masoumeh

    2011-04-22

    The bed nucleus of the stria terminalis (BST) is a limbic structure involved in cardiovascular regulation and modulation of responses to stress. The BST contains high levels of muscarinic receptors. This study was performed to find the effects of cholinergic system of the BST on the cardiovascular regulation and the baroreflex modulation in rats. Drugs (50-100nl) were microinjected into the BST of 53 urethane anesthetized male rats. The mean arterial pressure and heart rate changes were measured. The baroreflex gain was evaluated by finding the slope of the reflex bradycardia in response to increases in mean arterial pressure due to phenylephrine injection (i.v.). We found that microinjection of acetylcholine (3 and 6nmol/50nl) into the BST increased mean arterial pressure and had no effect on heart rate. Local microinjection of homatropine abolished the effect of Ach on the cardiovascular responses indicating involvement of muscarinic receptors. Local injection of homatropine did not affect the reflexive bradycardia. Local injection of acetylcholine decreased the slope of the reflexive bradycardia indicating that Ach system of the BST inhibits the baroreflex. Acute ablation of the BST by cobalt chloride also significantly decreased the slope, indicating the excitatory action of the BST on the baroreflex parasympathetic component. In conclusion, we showed for the first time that microinjection of acetylcholine into the BST evokes a pressor response by activating the local muscarinic receptors. Release of Ach into the BST, probably during stress, inhibits the baroreflex, but with no stress, the BST facilitates the baroreflex. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans

    Science.gov (United States)

    Cui, J.; Wilson, T. E.; Shibasaki, M.; Hodges, N. A.; Crandall, C. G.

    2001-01-01

    To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

  7. Diminished baroreflex control of heart rate responses in otoconia-deficient C57BL/6JEi head tilt mice.

    Science.gov (United States)

    Xue, Baojian; Skala, Karl; Jones, Timothy A; Hay, Meredith

    2004-08-01

    The maintenance of stable blood pressure during postural changes is known to involve integration of vestibular and cardiovascular central regulatory mechanisms. Sensory activity in the vestibular system plays an important role in cardiovascular regulation. The purpose of this study was to determine the role of vestibular gravity receptors in normal baroreflex function. Baroreflex heart rate (HR) responses to changes in blood pressure (BP) in otoconia-deficient head tilt (het) mice (n = 8) were compared with their wild-type littermates (n = 12). The study was carried out in conscious male mice chronically implanted with arterial and venous catheters for recording BP and HR and for the infusion of vasoactive drugs. Resting HR was higher in the het mice (661 +/- 13 beats/min) than in the wild-type mice (579 +/- 20 beats/min). BP was comparable in the het (113 +/- 4 mmHg) and wild-type mice (104 +/- 4 mmHg). The slopes of reflex decreases in HR in response to phenylephrine (PE) were blunted in the het mice (-5.5 +/- 1.5 beats x min(-1) x mmHg(-1)) compared with the wild-type mice (-8.5 +/- 0.9 beats x min(-1) x mmHg(-1)). Likewise, reflex tachycardic responses to decreases in BP with sodium nitroprusside (SNP) were significantly blunted in the het mice (-0.8 +/- 0.3 beats x min(-1) x mmHg(-1)) versus the wild-type mice (-2.2 +/- 0.6 beats x min(-1) x mmHg(-1)). Frequency-domain analysis of the HR variability suggests that under resting conditions, parasympathetic contribution was lower in the het versus wild-type mice. Mapping of the expression of immediate-early gene product, c-Fos, in forebrain and brain stem nuclei in response to a BP challenge showed no differences between the wild-type and het mice. These results suggest that tonic activity of gravity receptors modulates and is required for normal function of the cardiac baroreflexes.

  8. A single inhalation exposure to acrolein desensitizes baroreflex responsiveness in Wistar-Kyoto and Spontaneously Hypertensive rats.

    Science.gov (United States)

    Arterial baroreflex is one of the body's homeostatic mechanisms that regulate blood pressure (BP) by changing heart rate (HR) and vasoconstriction. Increases in BP reflexively cause HR to decrease, whereas decreases in BP depress the baroreflex and cause HR to rise. As such, baro...

  9. Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

    Science.gov (United States)

    Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

    2002-01-01

    The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.

  10. Baroreflexes of the rat. V. Tetanus-induced potentiation of ADN A-fiber responses at the NTS.

    Science.gov (United States)

    Tang, Xiaorui; Dworkin, Barry R

    2007-12-01

    In a long-term neuromuscular blocked (NMB) rat preparation, tetanic stimulation of the aortic depressor nerve (ADN) enhanced the A-fiber evoked responses (ERs) in the cardiovascular region, the nucleus of the solitary tract (dmNTS). The potentiation persisted for at least several hours and may be a mechanism for adaptive adjustment of the gain of the baroreflex, with functional implications for blood pressure regulation. Using a capacitance electrode, we selectively stimulated A-fibers and acquired a stable 10-h "A-fiber only" ER baseline at the dmNTS. Following baseline, an A+C-fiber activating tetanus was applied to the ADN. The tetanus consisted of 1,000 "high current" pulses (10 trains; 300 mus, 100 Hz, 1 s), with intertrain interval of 9 s. A 10-h A-fiber only posttetanic test phase repeated the stimulus pattern of the baseline. Fourteen tetanus experiments were done in 12 rats. Compared with the baseline before tetanus, the A-fiber ER magnitudes of posttetanus hours were larger [F(13, 247) = 3.407, P ADN A+C fiber-activating tetanus produced increases in the magnitude of the A-fiber ERs in the dmNTS that persisted for several hours. In an additional rat, application of an NMDA receptor antagonist, prior to the tetanus, blocked the potentiation effect. The stimulus protocols, magnitude and duration of the effect, and pharmacology resemble associative long-term potentiation (LTP).

  11. Influence of menstrual cycle phase on muscle metaboreflex control of cardiac baroreflex sensitivity, heart rate and blood pressure in humans.

    Science.gov (United States)

    Hartwich, Doreen; Aldred, Sarah; Fisher, James P

    2013-01-01

    We sought to determine whether menstrual cycle phase influences muscle metaboreflex control of spontaneous cardiac baroreflex sensitivity (cBRS), blood pressure (BP) and heart rate (HR). Twenty-three young women not taking oral contraceptives were studied during the early (EF; low oestrogen, low progesterone) and late follicular menstrual phases (LF; high oestrogen, low progesterone). Protocol 1 consisted of leg cycling at low (21 ± 2 W) and moderate workloads (71 ± 3 W) in free-flow conditions and with partial flow restriction (bilateral thigh-cuff inflation at 100 mmHg) to activate the muscle metaboreflex. Protocol 2 consisted of rhythmic hand-grip exercise with incremental upper arm-cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post-exercise ischaemia. Leg cycling decreased cBRS (EF, 20 ± 5, 6 ± 1 and 1 ± 0.1 ms mmHg(-1); and LF, 19 ± 3, 6 ± 0.4, 1 ± 0.1 ms mmHg(-1) during rest, low- and moderate-intensity leg cycling, respectively) and increased HR in an intensity-dependent manner, while BP remained unchanged. Partial flow restriction during leg cycling decreased cBRS, and increased HR and BP. During post-exercise ischaemia, HR and BP remained elevated, while cBRS remained suppressed (EF, 4.2 ± 0.6 ms mmHg(-1); and LF, 4.7 ± 0.5 ms mmHg(-1); P < 0.05 versus rest). Cardiac baroreflex sensitivity was unchanged during hand-grip with and without partial flow restriction and post-exercise ischaemia. No differences in cBRS, HR or BP responses were observed between EF and LF at any time during either protocol. These data indicate that endogenous fluctuations in oestrogen between the EF and LF phases of the menstrual cycle do not influence muscle metaboreflex control of cBRS, BP or HR in young women.

  12. Spontaneous baroreflex sensitivity

    DEFF Research Database (Denmark)

    Barthel, Petra; Bauer, Axel; Müller, Alexander;

    2012-01-01

    Low baroreflex sensitivity (BRS) indicates poor prognosis after acute myocardial infarction. Noninvasive BRS assessment is complicated by nonstationarities and noise in electrocardiogram and pressure signals. Phase-rectified signal averaging is a novel signal processing technology overcoming...

  13. Reductions in carotid chemoreceptor activity with low-dose dopamine improves baroreflex control of heart rate during hypoxia in humans.

    Science.gov (United States)

    Mozer, Michael T; Holbein, Walter W; Joyner, Michael J; Curry, Timothy B; Limberg, Jacqueline K

    2016-07-01

    The purpose of the present investigation was to examine the contribution of the carotid body chemoreceptors to changes in baroreflex control of heart rate with exposure to hypoxia. We hypothesized spontaneous cardiac baroreflex sensitivity (scBRS) would be reduced with hypoxia and this effect would be blunted when carotid chemoreceptor activity was reduced with low-dose dopamine. Fifteen healthy adults (11 M/4 F) completed two visits randomized to intravenous dopamine or placebo (saline). On each visit, subjects were exposed to 5-min normoxia (~99% SpO2), followed by 5-min hypoxia (~84% SpO2). Blood pressure (intra-arterial catheter) and heart rate (ECG) were measured continuously and scBRS was assessed by spectrum and sequence methodologies. scBRS was reduced with hypoxia (P dopamine (P dopamine (P dopamine did not attenuate the decrease in baroreflex sensitivity to falling pressures (scBRS "down-down"; P > 0.05). Present findings are consistent with a reduction in scBRS with systemic hypoxia. Furthermore, we show this effect is partially mediated by the carotid body chemoreceptors, given the fall in scBRS is attenuated when activity of the chemoreceptors is reduced with low-dose dopamine. However, the improvement in scBRS with dopamine appears to be specific to rising blood pressures. These results may have important implications for impairments in baroreflex function common in disease states of acute and/or chronic hypoxemia, as well as the experimental use of dopamine to assess such changes.

  14. Carotid Baroreflex Function During Prolonged Exercise

    Science.gov (United States)

    Raven, P. B.

    1999-01-01

    Astronauts are often required to work (exercise) at moderate to high intensities for extended periods while performing extra-vehicular activities (EVA). Although the physiologic responses associated with prolonged exercise have been documented, the mechanisms involved in blood pressure regulation under these conditions have not yet been fully elucidated. An understanding of this issue is pertinent to the ability of humans to perform work in microgravity and complies with the emphasis of NASA's Space Physiology and Countermeasures Program. Prolonged exercise at a constant workload is know to result in a progressive decrease in mean arterial pressure (MAP) concomitant with a decrease in stroke volume and a compensatory increase in heart rate. The continuous decrease in MAP during the exercise, which is related to the thermoregulatory redistribution of circulating blood volume to the cutaneous circulation, raises the question as to whether there is a loss of baroreflex regulation of arterial blood pressure. We propose that with prolongation of the exercise to 60 minutes, progressive increases on central command reflect a progressive upward resetting of the carotid baroreflex (CBR) such that the operating point of the CBR is shifted to a pressure below the threshold of the reflex rendering it ineffectual in correcting the downward drift in MAP. In order to test this hypothesis, experiments have been designed to uncouple the global hemodynamic response to prolonged exercise from the central command mediated response via: (1) continuous maintenance of cardiac filling volume by intravenous infusion of a dextran solution; and (2) whole body surface cooling to counteract thermoregulatory cutaneous vasodialation. As the type of work (exercise) performed by astronauts is inherently arm and upper body dependent, we will also examine the physiologic responses to prolonged leg cycling and arm ergometry exercise in the supine positions with and without level lower body negative

  15. Resetting of the carotid arterial baroreflex during dynamic exercise in humans

    DEFF Research Database (Denmark)

    Norton, K H; Boushel, Robert Christopher; Andersen, Line Strange

    1999-01-01

    alone was performed at 50 and 75% VO(2 max), and L exercise combined with arm (A) exercise (L + A) was performed at 75 and 100% VO(2 max). O(2) consumption and heart rate (HR) increased in direct relation with the increases in exercise intensity. The threshold and saturation pressures of the carotid.......07). Similar changes were observed for the carotid-vasomotor reflex. In addition, as exercise intensity increased, the operating point (the prestimulus blood pressure) of the CBR was significantly relocated further from the centering point (G(max)) of the stimulus-response curve and was at threshold during 100......% VO(2 max). These findings identify the continuous classic rightward and upward resetting of the CBR, without a change in G(max), during increases in dynamic exercise intensity to maximal effort....

  16. Dose-response relationship of baroreflex sensitivity and heart rate variability to individually-tailored exercise training in patients with heart failure.

    Science.gov (United States)

    Iellamo, Ferdinando; Manzi, Vincenzo; Caminiti, Giuseppe; Sposato, Barbara; Massaro, Michele; Cerrito, Anna; Rosano, Giuseppe; Volterrani, Maurizio

    2013-06-20

    Heart Rate Variability (HRV) and Baroreflex Sensitivity (BRS) are impaired in patients with Chronic Heart Failure (CHF) and carry negative prognosis. Exercise training improves these parameters. However, the relationship between exercise training with HRV and BRS has been investigated without regard for individual training loads. We tested the hypothesis that in CHF patients changes in HRV and BRS are dose-response related to individual volume/intensity training load (TL). Twenty patients with stable postinfarction CHF under optimal medical treatment were randomized to either aerobic continuous training (ACT) or aerobic interval training (AIT) for 12weeks. Individualized TL was monitored by the Training Impulses (TRIMPi) method, which was determined using the individual HR and lactate profiling determined during a treadmill test at baseline. HRV (standard deviation of mean R-R interval) and BRS were assessed at rest and 3weeks apart, throughout the study. HRV, BRS and R-R interval increased significantly with training, being very highly correlated to the dose of exercise with a second-order regression model (r(2) ranged from 0.75 to 0.96; Pincrease in functional capacity. No significant differences were detected between ACT and AIT in any variable. These results suggest that improvements in HRV and BRS by exercise training in CHF patients are dose related to TL in a non-linear fashion on an individual basis, with optimal results at moderate doses of exercise. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. [Baroreflex failure after chemodectoma resection].

    Science.gov (United States)

    Gómez Esteban, J C; Boyero, S; Fernández, C; Sagasta, A; Pérez, T; Velasco, F; Allue, I; Lezcano, E; Zarranz, J J

    2004-10-01

    Baroreflex failure after chemodectoma resection We present a case of baroreflex failure secondary to a unilateral injury of the glossopharyngeal nerve. The patient was operated for a left-sided chemodectoma in the carotid body. Some months after surgery she started to report presyncopal episodes exacerbated by mental stress and when standing up. During these episodes, the patient presented hypertensive crises and tachycardia. However, blood pressure was below normal ranges at rest. The diagnosis was baroreflex failure secondary to unilateral injury of the glossopharyngeal nerve. The case reported herein illustrates the fact that the presence of a bilateral injury is not essential for the occurrence of this disorder.

  18. Comparison of Baroreflex Sensitivity to Fall and Rise in Blood Pressure Induced by the Valsalva Maneuver

    Science.gov (United States)

    Wada, Naoki; Singer, Wolfgang; Gehrking, Tonette L.; Sletten, David M.; Schmelzer, James D.; Low, Phillip A.

    2014-01-01

    The baroreflex plays a key role in human blood pressure (BP) regulation. Its efferent limb consists of a vagal and a sympathetic component. The Valsalva maneuver is widely used to quantify vagal baroreflex function (vagal baroreflex sensitivity, BRS_vagal), but most studies have focused on the R-R interval response to BP decrement, even though the subsequent response to an increment in BP is important and different. We sought to evaluate if BRS_vagal can be determined from the rise in BP during phase III-IV of the Valsalva maneuver (BRSvagalinc), to assess the association between BRSvagalinc and BRS_vagal derived from the preceeding BP decrement (BRSvagaldec), and to validate BRSvagalinc as index of autonomic function. We studied patients with severe autonomic failure (n=49, 25 female), mild autonomic failure (n=25, 11 female), and matched normal controls (n=29, 15 female). BRSvagalinc and BRSvagaldec were calculated as the regression slope of R-R interval and systolic BP during phase III-IV and early phase II of the Valsalva maneuver, respectively, and compared with other autonomic indices across groups. BRSvagalinc could be calculated in all subjects and correlated highly with BRSvagaldec (r=0.72, p<0.001). BRSvagalinc also significantly correlated with BP changes during phase II and IV of the Valsalva maneuver and sympathetic barosensitivity. BRSvagalinc was significantly different between groups, being highest in controls and lowest in patients with severe autonomic failure. Vagal BRS, determined by relating R-R interval to BP increase following phase III, is a valuable autonomic index, provides additional information about vagal baroreflex function, and reflects overall severity of autonomic failure. PMID:24597842

  19. Baroreflex control of renal sympathetic nerve activity and heart rate in near-term fetal sheep.

    Science.gov (United States)

    Booth, Lindsea C; Gunn, Alistair J; Malpas, Simon C; Barrett, Carolyn J; Davidson, Joanne O; Guild, Sarah-Jane; Bennet, Laura

    2011-08-01

    Late preterm infants, born between 34 and 36 weeks gestation, have significantly higher morbidity than neonates born at full term, which may be partly related to reduced sensitivity of the arterial baroreflex. The present study assessed baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in near-term fetal sheep at 123 ± 1 days gestation. At this age, although fetuses are not fully mature in some respects (term is 147 days), sleep-state cycling is established [between high-voltage, low-frequency (HV) and low-voltage, high-frequency (LV) sleep], and neural myelination is similar to the term human infant. Fetal sheep were instrumented to record blood pressure (BP), HR (n = 15) and RSNA (n = 5). Blood pressure was manipulated using vasoactive drugs, phenylephrine and sodium nitroprusside. In both HV and LV sleep, phenylephrine was associated with increased arterial BP and decreased HR. In HV sleep, phenylephrine was associated with a fall in RSNA, from 124 ± 14 to 58 ± 11% (P fall in BP after sodium nitroprusside was associated with a significant increase in HR during LV but not HV sleep, and there was no significant effect of hypotension on RSNA. These data demonstrate that in near-term fetal sheep baroreflex activity is only partly active and is highly modulated by sleep state. Critically, there was no RSNA response to marked hypotension; this finding has implications for the ability of the late preterm fetus to adapt to low BP.

  20. Effects of prolonged bed rest on the total peripheral resistance baroreflex

    Science.gov (United States)

    Xiao, X.; Mukkamala, R.; Sheynberg, N.; Williams, G. H.; Cohen, R. J.; Mark, R. G. (Principal Investigator)

    2002-01-01

    Orthostatic intolerance following prolonged exposure to microgravity continues to be a primary concern of the human space program. Reduced autonomic tone has been demonstrated to contribute to this phenomenon, and the heart rate baroreflex, in particular, has been repeatedly shown to be impaired. However, only the works of Yelle et al. have attempted to address the role of the total peripheral resistance (TPR) baroreflex, a potentially more significant contributor to blood pressure regulation. We applied a previously developed method for estimating the static gains of both the arterial and cardiopulmonary TPR baroreflexes to data obtained before and after 16-day bed rest. Reductions in the estimated static gains of the arterial (statistically significant) and cardiopulmonary TPR baroreflexes were found after bed rest. This study supports the works of Yelle et al, which imply that the TPR baroreflex is reduced after spaceflight.

  1. GABA modulates baroreflex in the ventral tegmental area in rat.

    Science.gov (United States)

    Hatam, Masoumeh; Rasoulpanah, Minoo; Nasimi, Ali

    2015-12-01

    There are some reports demonstrating the cardiovascular functions of the ventral tegmental area (VTA). About 20-30% of the VTA neurons are GABAergic, which might play a role in baroreflex modulation. This study was performed to find the effects of GABA(A), GABA(B) receptors and reversible synaptic blockade of the VTA on baroreflex. Drugs were microinjected into the VTA of urethane anesthetized rats, and the maximum change of blood pressure and the gain of the reflex bradycardia in response to intravenous phenylephrine (Phe) injection were compared with the preinjection and the control values. Microinjection of bicuculline methiodide (BMI, 100 pmol/100 nl), a GABA(A) antagonist, into the VTA strongly decreased the Phe-induced hypertension, indicating that GABA itself attenuated the baroreflex. Muscimol, a GABA(A) agonist (30 mM, 100 nl), produced no significant changes. Baclofen, a GABA(B) receptor agonist (1000 pmole/100 nl), moderately attenuated the baroreflex, however phaclofen, a GABA(B) receptor antagonist (1000 pmole/100 nl), had no significant effect. In conclusion, for the first time, we demonstrated that GABA(A) receptors of the VTA strongly attenuate and GABA(B) receptors of the VTA moderately attenuate baroreflex in rat. © 2015 Wiley Periodicals, Inc.

  2. Activation of NTS A2a adenosine receptors differentially resets baroreflex control of renal vs. adrenal sympathetic nerve activity.

    Science.gov (United States)

    Ichinose, Tomoko K; O'Leary, Donal S; Scislo, Tadeusz J

    2009-04-01

    The role of nucleus of solitary tract (NTS) A(2a) adenosine receptors in baroreflex mechanisms is controversial. Stimulation of these receptors releases glutamate within the NTS and elicits baroreflex-like decreases in mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), whereas inhibition of these receptors attenuates HR baroreflex responses. In contrast, stimulation of NTS A(2a) adenosine receptors increases preganglionic adrenal sympathetic nerve activity (pre-ASNA), and the depressor and sympathoinhibitory responses are not markedly affected by sinoaortic denervation and blockade of NTS glutamatergic transmission. To elucidate the role of NTS A(2a) adenosine receptors in baroreflex function, we compared full baroreflex stimulus-response curves for HR, RSNA, and pre-ASNA (intravenous nitroprusside/phenylephrine) before and after bilateral NTS microinjections of selective adenosine A(2a) receptor agonist (CGS-21680; 2.0, 20 pmol/50 nl), selective A(2a) receptor antagonist (ZM-241385; 40 pmol/100 nl), and nonselective A(1) + A(2a) receptor antagonist (8-SPT; 1 nmol/100 nl) in urethane/alpha-chloralose anesthetized rats. Activation of A(2a) receptors decreased the range, upper plateau, and gain of baroreflex-response curves for RSNA, whereas these parameters all increased for pre-ASNA, consistent with direct effects of the agonist on regional sympathetic activity. However, no resetting of baroreflex-response curves along the MAP axis occurred despite the marked decreases in baseline MAP. The antagonists had no marked effects on baseline variables or baroreflex-response functions. We conclude that the activation of NTS A(2a) adenosine receptors differentially alters baroreflex control of HR, RSNA, and pre-ASNA mostly via non-baroreflex mechanism(s), and these receptors have virtually no tonic action on baroreflex control of these sympathetic outputs.

  3. Changes in plasma volume and baroreflex function following resistance exercise

    Science.gov (United States)

    Ploutz, L. L.; Tatro, D. L.; Dudley, G. A.; Convertino, V. A.

    1993-01-01

    The dynamics of change in plasma volume (PV) and baroreflex responses have been reported over 24 h immediately following maximal cycle exercise. The purpose of this study was to determine if PV and baroreflex showed similar changes for 24 h after resistance exercise. Eight men were studied on 2 test days, 1 week apart. On 1 day, per cent change (% delta) in PV was estimated at 0,3, and 6 h after resistance exercise using haematocrit and haemoglobin. Baseline PV was measured 24 h after exercise using Evans blue dye. The carotid baroreceptor-cardiac reflex response was measured before, and 3, 6, 9, 12, and 24 h post-exercise. Each subject performed six sets of the bench press and leg press with 10 repetitions per set with a load that induced failure within each set. On a control day, the protocol was used without exercise. Plasma volume did not change during the control day. There was a 20% decrease in PV immediately post-exercise; the recovery of the PV was rapid and complete within 3 h. PV was 20% greater 24 h post-exercise than on the control day. There were no differences in any of the baroreflex measurements. Therefore, it is suggested that PV shifts may occur without altering baroreflex sensitivity.

  4. Beneficial effects of physical activity on baroreflex control in the elderly.

    Science.gov (United States)

    La Rovere, Maria Teresa; Pinna, Gian Domenico

    2014-07-01

    The baroreflex mechanisms, by controlling autonomic outflow to the heart and circulation, contribute importantly to neural circulatory control. The main function of the baroreflex is to prevent wide fluctuations in arterial blood pressure and to maintain the physiological homeostasis under basal resting conditions and in response to acute stress. Baroreflex-mediated changes in autonomic outflow affect heart rate, myocardial contractility, and peripheral vascular resistance. The baroreflex control of heart rate is of particular interest in pathological conditions, since it has been associated with increased propensity for cardiac mortality and sudden death. Aging is associated with significant cardiovascular modifications. The changes in baroreflex function that occur with age have been systematically studied by several methodological approaches. The available evidence indicates a reduced arterial baroreflex control of heart rate favoring an increase in sympathetic and a decrease in parasympathetic drive to the heart as well as an impairment in the baroreceptor control of blood pressure. Both kinds of changes have resultant clinical implications. Exercise training can modulate the age-related decline in baroreflex function and the attending abnormalities in autonomic control, thus accounting for some of the beneficial effects of physical activity in reducing the risk of cardiovascular morbidity and mortality.

  5. Leptin impairs cardiovagal baroreflex function at the level of the solitary tract nucleus.

    Science.gov (United States)

    Arnold, Amy C; Shaltout, Hossam A; Gallagher, Patricia E; Diz, Debra I

    2009-11-01

    Circulating leptin is elevated in some forms of obesity-related hypertension, associated with impaired baroreflex function. Leptin receptors are present on vagal afferent fibers and neurons within the solitary tract nucleus, providing an anatomic distribution consistent with baroreflex modulation. Although solitary tract nucleus microinjection of 144 fmol/60 nL of leptin had no significant effect on baroreflex sensitivity for control of the heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats, 500 fmol of leptin impaired baroreflex sensitivity for bradycardia in response to increases in pressure (1.15+/-0.04 versus 0.52+/-0.12 ms/mm Hg; P<0.01). Transgenic ASrAOGEN rats with low brain angiotensinogen have an upregulation of the leptin receptor and p85 alpha mRNA in the dorsal medulla relative to Sprague-Dawley rats. Consistent with these observations, the response to leptin was enhanced in ASrAOGEN rats, because both the 144-fmol (1.46+/-0.08 versus 0.75+/-0.10 ms/mm Hg; P<0.001) and 500-fmol (1.36+/-0.32 versus 0.44+/-0.06 ms/mm Hg; P<0.05) leptin microinjections impaired baroreflex sensitivity. At these doses, leptin microinjection had no effect on resting pressure, heart rate, or the tachycardic response to decreases in pressure in Sprague-Dawley or ASrAOGEN rats. Thus, exogenous leptin at sites within the solitary tract nucleus impairs the baroreflex sensitivity for bradycardia induced by increases in arterial pressure, consistent with a permissive role in mediating increases in arterial pressure. Baroreflex inhibition was enhanced in animals with evidence of increased leptin receptor and relevant signaling pathway mRNA.

  6. Impaired baroreflex function in mice overexpressing alpha-synuclein

    Directory of Open Access Journals (Sweden)

    Sheila eFleming

    2013-07-01

    Full Text Available Cardiovascular autonomic dysfunction, such as orthostatic hypotension consequent to baroreflex failure and cardiac sympathetic denervation, is frequently observed in the synucleinopathy Parkinson’s disease (PD. In the present study, the baroreceptor reflex was assessed in mice overexpressing human wildtype alpha-synuclein (Thy1-aSyn, a genetic mouse model of synucleinopathy. The beat-to-beat change in heart rate, computed from R-R interval, in relation to blood pressure was measured in anesthetized and conscious mice equipped with arterial blood pressure telemetry transducers during transient bouts of hypertension and hypotension. Compared to wildtype, tachycardia following nitroprusside-induced hypotension was significantly reduced in Thy1-aSyn mice. Thy1-aSyn mice also showed an abnormal cardiovascular response (i.e., diminished tachycardia to muscarinic blockade with atropine. We conclude that Thy1-aSyn mice have impaired basal and dynamic range of sympathetic and parasympathetic-mediated changes in heart rate and will be a useful model for long-term study of cardiovascular autonomic dysfunction associated with PD.

  7. Urotensin Ⅱ inhibits carotid sinus baroreflex in anesthetized male rats

    Institute of Scientific and Technical Information of China (English)

    Yu-ming WU; Hong-mei XUE; Lin XIAO; Rui-rong HE

    2007-01-01

    Aim: To study the effects of urotensin Ⅱ (UV) on the carotid sinus baroreflex (CSB). Methods: The functional curve of carotid sinus baroreflex was measured by recording changes in arterial pressure in anesthetized male rats with perfused isolated carotid sinus. Results: UⅡ at the concentration of 3 nmol/L had no effect on the CSB, while at the concentration of 30, 300 and 3000 nmol/L inhibited the CSB, shifting the functional curve of the baroreflex upward and to the right. There was a marked decrease in peak slope and reflex decrease in blood pressure. These effects of UⅡ were concentration-dependent. Pretreatment with verapamil (an antagonist of the L-type calcium channel, 10 μmol/L) partially eliminated the above effects of UⅡ (300 nmol/L) on the CSB. Pretreatment with BIM-23127 (3 μmol/L),an antagonist of human and rat UⅡ receptors, abolished the actions of UⅡ on the CSB. Pretreatment with, NG-nitro-L-arginine methyl ester (L-NAME) 100 μmol/L did not affect the inhibitory effects of UⅡ (300 nmol/L) on the CSB. Conclusion: These data suggest that UⅡ exerts an inhibitory action on the isolated CSB. Such an action of UV is predominantly mediated by the UⅡ receptors in vascular smooth muscles, resulting in the opening of L-type calcium channels.

  8. Estimation of arterial and cardiopulmonary total peripheral resistance baroreflex gain values: validation by chronic arterial baroreceptor denervation.

    Science.gov (United States)

    Mukkamala, Ramakrishna; Kim, Jong-Kyung; Li, Ying; Sala-Mercado, Javier; Hammond, Robert L; Scislo, Tadeusz J; O'Leary, Donal S

    2006-05-01

    Feedback control of total peripheral resistance (TPR) by the arterial and cardiopulmonary baroreflex systems is an important mechanism for short-term blood pressure regulation. Existing methods for measuring this TPR baroreflex mechanism typically aim to quantify only the gain value of one baroreflex system as it operates in open-loop conditions. As a result, the normal, integrated functioning of the arterial and cardiopulmonary baroreflex control of TPR remains to be fully elucidated. To this end, the laboratory of Mukkamala et al. (Mukkamala R, Toska K, and Cohen RJ. Am J Physiol Heart Circ Physiol 284: H947-H959, 2003) previously proposed a potentially noninvasive technique for estimating the closed-loop (dimensionless) gain values of the arterial TPR baroreflex (GA) and the cardiopulmonary TPR baroreflex (GC) by mathematical analysis of the subtle, beat-to-beat fluctuations in arterial blood pressure, cardiac output, and stroke volume. Here, we review the technique with additional details and describe its experimental evaluation with respect to spontaneous hemodynamic variability measured from seven conscious dogs, before and after chronic arterial baroreceptor denervation. The technique was able to correctly predict the group-average changes in GA and GC that have previously been shown to occur following chronic arterial baroreceptor denervation. That is, reflex control by the arterial TPR baroreflex was virtually abolished (GA = -2.1 +/- 0.6 to 0.3 +/- 0.2; P TPR baroreflex more than doubled (GC = -0.7 +/- 0.4 to -1.8 +/- 0.2; P TPR baroreflex functioning in both humans and animals in health and disease.

  9. Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension.

    Science.gov (United States)

    Iliescu, Radu; Tudorancea, Ionut; Irwin, Eric D; Lohmeier, Thomas E

    2013-10-01

    The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation-current therapies in patients with resistant hypertension, who are commonly obese-restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1-4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

  10. Uptake blockade of endocannabinoids in the NTS modulates baroreflex-evoked sympathoinhibition.

    Science.gov (United States)

    Brozoski, Daniel T; Dean, Caron; Hopp, Francis A; Seagard, Jeanne L

    2005-10-19

    Previous studies supporting a possible physiological role for an endogenous cannabinoid, arachidonylethanolamide (AEA, anandamide), showed a significant increase in AEA content in the nucleus tractus solitarius (NTS) after an increase in blood pressure (BP) and prolonged baroreflex inhibition of renal sympathetic nerve activity (RSNA) after exogenous AEA microinjections into the NTS. These results, along with other studies, support the hypothesis that endogenous AEA can modulate the baroreflex through cannabinoid CB(1) receptor activation within the NTS. This study was performed to characterize the physiological role of endogenously released cannabinoids (endocannabinoids) in regulating baroreflex control of RSNA through actions in the NTS. Endocannabinoid effects were assessed by measuring the RSNA baroreflex response to increased pressure after bilateral microinjections of AM404, an endocannabinoid transport inhibitor, into the NTS of adult male Sprague Dawley rats. AM404 blocks uptake of endocannabinoids and enhances the effects of any endocannabinoids released [M. Beltramo, et al., Functional role of high-affinity anandamide transport, as revealed by selective inhibition, Science 277 (5329) (1997) 1094-1097.] into the NTS. Therefore, it was hypothesized that microinjections of AM404 should exhibit effects similar to microinjections of exogenous AEA. In this study, AM404 microinjections into the NTS were found to significantly prolong baroreflex inhibition of RSNA compared to control, similar to effects of exogenous AEA. This effect is thought to result from an increased endocannabinoid presence in the NTS, leading to prolonged CB(1) receptor activation. These results indicate that endocannabinoids released in the NTS have the potential to modulate baroreflex control at this site in the central baroreflex pathway.

  11. Augmented baroreflex heart rate gain after moderate-intensity, dynamic exercise

    Science.gov (United States)

    Halliwill, J. R.; Taylor, J. A.; Hartwig, T. D.; Eckberg, D. L.

    1996-01-01

    The occurrence of a sustained vasodilation and hypotension after acute, dynamic exercise suggests that exercise may alter arterial baroreflex mechanisms. Therefore, we assessed systemic hemodynamics, baroreflex regulation of heart rate, and cardiac vagal tone after 60 min of cycling at 60% peak oxygen consumption in 12 healthy, untrained men and women (ages 21-28 yr). We derived sigmoidal carotid-cardiac baroreflex relations by measurement of R-R interval changes induced by ramped, stepwise, R-wave-triggered changes in external neck pressure from 40 to -65 mmHg. We estimated tonic cardiac vagal control with power spectral analysis of R-R interval variability in the respiratory frequency band (0.2-0.3 Hz) during frequency- and tidal volume-controlled breathing. Both mean arterial pressure and total peripheral resistance were reduced postexercise [pressure: from 86 +/- 2 (mean +/- SE) to 81 +/- 2 mmHg; resistance: from 23 +/- 2 to 16 +/- 1 units; both P exercise, whereas heart rate and plasma norepinephrine levels were elevated. Thus moderate-intensity, dynamic exercise increases heart rate and cardiac output, reduces peripheral vascular resistance, and augments baroreflex responsiveness. Our data suggest that augmented baroreflex heart rate gain restrains rather than contributes to postexercise hypotension, which appears to be mediated predominately by vasodilation.

  12. [Comparison of three methods for the estimation of spontaneous cardiac baroreflex sensitivity in normotensive and hypertensive subjects].

    Science.gov (United States)

    Ducher, M; Siché, J P; Fauvel, J P; Gustin, M P; Pozet, N; Paultre, C; Cerutti, C

    1995-08-01

    This study aimed at comparing estimations of spontaneous cardiac baroreflex sensitivity (BRS) obtained with 3 different methods from continuous non-invasive blood pressure recordings in humans. A new method, allowing the quantification of the statistical dependence between values of 2 parameters (Z coefficient), was applied to beat-to-beat systolic blood pressure (SBP) and heart period (HP) values. SBP and HP values with positive Z coefficient and corresponding to baroreflex activity (SBP and HP values both lower or higher than the modal values) were submitted to a linear regression and the regression coefficient (Zgain) was taken as an index of BRS. Second, cross-spectral analysis of SBP and HP gave a BRS value (Csgain) computed as the average value of transfer function moduli for frequencies between 0.07 and 0.14 Hz, with coherence between SBP and HP greater than 0.5. The third method relies on the analysis of linear sequences (r > 0.97) containing at least 3 values of SBP and HP varying in the same direction. The average regression coefficient obtained from all selected SBP and HP sequences is the index of BRS (Seqgain). SBP and HR were recorded during 1 hour with a Finapres in 10 healthy male volunteers (NT), 23 to 32 year-old (SBP: 123 +/- 2 mmHg) and 10 recent and untreated hypertensive subjects (HT) (SBP: 152 +/- 6 mmHg). [table: see text] These results show that, in both groups, Zgain and Seqgain correlated with Csgain. No correlation was found between Zgain and Seqgain in healthy volunteers whereas the correlation was strong in hypertensives probably due to more heterogeneous SBP levels and BRS values in these subjects. This suggests that these methods are sensitive to different ways of response of the baroreflex.

  13. Stimulation of the cardiopulmonary baroreflex enhances ventricular contractility in awake dogs: a mathematical analysis study.

    Science.gov (United States)

    Sala-Mercado, Javier A; Moslehpour, Mohsen; Hammond, Robert L; Ichinose, Masashi; Chen, Xiaoxiao; Evan, Sell; O'Leary, Donal S; Mukkamala, Ramakrishna

    2014-08-15

    The cardiopulmonary baroreflex responds to an increase in central venous pressure (CVP) by decreasing total peripheral resistance and increasing heart rate (HR) in dogs. However, the direction of ventricular contractility change is not well understood. The aim was to elucidate the cardiopulmonary baroreflex control of ventricular contractility during normal physiological conditions via a mathematical analysis. Spontaneous beat-to-beat fluctuations in maximal ventricular elastance (Emax), which is perhaps the best available index of ventricular contractility, CVP, arterial blood pressure (ABP), and HR were measured from awake dogs at rest before and after β-adrenergic receptor blockade. An autoregressive exogenous input model was employed to jointly identify the three causal transfer functions relating beat-to-beat fluctuations in CVP to Emax (CVP → Emax), which characterizes the cardiopulmonary baroreflex control of ventricular contractility, ABP to Emax, which characterizes the arterial baroreflex control of ventricular contractility, and HR to Emax, which characterizes the force-frequency relation. The CVP → Emax transfer function showed a static gain of 0.037 ± 0.010 ml(-1) (different from zero; P < 0.05) and an overall time constant of 3.2 ± 1.2 s. Hence, Emax would increase and reach steady state in ∼16 s in response to a step increase in CVP, without any change to ABP or HR, due to the cardiopulmonary baroreflex. Following β-adrenergic receptor blockade, the CVP → Emax transfer function showed a static gain of 0.0007 ± 0.0113 ml(-1) (different from control; P < 0.10). Hence, Emax would change little in steady state in response to a step increase in CVP. Stimulation of the cardiopulmonary baroreflex increases ventricular contractility through β-adrenergic receptor system mediation.

  14. The gain of the baroreflex bradycardia is reduced by microinjection of NMDA receptor antagonists into the nucleus tractus solitarii of awake rats.

    Science.gov (United States)

    Frigero, M; Bonagamba, L G; Machado, B H

    2000-02-14

    The baroreflex activation with phenylephrine infusion produces a bradycardic response. In the present study, the role of NMDA receptors in the nucleus tractus solitarii (NTS) in the processing of the parasympathetic component of the baroreflex was evaluated using acid phosphonivaleric (AP-5), a selective NMDA receptor antagonist. Baroreflex activation was performed before and after bilateral microinjection of AP-5 into the intermediate commissural NTS (0.5 mm lateral to the midline). Microinjection of the vehicle (saline, 0.9%) or a dose of 2 nmol/50 nl of AP-5 into the NTS produced no effect on the gain of the baroreflex while a dose of 10 nmol/50 nl of AP-5 produced a significant reduction in the gain of the baroreflex 2 min after microinjection [-1.43+/-0.22 vs. -0. 43+/-0.03 bpm/mmHg, (n=6)], with a return to control levels 10 min after the microinjections. The dose of 10 nmol/50 nl was selective for NMDA receptors considering that the cardiovascular responses to microinjection of AMPA (0.05 pmol/50 nl), a non-NMDA receptor agonist, were not affected by this dose of AP-5 and the responses to microinjection of NMDA (2 nmol/50 nl) were blocked. The data show that the bradycardic response to baroreflex activation was blocked by AP-5 microinjected into the NTS, indicating that the neurotransmission of the parasympathetic component of the baroreflex is mediated by NMDA receptors in the NTS.

  15. Reduced Baroreflex Sensitivity in Cluster Headache Patients

    DEFF Research Database (Denmark)

    Barloese, Mads C J; Mehlsen, Jesper; Brinth, Louise

    2015-01-01

    by baroreflex sensitivity (BRS) in CH patients. METHODS: Twenty-six active CH patients and an equal number of age-, sex-, and BMI-matched controls underwent head-up tilt table test and BRS was determined by the sequence method. RESULTS: Compared with controls, patients exhibited a blunted reactivity of RR...

  16. Determination of Vagal Baroreflex sensitivity in Normal Subjects

    Science.gov (United States)

    Wada, Naoki; Singer, Wolfgang; Gehrking, Tonette L.; Sletten, David M.; Schmelzer, James D.; Kihara, Mikihiro; Low, Phillip A.

    2014-01-01

    Introduction The Valsalva maneuver (VM) is used widely to quantify the sensitivity of the vagal baroreflex loop (vagal baroreflex sensitivity, BRS_v), but most studies have focused on the heart rate (HR) response to blood pressure (BP) decrement (BRS_v↓), even though the subsequent response to an increment in BP following the VM (BRS_v↑) is important and different. Methods We evaluated recordings of HR and BP in 187 normal subjects during the VM and determined both BRS_v↑ determined by relating HR to the BP increase following phase III and BRS_v↓. Results BRS_v↑ was related inversely to age. In addition, BRS_v↓, age, and magnitude of phase IV were independent predictors of BRS_v↑ in a multivariate model, accounting for 47% of the variance of BRS_v↑. Discussion The results indicate that both BRS_v↑ and BRS_v↓ become blunted with increasing age and that these indices relate to each other. PMID:24477673

  17. Important GABAergic mechanism within the NTS and the control of sympathetic baroreflex in SHR.

    Science.gov (United States)

    Moreira, Thiago S; Takakura, Ana C; Colombari, Eduardo

    2011-01-20

    Inhibitory neurotransmission has an important role in the processing of sensory afferent signals in the nucleus of the solitary tract (NTS), particularly in spontaneously hypertensive rats (SHR). In the present study, we tested the hypothesis that γ-aminobutyric acid (GABA) mediated neurotransmission within the NTS produces an inhibition of the baroreflex response of splanchnic sympathetic nerve discharge (sSND). In urethane-anesthetized, artificially ventilated and vagotomized male SHR and Wistar Kyoto (WKY) rats we compared baroreflex-response curves evoked after bilateral injections into the NTS of the GABA-A antagonist bicuculline (25pmol/50nl) or the GABA-B antagonist CGP 35348 (5nmol/50nl). Baseline MAP in SHR was higher than the WKY rats (SHR: 153±5, vs. WKY: 112±6mm Hg, pNTS induced a transient (5min) reduction in MAP (∆=-26±4 and -41±6mm Hg, respectively vs. saline ∆=+4±3mmHg, pNTS in WKY rats did not change MAP, sSND and sympathetic baroreflex gain. These data indicate that GABAergic mechanisms within the NTS act tonically reducing sympathetic baroreflex gain in SHR.

  18. Stimulation of NTS A1 adenosine receptors differentially resets baroreflex control of regional sympathetic outputs.

    Science.gov (United States)

    Scislo, Tadeusz J; Ichinose, Tomoko K; O'Leary, Donal S

    2008-01-01

    Previously we showed that pressor and differential regional sympathoexcitatory responses (adrenal > renal >/= lumbar) evoked by stimulation of A(1) adenosine receptors located in the nucleus of the solitary tract (NTS) were attenuated/abolished by baroreceptor denervation or blockade of glutamatergic transmission in the NTS, suggesting A(1) receptor-elicited inhibition of glutamatergic transmission in baroreflex pathways. Therefore we tested the hypothesis that stimulation of NTS A(1) adenosine receptors differentially inhibits/resets baroreflex responses of preganglionic adrenal (pre-ASNA), renal (RSNA), and lumbar (LSNA) sympathetic nerve activity. In urethane-chloralose-anesthetized male Sprague-Dawley rats (n = 65) we compared baroreflex-response curves (iv nitroprusside and phenylephrine) evoked before and after bilateral microinjections into the NTS of A(1) adenosine receptor agonist (N(6)-cyclopentyladenosine, CPA; 0.033-330 pmol/50 nl). CPA evoked typical dose-dependent pressor and differential sympathoexcitatory responses and similarly shifted baroreflex curves for pre-ASNA, RSNA, and LSNA toward higher mean arterial pressure (MAP) in a dose-dependent manner; the maximal shifts were 52.6 +/- 2.8, 48.0 +/- 3.6, and 56.8 +/- 6.7 mmHg for pre-ASNA, RSNA, and LSNA, respectively. These shifts were not a result of simple baroreceptor resetting because they were two to three times greater than respective increases in baseline MAP evoked by CPA. Baroreflex curves for pre-ASNA were additionally shifted upward: the maximal increases of upper and lower plateaus were 41.8 +/- 16.4% and 45.3 +/- 8.7%, respectively. Maximal gain (%/mmHg) measured before vs. after CPA increased for pre-ASNA (3.0 +/- 0.6 vs. 4.9 +/- 1.3), decreased for RSNA (4.1 +/- 0.6 vs. 2.3 +/- 0.3), and remained unaltered for LSNA (2.1 +/- 0.2 vs. 2.0 +/- 0.1). Vehicle control did not alter the baroreflex curves. We conclude that the activation of NTS A(1) adenosine receptors differentially inhibits

  19. Probing human response times

    Science.gov (United States)

    Johansen, Anders

    2004-07-01

    In a recent preprint (Dialog in e-mail traffic, preprint cond-mat/0304433), the temporal dynamics of an e-mail network has been investigated by Eckmann, Moses and Sergi. Specifically, the time period between an e-mail message and its reply were recorded. It will be shown here that their data agrees quantitatively with the frame work proposed to explain a recent experiment on the response of “internauts” to a news publication (Physica A 296(3-4) (2001) 539) despite differences in communication channels, topics, time-scale and socio-economic characteristics of the two population. This suggest a generalized response time distribution ∼ t-1 for human populations in the absence of deadlines with important implications for psychological and social studies as well the study of dynamical networks.

  20. Gender Differences in Baroreflex Sensitivity after Bed Rest

    Science.gov (United States)

    Arzeno, Natalia M.; Stenger, M. B.; Ribeiro, L. C.; Lee, S. M.; Platts, S. H.

    2009-01-01

    Two potential contributing factors to post-spaceflight orthostatic intolerance are decreases in baroreflex sensitivity (BRS) and sympathetic nervous system response. The purpose of this study was to examine the shape of the BRS curve and sympathetic response to a wide range of blood pressures (BP) before and during 6 head-down bed rest (BR). METHODS: Normal volunteers were tested one day before BR (20M, 1 0F) and near BR days 30 (20M, 10F), 60 (16M, 8F), and 90 (1 0M, 5F). BP was pharmacologically manipulated by 10-min infusions of phenylephrine (PE) and sodium nitroprusside (SNP) at 3 increasing concentrations with a 20-min rest between PE and SNP. Electrocardiogram and continuous finger blood pressure were recorded. A blood sample was drawn at the end of each infusion to measure plasma norepinephrine levels. The spontaneous baroreflex slope (SBS), a measure of BRS, was calculated as the slope of a sequence of 3 or more beats in which the systolic BP (SBP) and following R-R interval (RR) both increased or decreased. The data included saturated responses at the upper but not the lower end of the BP range. Mean response curves were constructed using second-order mixed model analysis. Results are based on term significance in the models. RESULTS RR: RR was lower during BR than pre BR (pgenders were modeled by a linear response; compared to males, females had an attenuated (lower slope) RR response to changes in SBP (p=0.031). SBS: SBS vs SBP analysis showed a lower SBS during BR (pgender and BR. Not only do gender and BR baseline differences exist, but gender and BR also influence the slope and saturation of the BRS curves. Attenuated and saturating RR and SBS responses, as well as differences in baseline values, may contribute to the higher rates of orthostatic intolerance in women and after bed rest.

  1. Protein kinase A-dependent Neuronal Nitric Oxide Synthase Activation Mediates the Enhancement of Baroreflex Response by Adrenomedullin in the Nucleus Tractus Solitarii of Rats

    Directory of Open Access Journals (Sweden)

    Ho I-Chun

    2011-05-01

    Full Text Available Abstract Background Adrenomedullin (ADM exerts its biological functions through the receptor-mediated enzymatic mechanisms that involve protein kinase A (PKA, or neuronal nitric oxide synthase (nNOS. We previously demonstrated that the receptor-mediated cAMP/PKA pathway involves in ADM-enhanced baroreceptor reflex (BRR response. It remains unclear whether ADM may enhance BRR response via activation of nNOS-dependent mechanism in the nucleus tractus solitarii (NTS. Methods Intravenous injection of phenylephrine was administered to evoke the BRR before and at 10, 30, and 60 min after microinjection of the test agents into NTS of Sprague-Dawley rats. Western blotting analysis was used to measure the level and phosphorylation of proteins that involved in BRR-enhancing effects of ADM (0.2 pmol in NTS. The colocalization of PKA and nNOS was examined by immunohistochemical staining and observed with a laser confocal microscope. Results We found that ADM-induced enhancement of BRR response was blunted by microinjection of NPLA or Rp-8-Br-cGMP, a selective inhibitor of nNOS or protein kinase G (PKG respectively, into NTS. Western blot analysis further revealed that ADM induced an increase in the protein level of PKG-I which could be attenuated by co-microinjection with the ADM receptor antagonist ADM22-52 or NPLA. Moreover, we observed an increase in phosphorylation at Ser1416 of nNOS at 10, 30, and 60 min after intra-NTS administration of ADM. As such, nNOS/PKG signaling may also account for the enhancing effect of ADM on BRR response. Interestingly, biochemical evidence further showed that ADM-induced increase of nNOS phosphorylation was prevented by co-microinjection with Rp-8-Br-cAMP, a PKA inhibitor. The possibility of PKA-dependent nNOS activation was substantiated by immunohistochemical demonstration of co-localization of PKA and nNOS in putative NTS neurons. Conclusions The novel finding of this study is that the signal transduction cascade that

  2. Human sexual response.

    Science.gov (United States)

    Basson, Rosemary

    2015-01-01

    The human sexual response to sexually arousing stimuli is a motivational incentive-based cycle comprising subjective experience and physiologic changes. Clinical and empirical data support a circular model of overlapping phases of variable order. Brain imaging data of sexual arousal identify areas of cerebral activation and inhibition reflecting a complex network of cognitive, motivational, emotional, and autonomic components. Psychologic and biologic factors influence the brain's appraisal and processing of sexual stimuli to allow or disallow subsequent arousal. The sexual and non-sexual outcomes influence motivation to future sexual intimacy. Variability is marked both between individuals and within a person's sexual life, influenced by multiple factors, including stage of life cycle, mental health, and relationship happiness. Neurologic disease can interrupt the cycle at many points: by limiting motivation, reducing ability to attend to and feel sexual stimuli, and accomplishing the movements needed to stimulate and experience intercourse. Impairments to genital congestion, penile erection, and orgasm may also occur. Disease-associated changes to the interpersonal relationship and self-image plus frequently comorbid depression will tend to lessen motivation and temper the brain's appraisal of sexual stimuli, so precluding arousal. Therapy begins by explaining the sexual response cycle, clarifying the points of interruption in the patient's own cycle so as to guide treatment.

  3. Prolonged Baroreflex Activation Abolishes Salt-Induced Hypertension After Reductions in Kidney Mass.

    Science.gov (United States)

    Hildebrandt, Drew A; Irwin, Eric D; Lohmeier, Thomas E

    2016-12-01

    Chronic electric activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated for therapy in patients with resistant hypertension. However, patients with significant impairment of renal function have been largely excluded from clinical trials. Thus, there is little information on blood pressure and renal responses to baroreflex activation in subjects with advanced chronic kidney disease, which is common in resistant hypertension. Changes in arterial pressure and glomerular filtration rate were determined in 5 dogs after combined unilateral nephrectomy and surgical excision of the poles of the remaining kidney to produce ≈70% reduction in renal mass. After control measurements, sodium intake was increased from ≈45 to 450 mol/d. While maintained on high salt, animals experienced increases in mean arterial pressure from 102±4 to 121±6 mm Hg and glomerular filtration rate from 40±2 to 45±2 mL/min. During 7 days of baroreflex activation, the hypertension induced by high salt was abolished (103±6 mm Hg) along with striking suppression of plasma norepinephrine concentration from 139±21 to 81±9 pg/mL, but despite pronounced blood pressure lowering, there were no significant changes in glomerular filtration rate (43±2 mL/min). All variables returned to prestimulation values during a recovery period. These findings indicate that after appreciable nephron loss, chronic suppression of central sympathetic outflow by baroreflex activation abolishes hypertension induced by high salt intake. The sustained antihypertensive effects of baroreflex activation occur without significantly compromising glomerular filtration rate in remnant nephrons. © 2016 American Heart Association, Inc.

  4. Mental stress-induced increase in blood pressure is not related to baroreflex sensitivity in middle-aged healthy men.

    Science.gov (United States)

    Fauvel, J P; Cerutti, C; Quelin, P; Laville, M; Gustin, M P; Paultre, C Z; Ducher, M

    2000-04-01

    The baroreflex that acts to blunt blood pressure (BP) variations through opposite variations in heart rate should limit the BP increase produced by an emotional challenge. However, relations between baroreflex sensitivity and BP reactivity induced by a psychological stress in a large group of adults have never been firmly established. In 280 healthy men, rest (10 minutes) and stress (5 minutes) BP and heart rate were recorded beat to beat by a blood pressure monitor. The mental stress was elicited by a well-standardized computerized version of a word color conflict stress test (Stroop Color Test). Rest and stress baroreflex sensitivity was assessed by the cross-spectral analysis of BP and heart rate and by the sequence method. The stress-induced increase in systolic BP (22.4+/-0.1 mm Hg) was not correlated with resting baroreflex sensitivity but was slightly correlated (r=0.2, P<0.001) with BP variability assessed either by standard deviation or by mid-frequency band spectral power. Our results suggested that a centrally mediated sympathetic stimulation overcame cardiac autonomic regulation and emphasized the role of the sympathetic vasoconstriction in the pressure response at the onset of the stressing stimulation. During the sustained sympathoexcitatory phase, the cardiac baroreflex blunts BP variations but at a lower sensitivity.

  5. Baroreflex sensitivity and essential hypertension in adolescents.

    Science.gov (United States)

    Honzíková, N; Fiser, B

    2009-01-01

    It has been known for many years that baroreflex sensitivity is lowered in hypertensive patients. There are several known factors implicating this association, e.g. high blood pressure leads to remodeling of the carotid arterial wall, to its stiffness and to a diminished activation of baroreceptors; leptin released from a fatty tissue activates the sympathetic nervous system etc. On the other hand, low baroreflex sensitivity (BRS, usually quantified in ms/mmHg) can be inborn. Studies on primary hypertension in children and adolescents have brought new information about the role of baroreflex in the development of an early stage of primary hypertension. BRS lower than 3.9 ms/mmHg was found in 5 % of healthy subjects. This value approaches the critical value for the risk of sudden cardiac death in patients after myocardial infarction and corresponds to the value present in hypertensive patients. A decreased BRS and BRSf (baroreflex sensitivity expressed in mHz/mmHg, index independent of the mean cardiac interval), was found not only in children with hypertension, but also in those with white-coat hypertension. This is in accordance with a single interpretation. The decrease of BRS/BRSf precedes a pathological blood pressure increase. The contribution of obesity and BRS/BRSf to the development of hypertension in adolescents was also compared. Both factors reach a sensitivity and a specificity between 60 % and 65 %, but there is no correlation between the values of the body mass index and BRS either in the group of hypertensive patients or in healthy controls. If a receiver operating curve (sensitivity versus specificity) is plotted for both values together using logistic regression analysis, a sensitivity higher than 70 % and a specificity over 80 % are reached. This means that low baroreflex sensitivity is an independent risk factor for the development of primary hypertension. Studies demonstrate that adolescents with increased blood pressure and with BRS under 7 ms

  6. Marked sympathetic activation and baroreflex dysfunction in true resistant hypertension.

    Science.gov (United States)

    Grassi, Guido; Seravalle, Gino; Brambilla, Gianmaria; Pini, Claudio; Alimento, Marina; Facchetti, Rita; Spaziani, Domenico; Cuspidi, Cesare; Mancia, Giuseppe

    2014-12-20

    An increase in sympathetic drive to the heart and the peripheral circulation characterizes mild and severe essential hypertension. However, it remains unsettled whether sympathetic cardiovascular influences are potentiated in true resistant hypertension (RHT). In 32 RHT patients treated with 4.6 ± 0.3 drugs (mean ± SEM) and aged 58.6 ± 2.1 years, 35 non-resistant treated hypertensives (HT) and 19 normotensive controls (NT), all age-matched with RHT, we measured clinic, 24-hour ambulatory and beat-to-beat blood pressures (BP), heart rate (HR, EKG), muscle sympathetic nerve traffic (MSNA, microneurography) and spontaneous baroreflex MSNA-sensitivity. BP values were markedly greater in RHT patients than in NT and HT (172.2 ± 1.7/100.7 ± 1.2 vs 132.1 ± 1.3/82.1 ± 0.9 and 135.5 ± 1.2/83.6 ± 0.9 mmHg, P < 0.01). This was paralleled by a significant and marked increase in MSNA (87.8 ± 2.0 vs 46.8 ± 2.6 and 59.3 ± 1.7 and bursts/100 heartbeats, P < 0.01). In multiple regression analysis the MSNA increase observed in RHT was significantly related to hemodynamic, hormonal and metabolic variables. It was also significantly related to plasma aldosterone values as well as spontaneous baroreflex MSNA-sensitivity, which were the variables that at the multivariate analysis were more closely related to the adrenergic activation of RHT after adjustment for confounders, including antihypertensive treatment (r(2)partial=0.04405 and r(2)partial=0.00878, P<0.05 for both). These data represent the first evidence that RHT is a state of marked adrenergic overdrive, greater for magnitude than that detectable in HT. They also suggest that impaired baroreflex mechanisms, along with hemodynamic and neurohumoral factors, may be responsible for the phenomenon. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Baroreflex Sensitivity Decreases During 90-Day Bed Rest

    Science.gov (United States)

    Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

    2008-01-01

    Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (pdecreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (pdecrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

  8. Cool dialysate reduces asymptomatic intradialytic hypotension and increases baroreflex variability.

    Science.gov (United States)

    Chesterton, Lindsay J; Selby, Nicholas M; Burton, James O; McIntyre, Chris W

    2009-04-01

    Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in chronic hemodialysis (HD) patients and can be ameliorated by cool temperature HD. The baroreflex arc is under autonomic control and is essential in the short-term regulation of blood pressure (BP). This study aimed to investigate if the baroreflex sensitivity (BRS) response to HD differed between standard and cool-temperature dialysate. Ten patients (mean age 67+/-2 years) prone to IDH were recruited into a randomized, crossover study to compare BRS variation at dialysate temperatures of 37 degrees C (HD(37)) and 35 degrees C (HD(35)). Each patient underwent continuous beat-to-beat BP monitoring during a dialysis session of HD(37) and HD(35). During HD(37) 2 patients developed symptomatic IDH, as opposed to 1 with HD(35). However, asymptomatic IDH occurred with a frequency of 0.4 episodes per session with HD(35) and 6.2 episodes per session during HD(37) (odds ratio15.5; 95%CI 5.6-14.2). Although absolute BRS measurements did not differ between the 2 modalities, BRS variability increased during HD(35). Our study has demonstrated that in IDH-prone patients, cool HD resulted in a reduction in heart rate and a greater reduction in cardiac output and stroke volume. Mean arterial pressure was maintained through a significantly greater increase in total peripheral resistance. Furthermore, although absolute BRS values during HD were not significantly altered by a reduction in dialysate temperature, there was a greater percentage increase in BRS values during cool HD. Understanding the varied causes of, and categorizing impaired hemodynamic responses to HD will enable further individualization of HD prescriptions according to patient need.

  9. Does the Menstrual Cycle Influence the Sensitivity of Vagally Mediated Baroreflexes?

    Science.gov (United States)

    2002-06-01

    infusion of vasoactive drugs , sug- gesting that cardiac vagal control is not influenced by elevated sympathetic nervous activity associated with the normal... diuretics or exercise training does not alter the carotid–cardiac baroreflex [23,24]. Blood volume fluctuations of the order of 10–15% have been reported...endothelium-dependent responses in canine coronary arteries. Am. J. Physiol. 261, R1022–R1027 26 Shan, J., Resnick, L., Wu, X. and Pang, P. (1994) Vascular

  10. Role of aortic arch vascular mechanics in cardiovagal baroreflex sensitivity.

    Science.gov (United States)

    Klassen, Stephen A; Chirico, Daniele; Dempster, Kylie S; Shoemaker, J Kevin; O'Leary, Deborah D

    2016-07-01

    Cardiovagal baroreflex sensitivity (cvBRS) measures the efficiency of the cardiovagal baroreflex to modulate heart rate in response to increases or decreases in systolic blood pressure (SBP). Given that baroreceptors are located in the walls of the carotid sinuses (CS) and aortic arch (AA), the arterial mechanics of these sites are important contributors to cvBRS. However, the relative contribution of CS and AA mechanics to cvBRS remains unclear. This study employed sex differences as a model to test the hypothesis that differences in cvBRS between groups would be explained by the vascular mechanics of the AA but not the CS. Thirty-six young, healthy, normotensive individuals (18 females; 24 ± 2 yr) were recruited. cvBRS was measured using transfer function analysis of the low-frequency region (0.04-0.15 Hz). Ultrasonography was performed at the CS and AA to obtain arterial diameters for the measurement of distensibility. Local pulse pressure (PP) was taken at the CS using a hand-held tonometer, whereas AA PP was estimated using a transfer function of brachial PP. Both cvBRS (25 ± 11 vs. 19 ± 7 ms/mmHg, P = 0.04) and AA distensibility (16.5 ± 6.0 vs. 10.5 ± 3.8 mmHg(-1) × 10(-3), P = 0.02) were greater in females than males. Sex differences in cvBRS were eliminated after controlling for AA distensibility (P = 0.19). There were no sex differences in CS distensibility (5.32 ± 2.3 vs. 4.63 ± 1.3 mmHg(-1) × 10(-3), P = 0.32). The present data demonstrate that AA mechanics are an important contributor to differences in cvBRS.

  11. Influence of baroreflex on volume elasticity of heart and aorta in the rabbit.

    Science.gov (United States)

    Wronski, T; Seeliger, E; Persson, P B; Harnath, A; Flemming, B

    2002-03-01

    Optimal ventriculoaortic coupling includes tuning of elastic properties. The ratio of effective arterial elastance and left ventricular endsystolic elastance is often taken as a measure for mechanical and energetical efficiency. The present study determined the time course of ventricular and aortic volume elasticity (VE = dp/dV) throughout a complete heartbeat. This was achieved by using changes of eigenfrequency of two catheter-transducer systems under closed chest conditions in rabbits. Short-term VE modulation was studied by a baroreflex response, as induced by pressure changes applied to the carotid sinus. Long-term changes were studied in atherosclerotic rabbits (12 wk of high-cholesterol feeding). The time course and mean values of ventricular and aortic VE were changed by the baroreflex stimulus. Cholesterol feeding diminished the response. The degree of ventriculoaortic coupling, as quantified by VE(Aorta)/VE(Ventricle) ratio, varied during a single ejection period. The large span allows either maximal energetical efficiency or maximal stroke work. Although normal rabbits adjusted their ventriculoaortic coupling during baroreflex input, the cholesterol-fed rabbits failed to do so.

  12. Exercise training fails to modify arterial baroreflex sensitivity in ovariectomized female rats.

    Science.gov (United States)

    Minami, Naoyoshi; Mori, Nobuyoshi; Nagasaka, Makoto; Ito, Osamu; Ogawa, Mika; Kurosawa, Hajime; Kanazawa, Masayuki; Kohzuki, Masahiro

    2007-04-01

    In men, exercise training attenuates age-related reduction in baroreflex sensitivity, which is related to cardiovascular health. It is unknown, however, if this holds true for post-menopausal women. We examined the effects of exercise training on baroreceptor-heart rate (HR) reflex sensitivity in ovariectomized (OVX) and sham-operated (SO) Wistar-Kyoto rats. At the age of 8 weeks, OVX and SO rats were assigned to either sedentary or exercise-trained group. Exercise training was performed on a treadmill 5 days per week. At the age of 20 weeks, baroreflex sensitivity in response to increases in blood pressure (BRSinc) and decreases in blood pressure (BRSdec) were evaluated by injections of phenylephrine and sodium nitroprusside, respectively. Both BRSinc and BRSdec were significantly reduced in sedentary OVX rats compared with sedentary SO rats. Exercise training decreased resting HR and BRSdec, but had no effect on BRSinc in SO rats. In OVX rats, exercise training decreased resting HR but modified neither BRSdec nor BRSinc. We conclude that withdrawal of female sex hormones in normotensive female rats is associated with reduced baroreflex sensitivity in response to both increase and decrease in blood pressure and that exercise training fails to modulate the decline of BRSinc associated with withdrawal of female sex hormones. To maintain high level of BRSinc in post-menopausal women, hormone replacement therapy may be needed.

  13. Predominant role of neural arc in sympathetic baroreflex resetting of spontaneously hypertensive rats.

    Science.gov (United States)

    Sata, Yusuke; Kawada, Toru; Shimizu, Shuji; Kamiya, Atsunori; Akiyama, Tsuyoshi; Sugimachi, Masaru

    2015-01-01

    There is ongoing controversy over whether neural or peripheral factors are the predominant cause of hypertension. The closed-loop negative feedback operation of the arterial baroreflex hampers understanding of how arterial pressure (AP) is determined through the interaction between neural and peripheral factors. METHODS AND RESULTS: A novel analysis of an isolated open-loop baroreceptor preparation to examine sympathetic nervous activity (SNA) and AP responses to changes in carotid sinus pressure (CSP) in adult spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was conducted. In the neural arc (CSP-SNA relationship), the midpoint pressure (128.9±3.8 vs. 157.9±8.1 mmHg, P<0.001) and the response range of SNA to CSP (90.5±3.7 vs. 115.4±7.6%/mmHg, P=0.011) were higher in SHR. In the peripheral arc (SNA-AP relationship), slope and intercept did not differ. A baroreflex equilibrium diagram was obtained by depicting neural and peripheral arcs in a pressure-SNA plane with rescaled SNA (% in WKY). The operating-point AP (111.3±4.4 vs. 145.9±5.2 mmHg, P<0.001) and SNA (90.8±3.2 vs. 125.1±6.9% in WKY, P<0.001) were shifted towards a higher level in SHR. The shift of the neural arc towards a higher SNA range indicated a predominant contribution to baroreflex resetting in SHR. Notwithstanding the resetting, the carotid sinus baroreflex in SHR preserved an ability to reduce AP if activated with a high enough pressure.

  14. RESTING SYMPATHETIC BAROREFLEX SENSITIVITY IN SUBJECTS WITH LOW AND HIGH TOLERANCE TO CENTRAL HYPOVOLEMIA INDUCED BY LOWER BODY NEGATIVE PRESSURE

    Directory of Open Access Journals (Sweden)

    Carmen eHinojosa-Laborde

    2014-06-01

    Full Text Available Central hypovolemia elicited by orthostasis or hemorrhage triggers sympathetically-mediated baroreflex responses to maintain organ perfusion; these reflexes are less sensitive in patients with orthostatic intolerance, and during conditions of severe blood loss, may result in cardiovascular collapse (decompensatory or circulatory shock. The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. We tested the hypothesis that resting muscle sympathetic nerve activity (MSNA and sympathetic baroreflex sensitivity (BRS are attenuated in male and female subjects who have low tolerance (LT to central hypovolemia induced by lower body negative pressure (LBNP. MSNA and diastolic arterial pressure (DAP were recorded in 47 human subjects who subsequently underwent LBNP to tolerance (onset of presyncopal symptoms. LT subjects experienced presyncopal symptoms prior to completing LBNP of -60 mm Hg, and subjects with high tolerance (HT experienced presyncopal symptoms after completing LBNP after -60 mmHg. Contrary to our hypothesis, resting MSNA burst incidence was not different between LT and HT subjects, and was not related to time to presyncope. BRS was assessed as the slope of the relationship between spontaneous fluctuations in DAP and MSNA during 5 min of supine rest. MSNA burst incidence/DAP correlations were greater than or equal to 0.5 in 37 subjects (LT: n= 9; HT: n=28, and BRS was not different between LT and HT (-1.8 ± 0.3 vs. -2.2 ± 0.2 bursts•(100 beats-1•mmHg-1, p=0.29. We conclude that tolerance to central hypovolemia is not related to either resting MSNA or sympathetic BRS.

  15. Baroreflex failure: a neglected type of secondary hypertension.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Wieling, W.; Karemaker, J.M.; Lenders, J.W.M.

    2004-01-01

    The arterial baroreflex buffers abrupt transients of blood pressure and prevents pressure from rising or falling excessively. In experimental animals, baroreceptor denervation results in temporary or permanent increases in blood pressure level and variability, depending on the extent of denervation.

  16. Is baroreflex control of sympathetic activity and heart rate active in the preterm fetal sheep?

    Science.gov (United States)

    Booth, Lindsea C; Malpas, Simon C; Barrett, Carolyn J; Guild, Sarah-Jane; Gunn, Alistair J; Bennet, Laura

    2009-03-01

    The arterial baroreflex is a fundamental reflex that buffers rapid changes in arterial blood pressure (BP) via regulation of the heart rate and sympathetic nerve activity to the vasculature. In adults a sigmoidal relationship between BP and both heart rate and sympathetic nerve activity is well documented. Its role in blood pressure control before birth is unclear. Preterm babies have a high incidence of low BP, especially in the first few days of life, which could be related, in part, to immaturity of the baroreflex. In the present study, we investigated the baroreflex control of fetal heart rate and renal sympathetic nerve activity (RSNA) in preterm fetal sheep in utero (102 +/- 1 days of gestation; term 140 days). Phenylephrine was associated with a significant increase in BP from 38 +/- 2 to 58 +/- 3 mmHg and a decrease in heart rate (HR) from 177 +/- 4 to 116 +/- 8 beats per minute (bpm). Sodium nitroprusside was associated with a significant fall in BP from 38 +/- 2 to 26 +/- 1 mmHg and an increase in HR from 182 +/- 4 to 274 +/- 8 bpm. However, the time between the 50% changes in BP and HR was significantly greater after hypotension than hypertension (31 +/- 8 s vs. 14 +/- 5 s, P < 0.05). No significant changes in RSNA occurred with either stimulus. This suggests that there are different maturational tempos for the components of the central autonomic response to altered blood pressure.

  17. Baroreflex dysfunction promotes the induction of atherosclerosis in rats

    Institute of Scientific and Technical Information of China (English)

    Guo-junCAI; Chao-yuMIAO; He-huiXIE; Ding-fengSU

    2004-01-01

    AIM: To testify the hypothesis that arterial baroreflex dysfunction promotes the induction of atherosclerosis. METHODSAND RESULTS: Experiment 1 : The baroreflex sensitivity (BRS) was measured in 30 SD rats in conscious state with a computerized blood pressure monitoring system. Four weeks later, the rats were fed with a high-cholesterol diet for 8-week duration to induce atherosclerosis. The hearts and aortae were removed for pathological examination and the scores of coronary and aortic

  18. Transcompartmental inflammatory responses in humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A;

    2014-01-01

    OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following...... measured. MEASUREMENTS AND MAIN RESULTS: IV endotoxin elicited a systemic inflammatory response with a time-dependent increase and peak in tumor necrosis factor-α, interleukin-6, and leukocyte counts (all p ...-α, interleukin-6, and albumin (all p inflammatory response was observed after 2-4 hours, with no change in plasma tumor necrosis factor-α. CONCLUSIONS: Acute lung or systemic inflammation in humans is followed by a transcompartmental proinflammatory response, the degree and differential...

  19. Baroreflex gain and vasomotor sympathetic modulation in resistant hypertension.

    Science.gov (United States)

    Freitas, Isabelle Magalhães Guedes; de Almeida, Leonardo Barbosa; Pereira, Natália Portela; Mira, Pedro Augusto de Carvalho; de Paula, Rogério Baumgratz; Martinez, Daniel Godoy; Toschi-Dias, Edgar; Laterza, Mateus Camaroti

    2017-06-01

    The aim of this study was to determine the gain and latency of arterial baroreflex control of heart rate in patients with resistant hypertension compared to patients with essential hypertension and normotensive subjects. Eighteen patients with resistant hypertension (56 ± 10 years, mean of four antihypertensive drugs), 17 patients with essential hypertension (56 ± 11 years, mean of two antihypertensive drugs), and 17 untreated normotensive controls (50 ± 15 years) were evaluated by spectral analysis of the spontaneous fluctuations of arterial pressure (beat-to-beat) and heart rate (ECG). This analysis estimated vasomotor and cardiac autonomic modulations, respectively. The transfer function analysis quantified the gain and latency of the response of output signal (RR interval) per unit of spontaneous change of input signal (systolic arterial pressure). The gain was similarly lower in patients with resistant hypertension and patients with essential hypertension in relation to normotensive subjects (4.67 ± 2.96 vs. 6.60 ± 3.30 vs. 12.56 ± 8.81 ms/mmHg; P resistant hypertension when compared to patients with essential hypertension and normotensive subjects (-4.01 ± 3.19 vs. -2.91 ± 2.10 vs. -1.82 ± 1.09 s; P = 0.04, respectively). In addition, the index of vasomotor sympathetic modulation was significantly increased only in patients with resistant hypertension when compared to patients with essential hypertension and normotensive subjects (4.04 ± 2.86 vs. 2.65 ± 1.88 vs. 2.06 ± 1.70 mmHg(2); P resistant hypertension have reduced gain and increased latency of arterial baroreflex control of heart rate. These patients also have increased vasomotor sympathetic modulation.

  20. Baroreflex sensitivity differs among same strain Wistar rats from the same laboratory

    Directory of Open Access Journals (Sweden)

    Celso Ferreira

    2011-09-01

    Full Text Available Previous studies evidenced that a portion of normotensive Sprague–Dawley rats spontaneously exhibit lower baroreflex sensitivity, however, it was no yet investigated in Wistar rats. We aimed to compare baroreflex sensitivity among rats from the same strain and the same laboratory. Male Wistar normotensive rats (300-400g were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure and heart rate. Baroreflex was calculated as the derivative of the variation of heart rate in function of the mean arterial pressure variation (ΔHR/ΔMAP tested with a depressor dose of sodium nitroprusside (50 μg/kg and with a pressor dose of phenylephrine (8μg/kg in the right femoral venous approach through an inserted cannula. We divided the rats into four groups: i high bradycardic baroreflex, baroreflex gain less than -2 tested with phenylephrine; ii low bradycardic baroreflex, baroreflex gain between -1 and -2 tested with phenylephrine; iii high tachycardic baroreflex, baroreflex gain less than -3 tested with sodium nitroprusside; and iv low tachycardic baroreflex, baroreflex gain between -1 and -3 tested with sodium nitroprusside. Approximately 71% of the rats presented a decrease in bradycardic reflex while around half showed an increase in tachycardic reflex. No significant changes in basal mean arterial pressure and heart rate, tachycardic and bradycardic peak and heart rate range were observed. There was a significant change in baroreflex sensitivity among rats from the same strain and the same laboratory.

  1. Dynamic aerobic exercise induces baroreflex improvement in diabetic rats.

    Science.gov (United States)

    Jorge, Luciana; da Pureza, Demilto Y; da Silva Dias, Danielle; Conti, Filipe Fernandes; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2012-01-01

    The objective of the present study was to investigate the effects of an acute aerobic exercise on arterial pressure (AP), heart rate (HR), and baroreflex sensitivity (BRS) in STZ-induced diabetic rats. Male Wistar rats were divided into control (n = 8) and diabetic (n = 8) groups. AP, HR, and BRS, which were measured by tachycardic and bradycardic (BR) responses to AP changes, were evaluated at rest (R) and postexercise session (PE) on a treadmill. At rest, STZ diabetes induced AP and HR reductions, associated with BR impairment. Attenuation in resting diabetes-induced AP (R: 103 ± 2 versus PE: 111 ± 3 mmHg) and HR (R: 290 ± 7 versus PE: 328 ± 10 bpm) reductions and BR dysfunction (R: -0.70 ± 0.06 versus PE: -1.21 ± 0.09 bpm/mmHg) was observed in the postexercise period. In conclusion, the hemodynamic and arterial baro-mediated control of circulation improvement in the postexercise period reinforces the role of exercise in the management of cardiovascular risk in diabetes.

  2. Capsaicin facilitates carotid sinus baroreflex in anesthetized rats.

    Science.gov (United States)

    Zhang, Hao; Liu, Yi-Xian; Wu, Yu-Ming; Wang, Sheng; He, Rui-Rong

    2004-04-25

    The effects of capsaicin (CAP) on the carotid sinus baroreflex were studied in 30 anaesthetized rats with perfused isolated carotid sinus. The results are as follows. (1) By perfusing the isolated carotid sinus with CAP (1 micromol/L), the functional curve of the baroreflex was shifted to the left and downward, with a peak slope (PS) increasing from 0.34+/-0.01 to 0.42+/-0.01 (PPS and RD induced by capsaicin were dose-dependent. (2) By pretreatment with ruthenium red (RR, 100 micromol/L), an antagonist of vanilloid receptor subtype 1 (VR(1)), the above effects of CAP on carotid baroreflex were abolished. (3) The CAP-induced change in the baroreflex was also eliminated by pretreatment with glibenclamide (20 microm ol/L), a K(ATP) channel blocker. On the basis of the results, it is concluded that CAP facilitates the carotid baroreflex, an effect of which may be resulted from the opening of K(ATP) channels mediated by VR(1).

  3. Arterial baroreflex function and left ventricular hypertrophy

    Institute of Scientific and Technical Information of China (English)

    MIAO Chao-Yu; SU Ding-Feng

    2004-01-01

    It is well known that the arterial baroreflex(ABR)plays a key role in the regulation of heart rate and stabilization of blood pressure.Currently,it appears that ABR dysfunction is involved in the pathophysiology of cardiovascular disease states.Since the mid-1990s,a number of studies have been carried out in our laboratory to explore the pathological significance of ABR function in cardiovascular damage.This minireview summarizes our research work on the topic of ABR and left ventricular hypertrophy(LVH).On the basis of discussion concerning the importance of ABR dysfunction in hypertensive LVH and sinoaortic denervation-induced LVH,we advance a new strategy for reversal of LVH,that is,restoration of impaired ABR function.We tested this hypothesis in animal models with ABR deficiency.It was found that improvement of impaird ABR function with long-term treatment of ketanserin or candesartan was accompanied by reversal of LVH.The preliminary results indicate that it is feasible to target ABR for treatment of LVH.

  4. Hydrogen sulfide facilitates carotid sinus baroreflex in anesthetized rats

    Institute of Scientific and Technical Information of China (English)

    Lin XIAO; Yu-ming WU; Hao ZHANG; Yi-xian LIU; Rui-rong HE

    2006-01-01

    Aim:To study effects of hydrogen sulfide (H2S)on the carotid sinus baroreflex (CSB).Methods:The functional curve of the carotid sinus baroreflex was measured by recording changes in arterial pressure in anesthetized male rats with perfused carotid sinus.Results:H2S(derived from sodium hydrosulfide)at concentrations of 25,50,and 100 μmol/L facilitated the CSB,shifting the functional curve of the baroreflex downward and to the left.There was a marked increase in peak slope(PS)and reflex decrease in blood pressure(RD).Effects were concentration-dependent.Pretreatment with glibenclamide(20 μmol/L),a KATP channel blocker,abolished the above effects of H2S on CSB.Pretreatment with Bay K8644 (an agonist of calcium channels;500 nmol/L)eliminated the effect of H2S on CSB.An inhibitor of cystathionine γ-lyase(CSE),DL-propargylglycine(PPG;200 μmol/L),inhibited CSB in male rats and shifted the functional curve of the baroreflex upward and to the right.Conclusion:These data suggest that exogenous H2S exerts a facilitatory role on isolated CSB through opening KATP channels and further closing the calcium channels in vascular smooth muscle.Endogenous H2S may activate the activity of the CSB in vivo.

  5. Determination of baroreflex sensitivity during the modified Oxford maneuver by trigonometric regressive spectral analysis.

    Directory of Open Access Journals (Sweden)

    Julia Gasch

    Full Text Available BACKGROUND: Differences in spontaneous and drug-induced baroreflex sensitivity (BRS have been attributed to its different operating ranges. The current study attempted to compare BRS estimates during cardiovascular steady-state and pharmacologically stimulation using an innovative algorithm for dynamic determination of baroreflex gain. METHODOLOGY/PRINCIPAL FINDINGS: Forty-five volunteers underwent the modified Oxford maneuver in supine and 60° tilted position with blood pressure and heart rate being continuously recorded. Drug-induced BRS-estimates were calculated from data obtained by bolus injections of nitroprusside and phenylephrine. Spontaneous indices were derived from data obtained during rest (stationary and under pharmacological stimulation (non-stationary using the algorithm of trigonometric regressive spectral analysis (TRS. Spontaneous and drug-induced BRS values were significantly correlated and display directionally similar changes under different situations. Using the Bland-Altman method, systematic differences between spontaneous and drug-induced estimates were found and revealed that the discrepancy can be as large as the gain itself. Fixed bias was not evident with ordinary least products regression. The correlation and agreement between the estimates increased significantly when BRS was calculated by TRS in non-stationary mode during the drug injection period. TRS-BRS significantly increased during phenylephrine and decreased under nitroprusside. CONCLUSIONS/SIGNIFICANCE: The TRS analysis provides a reliable, non-invasive assessment of human BRS not only under static steady state conditions, but also during pharmacological perturbation of the cardiovascular system.

  6. The repeated sit-to-stand maneuver is a superior method for cardiac baroreflex assessment: a comparison with the modified Oxford method and Valsalva maneuver.

    Science.gov (United States)

    Horsman, H M; Tzeng, Y C; Galletly, D C; Peebles, K C

    2014-12-01

    Baroreflex assessment has diagnostic and prognostic utility in the clinical and research environments, and there is a need for a reliable, simple, noninvasive method of assessment. The repeated sit-to-stand method induces oscillatory changes in blood pressure (BP) at a desired frequency and is suitable for assessing dynamic baroreflex sensitivity (BRS). However, little is known about the reliability of this method and its ability to discern fundamental properties of the baroreflex. In this study we sought to: 1) evaluate the reliability of the sit-to-stand method for assessing BRS and compare its performance against two established methods (Oxford method and Valsalva maneuver), and 2) examine whether the frequency of the sit-to-stand method influences hysteresis. Sixteen healthy participants underwent three trials of each method. For the sit-to-stand method, which was performed at 0.1 and 0.05 Hz, BRS was quantified as an integrated response (BRSINT) and in response to falling and rising BP (BRSDOWN and BRSUP, respectively). Test retest reliability was assessed using the intraclass correlation coefficient (ICC). Irrespective of frequency, the ICC for BRSINT during the sit-to-stand method was ≥0.88. The ICC for a rising BP evoked by phenylephrine (PEGAIN) in the Oxford method was 0.78 and ≤0.5 for the remaining measures. During the sit-to-stand method, hysteresis was apparent in all participants at 0.1 Hz but was absent at 0.05 Hz. These findings indicate the sit-to-stand method is a statistically reliable BRS assessment tool and suitable for the examination of baroreflex hysteresis. Using this approach we showed that baroreflex hysteresis is a frequency-dependent phenomenon.

  7. Four faces of baroreflex failure: hypertensive crisis, volatile hypertension, orthostatic tachycardia, and malignant vagotonia

    Science.gov (United States)

    Ketch, Terry; Biaggioni, Italo; Robertson, RoseMarie; Robertson, David

    2002-01-01

    BACKGROUND: The baroreflex normally serves to buffer blood pressure against excessive rise or fall. Baroreflex failure occurs when afferent baroreceptive nerves or their central connections become impaired. In baroreflex failure, there is loss of buffering ability, and wide excursions of pressure and heart rate occur. Such excursions may derive from endogenous factors such as stress or drowsiness, which result in quite high and quite low pressures, respectively. They may also derive from exogenous factors such as drugs or environmental influences. METHODS AND RESULTS: Impairment of the baroreflex may produce an unusually broad spectrum of clinical presentations; with acute baroreflex failure, a hypertensive crisis is the most common presentation. Over succeeding days to weeks, or in the absence of an acute event, volatile hypertension with periods of hypotension occurs and may continue for many years, usually with some attenuation of pressor surges and greater prominence of depressor valleys during long-term follow-up. With incomplete loss of baroreflex afferents, a mild syndrome of orthostatic tachycardia or orthostatic intolerance may appear. Finally, if the baroreflex failure occurs without concomitant destruction of the parasympathetic efferent vagal fibers, a resting state may lead to malignant vagotonia with severe bradycardia and hypotension and episodes of sinus arrest. CONCLUSIONS: Although baroreflex failure is not the most common cause of the above conditions, correct differentiation from other cardiovascular disorders is important, because therapy of baroreflex failure requires specific strategies, which may lead to successful control.

  8. Pial artery and subarachnoid width response to apnoea in normal humans.

    Science.gov (United States)

    Wszedybyl-Winklewska, Magdalena; Wolf, Jacek; Swierblewska, Ewa; Kunicka, Katarzyna; Gruszecki, Marcin; Guminski, Wojciech; Winklewski, Pawel J; Frydrychowski, Andrzej F; Bieniaszewski, Leszek; Narkiewicz, Krzysztof

    2015-09-01

    Little is known about intracranial pressure (ICP)-cerebral haemodynamic interplay during repetitive apnoea. A recently developed method based on near-infrared transillumination/backscattering sounding (NIR-T/BSS) noninvasively measures changes in pial artery pulsation (cc-TQ) as well as subarachnoid width (sas-TQ) in humans. We tested the complex response of the pial artery and subarachnoid width to apnoea using this method. The pial artery and subarachnoid width response to consecutive apnoeas lasting 30, 60 s and maximal breath-hold (91.1 ± 23.1 s) were studied in 20 healthy volunteers. The cc-TQ and sas-TQ were measured using NIR-T/BSS; cerebral blood flow velocity (CBFV), pulsatility index and resistive index were measured using Doppler ultrasound of the left internal carotid artery; heart rate (HR) and beat-to-beat SBP and DBP blood pressure were recorded using a Finometer; end-tidal CO2 (EtCO2) was measured using a medical gas analyser. Apnoea evoked a multiphasic response in blood pressure, pial artery compliance and ICP. First, SBP declined, which was accompanied by an increase in cc-TQ and sas-TQ. Directly after these changes, SBP exceeded baseline values, which was followed by a decline in cc-TQ and the return of sas-TQ to baseline. During these initial changes, CBFV remained stable. Towards the end of the apnoea, BP, cc-TQ and CBFV increased, whereas pulsatility index, resistive index and sas-TQ declined. Changes in sas-TQ were linked to changes in EtCO2, HR and SBP. Apnoea is associated with ICP swings, closely reflecting changes in EtCO2, HR and peripheral BP. The baroreflex influences the pial artery response.

  9. Mechanisms of spontaneous baroreflex impairment in lyon hypertensive rats.

    Science.gov (United States)

    Lantelme, P; Cerutti, C; Lo, M; Paultre, C Z; Ducher, M

    1998-09-01

    This experiment aimed at 1) comparing the spontaneous baroreflex sensitivity (SBRS) in Lyon genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats and 2) assessing some aspects of the mechanisms of its impairment in LH rats. Baroreflex was studied in control animals after an early chronic converting enzyme inhibition with perindopril and after a 4-wk infusion of ANG II in perindopril-treated rats. The SBRS was determined with a previously validated method, using statistical dependence between blood pressure (BP) and heart rate values recorded in freely moving animals. LH rats exhibited high BP, cardiac hypertrophy, and decreased SBRS (LH, 1.3 +/- 0.2; LN, 2.5 +/- 0.4; LL, 2.2 +/- 0.4 beats . min-1 . mmHg-1). Perindopril prevented the development of hypertension and cardiac hypertrophy and normalized SBRS. BP rose in LH and LL rats after ANG II infusion, but only LH rats, which developed a cardiac hypertrophy, had an impaired SBRS (LH, 1.1 +/- 0.2; LN, 2.5 +/- 0.2; LL, 2.8 +/- 0.3 beats . min-1 . mmHg-1). This impairment was partially reversed by an acute ANG II blockade with losartan. These results demonstrate that high BP does not account for the decreased SBRS in LH rats. SBRS impairment could result either from cardiac hypertrophy or from the direct effect of ANG II on the baroreflex loop.

  10. Baroreflex control of sympathetic activity in experimental hypertension

    Directory of Open Access Journals (Sweden)

    M.C.C. Irigoyen

    1998-09-01

    Full Text Available The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100% was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

  11. Haemodynamic instability during thyroid surgery: a baroreflex-mediated neurogenic phenomenon?

    Science.gov (United States)

    Nouraei, S A R; Davies, M R; Obholzer, R; Sandhu, G S; Porter, F

    2006-03-01

    We present a case of marked intra-operative blood pressure instability in a euthyroid, fit 33-year-old female undergoing elective hemithyroidectomy. This led to significant haemodynamic compromise, cardiac failure and end-organ damage. There was no evidence of a vasoactive endocrine cause, and the nature and timing of the event strongly pointed towards baroreflex-mediated neurogenic sympathetic dysfunction. This can occur during carotid surgery and neck dissection. Although haemodynamic fluctuations may happen during thyroid surgery, their severity in this case was unusual. We believe this could have been a rebound phenomenon in response to acute decompression of the carotid artery which had been compressed by an enlarging cyst. We suggest that in similar cases blockade of the carotid sinus could attenuate such responses.

  12. In vivo expression of angiotensin-(1-7) lowers blood pressure and improves baroreflex function in transgenic (mRen2)27 rats.

    Science.gov (United States)

    Garcia-Espinosa, Maria A; Shaltout, Hossam A; Gallagher, Patricia E; Chappell, Mark C; Diz, Debra I

    2012-08-01

    Transgenic (mRen2)27 rats are hypertensive with impaired baroreflex sensitivity for control of heart rate compared with Hannover Sprague-Dawley rats. We assessed blood pressure and baroreflex function in male hemizygous (mRen2)27 rats (30-40 weeks of age) instrumented for arterial pressure recordings and receiving into the cisterna magna either an Ang-(1-7) fusion protein or a control fusion protein (CTL-FP). The maximum reduction in mean arterial pressure achieved was -38 ± 7 mm Hg on day 3, accompanied by a 55% enhancement in baroreflex sensitivity in Ang-(1-7) fusion protein-treated rats. Both the high-frequency alpha index (HF-α) and heart rate variability increased, suggesting increased parasympathetic tone for cardiac control. The mRNA levels of several components of the renin-angiotensin system in the dorsal medulla were markedly reduced including renin (-80%), neprilysin (-40%), and the AT1a receptor (-40%). However, there was a 2-fold to 3-fold increase in the mRNA levels of the phosphatases PTP-1b and dual-specificity phosphatase 1 in the medulla of Ang-(1-7) fusion protein-treated rats. Our finding that replacement of Ang-(1-7) in the brain of (mRen2)27 rats reverses in part the hypertension and baroreflex impairment is consistent with a functional deficit of Ang-(1-7) in this hypertensive strain. We conclude that the increased mRNA expression of phosphatases known to counteract the phosphoinositol 3 kinase and mitogen-activated protein kinases, and the reduction of renin and AT1a receptor mRNA levels may contribute to the reduction in arterial pressure and improvement in baroreflex sensitivity in response to Ang-(1-7).

  13. Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension

    OpenAIRE

    Iliescu, Radu; Tudorancea, Ionut; Irwin, Eric D; Lohmeier, Thomas E.

    2013-01-01

    The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analy...

  14. Electrical stimulation of the aortic depressor nerve in conscious rats overcomes the attenuation of the baroreflex in chronic heart failure.

    Science.gov (United States)

    Pinto, Tomás O C Teixeira; Lataro, Renata M; Castania, Jaci A; Durand, Marina T; Silva, Carlos A A; Patel, Kaushik P; Fazan, Rubens; Salgado, Helio C

    2016-04-01

    Chronic heart failure (CHF) is characterized by autonomic dysfunction combined with baroreflex attenuation. The hypotensive and bradycardic responses produced by electrical stimulation of the aortic depressor nerve (ADN) were examined in conscious CHF and control male Wistar rats (12-13 wk old). Furthermore, the role of parasympathetic and sympathetic nervous system in mediating the cardiovascular responses to baroreflex activation was evaluated by selective β1-adrenergic and muscarinic receptor antagonists. CHF was induced by myocardial infarction. After 6 wk, the subjects were implanted with electrodes for ADN stimulation. Twenty-four hours later, electrical stimulation of the ADN was applied for 20 s using five different frequencies (5, 15, 30, 60, and 90 Hz), while the arterial pressure was recorded by a catheter implanted into the femoral artery. Electrical stimulation of the ADN elicited progressive and similar hypotensive and bradycardic responses in control (n = 12) and CHF (n = 11) rats, while the hypotensive response was not affected by methylatropine. Nevertheless, the reflex bradycardia was attenuated by methylatropine in control, but not in CHF rats. Atenolol did not affect the hypotensive or bradycardic response in either group. The ADN function was examined under anesthesia through electroneurographic recordings. The arterial pressure-ADN activity relationship was attenuated in CHF rats. In conclusion, despite the attenuation of baroreceptor function in CHF rats, the electrical stimulation of the ADN elicited a stimulus-dependent hypotension and bradycardia of similar magnitude as observed in control rats. Therefore, electrical activation of the aortic baroreflex overcomes both the attenuation of parasympathetic function and the sympathetic overdrive.

  15. Closed-loop spontaneous baroreflex transfer function is inappropriate for system identification of neural arc but partly accurate for peripheral arc: predictability analysis.

    Science.gov (United States)

    Kamiya, Atsunori; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

    2011-04-01

    Although the dynamic characteristics of the baroreflex system have been described by baroreflex transfer functions obtained from open-loop analysis, the predictability of time-series output dynamics from input signals, which should confirm the accuracy of system identification, remains to be elucidated. Moreover, despite theoretical concerns over closed-loop system identification, the accuracy and the predictability of the closed-loop spontaneous baroreflex transfer function have not been evaluated compared with the open-loop transfer function. Using urethane and α-chloralose anaesthetized, vagotomized and aortic-denervated rabbits (n = 10), we identified open-loop baroreflex transfer functions by recording renal sympathetic nerve activity (SNA) while varying the vascularly isolated intracarotid sinus pressure (CSP) according to a binary random (white-noise) sequence (operating pressure ± 20 mmHg), and using a simplified equation to calculate closed-loop-spontaneous baroreflex transfer function while matching CSP with systemic arterial pressure (AP). Our results showed that the open-loop baroreflex transfer functions for the neural and peripheral arcs predicted the time-series SNA and AP outputs from measured CSP and SNA inputs, with r2 of 0.8 ± 0.1 and 0.8 ± 0.1, respectively. In contrast, the closed-loop-spontaneous baroreflex transfer function for the neural arc was markedly different from the open-loop transfer function (enhanced gain increase and a phase lead), and did not predict the time-series SNA dynamics (r2; 0.1 ± 0.1). However, the closed-loop-spontaneous baroreflex transfer function of the peripheral arc partially matched the open-loop transfer function in gain and phase functions, and had limited but reasonable predictability of the time-series AP dynamics (r2, 0.7 ± 0.1). A numerical simulation suggested that a noise predominantly in the neural arc under resting conditions might be a possible mechanism responsible for our findings. Furthermore

  16. Inter-individual Relationships between Sympathetic Arterial Baroreflex Function and Cerebral Perfusion Control in Healthy Males

    OpenAIRE

    Trevor Witter; Yu-Chieh Tzeng; Terry O'Donnell; Jessica Kusel; Bridget Walker; Mary Berry; Chloe E. Taylor

    2017-01-01

    Maintenance of adequate cerebral perfusion during normal physiological challenges requires integration between cerebral blood flow (CBF) and systemic blood pressure control mechanisms. Previous studies have shown that cardiac baroreflex sensitivity (BRS) is inversely related to some measures of cerebral autoregulation. However, interactions between the sympathetic arterial baroreflex and cerebral perfusion control mechanisms have not been explored. To determine the nature and magnitude of the...

  17. A comparison of autonomic responses in humans induced by two simulation models of weightlessness: lower body positive pressure and 6 degrees head-down tilt.

    Science.gov (United States)

    Fu, Q; Sugiyama, Y; Kamiya, A; Mano, T

    2000-04-12

    Six-degree head-down tilt (HDT) is well accepted as an effective weightlessness model in humans. However, some researchers utilized lower body positive pressure (LBPP) to simulate the cardiovascular and renal effects of a decreased gravitational stress. In order to determine whether LBPP was a suitable model for simulated weightlessness, we compared the differences between these two methods. Ten healthy males, aged 21-41 years, were subjected to graded LBPP at 10, 20 and 30 mmHg, as well as 6 degrees HDT. Muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve along with cardiovascular variables. We found that MSNA decreased by 27% to a similar extent both at low levels of LBPP (10 and 20 mmHg) and HDT. However, at a high level of LBPP (30 mmHg), MSNA tended to increase. Mean arterial pressure was elevated significantly by 11% (10 mmHg) at 30 mmHg LBPP, but remained unchanged at low levels of LBPP and HDT. Heart rate did not change during the entire LBPP and HDT procedures. Total peripheral resistance markedly increased by 36% at 30 mmHg LBPP, but decreased by 9% at HDT. Both stroke volume and cardiac output tended to decrease at 30 mmHg LBPP, but increased at HDT. These results suggest that although both LBPP and HDT induce fluid shifts from the lower body toward the thoracic compartment, autonomic responses are different, especially at LBPP greater than 20 mmHg. We note that high levels of LBPP (>20 mmHg) activate not only cardiopulmonary and arterial baroreflexes, but also intramuscular mechanoreflexes, while 6 degrees HDT only activates cardiopulmonary baroreflexes. We conclude that LBPP is not a suitable model for simulated weightlessness in humans.

  18. Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

    Science.gov (United States)

    Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

    2017-02-01

    Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

  19. [Immune response genes products in human physiology].

    Science.gov (United States)

    Khaitov, R M; Alekseev, L P

    2012-09-01

    Current data on physiological role of human immune response genes' proteomic products (antigens) are discussed. The antigens are specified by a very high level of diversity that mediates a wide specter ofphysiological functions. They actually provide integrity and biological stability of human as species. These data reveal new ideas on many pathological processes as well as drafts new approaches for prophylaxis and treatment.

  20. Biofeedback of baroreflex sensitivity in patients with mild essential hypertension.

    Science.gov (United States)

    Overhaus, Sabine; Rüddel, Heinz; Curio, Immo; Mussgay, Lutz; Scholz, O Berndt

    2003-01-01

    An attempt was made to reduce blood pressure by increasing the baroreflex sensitivity (BRS) via biofeedback. Six patients with mild essential hypertension and 5 normotensive participants were studied during 8 biofeedback sessions. Each session consisted of 5 trials, 5 min each. The first and the last trials served as baselines of heart rate, blood pressure, respiration, and BRS. During the 3 middle trials the BRS was calculated online using the sequencing technique. The resulting value was used as a visual analogue feedback signal. Participants were asked to increase BRS. The mean BRS was 8.3 [ms/mmHg] for the hypertensive patients and 12.2 [ms/mmHg] for the normotensive participants. During biofeedback trials as well as across sessions neither the hypertensive nor the normotensive group showed a statistically significant increase of BRS, only heart rate variability increased significantly. Contrary to expectation blood pressure increased in both groups. One hypertensive subject made significant progress during the training by performing valsalva maneuvers. The data show that BRS is reduced in hypertensive subjects. The increase of the heart rate variability could be a sign of the activation of the baroreflex although the BRS itself did not increase. Despite the successful technical and organizational implementation of this biofeedback approach, it was not effective to systematically reduce blood pressure. A further development in the direction of guiding the patient to use the valsalva breathing pattern and/or a prolonged duration of the biofeedback training might be promising.

  1. Effects of peritoneal dialysis fluid biocompatibility on baroreflex sensitivity.

    Science.gov (United States)

    John, S G; Selby, N M; McIntyre, C W

    2008-04-01

    Conventional low biocompatibility peritoneal dialysis (PD) fluid composition has been driven by manufacturing expediency and cost limitations. PD is associated with significant acute changes in cardiovascular functional parameters, at least in part influenced by fluid composition. Short-term control of blood pressure (BP) is under control of the baroreflex arc. The aim of this study was to investigate the effects of PD fluid biocompatibility on baroreflex sensitivity (BRS). We studied 10 non-diabetic established continuous ambulatory PD patients, in a randomized crossover trial comparing conventional and biocompatible PD fluids. Systemic hemodynamics were continuously monitored using digital pulse-wave analysis. Plasma glucose and insulin were assessed during treatment with both 1.36% and 3.86% glucose-containing fluids. BRS was calculated offline from continuous BP and interbeat interval data. BRS was significantly higher with conventional PD fluid during both 1.36% (Pinsulin concentrations, and ultrafiltration volumes were significantly higher during the 3.86% dwell than the 1.36% dwell, but there were no differences between standard and biocompatible fluids. We have demonstrated for the first time that PD fluid biocompatibility rapidly affects BRS. These changes occur against a background of cardiovascular variability, hyperinsulinemia, and hyperglycemia. Further research is needed to explore the mechanism and, more importantly, the consequences of these findings.

  2. T-cell response in human leishmaniasis

    DEFF Research Database (Denmark)

    Kharazmi, A; Kemp, K; Ismail, A

    1999-01-01

    In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered......+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans....

  3. Ablation of NK1 Receptors in Rat Nucleus Tractus Solitarii Blocks Baroreflexes

    National Research Council Canada - National Science Library

    Riley, Jeffrey; Lin, Li-Hsien; Chianca, Jr, Deoclecio A; Talman, William T

    2002-01-01

    .... The neurokinin-1 receptors at which SP may act have been identified in the nucleus tractus solitarii, but there remains uncertainty if the neurons at which SP acts are critical to baroreflex transmission...

  4. Baroreflex sensitivity during rest and executive functioning in attention-deficit/hyperactivity disorder. The TRAILS study.

    NARCIS (Netherlands)

    Dietrich, A.; Althaus, M.; Hartman, C.A.; Buitelaar, J.K.; Mindera, R.B.; Hoofdakker, B.J. van den; Hoekstra, P.J.

    2012-01-01

    Children with attention-deficit/hyperactivity disorder (ADHD) often show executive function (EF) problems and neurophysiological hypoarousal. Baroreceptor activation, as part of the baroreflex short-term blood pressure regulatory mechanism, has been linked to cortical inhibition and attenuated cogni

  5. Baroreflex sensitivity during rest and executive functioning in attention-deficit/hyperactivity disorder. The TRAILS study

    NARCIS (Netherlands)

    Dietrich, A.; Althaus, M.; Hartman, C.A.; Buitelaar, J.K.; Minderaa, R.B.; van den Hoofdakker, B.J.; Hoekstra, P.J.

    2012-01-01

    Children with attention-deficit/hyperactivity disorder (ADHD) often show executive function (EF) problems and neurophysiological hypoarousal. Baroreceptor activation, as part of the baroreflex short-term blood pressure regulatory mechanism, has been linked to cortical inhibition and attenuated cogni

  6. Cardiac baroreflex function and dynamic cerebral autoregulation in elderly Masters athletes

    NARCIS (Netherlands)

    Aengevaeren, V.L.; Claassen, J.A.H.R.; Levine, B.D.; Zhang, R.

    2013-01-01

    Cerebral blood flow (CBF) is stably maintained through the combined effects of blood pressure (BP) regulation and cerebral autoregulation. Previous studies suggest that aerobic exercise training improves cardiac baroreflex function and beneficially affects BP regulation, but may negatively affect ce

  7. Human Metapneumovirus Antagonism of Innate Immune Responses

    Directory of Open Access Journals (Sweden)

    Xiaoyong Bao

    2012-12-01

    Full Text Available  Human metapneumovirus (hMPV is a recently identified RNA virus belonging to the Paramyxoviridae family, which includes several major human and animal pathogens. Epidemiological studies indicate that hMPV is a significant human respiratory pathogen with worldwide distribution. It is associated with respiratory illnesses in children, adults, and immunocompromised patients, ranging from upper respiratory tract infections to severe bronchiolitis and pneumonia. Interferon (IFN represents a major line of defense against virus infection, and in response, viruses have evolved countermeasures to inhibit IFN production as well as IFN signaling. Although the strategies of IFN evasion are similar, the specific mechanisms by which paramyxoviruses inhibit IFN responses are quite diverse. In this review, we will present an overview of the strategies that hMPV uses to subvert cellular signaling in airway epithelial cells, the major target of infection, as well as in primary immune cells.

  8. The Effect of Physical Resistance Training on Baroreflex Sensitivity of Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Moisés Felipe Pereira Gomes

    Full Text Available Abstract Background: Baroreceptors act as regulators of blood pressure (BP; however, its sensitivity is impaired in hypertensive patients. Among the recommendations for BP reduction, exercise training has become an important adjuvant therapy in this population. However, there are many doubts about the effects of resistance exercise training in this population. Objective: To evaluate the effect of resistance exercise training on BP and baroreceptor sensitivity in spontaneously hypertensive rats (SHR. Method: Rats SHR (n = 16 and Wistar (n = 16 at 8 weeks of age, at the beginning of the experiment, were randomly divided into 4 groups: sedentary control (CS, n = 8; trained control (CT, n = 8; sedentary SHR (HS, n = 8 and trained SHR (HT, n = 8. Resistance exercise training was performed in a stairmaster-type equipment (1.1 × 0.18 m, 2 cm between the steps, 80° incline with weights attached to their tails, (5 days/week, 8 weeks. Baroreceptor reflex control of heart rate (HR was tested by loading/unloading of baroreceptors with phenylephrine and sodium nitroprusside. Results: Resistance exercise training increased the soleus muscle mass in SHR when compared to HS (HS 0.027 ± 0.002 g/mm and HT 0.056 ± 0.003 g/mm. Resistance exercise training did not alter BP. On the other hand, in relation to baroreflex sensitivity, bradycardic response was improved in the TH group when compared to HS (HS -1.3 ± 0.1 bpm/mmHg and HT -2.6 ± 0.2 bpm/mmHg although tachycardia response was not altered by resistance exercise (CS -3.3 ± 0.2 bpm/mmHg, CT -3.3 ± 0.1 bpm/mmHg, HS -1.47 ± 0.06 bpm/mmHg and HT -1.6 ± 0.1 bpm/mmHg. Conclusion: Resistance exercise training was able to promote improvements on baroreflex sensitivity of SHR rats, through the improvement of bradycardic response, despite not having reduced BP.

  9. Dynamic baroreflex control of blood pressure: influence of the heart vs. peripheral resistance.

    Science.gov (United States)

    Liu, Huang-Ku; Guild, Sarah-Jane; Ringwood, John V; Barrett, Carolyn J; Leonard, Bridget L; Nguang, Sing-Kiong; Navakatikyan, Michael A; Malpas, Simon C

    2002-08-01

    The aim in the present experiments was to assess the dynamic baroreflex control of blood pressure, to develop an accurate mathematical model that represented this relationship, and to assess the role of dynamic changes in heart rate and stroke volume in giving rise to components of this response. Patterned electrical stimulation [pseudo-random binary sequence (PRBS)] was applied to the aortic depressor nerve (ADN) to produce changes in blood pressure under open-loop conditions in anesthetized rabbits. The stimulus provided constant power over the frequency range 0-0.5 Hz and revealed that the composite systems represented by the central nervous system, sympathetic activity, and vascular resistance responded as a second-order low-pass filter (corner frequency approximately 0.047 Hz) with a time delay (1.01 s). The gain between ADN and mean arterial pressure was reasonably constant before the corner frequency and then decreased with increasing frequency of stimulus. Although the heart rate was altered in response to the PRBS stimuli, we found that removal of the heart's ability to contribute to blood pressure variability by vagotomy and beta(1)-receptor blockade did not significantly alter the frequency response. We conclude that the contribution of the heart to the dynamic regulation of blood pressure is negligible in the rabbit. The consequences of this finding are examined with respect to low-frequency oscillations in blood pressure.

  10. Time-dependent effects of training on cardiovascular control in spontaneously hypertensive rats: role for brain oxidative stress and inflammation and baroreflex sensitivity.

    Directory of Open Access Journals (Sweden)

    Gustavo S Masson

    Full Text Available Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR. Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training and sedentary (S SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC, NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR, p38 MAPK and ERK1/2 expression (Western blotting, NF-κB content (electrophoretic mobility shift assay and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control showed increased mean arterial pressure (172±3 mmHg, pressure variability and heart rate (358±7 b/min, decreased baroreflex sensitivity and heart rate variability, increased p47phox and reactive oxygen species production, elevated NF-κB activity and increased TNF-α and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04±0.31 vs. 2.31±0.19 b/min/mmHg in SHR-S. These responses were followed by increased vagal component of heart rate variability (1.9-fold and resting bradycardia (-13% at the 4th week, and, by reduced vasomotor component of pressure variability (-28% and decreased mean arterial pressure (-7% only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro

  11. Influence of fluvastatin on cardiac function and baroreflex sensitivity in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Fang XIE; Chao SUN; Li-hua SUN; Jing-yuan LI; Xin CHEN; Hui CHE; Guan-yi LU; Bao-feng YANG; Jing AI

    2011-01-01

    Aim: To investigate whether fluvastatin is able to ameliorate the impaired cardiac function or baroreflex sensitivity (BRS) in rats with type 1 diabetes.Methods: Type 1 diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) and then administered fluvastatin (1.5,cardiac function and BRS were measured in diabetic rats after fluvastatin treatment for 30 d.Results: The polydipsia, polyphagia and abnormal biochemical indexes of blood were significantly ameliorated by the the 3.0- and 6.0-mg doses of fluvastatin in STZ-induced diabetic rats. FBG was decreased in diabetic rats after fluvastatin treatment for 30 d. The left ventricular systolic pressure (LVSP) and the maximum rate of change of left ventricular pressure in the isovolumic contraction and relaxation period (±dp/dtmax) were elevated, and left ventricular diastolic pressure (LVEDP) was decreased by fluvastatin. The attenuated heart rate responses to arterial blood pressure (ABP) increase induced by phenylephrine (PE) and ABP decrease induced by sodium nitroprusside (SNP) were reversed by the 3.0-mg dose of fluvastatin.Conclusion: Fluvastatin regulates blood lipid levels and decreases the FBG level in diabetic rats. These responses can protect the diabetic heart from complications by improving cardiac function and BRS.

  12. Skeletal muscle responses to unweighting in humans

    Science.gov (United States)

    Dudley, Gary A.

    1991-01-01

    An overview of earth-based studies is presented emphasizing the data on muscular strength and size derived from experiments under simulated microgravity. The studies involve the elimination of weight-bearing responsibility of lower-limb human musculature to simulate the unweighting effects of space travel in the absence of exercise. Reference is given to bedrest and unilateral lower-limb suspension, both of which provide data that demonstrate the decreased strength of the knee extensors of 20-25 percent. The response is related to the decrease in cross-sectional area of the knee extensors which is a direct indication of muscle-fiber atrophy. Most of the effects of unweighting are associated with extensor muscles in the lower limbs and not with postural muscles. Unweighting is concluded to cause significant adaptations in the human neuromuscular system that require further investigation.

  13. DNA repair responses in human skin cells

    Energy Technology Data Exchange (ETDEWEB)

    Hanawalt, P.C.; Liu, S.C.; Parsons, C.S.

    1981-07-01

    Sunlight and some environmental chemical agents produce lesions in the DNA of human skin cells that if unrepaired may interfere with normal functioning of these cells. The most serious outcome of such interactions may be malignancy. It is therefore important to develop an understanding of mechanisms by which the lesions may be repaired or tolerated without deleterious consequences. Our models for the molecular processing of damaged DNA have been derived largely from the study of bacterial systems. Some similarities but significant differences are revealed when human cell responses are tested against these models. It is also of importance to learn DNA repair responses of epidermal keratinocytes for comparison with the more extensive studies that have been carried out with dermal fibroblasts. Our experimental results thus far indicate similarities for the excision-repair of ultraviolet-induced pyrimidine dimers in human keratinocytes and fibroblasts. Both the monoadducts and the interstrand crosslinks produced in DNA by photoactivated 8-methoxypsoralen (PUVA) can be repaired in normal human fibroblasts but not in those from xeroderma pigmentosum patients. The monoadducts, like pyrimidine dimers, are probably the more mutagenic/carcinogenic lesions while the crosslinks are less easily repaired and probably result in more effective blocking of DNA function. It is suggested that a split-dose protocol that maximizes the production of crosslinks while minimizing the yield of monoadducts may be more effective and potentially less carcinogenic than the single ultraviolet exposure regimen in PUVA therapy for psoriasis.

  14. Assessing the strength of cardiac and sympathetic baroreflex controls via transfer entropy during orthostatic challenge

    Science.gov (United States)

    Porta, Alberto; Marchi, Andrea; Bari, Vlasta; De Maria, Beatrice; Esler, Murray; Lambert, Elisabeth; Baumert, Mathias

    2017-05-01

    The study assesses the strength of the causal relation along baroreflex (BR) in humans during an incremental postural challenge soliciting the BR. Both cardiac BR (cBR) and sympathetic BR (sBR) were characterized via BR sequence approaches from spontaneous fluctuations of heart period (HP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA). A model-based transfer entropy method was applied to quantify the strength of the coupling from SAP to HP and from DAP to MSNA. The confounding influences of respiration were accounted for. Twelve young healthy subjects (20-36 years, nine females) were sequentially tilted at 0°, 20°, 30° and 40°. We found that (i) the strength of the causal relation along the cBR increases with tilt table inclination, while that along the sBR is unrelated to it; (ii) the strength of the causal coupling is unrelated to the gain of the relation; (iii) transfer entropy indexes are significantly and positively associated with simplified causality indexes derived from BR sequence analysis. The study proves that causality indexes are complementary to traditional characterization of the BR and suggests that simple markers derived from BR sequence analysis might be fruitfully exploited to estimate causality along the BR. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

  15. Neural blockade during exercise augments central command's contribution to carotid baroreflex resetting

    Science.gov (United States)

    Querry, R. G.; Smith, S. A.; Stromstad, M.; Ide, K.; Raven, P. B.; Secher, N. H.

    2001-01-01

    This investigation was designed to determine central command's role on carotid baroreflex (CBR) resetting during exercise. Nine volunteer subjects performed static and rhythmic handgrip exercise at 30 and 40% maximal voluntary contraction (MVC), respectively, before and after partial axillary neural blockade. Stimulus-response curves were developed using the neck pressure-neck suction technique and a rapid pulse train protocol (+40 to -80 Torr). Regional anesthesia resulted in a significant reduction in MVC. Heart rate (HR) and ratings of perceived exertion (RPE) were used as indexes of central command and were elevated during exercise at control force intensity after induced muscle weakness. The CBR function curves were reset vertically with a minimal lateral shift during control exercise and exhibited a further parallel resetting during exercise with neural blockade. The operating point was progressively reset to coincide with the centering point of the CBR curve. These data suggest that central command was a primary mechanism in the resetting of the CBR during exercise. However, it appeared that central command modulated the carotid-cardiac reflex proportionately more than the carotid-vasomotor reflex.

  16. Delegating responsibilities in human-robot teams

    Science.gov (United States)

    DeKoven, Elyon A. M.; Bechtel, Bob; Zaientz, Jack; Lisse, Sean; Murphy, Anne K. G.

    2006-05-01

    Trends in combat technology research point to an increasing role for uninhabited vehicles and other robotic elements in modern warfare tactics. However, real-time control of multiple uninhabited battlefield robots and other semi-autonomous systems, in diverse fields of operation, is a difficult problem for modern warfighters that, while identified, has not been adequately addressed. Soar Technology is applying software agent technology to simplify demands on the human operator. Our goal is to build intelligent systems capable of finding the best balance of control between the human and autonomous system capabilities. We are developing an Intelligent Control Framework (ICF) from which to create agent-based systems that are able to dynamically delegate responsibilities across multiple robotic assets and the human operator. This paper describes proposed changes to our ICF architecture based on principles of human-machine teamwork derived from collaborative discourse theory. We outline the principles and the new architecture, and give examples of the benefits that can be realized from our approach.

  17. Corporate Social Responsibility and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2006-01-01

    rather than public regulation. The UN Global Compact and the UN Norms on human rights responsibilities for transnational and other corporations are discussed as examples of changes in international UN based regulation of corporations in relation to CSR topics, and as examples of network governance......Taking its point of departure in the aims of the United Nations, the article discusses challenges to international law making and the UN in the relatively immediate future in view of the increasing role and influence of corporations. This is done addressing challenges posed by globalisation...

  18. Human response to vibration in residential environments.

    Science.gov (United States)

    Waddington, David C; Woodcock, James; Peris, Eulalia; Condie, Jenna; Sica, Gennaro; Moorhouse, Andrew T; Steele, Andy

    2014-01-01

    This paper presents the main findings of a field survey conducted in the United Kingdom into the human response to vibration in residential environments. The main aim of this study was to derive exposure-response relationships for annoyance due to vibration from environmental sources. The sources of vibration considered in this paper are railway and construction activity. Annoyance data were collected using questionnaires conducted face-to-face with residents in their own homes. Questionnaires were completed with residents exposed to railway induced vibration (N = 931) and vibration from the construction of a light rail system (N = 350). Measurements of vibration were conducted at internal and external positions from which estimates of 24-h vibration exposure were derived for 1073 of the case studies. Sixty different vibration exposure descriptors along with 6 different frequency weightings were assessed as potential predictors of annoyance. Of the exposure descriptors considered, none were found to be a better predictor of annoyance than any other. However, use of relevant frequency weightings was found to improve correlation between vibration exposure and annoyance. A unified exposure-response relationship could not be derived due to differences in response to the two sources so separate relationships are presented for each source.

  19. Entropy Generation Analysis of Human Thermal Stress Responses

    OpenAIRE

    Boregowda, Satish C.; Choate, Robert E.; Rodney Handy

    2012-01-01

    The present study involves application of an open system entropy generation formulation to analyze human thermal stress responses. The time-series human thermal stress response data are obtained by conducting a simulation using a validated finite-element human thermal model (FEHTM). These simulated human thermal response data are used as an input to the entropy generation expression to obtain human entropy generation (HEG) values. The effects of variables such as air temperature, relative hum...

  20. Noninvasive transcutaneous bionic baroreflex system prevents severe orthostatic hypotension in patients with spinal cord injury.

    Science.gov (United States)

    Yoshida, Masayoshi; Murayama, Yoshinori; Chishaki, Akiko; Sunagawa, Kenji

    2008-01-01

    Central baroreflex failure in patients with spinal cord injury results in serious orthostatic hypotension. We examined if transcutaneous electrical stimulation regulates arterial pressure in those patients. We identified skin regions capable of increasing arterial pressure and determined respective transfer function. Using the transfer function, we designed the feedback regulator (i.e., bionic baroreflex system) to control arterial pressure. Orthostatic stress decreased arterial pressure profoundly. Activation of bionic regulator restored and maintained arterial pressure at pre-specified levels. We conclude that the transcutaneous bionic system is noninvasive and capable of stabilizing arterial pressure in patients with spinal cord injury.

  1. The Neural Baroreflex Pathway in Subjects With Metabolic Syndrome

    Science.gov (United States)

    Zanoli, Luca; Empana, Jean-Philippe; Estrugo, Nicolas; Escriou, Guillaume; Ketthab, Hakim; Pruny, Jean-Francois; Castellino, Pietro; Laude, Dominique; Thomas, Frederique; Pannier, Bruno; Jouven, Xavier; Boutouyrie, Pierre; Laurent, Stephane

    2016-01-01

    Abstract The mechanisms that link metabolic syndrome (MetS) to increased cardiovascular risk are incompletely understood. We examined whether MetS is associated with the neural baroreflex pathway (NBP) and whether any such associations are independent of blood pressure values. This study involved the cross-sectional analysis of data on 2835 subjects aged 50 to 75 years from the Paris Prospective Study 3. The prevalence of MetS was defined according to the American Heart Association/National Heart Blood and Lung Institute definition. NBP values were calculated from the fluctuation of the common carotid distension rate and heart rate using fast Fourier transformation and cross-spectral analysis. The prevalence of MetS was 20.1% in men and 10.4% in women. Compared with controls, subjects with MetS (≥3 components), and those at risk for MetS (1–2 components) had lower NBP (−5.3% and −2.3%, respectively) and higher carotid stiffness (+13.5% and +6.8%, respectively). The negative association between MetS components and NBP was confirmed, even after adjustment for age, sex, and carotid stiffness. After stratification for blood pressure (BP) levels, NBP was reduced only in MetS subjects and those at risk with high BP. The NBP was positively associated with carotid stiffness in controls and subjects at risk for MetS. This association was lost in subjects with MetS, regardless of BP levels. Subjects with MetS had reduced NBP values. The role of BP is fundamental in the reduction of NBP. The mechanisms that link carotid stiffness and NBP are inactive in subjects with MetS, independent of BP levels. PMID:26765449

  2. "Regulation of the intracerebroventricular administration of brain-derived neurotrophic factor on baroreflex function and insulin sensitivity in rats".

    Science.gov (United States)

    Wang, Ming-Fu; Chan, Yin-Ching; Lee, Hsu-Tung; Hong, Ling-Zong

    2012-06-30

    "In addition to its well-established neurotrophic effects, brain-derived neurotrophic factor (BDNF) has also been shown to regulate glucose metabolism. The present study was conducted to determine whether BDNF has effects on baroreflex sensitivity (BRS) and whole-body insulin sensitivity through modulation of autonomic nervous function in normal rats. Male Sprague-Dawley rats were treated with intracerebroventricular BDNF (20 μg per rat, 10μl; BDNF) or artificial cerebrospinal fluid (10 μl; control) at an infusion rate of 1 μl/min in conscious state. The whole-body insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp technique. BRS in response to phenylephrine (PE-BRS) or sodium nitroprusside (NP-BRS) was assessed using linear regression analysis. The sympathetic and parasympathetic influences on BRS were investigated by pharmacological autonomic blockade. When compared to the control rats, blood glucose levels were slightly but significantly decreased in BDNF-treated rats. However, plasma insulin levels were reduced by about 30%. The whole-body insulin sensitivity was increased in BDNF-treated rats. In addition, blood pressure was increased but heart rate remained unchanged after BDNF treatment. Enhanced PE-BRS was also observed in the BDNF-treated rats, which was attributed to the abnormal parasympathetic activation as revealed by the results of the pharmacological blockade study with methylatropine. Results of the present demonstrate that central BDNF plays an important role in the regulation of whole-body insulin sensitivity and baroreflex function. The data indicate that the alteration of autonomic nervous function may play a role in the effects of BDNF."

  3. Influence of heat stress on arterial baroreflex control of heart rate in the baboon.

    Science.gov (United States)

    Gorman, A J; Proppe, D W

    1982-07-01

    The influence of environmental heat stress on the arterial baroreflex control of heart rate (HR) was studied in eight conscious, chronically instrumented baboons. Inflations of balloon occluders around the inferior vena cava (IVC) and thoracic descending aorta (DA) were used to produce acute, graded changes in mean arterial blood pressure (MABP) in 5 mm Hg intervals ranging from +/- 5 to +/- 25 mm Hg. After determination of the HR responses to changes in MABP in the normothermic baboon (blood temperature less than or equal to 37.6 degrees C), the animal was subjected to environmental heating to produce hyperthermia. When blood temperature reached approximately 39.5 degrees C, HR responses to graded DA and IVC occlusions were again determined. During hyperthermia, the HR sensitivity (delta HR/ delta MABP) to MABP changes was markedly diminished for reductions in MABP and significantly enhanced for increases in MABP. To determine whether these alterations in the HR response to changes in MABP were due to an alteration of the baroreflex control of HR, full, sigmoid-shaped HR-MABP curves for both the normothermic and hyperthermic states were constructed and characterized by total HR range, estimated slope of the steep portion of the curve, and MABP at the midpoint of the HR range (BP50). During hyperthermia (1) the whole HR-MABP curve shifted significantly upward by 35-40 beats/min, (2) total HR range, the estimated slope, and BP50 did not change, and (3) the control point (pre-occlusion HR-MABP value) curves were also constructed during either beta-adrenergic blockade or cholinergic (Ch)-receptor blockade in the normothermic and hyperthermic state. Similar to that seen for the unblocked heart, the whole HR-MABP curves were also shifted upward during hyperthermia in this group of baboons with no alteration in the total HR range, the estimated slope, or BP50. The upward shift in the HR-MABP curve during Ch-receptor blockade, unlike during beta-receptor blockade, was

  4. Cell Culture Assay for Human Noroviruses [response

    Energy Technology Data Exchange (ETDEWEB)

    Straub, Tim M.; Honer Zu Bentrup, Kerstin; Orosz Coghlan, Patricia; Dohnalkova, Alice; Mayer, Brooke K.; Bartholomew, Rachel A.; Valdez, Catherine O.; Bruckner-Lea, Cindy J.; Gerba, Charles P.; Abbaszadegan, Morteza A.; Nickerson, Cheryl A.

    2007-07-01

    We appreciate the comments provided by Leung et al., in response to our recently published article “In Vitro Cell Culture Infectivity Assay for Human Noroviruses” by Straub et al. (1). The specific aim of our project was to develop an in vitro cell culture infectivity assay for human noroviruses (hNoV) to enhance risk assessments when they are detected in water supplies. Reverse transcription (RT) qualitative or quantitative PCR are the primary assays for waterborne NoV monitoring. However, these assays cannot distinguish between infectious vs. non-infectious virions. When hNoV is detected in water supplies, information provided by our infectivity assay will significantly improve risk assessment models and protect human health, regardless of whether we are propagating NoV. Indeed, in vitro cell culture infectivity assays for the waterborne pathogen Cryptosporidium parvum that supplement approved fluorescent microscopy assays, do not result in amplification of the environmentally resistant hard-walled oocysts (2). However, identification of life cycle stages in cell culture provides evidence of infectious oocysts in a water supply. Nonetheless, Leung et al.’s assertion regarding the suitability of our method for the in vitro propagation of high titers of NoV is valid for the medical research community. In this case, well-characterized challenge pools of virus would be useful for developing and testing diagnostics, therapeutics, and vaccines. As further validation of our published findings, we have now optimized RT quantitative PCR to assess the level of viral production in cell culture, where we are indeed finding significant increases in viral titer. The magnitude and time course of these increases is dependent on both virus strain and multiplicity of infection. We are currently preparing a manuscript that will discuss these findings in greater detail, and the implications this may have for creating viral challenge pools

  5. Cardiac baroreflex gain is frequency dependent: insights from repeated sit-to-stand maneuvers and the modified Oxford method.

    Science.gov (United States)

    Horsman, Helen M; Peebles, Karen C; Galletly, Duncan C; Tzeng, Yu-Chieh

    2013-07-01

    Cardiac baroreflex gain is usually quantified as the reflex alteration in heart rate during changes in blood pressure without considering the effect of the rate of change in blood pressure on the estimated gain. This study sought to (i) characterize baroreflex gain as a function of blood pressure oscillation frequencies using a repeat sit-to-stand method and (ii) compare baroreflex gain values obtained using the sit-to-stand method against the modified Oxford method. Fifteen healthy individuals underwent the repeated sit-to-stand method in which blood pressure oscillations were driven at 0.03, 0.05, 0.07, and 0.1 Hz. Sixteen healthy participants underwent the sit-to-stand and modified Oxford methods to examine their agreement. Sit-to-stand baroreflex gain was highest at 0.05 Hz (8.8 ± 3.2 ms·mm Hg(-1)) and lowest at 0.1 Hz (5.8 ± 3.0 ms·mm Hg(-1)). Baroreflex gains at 0.03 Hz (7.7 ± 3.0 ms·mm Hg(-1)) and 0.07 Hz (7.5 ± 3.3 ms·mm Hg(-1)) were not different from the baroreflex gain at 0.05 Hz. There was moderate correlation between phenylephrine gain and sit-to-stand gain (r values ranged from 0.52 to 0.75; all frequencies, p sit-to-stand gain (r values ranged from -0.07 to 0.22; all p sit-to-stand gain showed poor agreement and a positive proportional bias. These results show that baroreflex gains derived from these 2 methods cannot be used interchangeably. Furthermore, cardiac baroreflex gain is frequency dependent between 0.03 Hz and 0.1 Hz, which challenges the conventional practice of summarizing baroreflex gain as a single number.

  6. Arterial baroreflex function does not influence telomere length in kidney of rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-fei ZHANG; Rui-fang YANG; Jin WANG; Lei ZHAO; Ling LI; Fu-ming SHEN; Ding-feng SU

    2006-01-01

    Aim:To investigate the relationship between arterial baroreflex (ABR) function and telomere length in kidney of rats.Methods:Stroke-prone spontaneously hypertensive rats (SHR-SP) and sinoaortic denervated rats (SAD) were used as models with depressed arterial baroreflex.In the first experiments,SHR-SP rats were examined at the age of 24 weeks for both sexes and 40 weeks for female rats. In the second experiments,SAD rats were studied 4 and 35 weeks after SAD operation.Blood pressure was continuously recorded for 4 h in a conscious state. After the determination of baroreflex sensitivity (BRS),the terminal restriction fragment (TRF) of rat kidney was analyzed using Southern blot.Results:The TRF length was found shorter in:a) male SHR-SP compared with age-matched female SHR-SP;b) female SHR-SP 40 weeks of age compared with 24 weeks of age; c) in rats 35 weeks after operation compared with rats 4 weeks post operation in both sham-operated and SAD rats.Conclusion:In SHR-SP,the TRF length did not correlate with BRS.In addition.SAD did not affect TRF length at either 4 or 35 weeks post-surgery.It may be concluded that baroreflex function does not influence the terminal restriction fragment (TRF) length in rats.

  7. Reduced baroreflex sensitivity in alcoholic cirrhosis: relations to hemodynamics and humoral systems

    DEFF Research Database (Denmark)

    Møller, Søren; Iversen, Jens S; Henriksen, Jens H;

    2007-01-01

    In cirrhosis, arterial vasodilatation leads to central hypovolemia and activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. As the liver disease and circulatory dysfunction may affect baroreflex sensitivity (BRS), we assessed BRS in a large group of patients with cirrh...

  8. Baroreflex Sensitivity And Autonomic Nervous System Function In Carotid Sinus Hypersensitivity

    DEFF Research Database (Denmark)

    Brinth, Louise Schouborg; Pors, Kirsten; Theibel, Ann Cathrine

    2015-01-01

    Syncope in the elderly may be caused by an apparent hypersensitivity in the high pressure baroreflex control of heart rate and blood pressure - carotid sinus hypersensitivity. Previous studies have found ambiguous results regarding the baroreceptor sensitivity in patients with carotid sinus hyper...... sensitivity may not follow the same neuronal pathways as those responding to the crude external pressures applied during carotid sinus massage...

  9. Insulin acts in the arcuate nucleus to increase lumbar sympathetic nerve activity and baroreflex function in rats

    National Research Council Canada - National Science Library

    Cassaglia, Priscila A; Hermes, Sam M; Aicher, Sue A; Brooks, Virginia L

    2011-01-01

    Non‐technical summary  Though the pancreatic hormone insulin is known to act in the brain to increase sympathetic nerve activity and baroreflex control of sympathetic nerve activity, its specific site of action had yet to be identified...

  10. The Effects of Bupivacaine and Ropivacaine on Baroreflex Sensitivity With or Without Respiratory Acidosis and Alkalosis in Rats

    National Research Council Canada - National Science Library

    Watanabe, Yukinaga; Dohi, Shuji; Iida, Hiroki; Ishiyama, Tadahiko

    1997-01-01

    ...) depression that could be enhanced in the presence of respiratory acidosis.We examined a potential suppression of baroreflex function with bupivacaine and ropivacaine during hypercapnic acidosis or hypocapnic alkalosis...

  11. Summary of human responses to ventilation

    Energy Technology Data Exchange (ETDEWEB)

    Seppanen, Olli A.; Fisk, William J.

    2004-06-01

    The effects of ventilation on indoor air quality and health is a complex issue. It is known that ventilation is necessary to remove indoor generated pollutants from indoor air or dilute their concentration to acceptable levels. But, as the limit values of all pollutants are not known, the exact determination of required ventilation rates based on pollutant concentrations and associated risks is seldom possible. The selection of ventilation rates has to be based also on epidemiological research (e.g. Seppanen et al., 1999), laboratory and field experiments (e.g. CEN 1996, Wargocki et al., 2002a) and experience (e.g. ECA 2003). Ventilation may also have harmful effects on indoor air quality and climate if not properly designed, installed, maintained and operated as summarized by Seppdnen (2003). Ventilation may bring indoors harmful substances that deteriorate the indoor environment. Ventilation also affects air and moisture flow through the building envelope and may lead to moisture problems that deteriorate the structures of the building. Ventilation changes the pressure differences over the structures of building and may cause or prevent the infiltration of pollutants from structures or adjacent spaces. Ventilation is also in many cases used to control the thermal environment or humidity in buildings. Ventilation can be implemented with various methods which may also affect health (e.g. Seppdnen and Fisk, 2002, Wargocki et al., 2002a). In non residential buildings and hot climates, ventilation is often integrated with air-conditioning which makes the operation of ventilation system more complex. As ventilation is used for many purposes its health effects are also various and complex. This paper summarizes the current knowledge on positive and negative effects of ventilation on health and other human responses. The focus of the paper is on office-type working environment and residential buildings. In the industrial premises the problems of air quality are usually

  12. Effects of Interaction Between Ventricular Assist Device Assistance and Autoregulated Mock Circulation Including Frank-Starling Mechanism and Baroreflex.

    Science.gov (United States)

    Jansen-Park, So-Hyun; Mahmood, Mohammad Nauzef; Müller, Indra; Turnhoff, Lisa Kathrin; Schmitz-Rode, Thomas; Steinseifer, Ulrich; Sonntag, Simon Johannes

    2016-10-01

    A mock heart circulation loop (MHCL) is a hydraulic model simulating the human circulatory system. It allows in vitro investigations of the interaction between cardiac assist devices and the human circulatory system. In this study, a preload sensitive MHCL, the MHCLAUTO , was developed to investigate the interaction between the left ventricle and left ventricular assist devices (LVADs). The Frank-Starling mechanism was modeled by regulating the stroke volume (SV) based on the measured mean diastolic left atrial pressure (MLAPdiast ). The baroreflex autoregulation mechanism was implemented to maintain a constant mean aortic pressure (MAP) by varying ventricular contractility (Emax ), heart rate (HR), afterload/systemic vascular resistance (SVR) and unstressed venous volume (UVV). The DP3 blood pump (Medos Medizintechnik GmbH) was used to simulate the LVAD. Characteristic parameters were measured in pathological conditions both with and without LVAD to assess the hemodynamic effect of LVAD on the MHCLAUTO . The results obtained from the MHCLAUTO show a high correlation to literature data. The study demonstrates the possibility of using the MHCLAUTO as a research tool to better understand the physiological interactions between cardiac implants and human circulation.

  13. A Commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It"

    Science.gov (United States)

    Everett, Jeff

    2013-01-01

    In this commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It" (McPhail 2013), the author discusses how McPhail's paper examines human rights teaching principles, the question of why corporations and business schools should respect and teach human rights, and how business…

  14. A Commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It"

    Science.gov (United States)

    Everett, Jeff

    2013-01-01

    In this commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It" (McPhail 2013), the author discusses how McPhail's paper examines human rights teaching principles, the question of why corporations and business schools should respect and teach human rights, and how business…

  15. Blood pressure reduction combining baroreflex restoration for stroke prevention in hypertension in rats

    Directory of Open Access Journals (Sweden)

    Shu-Wei Song

    2010-07-01

    Full Text Available Blood pressure reduction is an important and effective strategy in stroke prevention in hypertensives. Recently, we found that baroreflex restoration was also crucial in stroke prevention. The present work was designed to test the hypothesis that a combination of blood pressure reduction and baroreflex restoration may be a new strategy for stroke prevention. In Experiment 1, the effects of ketanserin (0.3, 1, 3, 10 mg/kg, amlodipine (0.3, 1, 2, 3 mg/kg and their combination (1+0.3, 1+1, 1+2, 1+3 mg/kg on blood pressure and baroreflex sensitivity (BRS of stroke-prone spontaneously hypertensive rats (SHR-SP were determined under conscious state. It was found that both amlodipine and ketanserin decreased blood pressure dose-dependently. Ketanserin enfanced BRS from a very small dose but amlodipine enfanced BRS only at largest dose used. At the dose of 1 + 2 mg/kg (ketanserin + amlodipine, the combination possessed the largest synergism on blood pressure reduction. In Experiments 2 and 3, SHR-SP and two-kidney, two-clip (2K2C renovascular hypertensive rats received life-long treatments with ketanserin (1 mg/kg and amlodipine (2 mg/kg or their combination (0.5+1, 1+2, 2+4 mg/kg. The survival time was recorded and the brain lesion was examined. It was found that all kinds of treatments prolonged the survival time of SHR-SP and 2K2C rats. The combination possessed a significantly better effect on stroke prevention than mono-therapies. In conclusion, combination of blood pressure reduction and baroreflex restoration may be a new strategy for the prevention of stroke in hypertension.

  16. Shortening baroreflex delay in hypertrophic cardiomyopathy patients – an unknown effect of β-blockers

    Science.gov (United States)

    Katarzynska-Szymanska, Agnieszka; Ochotny, Romuald; Oko-Sarnowska, Zofia; Wachowiak-Baszynska, Hanna; Krauze, Tomasz; Piskorski, Jaroslaw; Gwizdala, Adrian; Mitkowski, Przemyslaw; Guzik, Przemyslaw

    2013-01-01

    Aims Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and impaired diastolic and systolic function. Abnormal sympathetic–parasympathetic balance is a potential stimulus for left ventricular hypertrophy in HCM patients. β-Blockers are routinely used in HCM for their strong negative inotropic effect; however, these drugs also influence the sympathetic–parasympathetic balance. This study aimed to determine the autonomic control of the cardiovascular system and the autonomic effects of β-blockers in HCM patients treated or untreated with β-blockers. Methods Among 51 HCM outpatients (18–70 years old; 29 men) there were 19 individuals with no medication and 32 subjects treated with a β-blocker. Fourteen age- and gender-matched (23–70 years old; nine men) healthy volunteers were enrolled in the control group. Continuous, non-invasive finger blood pressure was recorded during supine rest for 30 min. Autonomic regulation of the cardiovascular system was measured by heart rate variability and spontaneous baroreflex function (cross-correlation sequence method). Results The mean pulse interval, time domain and spectral measures of heart rate variability and baroreflex sensitivity were comparable between HCM patients, treated or not with β-blockers, and the control group. However, the delay of the baroreflex was significantly longer in HCM patients who were not treated with β-blockers [2.0 (1.6–2.3) s] in comparison with HCM patients receiving β-blockers [1.4 (1.1–1.8) s; P = 0.0072] or control subjects [1.2 (0.8–1.8) s; P = 0.0025]. This delay did not differ between HCM patients treated with β-blockers and the control group. Conclusions Hypertrophic cardiomyopathy not treated with β-blockers is accompanied by prolonged baroreflex delay. The use of β-blockers normalizes this delay. PMID:23126403

  17. Baroreflex deficit blunts exercise training-induced cardiovascular and autonomic adaptations in hypertensive rats.

    Science.gov (United States)

    Moraes-Silva, I C; De La Fuente, R N; Mostarda, C; Rosa, K; Flues, K; Damaceno-Rodrigues, N R; Caldini, E G; De Angelis, K; Krieger, E M; Irigoyen, M C

    2010-03-01

    1. Baroreceptors regulate moment-to-moment blood pressure (BP) variations, but their long-term effect on the cardiovascular system remains unclear. Baroreceptor deficit accompanying hypertension contributes to increased BP variability (BPV) and sympathetic activity, whereas exercise training has been associated with an improvement in these baroreflex-mediated changes. The aim of the present study was to evaluate the autonomic, haemodynamic and cardiac morphofunctional effects of long-term sinoaortic baroreceptor denervation (SAD) in trained and sedentary spontaneously hypertensive rats (SHR). 2. Rats were subjected to SAD or sham surgery and were then further divided into sedentary and trained groups. Exercise training was performed on a treadmill (five times per week, 50-70% maximal running speed). All groups were studied after 10 weeks. 3. Sinoaortic baroreceptor denervation in SHR had no effect on basal heart rate (HR) or BP, but did augment BPV, impairing the cardiac function associated with increased cardiac hypertrophy and collagen deposition. Exercise training reduced BP and HR, re-established baroreflex sensitivity and improved both HR variability and BPV. However, SAD in trained SHR blunted all these improvements. Moreover, the systolic and diastolic hypertensive dysfunction, reduced left ventricular chamber diameter and increased cardiac collagen deposition seen in SHR were improved after the training protocol. These benefits were attenuated in trained SAD SHR. 4. In conclusion, the present study has demonstrated that the arterial baroreflex mediates cardiac disturbances associated with hypertension and is crucial for the beneficial cardiovascular morphofunctional and autonomic adaptations induced by chronic exercise in hypertension.

  18. Baroreflex function: determinants in healthy subjects and disturbances in diabetes, obesity and metabolic syndrome.

    Science.gov (United States)

    Skrapari, Ioanna; Tentolouris, Nicholas; Katsilambros, Nicholas

    2006-08-01

    Arterial baroreceptors play an important role in the short-term regulation of arterial pressure, by reflex chronotropic effect on the heart and by reflex regulation of sympathetic outflow. Baroreflex sensitivity (BRS) represents an index of arterial baroreceptors function. Several methods of measuring BRS are available nowadays. Different factors influence BRS in the healthy population, including sex, age, blood pressure, heart rate, body fatness, arterial stiffness, blood glucose and insulin levels, as well as physical activity. Baroreceptors dysfunction is evident in diseases such as coronary artery disease, heart failure, arterial hypertension, diabetes mellitus and obesity. The underlying mechanism of BRS attenuation in diabetes or obesity is not yet well known; however, there is increasing evidence that it is at least partly related to autonomic nervous system dysfunction and particularly to sympathetic overactivity that accompanies these diseases. Blunted BRS provides prognostic information for cardiovascular diseases and possibly for diabetes, while its' prognostic information for obesity is not yet established. This review deals with the mechanisms affecting baroreflex function, the newer techniques of BRS estimation and the most recent insights of baroreflex function in the healthy population and in various diseases with emphasis on diabetes and obesity. In addition, the clinical implication of a reduced BRS in these disorders is discussed.

  19. The vestibulosympathetic reflex in humans: neural interactions between cardiovascular reflexes

    Science.gov (United States)

    Ray, Chester A.; Monahan, Kevin D.

    2002-01-01

    1. Over the past 5 years, there has been emerging evidence that the vestibular system regulates sympathetic nerve activity in humans. We have studied this issue in humans by using head-down rotation (HDR) in the prone position. 2. These studies have clearly demonstrated increases in muscle sympathetic nerve activity (MSNA) and calf vascular resistance during HDR. These responses are mediated by engagement of the otolith organs and not the semicircular canals. 3. However, differential activation of sympathetic nerve activity has been observed during HDR. Unlike MSNA, skin sympathetic nerve activity does not increase with HDR. 4. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes (i.e. barorereflexes and skeletal muscle reflexes) has shown an additive interaction for MSNA. 5. The additive interaction between the baroreflexes and vestibulosympathetic reflex suggests that the vestibular system may assist in defending against orthostatic challenges in humans by elevating MSNA beyond that of the baroreflexes. 6. In addition, the further increase in MSNA via otolith stimulation during isometric handgrip, when arterial pressure is elevated markedly, indicates that the vestibulosympathetic reflex is a powerful activator of MSNA and may contribute to blood pressure and flow regulation during dynamic exercise. 7. Future studies will help evaluate the importance of the vestibulosympathetic reflex in clinical conditions associated with orthostatic hypotension.

  20. Exaggerated haemodynamic and neural responses to involuntary contractions induced by whole‐body vibration in normotensive obese versus lean women

    National Research Council Canada - National Science Library

    Dipla, Konstantina; Kousoula, Dimitra; Zafeiridis, Andreas; Karatrantou, Konstantina; Nikolaidis, Michalis G; Kyparos, Antonios; Gerodimos, Vassilis; Vrabas, Ioannis S

    2016-01-01

    .... What is the main finding and its importance? During involuntary contractions induced by whole-body vibration, there were augmented blood pressure and spontaneous baroreflex responses in obese compared with lean women...

  1. Human Trafficking, Globalisation and Transnational Feminist Responses

    NARCIS (Netherlands)

    T-D. Truong (Thanh-Dam)

    2014-01-01

    textabstractThis paper presents a historical overview of feminist frameworks for analysis and advocacy on human trafficking. It traces the major differences and similarities in the forms of knowledge produced since the Anti-White Slavery campaigns nearly two centuries ago. It highlights how institut

  2. Human Trafficking, Globalisation and Transnational Feminist Responses

    NARCIS (Netherlands)

    T-D. Truong (Thanh-Dam)

    2014-01-01

    textabstractThis paper presents a historical overview of feminist frameworks for analysis and advocacy on human trafficking. It traces the major differences and similarities in the forms of knowledge produced since the Anti-White Slavery campaigns nearly two centuries ago. It highlights how institut

  3. Genomic responses in mouse models poorly mimic human inflammatory diseases.

    Science.gov (United States)

    Seok, Junhee; Warren, H Shaw; Cuenca, Alex G; Mindrinos, Michael N; Baker, Henry V; Xu, Weihong; Richards, Daniel R; McDonald-Smith, Grace P; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C; López, Cecilia M; Honari, Shari; Moore, Ernest E; Minei, Joseph P; Cuschieri, Joseph; Bankey, Paul E; Johnson, Jeffrey L; Sperry, Jason; Nathens, Avery B; Billiar, Timothy R; West, Michael A; Jeschke, Marc G; Klein, Matthew B; Gamelli, Richard L; Gibran, Nicole S; Brownstein, Bernard H; Miller-Graziano, Carol; Calvano, Steve E; Mason, Philip H; Cobb, J Perren; Rahme, Laurence G; Lowry, Stephen F; Maier, Ronald V; Moldawer, Lyle L; Herndon, David N; Davis, Ronald W; Xiao, Wenzhong; Tompkins, Ronald G

    2013-02-26

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

  4. Genomic responses in mouse models poorly mimic human inflammatory diseases

    Science.gov (United States)

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  5. Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Klippel, Brunella F; Duemke, Licia B; Leal, Marcos A; Friques, Andreia G F; Dantas, Eduardo M; Dalvi, Rodolfo F; Gava, Agata L; Pereira, Thiago M C; Andrade, Tadeu U; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C

    2016-01-01

    It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated. SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of β1-adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis. Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR-kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1.6- and ~1.5-fold, respectively

  6. Human response to an individually controlled microenvironment

    DEFF Research Database (Denmark)

    Melikov, Arsen Krikor; Knudsen, G.L.

    2007-01-01

    The response of 48 subjects to an individually controlled microenvironment was studied at room air temperatures of 20 degrees C, 22 degrees C, and 26 degrees C An individually controlled system (ICS) comprising personalized ventilation, an under-desk air terminal device supplying cool air, a chair...... who are comfortable with their microenvironment....

  7. Human response times in a graphic environment

    CERN Document Server

    Yule, A

    1972-01-01

    A summary of the results obtained from measuring the response times of the users of an interactive graphics system available on the CERN central computers is presented. These results are then used to find an optimum time to wait before rolling the user's program to disc.

  8. Bioethics: New Responsibility for Human Service Administrators.

    Science.gov (United States)

    Burke, Rebecca

    The paper highlights the poignancy with which problems and issues surface as the fields of special education and bioethics (the combination of ethics and the life sciences) intersect, and touches upon professionals' responsibility for protection of the persons in their care. (Author/SBH)

  9. Human Trafficking, Globalisation and Transnational Feminist Responses

    OpenAIRE

    Truong, Thanh-Dam

    2014-01-01

    textabstractThis paper presents a historical overview of feminist frameworks for analysis and advocacy on human trafficking. It traces the major differences and similarities in the forms of knowledge produced since the Anti-White Slavery campaigns nearly two centuries ago. It highlights how institutional and moral considerations – especially concerning the treatment of the female body as an instrument – have played a role in shaping the conceptual possibilities and directions of politics for ...

  10. Civil society response to human trafficking in South Asia

    Directory of Open Access Journals (Sweden)

    Faisal Yousaf

    2006-05-01

    Full Text Available In South Asia civil society organisations have led the way in encouraging governments to address the problem of human trafficking. A coordinated regional response by both governments and civil society organisations is urgently required.

  11. Human Respiratory Responses during High Performance Flight

    Science.gov (United States)

    1987-11-01

    6SZ United Kingdom (c) Copyright (C) Controller BHSO London 1987 Sunwmiy The respiratory responses of experienced militar , pilots have been...40 Merrifield J T, Flick C A. In-flight oxygen measurement equipment. Air Standardization Co-ordinating Committee : Aerospace Medico ! & Life Support...Flugrad Reyjavik ITALY Aeronautica Militare Ufficic del Delegate Nazionale alTAGARD 3 Piarzale Adenauer 00 i 44 Roms/EUR LUXEMBOURG See

  12. Blood pressure variability and baroreflex sensitivity are not different in spontaneously hypertensive rats and stroke-prone spontaneously hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Lin-shu ZHAN; Yun-feng GUAN; Ding-feng SU; Chao-yu MIAO

    2005-01-01

    Aim: To demonstrate and compare hemodynamic phenotypes of blood pressure (BP), blood pressure variability (BPV) and baroreflex sensitivity (BRS) in genetic hypertensive rats. Methods: BP was recorded continuously in conscious, freely moving rats using a computerized technique. BPV was expressed as the standard deviation of beat-to-beat BP values during a 1-h period. BRS was determined by measuring the heart period prolongation in response to the elevation in BP produced by an intravenous injection of phenylephrine. Results: Body weight and heart period were not different between spontaneously hypertensive rats (SHR)and stroke-prone spontaneously hypertensive rats (SHR-SP) at the age of 15weeks. The BP level was markedly higher in SHR-SP than SHR, whereas there were no significant differences in BPV and BRS. Quantitatively, systolic, diastolic and mean BP were significantly elevated by 36.9%, 42.9% and 39.5%, respectively,in SHR-SP compared with SHR (P<0.01). However, their variabilities were elevated only by 14.0%, 0.4% and 10.1%, respectively, without statistical significance (P>0.05). Conclusion: BPV and BRS were not changed in parallel with the BP alterations in SHR and SHR-SP.

  13. Ovarian hormone deprivation reduces oxytocin expression in Paraventricular Nucleus preautonomic neurons and correlates with baroreflex impairment in rats

    Directory of Open Access Journals (Sweden)

    Vitor Ulisses De Melo

    2016-10-01

    Full Text Available The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN. Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation.

  14. Ovarian Hormone Deprivation Reduces Oxytocin Expression in Paraventricular Nucleus Preautonomic Neurons and Correlates with Baroreflex Impairment in Rats

    Science.gov (United States)

    De Melo, Vitor U.; Saldanha, Rayssa R. M.; Dos Santos, Carla R.; De Campos Cruz, Josiane; Lira, Vitor A.; Santana-Filho, Valter J.; Michelini, Lisete C.

    2016-01-01

    The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic) neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN). Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry) within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation.

  15. Diffusion Based Modeling of Human Brain Response to External Stimuli

    CERN Document Server

    Namazi, Hamidreza

    2012-01-01

    Human brain response is the overall ability of the brain in analyzing internal and external stimuli in the form of transferred energy to the mind/brain phase-space and thus, making the proper decisions. During the last decade scientists discovered about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research there was less effort which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling of human EEG signal, as an alert state of overall human brain activity monitoring, due to receiving external stimuli, based on fractional diffusion equation. The results of this modeling show very good agreement with the real human EEG signal and thus, this model can be used as a strong representative of the human brain activity.

  16. The Effect of Physical Resistance Training on Baroreflex Sensitivity of Hypertensive Rats.

    Science.gov (United States)

    Gomes, Moisés Felipe Pereira; Borges, Mariana Eiras; Rossi, Vitor de Almeida; Moura, Elizabeth de Orleans C de; Medeiros, Alessandra

    2017-01-01

    Baroreceptors act as regulators of blood pressure (BP); however, its sensitivity is impaired in hypertensive patients. Among the recommendations for BP reduction, exercise training has become an important adjuvant therapy in this population. However, there are many doubts about the effects of resistance exercise training in this population. To evaluate the effect of resistance exercise training on BP and baroreceptor sensitivity in spontaneously hypertensive rats (SHR). Rats SHR (n = 16) and Wistar (n = 16) at 8 weeks of age, at the beginning of the experiment, were randomly divided into 4 groups: sedentary control (CS, n = 8); trained control (CT, n = 8); sedentary SHR (HS, n = 8) and trained SHR (HT, n = 8). Resistance exercise training was performed in a stairmaster-type equipment (1.1 × 0.18 m, 2 cm between the steps, 80° incline) with weights attached to their tails, (5 days/week, 8 weeks). Baroreceptor reflex control of heart rate (HR) was tested by loading/unloading of baroreceptors with phenylephrine and sodium nitroprusside. Resistance exercise training increased the soleus muscle mass in SHR when compared to HS (HS 0.027 ± 0.002 g/mm and HT 0.056 ± 0.003 g/mm). Resistance exercise training did not alter BP. On the other hand, in relation to baroreflex sensitivity, bradycardic response was improved in the TH group when compared to HS (HS -1.3 ± 0.1 bpm/mmHg and HT -2.6 ± 0.2 bpm/mmHg) although tachycardia response was not altered by resistance exercise (CS -3.3 ± 0.2 bpm/mmHg, CT -3.3 ± 0.1 bpm/mmHg, HS -1.47 ± 0.06 bpm/mmHg and HT -1.6 ± 0.1 bpm/mmHg). Resistance exercise training was able to promote improvements on baroreflex sensitivity of SHR rats, through the improvement of bradycardic response, despite not having reduced BP. Os barorreceptores atuam como reguladores da pressão arterial (PA); no entanto, sua sensibilidade encontra-se prejudicada em pacientes hipertensos. Dentre as recomendações para a redução da PA, o treinamento f

  17. Immune responses to chlamydial antigens in humans.

    Science.gov (United States)

    Hanna, L; Kerlan, R; Senyk, G; Stites, D P; Juster, R P; Jawetz, E

    1982-01-01

    Antibody titer, lymphocyte stimulation and leukocyte migration inhibition with chlamydial antigens were determined repeatedly over many months on human subjects. The volunteers were retrospectively placed into four groups on the basis of clinical, laboratory and epidemiologic criteria. Group A consisted of persons with proven or probable chlamydial infection, including an illness confirmed by chlamydial isolation or seroconversion, or a clinically compatible illness with positive serologic results. Group B were sexual partners or close contacts of group A individuals. Group C were laboratory workers with prolonged exposure to viable chlamydiae or their antigens. Group D included persons of comparable age as those in groups A and B, but lacking a history of symptomatic chlamydial infection or of contact with chlamydiae. Individual cases illustrated the rise of antibody and some cell mediated immunity reactions (CMI) with active chlamydial infection. By contrast, laboratory exposure resulted in elevation of CMI but not of antibody. Statistical analysis of the results in 46 volunteers tested repeatedly indicated a strong association of specific antibody with lymphocyte stimulation, but not with leukocyte migration inhibition. Regression analysis suggested that the type of exposure markedly influenced the relationship between antibody and lymphocyte stimulation. Measurement of immunotype-specific antibody titer by microimmunofluorescence (or an equally sensitive method) remains the best laboratory indicator of past chlamydial infection. Neither antibody nor CMI can, as yet, be definitely related to resistance to re-infection in humans.

  18. Carotid baroreceptor-muscle sympathetic relation in humans.

    Science.gov (United States)

    Rea, R F; Eckberg, D L

    1987-12-01

    The purpose of this study was to define the relation between carotid distending pressure and muscle sympathetic activity in humans. Carotid baroreceptors of nine healthy subjects were compressed or stretched for 5 s with graded neck pressure or suction (+40 to -65 mmHg), and muscle sympathetic nerve activity was recorded. The results delineate several features of human baroreflex function. First, the carotid-muscle sympathetic relation is well described by an inverse sigmoid function. Second, a linear relation exists between carotid distending pressure and sympathetic outflow over a range of approximately 25 mmHg. Third, sympathetic responses to changes of carotid pressures are asymmetric; increases of sympathetic activity during carotid compression are much greater than reductions of sympathetic activity during carotid stretch. Fourth, at rest, normal subjects operate near the threshold level for sympathetic excitation. Thus the carotid-muscle sympathetic baroreflex is poised to oppose reductions more effectively than elevations of arterial pressure, and the range of pressures over which the reflex is active is wider than thought hitherto.

  19. Gustofacial and olfactofacial responses in human adults.

    Science.gov (United States)

    Weiland, Romy; Ellgring, Heiner; Macht, Michael

    2010-11-01

    Adults' facial reactions in response to tastes and odors were investigated in order to determine whether differential facial displays observed in newborns remain stable in adults who exhibit a greater voluntary facial control. Twenty-eight healthy nonsmokers (14 females) tasted solutions of PROP (bitter), NaCl (salty), citric acid (sour), sucrose (sweet), and glutamate (umami) differing in concentration (low, medium, and high) and smelled different odors (banana, cinnamon, clove, coffee, fish, and garlic). Their facial reactions were video recorded and analyzed using the Facial Action Coding System. Adults' facial reactions discriminated between stimuli with opponent valences. Unpleasant tastes and odors elicited negative displays (brow lower, upper lip raise, and lip corner depress). The pleasant sweet taste elicited positive displays (lip suck), whereas the pleasant odors did not. Unlike newborns, adults smiled with higher concentrations of some unpleasant tastes that can be regarded as serving communicative functions. Moreover, adults expressed negative displays with higher sweetness. Except for the "social" smile in response to unpleasant tastes, adults' facial reactions elicited by tastes and odors mostly correspond to those found in newborns. In conclusion, adults' facial reactions to tastes and odors appear to remain stable in their basic displays; however, some additional reactions might reflect socialization influences.

  20. The DNA-damage response in human biology and disease

    DEFF Research Database (Denmark)

    Jackson, Stephen P; Bartek, Jiri

    2009-01-01

    , signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management....

  1. Male-line transgenerational responses in humans.

    Science.gov (United States)

    Pembrey, Marcus E

    2010-12-01

    Genomic imprinting establishes the principle of epigenetic marks placed in one generation influencing gene expression in the next generation. This led to speculation that epigenetic gametic inheritance might underlie a form of transgenerational adaptation to major environmental challenges, such that exposures in one generation correlate with outcomes in the next generation(s). An ongoing collaboration between Umeå University, Sweden and the Avon Longitudinal Study of Parents and Childhood, Bristol University, UK has documented transgenerational correlations between food supply during the early life of the paternal grandparents and the grandchild's longevity, including associations with cardiovascular and diabetic deaths, and correlations between the onset of paternal smoking in mid-childhood and the body mass index of future sons. Whilst the mediating molecular mechanism(s) is unknown, the sex-specific transmission patterns and exposure-sensitive periods suggest a pre-evolved transgenerational response mechanism.

  2. Human response to an individually controlled microenvironment

    DEFF Research Database (Denmark)

    Melikov, Arsen Krikor; Knudsen, G.L.

    2007-01-01

    The response of 48 subjects to an individually controlled microenvironment was studied at room air temperatures of 20 degrees C, 22 degrees C, and 26 degrees C An individually controlled system (ICS) comprising personalized ventilation, an under-desk air terminal device supplying cool air, a chair...... with convectively heated backrest, an under-desk radiant heating panel, and a floor-heating panel were used. The temperature of the air supplied from the personalized ventilation and the under-desk device was 20 degrees C The subjects were provided with control of the flow rate and direction of the personalized air...... at a room temperature of 22 degrees C without ICS. Thus, ICS will increase the number of satisfied occupants when applied in practice. The design and control of the ICS, as well as the background air distribution in a room, should be carefully considered in order to obtain the maximum number of occupants...

  3. Modeling baroreflex regulation of heart rate during orthostatic stress

    DEFF Research Database (Denmark)

    Olufsen, Mette; Tran, Hien T.; Ottesen, Johnny T.

    2006-01-01

    . The model uses blood pressure measured in the finger as an input to model heart rate dynamics in response to changes in baroreceptor nerve firing rate, sympathetic and parasympathetic responses, vestibulo-sympathetic reflex, and concentrations of norepinephrine and acetylcholine. We formulate an inverse...

  4. Human immune responses during schistosomiasis mansoni

    Directory of Open Access Journals (Sweden)

    Giovanni Gazzinelli

    1992-06-01

    Full Text Available Studies of immune responses as they occur in patients with schistosomiasis appear to progress relative to corrent technological advances, and to advance despite the understandable inability to pursue in vivo manipulations in this host/parasite system. Emphasis is most often placed on making immunological comparisons between such patient groups as reinfected/non-reinfected, intestinals/hepatosplenic, high/low intensities of infection, infected/uninfected within endemic areas, and those born of infected/uninfected mothers. Based on these types of comparisons, reasonable conjectures can be made regarding the immunological occurrences during this chronic exposure condition. Some consideration is now being given to the immune mechanisms of some of the observations made, and while some of these must then be carried back to experimental models for further manipulation-based analysis, new technological developments continue to assist in the field/bench ability to ask questions that might assist our understanding to a point where this knowledge can be applied to shaping developmental approaches to vaccine development and the goal of alleviating morbidity.O estudo da resposta imune de pacientes com esquistossomose progride em função do avanço tecnológico, apesar das dificuldades de manipulação in vivo deste complexo sistema parasita-hospedeiro. A ênfase nos estudos tem sido mais freqüentemente dirigida para comparações entre grupos característicos de indivíduos, tais como infectado/não infectado, reinfectado/ não reinfectado, assintomático/hepato-esplênico, com intensidade de infecção alta/baixa, etc. Baseado nessas comparações tem-se obtido informações que permitem conjecturas razoáveis com relação à regulação imunológica, susceptibilidade e resistência e até mesmo considerações sôbre mecanismos, que têm sido mais apropriadamente analisados, entretanto, em sistemas experimentais. Tais estudos têm como finalidade a

  5. Antihypertensive effect of Carica papaya via a reduction in ACE activity and improved baroreflex.

    Science.gov (United States)

    Brasil, Girlandia Alexandre; Ronchi, Silas Nascimento; do Nascimento, Andrews Marques; de Lima, Ewelyne Miranda; Romão, Wanderson; da Costa, Helber Barcellos; Scherer, Rodrigo; Ventura, José Aires; Lenz, Dominik; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Andrade, Tadeu Uggere

    2014-11-01

    The aims of this study were to evaluate the antihypertensive effects of the standardised methanolic extract of Carica papaya, its angiotensin converting enzyme inhibitory effects in vivo, its effect on the baroreflex and serum angiotensin converting enzyme activity, and its chemical composition. The chemical composition of the methanolic extract of C. papaya was evaluated by liquid chromatography-mass/mass and mass/mass spectrometry. The angiotensin converting enzyme inhibitory effect was evaluated in vivo by Ang I administration. The antihypertensive assay was performed in spontaneously hypertensive rats and Wistar rats that were treated with enalapril (10 mg/kg), the methanolic extract of C. papaya (100 mg/kg; twice a day), or vehicle for 30 days. The baroreflex was evaluated through the use of sodium nitroprusside and phenylephrine. Angiotensin converting enzyme activity was measured by ELISA, and cardiac hypertrophy was evaluated by morphometric analysis. The methanolic extract of C. papaya was standardised in ferulic acid (203.41 ± 0.02 µg/g), caffeic acid (172.60 ± 0.02 µg/g), gallic acid (145.70 ± 0.02 µg/g), and quercetin (47.11 ± 0.03 µg/g). The flavonoids quercetin, rutin, nicotiflorin, clitorin, and manghaslin were identified in a fraction of the extract. The methanolic extract of C. papaya elicited angiotensin converting enzyme inhibitory activity. The antihypertensive effects elicited by the methanolic extract of C. papaya were similar to those of enalapril, and the baroreflex sensitivity was normalised in treated spontaneously hypertensive rats. Plasma angiotensin converting enzyme activity and cardiac hypertrophy were also reduced to levels comparable to the enalapril-treated group. These results may be associated with the chemical composition of the methanolic extract of C. papaya, and are the first step into the development of a new phytotherapic product which could be used in the treatment of hypertension.

  6. Modulation of stimulus contrast on the human pupil orienting response.

    Science.gov (United States)

    Wang, Chin-An; Munoz, Douglas P

    2014-09-01

    The sudden appearance of a novel stimulus initiates a series of responses to orient the body for appropriate actions, including not only shifts of gaze and attention, but also transient pupil dilation. Modulation of pupil dynamics by stimulus properties is less understood, although its effects on other components of orienting have been extensively explored. Microstimulation of the superior colliculus evoked transient pupil dilation, and the initial component of pupil dilation evoked by microstimulation was similar to that elicited by the presentation of salient sensory stimuli, suggesting a coordinated role of the superior colliculus on this behavior, although evidence in humans is yet to be established. To examine pupil orienting responses in humans, we presented visual stimuli while participants fixated on a central visual spot. Transient pupil dilation in humans was elicited after presentation of a visual stimulus in the periphery. The evoked pupil responses were modulated systematically by stimulus contrast, with faster and larger pupil responses triggered by higher contrast stimuli. The pupil response onset latencies for high contrast stimuli were similar to those produced by the light reflex and significantly faster than the darkness reflex, suggesting that the initial component of pupil dilation is probably mediated by inhibition of the parasympathetic pathway. The contrast modulation was pronounced under different levels of baseline pupil size. Together, our results demonstrate visual contrast modulation on the orienting pupil response in humans.

  7. Hemifield dependence of responses to colour in human fusiform gyrus.

    Science.gov (United States)

    Gonzalez, Francisco; Relova, José Luis; Prieto, Angel; Peleteiro, Manuel; Romero, Maria C

    2006-08-01

    To investigate the hemifield dependence of visually evoked responses to colour in the human fusiform gyrus we recorded evoked potentials from subdural electrodes in a patient suffering from occipital epilepsy. The responses in the fusiform gyrus show a strong hemifield dependence and discriminate the onset from the offset of the stimulus. Additionally, we found responses to squares made of random dots, whereas no responses were found to squares with a homogeneous bright surface. Our findings further support the idea that the fusiform gyrus is related to colour and pattern perception. However, the hemifield dependence we found may indicate that further processing is required in order to combine information from both visual hemifields.

  8. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

    Science.gov (United States)

    Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

    2017-06-01

    Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4(+) T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment.

  9. Reduced baroreflex sensitivity and pulmonary dysfunction in alcoholic cirrhosis: effect of hyperoxia

    DEFF Research Database (Denmark)

    Møller, Søren; Iversen, J.S.; Krag, A.

    2010-01-01

    matched controls underwent hemodynamic and pulmonary investigations. BRS was assessed by cross-spectral analysis of variabilities between blood pressure and heart rate time series. A 100% oxygen test was performed with the assessment of arterial oxygen tensions (Pa(O(2))) and alveolar-arterial oxygen......Patients with cirrhosis exhibit impaired regulation of the arterial blood pressure, reduced baroreflex sensitivity (BRS), and prolonged QT interval. In addition, a considerable number of patients have a pulmonary dysfunction with hypoxemia, impaired lung diffusing capacity (Dl(CO)), and presence...

  10. Thermodynamic Modeling and Analysis of Human Stress Response

    Science.gov (United States)

    Boregowda, S. C.; Tiwari, S. N.

    1999-01-01

    A novel approach based on the second law of thermodynamics is developed to investigate the psychophysiology and quantify human stress level. Two types of stresses (thermal and mental) are examined. A Unified Stress Response Theory (USRT) is developed under the new proposed field of study called Engineering Psychophysiology. The USRT is used to investigate both thermal and mental stresses from a holistic (human body as a whole) and thermodynamic viewpoint. The original concepts and definitions are established as postulates which form the basis for thermodynamic approach to quantify human stress level. An Objective Thermal Stress Index (OTSI) is developed by applying the second law of thermodynamics to the human thermal system to quantify thermal stress or dis- comfort in the human body. The human thermal model based on finite element method is implemented. It is utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal stress responses under different environmental conditions. An innovative hybrid technique is developed to analyze human thermal behavior based on series of human-environment interaction simulations. Continuous monitoring of thermal stress is demonstrated with the help of OTSI. It is well established that the human thermal system obeys the second law of thermodynamics. Further, the OTSI is validated against the experimental data. Regarding mental stress, an Objective Mental Stress Index (OMSI) is developed by applying the Maxwell relations of thermodynamics to the combined thermal and cardiovascular system in the human body. The OMSI is utilized to demonstrate the technique of monitoring mental stress continuously and is validated with the help of series of experimental studies. Although the OMSI indicates the level of mental stress, it provides a strong thermodynamic and mathematical relationship between activities of thermal and cardiovascular systems of the human body.

  11. Improving Emergency Response and Human-Robotic Performance

    Energy Technology Data Exchange (ETDEWEB)

    David I. Gertman; David J. Bruemmer; R. Scott Hartley

    2007-08-01

    Preparedness for chemical, biological, and radiological/nuclear incidents at nuclear power plants (NPPs) includes the deployment of well trained emergency response teams. While teams are expected to do well, data from other domains suggests that the timeliness and accuracy associated with incident response can be improved through collaborative human-robotic interaction. Many incident response scenarios call for multiple, complex procedure-based activities performed by personnel wearing cumbersome personal protective equipment (PPE) and operating under high levels of stress and workload. While robotic assistance is postulated to reduce workload and exposure, limitations associated with communications and the robot’s ability to act independently have served to limit reliability and reduce our potential to exploit human –robotic interaction and efficacy of response. Recent work at the Idaho National Laboratory (INL) on expanding robot capability has the potential to improve human-system response during disaster management and recovery. Specifically, increasing the range of higher level robot behaviors such as autonomous navigation and mapping, evolving new abstractions for sensor and control data, and developing metaphors for operator control have the potential to improve state-of-the-art in incident response. This paper discusses these issues and reports on experiments underway intelligence residing on the robot to enhance emergency response.

  12. Humpback Dolphin (Genus Sousa) Behavioural Responses to Human Activities.

    Science.gov (United States)

    Piwetz, Sarah; Lundquist, David; Würsig, Bernd

    2015-01-01

    Humpback dolphins (genus Sousa) use shallow, near-shore waters throughout their range. This coastal distribution makes them vulnerable to recreational and commercial disturbances, especially near heavily populated and industrialized areas. Most research focusing on Sousa and human activities has emphasized direct impacts and threats, involving injury and death, with relatively little focus on indirect effects on dolphins, such as changes in behaviour that may lead to deleterious effects. Understanding behaviour is important in resolving human-wildlife conflict and is an important component of conservation. This chapter gives an overview of animal behavioural responses to human activity with examples from diverse taxa; reviews the scientific literature on behavioural responses of humpback dolphins to human activity throughout their range, including marine vessel traffic, dolphin tourism, cetacean-fishery interactions, noise pollution, and habitat alteration; and highlights information and data gaps for future humpback dolphin research to better inform behaviour-based management decisions that contribute to conservation efforts.

  13. Neural Correlates of the Cortisol Awakening Response in Humans

    OpenAIRE

    Boehringer, Andreas; Tost, Heike; Haddad, Leila; Lederbogen, Florian; Wüst, Stefan; Schwarz, Emanuel; Meyer-Lindenberg, Andreas

    2015-01-01

    The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (vox...

  14. Modeling human response errors in synthetic flight simulator domain

    Science.gov (United States)

    Ntuen, Celestine A.

    1992-01-01

    This paper presents a control theoretic approach to modeling human response errors (HRE) in the flight simulation domain. The human pilot is modeled as a supervisor of a highly automated system. The synthesis uses the theory of optimal control pilot modeling for integrating the pilot's observation error and the error due to the simulation model (experimental error). Methods for solving the HRE problem are suggested. Experimental verification of the models will be tested in a flight quality handling simulation.

  15. Aversive Pavlovian Responses Affect Human Instrumental Motor Performance

    Science.gov (United States)

    Rigoli, Francesco; Pavone, Enea Francesco; Pezzulo, Giovanni

    2012-01-01

    In neuroscience and psychology, an influential perspective distinguishes between two kinds of behavioral control: instrumental (habitual and goal-directed) and Pavlovian. Understanding the instrumental-Pavlovian interaction is fundamental for the comprehension of decision-making. Animal studies (as those using the negative auto-maintenance paradigm), have demonstrated that Pavlovian mechanisms can have maladaptive effects on instrumental performance. However, evidence for a similar effect in humans is scarce. In addition, the mechanisms modulating the impact of Pavlovian responses on instrumental performance are largely unknown, both in human and non-human animals. The present paper describes a behavioral experiment investigating the effects of Pavlovian conditioned responses on performance in humans, focusing on the aversive domain. Results showed that Pavlovian responses influenced human performance, and, similar to animal studies, could have maladaptive effects. In particular, Pavlovian responses either impaired or increased performance depending on modulator variables such as threat distance, task controllability, punishment history, amount of training, and explicit punishment expectancy. Overall, these findings help elucidating the computational mechanisms underlying the instrumental-Pavlovian interaction, which might be at the base of apparently irrational phenomena in economics, social behavior, and psychopathology. PMID:23060738

  16. Aversive Pavlovian responses affect human instrumental motor performance

    Directory of Open Access Journals (Sweden)

    Francesco eRigoli

    2012-10-01

    Full Text Available In neuroscience and psychology, an influential perspective distinguishes between two kinds of behavioural control: instrumental (habitual and goal-directed and Pavlovian. Understanding the instrumental-Pavlovian interaction is fundamental for the comprehension of decision-making. Animal studies (as those using the negative auto-maintenance paradigm, have demonstrated that Pavlovian mechanisms can have maladaptive effects on instrumental performance. However, evidence for a similar effect in humans is scarce. In addition, the mechanisms modulating the impact of Pavlovian responses on instrumental performance are largely unknown, both in human and non-human animals. The present paper describes a behavioural experiment investigating the effects of Pavlovian conditioned responses on performance in humans, focusing on the aversive domain. Results showed that Pavlovian responses influenced human performance, and, similar to animal studies, could have maladaptive effects. In particular, Pavlovian responses either impaired or increased performance depending on modulator variables such as threat distance, task controllability, punishment history, amount of training, and explicit punishment expectancy. Overall, these findings help elucidating the computational mechanisms underlying the instrumental-Pavlovian interaction, which might be at the base of apparently irrational phenomena in economics, social behaviour, and psychopathology.

  17. Carotid baroreflex function at the onset of cycling in men

    DEFF Research Database (Denmark)

    Barbosa, Thales C; Vianna, Lauro C; Hashimoto, Takeshi

    2016-01-01

    , with carotid baroreceptor stimulation by neck suction at -60 Torr applied 0-5, 10-15, and 30-35 s after the onset of exercise. Cardiovascular responses to neck suction during cycling were compared with those obtained at rest. An attenuated reflex decrease in heart rate following neck suction was detected...... during moderate-intensity exercise, compared with the response at rest (P suction elicited an augmented decrease in blood pressure at 0-5 and 10-15 s during low-intensity exercise and in all periods during...

  18. Ovarian response to recombinant human follicle-stimulating hormone

    DEFF Research Database (Denmark)

    Arce, Joan-Carles; Andersen, Anders Nyboe; Fernández-Sánchez, Manuel

    2014-01-01

    OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrat......OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH......) concentrations. DESIGN: Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-infertility centers in four countries. PATIENT(S): Two hundred sixty-five women aged ≤37 years. INTERVENTION(S): Controlled...

  19. SOCIALLY RESPONSIBLE HUMAN RESOURCE POLICIES AND PRACTICES: ACADEMICAND PROFESSIONAL VALIDATION

    Directory of Open Access Journals (Sweden)

    Barrena-Martínez, Jesus

    2017-01-01

    Full Text Available This article addresses the measurement and validation of socially responsible human resource policiesfrom academic and professional points of view. Corporate Social responsibility (CSR has made greatprogress in recent years in the theoretical realm, showing its importance through different perspectivessuch as the institutional theory, the stakeholder approach, the theory of legitimacy, and the process ofshared value. However, from an empirical standpoint, more research is needed to provide new indicatorsand evidence of testing socially responsible policies on business performance. This paper aims to devise aset of socially responsible human resource policies, demonstrate the validation of their content throughseveral practices, and review the analysis of their relative weights thanks to the contribution of a panelof academic experts and a professional pretest, conducted in large Spanish companies.

  20. Einstein, social responsibility of physicists and human rights in China

    Science.gov (United States)

    Fang, Li-Zhi

    2005-03-01

    Since Einstein first visited Shanghai on 1922, he was deeply and constantly concerned about the cases of injustice, suppression, and human rights abuses in China. The strong sense of social responsibility shown by Einstein is an illustrious role model for Chinese intellectual, especially physicists, who advocate the universal principle of human rights. I will briefly review this history. I will also briefly report what have been done and is doing by Chinese physicists in the long and difficult journey toward democracy and human rights of China.

  1. Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics

    Directory of Open Access Journals (Sweden)

    Nigel G. Kooreman

    2017-08-01

    Full Text Available There is growing interest in using embryonic stem cell (ESC and induced pluripotent stem cell (iPSC derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an “allogenized” mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.

  2. Baroreflex Activation Therapy in Congestive Heart Failure: Novel Findings and Future Insights.

    Science.gov (United States)

    Grassi, Guido; Brambilla, GianMaria; Pizzalla, Daniela Prata; Seravalle, Gino

    2016-08-01

    Congestive heart failure is characterized by hemodynamic and non-hemodynamic abnormalities, the latter including an activation of the sympathetic influences to the heart and peripheral circulation coupled with an impairment of baroreceptor control of autonomic function. Evidence has been provided that both these alterations are hallmark features of the disease with a specific relevance for the disease progression as well as for the development of life-threatening cardiac arrhythmias. In addition, a number of studies have documented in heart failure the adverse prognostic role of the sympathetic and baroreflex alterations, which both are regarded as major independent determinants of cardiovascular morbidity and mortality. This represents the pathophysiological and clinical background for the use of carotid baroreceptor activation therapy in the treatment of congestive heart failure. Promising data collected in experimental animal models of heart failure have supported the recent performance of pilot small-scale clinical studies, aimed at providing initial information in this area. The results of these studies demonstrated the clinical safety and efficacy of the intervention which has been tested in large-scale clinical studies. The present paper will critically review the background and main results of the published studies designed at defining the clinical impact of baroreflex activation therapy in congestive heart failure patients. Emphasis will be given to the strengths and limitations of such studies, which represent the background for the ongoing clinical trials testing the long-term effects of the device in heart failure patients.

  3. Clonidine, moxonidine, folic acid, and mecobalamin improve baroreflex function in stroke-prone, spontaneously hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Xiu-juan MA; Fu-ming SHEN; Ai-jun LIU; Ke-yong SHI; Ying-liang WU; Ding-feng SU

    2007-01-01

    Aim: To investigate the effect of clonidine, moxonidine, folic acid, and mecobalamin on arterial baroreflex (ABR) function in stroke-prone spontaneously hypertensive rats (SHR-SP) and the possible mechanisms involved.Methods: Eighty-one SHR-SP were divided into 7 groups. Four groups weredesignated for the intragastric (ig) administration of clonidine (1.0 and 10.0 μg/kg), moxonidine (0.1 and 1.0 mg/kg), folic acid (1.0 mg/kg), and mecobalamin(1.0 mg/kg). Three groups were for the intracerebroventricular (icv) injection of clonidine (4 μg/4 μL), moxonidine (5 μg/4 μL), and mecobalamin (20 μg/4 μL).Blood pressure (BP) was recorded in the conscious state for 30 min and baroreflex sensitivity (BRS) was determined respectively before and after drug administration. Results: Clonidine and moxonidine significantly decreased BP,prolonged the heart period (HP), and increased BRS when administered as either ig or icv injections. Both BP and HP were unchanged by ig folic acid or mecobalamin injection. However, BRS was significantly increased by both.Conclusion: Clonidine, moxonidine, folic acid, and mecobalamin improved impaired ABR function in SHR-SP. The central mechanism was involved in this effect of either clonidine or moxonidine. Mecobalamin improved ABR function through the peripheral mechanism.

  4. On the integration of the baroreflex control mechanism in a heterogeneous model of the cardiovascular system.

    Science.gov (United States)

    Blanco, P J; Trenhago, P R; Fernandes, L G; Feijóo, R A

    2012-04-01

    The aim of the present work is to describe the integration of a mathematical model for the baroreceptor reflex mechanism to provide regulatory action into a dimensionally heterogeneous (3D-1D-0D) closed-loop model of the cardiovascular system. Such heterogeneous model comprises a 1D description of the arterial tree, a 0D network for the venous, cardiac and pulmonary circulations and 3D patient-specific geometries for vascular districts of interest. Thus, the detailed topological description of the arterial network allows us to perform vasomotor control actions in a differentiated way, while gaining insight about the effects of the baroreflex regulation over hemodynamic quantities of interest throughout the entire network. Two examples of application are presented. Firstly, we simulate the hemorrhage in the abdominal aorta artery and analyze the action of the baroreflex over the system. Secondly, the self-regulated closed-loop model is applied to study the influence of the control action in the hemodynamic environment that determines the blood flow pattern in a cerebral aneurism in the presence of a regurgitating aortic valve.

  5. 17beta-estradiol modulates baroreflex sensitivity and autonomic tone of female rats.

    Science.gov (United States)

    Saleh, T M; Connell, B J

    2000-05-12

    The following experiments examine the role of estrogen as a central modulator of autonomic tone and baroreflex sensitivity in the female rat. Female Sprague-Dawley rats were ovariectomized and then supplemented daily for 7 days with a fixed dose of estrogen (5 microg/kg; sc) to produce a stable level of estrogen similar to that present at proestrous (17 pg/ml). The rats were then anaesthetized with sodium thiobutabarbital (100 mg/kg) and instrumented to record blood pressure, heart rate and both vagal and renal efferent nerve activities. The sensitivity of the cardiac baroreflex was tested using intravenous injection of multiple doses of either phenylephrine hydrochloride or sodium nitroprusside. Estrogen-supplemented female rats exhibited a significantly enhanced BRS as compared to male rats from a previous study (0.78 vs. 0.5). Furthermore, bolus injection of estrogen (1x10(-2) mg/kg; iv) in estrogen-supplemented female rats produced a significant increase in vagal nerve activity and a significant decrease in renal nerve activity which together resulted in a further enhancement of the BRS (0.78 vs. 2.4). Injection of the selective estrogen receptor antagonist, ICI 182,780, into nucleus ambiguus and the intrathecal space of the spinal cord blocked the respective changes in parasympathetic and sympathetic nerve activities indicating that intravenously administered estrogen modulates baseline autonomic tone via the activation of central estrogen receptors.

  6. Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response.

    Directory of Open Access Journals (Sweden)

    Anja Kathrin Wege

    Full Text Available BACKGROUND: Leishmania (L. species are the causative agent of leishmaniasis. Due to the lack of efficient vaccine candidates, drug therapies are the only option to deal with cutaneous leishmaniasis. Unfortunately, chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemination of drug-resistant parasites. An appropriate laboratory animal based model is still missing which allows testing of new drug strategies in the context of human immune cells in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Humanized mice were infected subcutaneously with stationary phase promastigote L. major into the footpad. The human immune response against the pathogen and the parasite host interactions were analyzed. In addition we proved the versatility of this new model to conduct drug research studies by the inclusion of orally given Miltefosine. We show that inflammatory human macrophages get infected with Leishmania parasites at the site of infection. Furthermore, a Leishmania-specific human-derived T cell response is initiated. However, the human immune system is not able to prevent systemic infection. Thus, we treated the mice with Miltefosine to reduce the parasitic load. Notably, this chemotherapy resulted in a reduction of the parasite load in distinct organs. Comparable to some Miltefosine treated patients, humanized mice developed severe side effects, which are not detectable in the classical murine model of experimental leishmaniasis. CONCLUSIONS/SIGNIFICANCE: This study describes for the first time L. major infection in humanized mice, characterizes the disease development, the induction of human adaptive and innate immune response including cytokine production and the efficiency of Miltefosine treatment in these animals. In summary, humanized mice might be beneficial for future preclinical chemotherapeutic studies in systemic (visceral leishmaniasis allowing the investigation of human immune response, side effects of the drug

  7. Seasonal changes in human immune responses to malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G

    1993-01-01

    Cellular as well as humorol immune responses to malaria antigens fluctuate in time in individuals living in molono-endemic areas, particularly where malaria transmission is seasonal. The most pronounced changes are seen in association with clinical attacks, but osymptomatic infection can also lead...... to apparent immune depression. However, recent data have shown that seasonal variation in cellular immune responses may occur even in the absence of detectable porositaemia. Here, Lars Hviid and Thor G. Theonder review the seasonal variation in human immune responses to malaria, and discuss its possible...

  8. Response of neotropical bat assemblages to human land use.

    Science.gov (United States)

    García-Morales, Rodrigo; Badano, Ernesto I; Moreno, Claudia E

    2013-10-01

    Neotropical bats are sensitive to human-induced habitat changes, and some authors believe bats can be used as bioindicators. In the literature, however, the results are disparate. Some results show bat diversity deceases as disturbance increases, whereas others indicate no effect. Determining the general response patterns of bats when they encounter different degrees of human-induced disturbance across the Neotropics would help to determine their usefulness as bioindicators. In a series of meta-analyses, we compared the occurrence frequency of bat species between well-preserved forests and human-use areas. We obtained data through an extensive review of published peer-reviewed articles, theses, and reports. The overall effect size indicated that human-use areas harbored more bat species than well-preserved forests. Different response patterns emerged when meta-analyses were conducted separately by family, feeding habit, vegetation stratum, and conservation status. Our results suggest that bat assemblages display strong responses to forest loss and land-use change and that the direction and magnitude of these responses depends on the bat group under study and the type of disturbance. Our results are consistent with the idea that bats are useful for assessing the effects of habitat changes in the Neotropics. However, with our meta-analyses we could not detect fine differences in bat feeding habits, especially within Phyllostomidae, or elucidate the effect of landscape configuration. © 2013 Society for Conservation Biology.

  9. Sex hormones and the immune response in humans

    NARCIS (Netherlands)

    Bouman, Annechien; Heineman, Maas Jan; Faas, Marijke M.

    2005-01-01

    In addition to their effects on sexual differentiation and reproduction, sex hormones appear to influence the immune system. This results in a sexual dimorphism in the immune response in humans: for instance, females produce more vigorous cellular and more vigorous humoral immune reactions, are more

  10. Immediate hypersensitivity responses in the immunopathogenesis of human onchocerciasis.

    Science.gov (United States)

    Ottesen, E A

    1985-01-01

    It is not clear what role immediate hypersensitivity immune responses have in the pathogenesis of human onchocerciasis, but it is certain that these responses are prominent both in the course of natural infection and during the Mazzotti reactions that follow treatment with diethylcarbamazine. In humans, the levels of total serum IgE associated with onchocerciasis are as high or higher than those associated with almost any helminth infection, although specific IgE antibodies to Onchocerca volvulus appear to be a small and still poorly characterized fraction of the total serum IgE. Evidence about the relationship of these prominent IgE responses in patients with onchocerciasis to the onchocercal skin disease that manifests as pruritus and papular eruptions is conflicting, but in a guinea pig model of ocular pathology induced by onchocerca microfilariae evidence for the pathogenetic importance of IgE and immediate hypersensitivity is much less equivocal. The suggestive findings from this model make it imperative to carry out similar studies of Onchocerca-affected human eyes to determine whether immediate hypersensitivity responses play a similar critical role in the pathogenesis of the ocular lesions in humans.

  11. Impaired baroreflex sensitivity and the risks of new-onset ambulatory hypertension, in an elderly population-based study

    NARCIS (Netherlands)

    Dauphinot, Virginie; Kossovsky, Michel P.; Gueyffier, Francois; Pichot, Vincent; Gosse, Philippe; Roche, Frederic; Barthelemy, Jean-Claude

    2013-01-01

    / Background: Impairment of the autonomic nervous system activity may be involved in the development of hypertension. Yet the prognostic values of heart rate variability and baroreflex sensitivity in the risk of new-onset ambulatory hypertension have not been investigated. We sought to assess the re

  12. Resting Sympathetic Baroreflex Sensitivity in Subjects with Low and High Tolerance to Central Hypovolemia Induced by Lower Body Negative Pressure

    Science.gov (United States)

    2014-06-01

    stress independent of baroreflex control. DISCLAIMER The opinions or assertions contained herein are the private views of the authors, and are not to be...is permitted, provided the original author(s) or licensor are credited and that the original publica - tion in this journal is cited, in accordance with

  13. Human Trafficking in Nepal: Post-Earthquake Risk and Response.

    Science.gov (United States)

    Gyawali, Bishal; Keeling, June; Kallestrup, Per

    2016-09-15

    As Nepal mourns the 1-year commemoration of the April 2015 earthquake and its aftershocks that killed more than 8500 people and left thousands injured and displaced, other more hidden repercussions of the resultant chaotic environment need attention: the increased risk of human trafficking. Considering that natural disasters provide a milieu for this illicit trade, there is a need for a robust response from stakeholders such as donors, civil society organizations, and government organizations against human trafficking following disasters such as the Nepal earthquake. Responsibility to prevent and fight trafficking should be explicitly included in the mandate of relief and rehabilitation mechanisms set up at the national level to coordinate the disaster relief response, serving to support populations in both rural and urban areas. (Disaster Med Public Health Preparedness. 2016;page 1 of 2).

  14. Collective response of human populations to large-scale emergencies

    CERN Document Server

    Bagrow, James P; Barabási, Albert-László; 10.1371/journal.pone.0017680

    2011-01-01

    Despite recent advances in uncovering the quantitative features of stationary human activity patterns, many applications, from pandemic prediction to emergency response, require an understanding of how these patterns change when the population encounters unfamiliar conditions. To explore societal response to external perturbations we identified real-time changes in communication and mobility patterns in the vicinity of eight emergencies, such as bomb attacks and earthquakes, comparing these with eight non-emergencies, like concerts and sporting events. We find that communication spikes accompanying emergencies are both spatially and temporally localized, but information about emergencies spreads globally, resulting in communication avalanches that engage in a significant manner the social network of eyewitnesses. These results offer a quantitative view of behavioral changes in human activity under extreme conditions, with potential long-term impact on emergency detection and response.

  15. Collective response of human populations to large-scale emergencies.

    Directory of Open Access Journals (Sweden)

    James P Bagrow

    Full Text Available Despite recent advances in uncovering the quantitative features of stationary human activity patterns, many applications, from pandemic prediction to emergency response, require an understanding of how these patterns change when the population encounters unfamiliar conditions. To explore societal response to external perturbations we identified real-time changes in communication and mobility patterns in the vicinity of eight emergencies, such as bomb attacks and earthquakes, comparing these with eight non-emergencies, like concerts and sporting events. We find that communication spikes accompanying emergencies are both spatially and temporally localized, but information about emergencies spreads globally, resulting in communication avalanches that engage in a significant manner the social network of eyewitnesses. These results offer a quantitative view of behavioral changes in human activity under extreme conditions, with potential long-term impact on emergency detection and response.

  16. The immune response of the human brain to abdominal surgery

    DEFF Research Database (Denmark)

    Forsberg, Anton; Cervenka, Simon; Jonsson Fagerlund, Malin

    2017-01-01

    OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans....... This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. METHODS: Eight males undergoing prostatectomy under general...... to change in [(11) C]PBR28 binding (p = 0.027). INTERPRETATION: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may...

  17. Anticipating Human Activities Using Object Affordances for Reactive Robotic Response.

    Science.gov (United States)

    Koppula, Hema S; Saxena, Ashutosh

    2016-01-01

    An important aspect of human perception is anticipation, which we use extensively in our day-to-day activities when interacting with other humans as well as with our surroundings. Anticipating which activities will a human do next (and how) can enable an assistive robot to plan ahead for reactive responses. Furthermore, anticipation can even improve the detection accuracy of past activities. The challenge, however, is two-fold: We need to capture the rich context for modeling the activities and object affordances, and we need to anticipate the distribution over a large space of future human activities. In this work, we represent each possible future using an anticipatory temporal conditional random field (ATCRF) that models the rich spatial-temporal relations through object affordances. We then consider each ATCRF as a particle and represent the distribution over the potential futures using a set of particles. In extensive evaluation on CAD-120 human activity RGB-D dataset, we first show that anticipation improves the state-of-the-art detection results. We then show that for new subjects (not seen in the training set), we obtain an activity anticipation accuracy (defined as whether one of top three predictions actually happened) of 84.1, 74.4 and 62.2 percent for an anticipation time of 1, 3 and 10 seconds respectively. Finally, we also show a robot using our algorithm for performing a few reactive responses.

  18. Social responsibility of nursing in policies of health humanization

    Directory of Open Access Journals (Sweden)

    Mercedes Trentini

    2011-07-01

    Full Text Available Background: new conceptions of the world have focused on restructuring health policies and designing a new healthcare model.Objective: to reflect on the humanization policy as part of health promotion with emphasis on nursing care.Content: The article mentions paradigm changes and refers to the biomedical model and the new condition of diversity in models of care practices for health promotion and co-responsibility of nursing in generating and sustaining the humanization of nursing care. It rethinks strategies and commitment to co-responsibility by nursing staff in promoting population health. Participation of nurses in promoting humanization care has shown signs of development in its acceptance, bonding healthcare service professionals and its users. An interview-conversation as a strategy for collecting information is highlighted, whether to care or to research based on a humanization framework.Conclusions: Sensitive listening, modality of dialogue, and the conversational interview method are relationship techniques and means to acquire skills for policy development in humanizing care in health promotion.

  19. Modulation of Human Immune Response by Fungal Biocontrol Agents

    Science.gov (United States)

    Konstantinovas, Cibele; de Oliveira Mendes, Tiago A.; Vannier-Santos, Marcos A.; Lima-Santos, Jane

    2017-01-01

    Although the vast majority of biological control agents is generally regarded as safe for humans and environment, the increased exposure of agriculture workers, and consumer population to fungal substances may affect the immune system. Those compounds may be associated with both intense stimulation, resulting in IgE-mediated allergy and immune downmodulation induced by molecules such as cyclosporin A and mycotoxins. This review discusses the potential effects of biocontrol fungal components on human immune responses, possibly associated to infectious, inflammatory diseases, and defective defenses. PMID:28217107

  20. Modeling the afferent dynamics of the baroreflex control system.

    Directory of Open Access Journals (Sweden)

    Adam Mahdi

    Full Text Available In this study we develop a modeling framework for predicting baroreceptor firing rate as a function of blood pressure. We test models within this framework both quantitatively and qualitatively using data from rats. The models describe three components: arterial wall deformation, stimulation of mechanoreceptors located in the BR nerve-endings, and modulation of the action potential frequency. The three sub-systems are modeled individually following well-established biological principles. The first submodel, predicting arterial wall deformation, uses blood pressure as an input and outputs circumferential strain. The mechanoreceptor stimulation model, uses circumferential strain as an input, predicting receptor deformation as an output. Finally, the neural model takes receptor deformation as an input predicting the BR firing rate as an output. Our results show that nonlinear dependence of firing rate on pressure can be accounted for by taking into account the nonlinear elastic properties of the artery wall. This was observed when testing the models using multiple experiments with a single set of parameters. We find that to model the response to a square pressure stimulus, giving rise to post-excitatory depression, it is necessary to include an integrate-and-fire model, which allows the firing rate to cease when the stimulus falls below a given threshold. We show that our modeling framework in combination with sensitivity analysis and parameter estimation can be used to test and compare models. Finally, we demonstrate that our preferred model can exhibit all known dynamics and that it is advantageous to combine qualitative and quantitative analysis methods.

  1. Are Children with Autism More Responsive to Animated Characters? A Study of Interactions with Humans and Human-Controlled Avatars

    Science.gov (United States)

    Carter, Elizabeth J.; Williams, Diane L.; Hodgins, Jessica K.; Lehman, Jill F.

    2014-01-01

    Few direct comparisons have been made between the responsiveness of children with autism to computer-generated or animated characters and their responsiveness to humans. Twelve 4-to 8-year-old children with autism interacted with a human therapist; a human-controlled, interactive avatar in a theme park; a human actor speaking like the avatar; and…

  2. Microarray analysis of human epithelial cell responses to bacterial interaction.

    Science.gov (United States)

    Mans, Jeffrey J; Lamont, Richard J; Handfield, Martin

    2006-09-01

    Host-pathogen interactions are inherently complex and dynamic. The recent use of human microarrays has been invaluable to monitor the effects of various bacterial and viral pathogens upon host cell gene expression programs. This methodology has allowed the host response transcriptome of several cell lines to be studied on a global scale. To this point, the great majority of reports have focused on the response of immune cells, including macrophages and dendritic cells. These studies revealed that the immune response to microbial pathogens is tailored to different microbial challenges. Conversely, the paradigm for epithelial cells has--until recently--held that the epithelium mostly served as a relatively passive physical barrier to infection. It is now generally accepted that the epithelial barrier contributes more actively to signaling events in the immune response. In light of this shift, this review will compare transcriptional profiling data from studies that involved host-pathogen interactions occurring with epithelial cells. Experiments that defined both a common core response, as well as pathogen-specific host responses will be discussed. This review will also summarize the contributions that transcriptional profiling analysis has made to our understanding of bacterial physio-pathogensis of infection. This will include a discussion of how host transcriptional responses can be used to infer the function of virulence determinants from bacterial pathogens interacting with epithelial mucosa. In particular, we will expand upon the lessons that have been learned from gastro-intestinal and oral pathogens, as well as from members of the commensal flora.

  3. Brain connectivity reflects human aesthetic responses to music

    Science.gov (United States)

    Sachs, Matthew E.; Ellis, Robert J.; Schlaug, Gottfried

    2016-01-01

    Humans uniquely appreciate aesthetics, experiencing pleasurable responses to complex stimuli that confer no clear intrinsic value for survival. However, substantial variability exists in the frequency and specificity of aesthetic responses. While pleasure from aesthetics is attributed to the neural circuitry for reward, what accounts for individual differences in aesthetic reward sensitivity remains unclear. Using a combination of survey data, behavioral and psychophysiological measures and diffusion tensor imaging, we found that white matter connectivity between sensory processing areas in the superior temporal gyrus and emotional and social processing areas in the insula and medial prefrontal cortex explains individual differences in reward sensitivity to music. Our findings provide the first evidence for a neural basis of individual differences in sensory access to the reward system, and suggest that social–emotional communication through the auditory channel may offer an evolutionary basis for music making as an aesthetically rewarding function in humans. PMID:26966157

  4. Modulation of human immune responses by bovine interleukin-10.

    Directory of Open Access Journals (Sweden)

    Gerco den Hartog

    Full Text Available Cytokines can be functionally active across species barriers. Bovine IL-10 has an amino acid sequence identity with human IL-10 of 76.8%. Therefore, the aim of this study was to evaluate whether bovine IL-10 has immunomodulatory activities on human monocytes and dendritic cells. Peripheral blood monocytes were isolated from healthy donors, and used directly or allowed to differentiate to dendritic cells under the influence of IL-4 and GM-CSF. Recombinant bovine IL-10 inhibited TLR induced activation of monocytes, and dose-dependently inhibited LPS-induced activation of monocyte-derived DCs comparable to human IL-10. By using blocking antibodies to either bovine IL-10 or the human IL-10 receptor it was demonstrated that inhibition of monocyte activation by bovine IL-10 was dependent on binding of bovine IL-10 to the human IL-10R. These data demonstrate that bovine IL-10 potently inhibits the activation of human myeloid cells in response to TLR activation. Bovine IL-10 present in dairy products may thus potentially contribute to the prevention of necrotizing enterocolitis and allergy, enhance mucosal tolerance induction and decrease intestinal inflammation and may therefore be applicable in infant foods and in immunomodulatory diets.

  5. The impact of skin colour on human photobiological responses

    OpenAIRE

    Fajuyigbe, Damilola; Young, Antony R.

    2016-01-01

    Terrestrial solar ultraviolet radiation (UVR) exerts both beneficial and adverse effects on human skin. Epidemiological studies show a lower incidence of skin cancer in people with pigmented skins compared to fair skins. This is attributed to photoprotection by epidermal melanin, as is the poorer vitamin D status of those with darker skins. We summarize a wide range of photobiological responses across different skin colours including DNA damage and immunosuppression. Some studies show the gen...

  6. Tirasemtiv amplifies skeletal muscle response to nerve activation in humans

    OpenAIRE

    Hansen,Richard; Saikali, Khalil G; Chou, Willis; Alan J Russell; Chen, Michael M.; Vijayakumar, Vipin; Stoltz, Randall R.; Baudry, Stephane; Enoka, Roger M.; Morgans, David J; Wolff, Andrew A.; Malik, Fady I

    2014-01-01

    Introduction: In this study we tested the hypothesis that tirasemtiv, a selective fast skeletal muscle troponin activator that sensitizes the sarcomere to calcium, could amplify the response of muscle to neuromuscular input in humans. Methods: Healthy men received tirasemtiv and placebo in a randomized, double-blind, 4-period, crossover design. The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot. The force–freque...

  7. Human neuronal cell protein responses to Nipah virus infection

    Directory of Open Access Journals (Sweden)

    Hassan Sharifah

    2007-06-01

    Full Text Available Abstract Background Nipah virus (NiV, a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches. Results Method for separation of the NiV-infected human neuronal cell proteins using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE was established. At least 800 protein spots were resolved of which seven were unique, six were significantly up-regulated and eight were significantly down-regulated. Six of these altered proteins were identified using mass spectrometry (MS and confirmed using MS/MS. The heterogenous nuclear ribonucleoprotein (hnRNP F, guanine nucleotide binding protein (G protein, voltage-dependent anion channel 2 (VDAC2 and cytochrome bc1 were present in abundance in the NiV-infected SK-N-MC cells in contrast to hnRNPs H and H2 that were significantly down-regulated. Conclusion Several human neuronal cell proteins that are differentially expressed following NiV infection are identified. The proteins are associated with various cellular functions and their abundance reflects their significance in the cytopathologic responses to the infection and the regulation of NiV replication. The potential importance of the ratio of hnRNP F, and hnRNPs H and H2 in regulation of NiV replication, the association of the mitochondrial protein with the cytopathologic responses to the infection and induction of apoptosis are highlighted.

  8. Auditory event-related response in visual cortex modulates subsequent visual responses in humans.

    Science.gov (United States)

    Naue, Nicole; Rach, Stefan; Strüber, Daniel; Huster, Rene J; Zaehle, Tino; Körner, Ursula; Herrmann, Christoph S

    2011-05-25

    Growing evidence from electrophysiological data in animal and human studies suggests that multisensory interaction is not exclusively a higher-order process, but also takes place in primary sensory cortices. Such early multisensory interaction is thought to be mediated by means of phase resetting. The presentation of a stimulus to one sensory modality resets the phase of ongoing oscillations in another modality such that processing in the latter modality is modulated. In humans, evidence for such a mechanism is still sparse. In the current study, the influence of an auditory stimulus on visual processing was investigated by measuring the electroencephalogram (EEG) and behavioral responses of humans to visual, auditory, and audiovisual stimulation with varying stimulus-onset asynchrony (SOA). We observed three distinct oscillatory EEG responses in our data. An initial gamma-band response around 50 Hz was followed by a beta-band response around 25 Hz, and a theta response around 6 Hz. The latter was enhanced in response to cross-modal stimuli as compared to either unimodal stimuli. Interestingly, the beta response to unimodal auditory stimuli was dominant in electrodes over visual areas. The SOA between auditory and visual stimuli--albeit not consciously perceived--had a modulatory impact on the multisensory evoked beta-band responses; i.e., the amplitude depended on SOA in a sinusoidal fashion, suggesting a phase reset. These findings further support the notion that parameters of brain oscillations such as amplitude and phase are essential predictors of subsequent brain responses and might be one of the mechanisms underlying multisensory integration.

  9. Alternative Responses to the Human Resource Challenge for CBR

    Directory of Open Access Journals (Sweden)

    Huib Cornielje

    2013-02-01

    Full Text Available This commentary outlines some ways of understanding CBR and offers corresponding suggestions for responding to the contemporary human resource challenge it is faced with. It is argued that CBR exists within an increasingly complex reality, characterised by new challenges, new approaches to development and numerous international principles and guidelines.  In response, the authors advocate the use of multiple research methods, participatory action and contextualised ways of addressing human resource issues.  They suggest that new understandings are required, for future CBR workers to be enablers of people with disabilities, agents of change in communities and societies, and champions of human rights.  The complex reality of CBR suggests the need for a CBR cadre which is capable of creative and reflective reasoning.  This might be achieved through the participatory development of contextualised training curricula, practical hands-on learning, the use of mentoring, and an emphasis on reflection and adaptability.

  10. Serotonin modulates striatal responses to fairness and retaliation in humans

    Science.gov (United States)

    Crockett, MJ; Apergis-Schoute, AM; Herrmann, B; Lieberman, MD; Müller, U; Robbins, TW; Clark, L

    2013-01-01

    Humans are willing to incur personal costs to punish others who violate social norms. Such ‘costly punishment’ is an important force for sustaining human cooperation, but the causal neurobiological determinants of punishment decisions remain unclear. Using a combination of behavioral, pharmacological and neuroimaging techniques, we show that manipulating the serotonin system in humans alters costly punishment decisions by modulating responses to fairness and retaliation in the striatum. Following dietary depletion of the serotonin precursor tryptophan, participants were more likely to punish those who treated them unfairly, and were slower to accept fair exchanges. Neuroimaging data revealed activations in the ventral and dorsal striatum that were associated with fairness and punishment, respectively. Depletion simultaneously reduced ventral striatal responses to fairness and increased dorsal striatal responses during punishment, an effect that predicted its influence on punishment behavior. Finally, we provide behavioral evidence that serotonin modulates specific retaliation, rather than general norm enforcement: depleted participants were more likely to punish unfair behavior directed toward themselves, but not unfair behavior directed toward others. Our findings demonstrate that serotonin modulates social value processing in the striatum, producing context-dependent effects on social behavior. PMID:23426678

  11. Effects of Baroreflex Activation Therapy on Ambulatory Blood Pressure in Patients With Resistant Hypertension.

    Science.gov (United States)

    Wallbach, Manuel; Lehnig, Luca-Yves; Schroer, Charlotte; Lüders, Stephan; Böhning, Enrico; Müller, Gerhard A; Wachter, Rolf; Koziolek, Michael J

    2016-04-01

    Baroreflex activation therapy (BAT) has been demonstrated to decrease office blood pressure (BP) in the randomized, double-blind Rheos trial. There are limited data on 24-hour BP changes measured by ambulatory BP measurements (ABPMs) using the first generation rheos BAT system suggesting a significant reduction but there are no information about the effect of the currently used, unilateral BAT neo device on ABPM. Patients treated with the BAT neo device for uncontrolled resistant hypertension were prospectively included into this study. ABPM was performed before BAT implantation and 6 months after initiation of BAT. A total of 51 patients were included into this study, 7 dropped out from analysis because of missing or insufficient follow-up. After 6 months, 24-hour ambulatory systolic (from 148 ± 17 mm Hg to 140 ± 23 mm Hg, Phypertension. Randomized controlled trials are needed to evaluate BAT effects on ABPM in patients with resistant hypertension accurately.

  12. Cell mediated immune response in human antirabies revaccination

    Directory of Open Access Journals (Sweden)

    Débora Regina Veiga

    1987-04-01

    Full Text Available The occurrence of secondary cell mediated immune response (CMI in human antirabies immunization was studied. The Puenzalida & Palácios vaccine was used because it is routinely used in Brazil. CMI was evaluated by lymphoblastic transformation indices obtained in whole blood culture in the presence of rabies and control (nervous tissue antigens. Eleven volunteers submitted to revaccination constituted the group under study, while three other volunteers submitted primo vaccination were utilized as control group. A clear secondary CMI to rabies antigen was detected in all the revaccinated volunteers who showed earlier and more intense response than the control group. Response to the control antigen, however, present in all the components of the first group was not detectable in two out of the three primovaccinated and very low in the third one.

  13. Neurobiological determinism: human freedom of choice and criminal responsibility.

    Science.gov (United States)

    Urbaniok, Frank; Laubacher, Arja; Hardegger, Judith; Rossegger, Astrid; Endrass, Jérôme; Moskvitin, Konstantin

    2012-04-01

    Several authors have argued that criminal behavior is generally caused by neurobiological deficits. This assumption not only questions the concept of free will and a person's responsibility for his or her own actions but also the principle of guilt in criminal law. When critically examining the current state of research, it becomes apparent that the results are not sufficient to support the existence of a universally valid neurobiological causality of criminal behavior. Moreover, the assumption of total neurobiological determination of human behavior and the impossibility of individual responsibility are characterized by both faulty empiricism and methodical misconceptions. The principle of relative determinism and the analysis of the offender's behavior at the time of the offense thus remain the central and cogent approach to the assessment of criminal responsibility.

  14. Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

    Science.gov (United States)

    Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

    2010-06-01

    This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

  15. Aortic depressor nerve stimulation does not impede dynamic characteristics of the carotid sinus baroreflex in normotensive or spontaneously hypertensive rats.

    Science.gov (United States)

    Kawada, Toru; Turner, Michael J; Shimizu, Shuji; Fukumitsu, Masafumi; Kamiya, Atsunori; Sugimachi, Masaru

    2017-03-08

    Recent clinical trials in patients with drug-resistant hypertension indicate that electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) can reduce arterial pressure (AP) for more than a year. To examine whether the electrical stimulation from one baroreflex system impedes normal short-term AP regulation via another unstimulated baroreflex system, we electrically stimulated the left aortic depressor nerve (ADN) while estimating the dynamic characteristics of the carotid sinus baroreflex in anesthetized normotensive Wistar-Kyoto (WKY, n=8) rats and spontaneously hypertensive rats (SHR, n=7). Isolated carotid sinus regions were perturbed for 20 min using a Gaussian white noise signal with a mean of 120 mmHg for WKY and 160 mmHg for SHR. Tonic ADN stimulation (2 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (73.4±14.0 vs. 51.6±11.3 arbitrary units in WKY, P = 0.012; and 248.7±33.9 vs. 181.1±16.6 arbitrary units in SHR, P = 0.018) and mean AP (90.8±6.6 vs. 81.2±5.4 mmHg in WKY, P=0.004; and 128.6±9.8 vs. 114.7±10.3 mmHg in SHR, P = 0.009). The slope of dynamic gain in the neural arc transfer function from carotid sinus pressure to sympathetic nerve activity was not different between trials with and without the ADN stimulation (12.55±0.93 vs. 13.03±1.28 dB/decade in WKY, P = 0.542; and 17.37±1.01 vs. 17.47±1.64 dB/decade in SHR, P = 0.946). These results indicate that the tonic ADN stimulation does not significantly modify the dynamic characteristics of the carotid sinus baroreflex.

  16. Neandertal versus Modern Human Dietary Responses to Climatic Fluctuations.

    Science.gov (United States)

    El Zaatari, Sireen; Grine, Frederick E; Ungar, Peter S; Hublin, Jean-Jacques

    2016-01-01

    The Neandertal lineage developed successfully throughout western Eurasia and effectively survived the harsh and severely changing environments of the alternating glacial/interglacial cycles from the middle of the Pleistocene until Marine Isotope Stage 3. Yet, towards the end of this stage, at the time of deteriorating climatic conditions that eventually led to the Last Glacial Maximum, and soon after modern humans entered western Eurasia, the Neandertals disappeared. Western Eurasia was by then exclusively occupied by modern humans. We use occlusal molar microwear texture analysis to examine aspects of diet in western Eurasian Paleolithic hominins in relation to fluctuations in food supplies that resulted from the oscillating climatic conditions of the Pleistocene. There is demonstrable evidence for differences in behavior that distinguish Upper Paleolithic humans from members of the Neandertal lineage. Specifically, whereas the Neandertals altered their diets in response to changing paleoecological conditions, the diets of Upper Paleolithic humans seem to have been less affected by slight changes in vegetation/climatic conditions but were linked to changes in their technological complexes. The results of this study also indicate differences in resource exploitation strategies between these two hominin groups. We argue that these differences in subsistence strategies, if they had already been established at the time of the first contact between these two hominin taxa, may have given modern humans an advantage over the Neandertals, and may have contributed to the persistence of our species despite habitat-related changes in food availabilities associated with climate fluctuations.

  17. Neandertal versus Modern Human Dietary Responses to Climatic Fluctuations.

    Directory of Open Access Journals (Sweden)

    Sireen El Zaatari

    Full Text Available The Neandertal lineage developed successfully throughout western Eurasia and effectively survived the harsh and severely changing environments of the alternating glacial/interglacial cycles from the middle of the Pleistocene until Marine Isotope Stage 3. Yet, towards the end of this stage, at the time of deteriorating climatic conditions that eventually led to the Last Glacial Maximum, and soon after modern humans entered western Eurasia, the Neandertals disappeared. Western Eurasia was by then exclusively occupied by modern humans. We use occlusal molar microwear texture analysis to examine aspects of diet in western Eurasian Paleolithic hominins in relation to fluctuations in food supplies that resulted from the oscillating climatic conditions of the Pleistocene. There is demonstrable evidence for differences in behavior that distinguish Upper Paleolithic humans from members of the Neandertal lineage. Specifically, whereas the Neandertals altered their diets in response to changing paleoecological conditions, the diets of Upper Paleolithic humans seem to have been less affected by slight changes in vegetation/climatic conditions but were linked to changes in their technological complexes. The results of this study also indicate differences in resource exploitation strategies between these two hominin groups. We argue that these differences in subsistence strategies, if they had already been established at the time of the first contact between these two hominin taxa, may have given modern humans an advantage over the Neandertals, and may have contributed to the persistence of our species despite habitat-related changes in food availabilities associated with climate fluctuations.

  18. Human regulatory B cells control the TFH cell response.

    Science.gov (United States)

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (TFH) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of TFH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on TFH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate TFH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing TFH cell maturation. In cocultures they differentiated B cells into CD138(+) plasma and IgD(-)CD27(+) memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented TFH cell development. Added to TFH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3(+)CXCR5(+)PD-1(+) follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on TFH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control TFH cell maturation, expand follicular regulatory T cells, and inhibit the TFH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the TFH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. Human Capital information: generating intangibles and social responsibility

    Directory of Open Access Journals (Sweden)

    Francisca Tejedo Romero

    2016-01-01

    Full Text Available Intangible resources have become the most important in the process of generating business' wealth in a sustainable way, namely the Human Capital. However, the success and survival of the companies is subject to the approval of its stakeholders. This means that companies take steps to ensure that their actions are perceived as legitimate, and one way is by providing voluntary information. Therefore, under the framework of the Theory of Legitimacy and Stakeholders, our goal is to analyze how Spanish companies are voluntarily reporting on its Human Capital in annual reports, information about the generation of intangibles (knowledge and social responsibility. Thus, using the methodology of content analysis, the empirical evidence shows that companies are reporting relatively little information on topics related to Human Capital being the topics related to training and development of employees the most disclosure. However, with regard to social responsibility, there is a rising trend to provide information concerning the policy of equality and diversity, risk prevention and the relationship between employers and employees.

  20. Crossing Thresholds - Human Responses to Tsunami Forcing in the Pacific

    Science.gov (United States)

    Goff, J. R.; Chague-Goff, C.

    2014-12-01

    The 11 March 2011 Tohoku-oki tsunami caused widespread devastation to coastal communities in Japan. This event however was merely the latest in a long line of similar occurrences throughout the Pacific over time. All the recent large tsunamis have had their predecessors, and a growing database of palaeotsunamis in the Pacific suggests that several past events have been either similar in magnitude or greater than their historical counterparts. Not only are we gathering data concerning Pacific palaeotsunamis but we are also identifying contemporaneous punctuated histories of changing human settlement patterns across the Pacific. In particular, the almost two millennia 'long pause' in eastward Polynesian migration and the abandonment of long distance sea-voyaging in the 15th century. It is suggested that large palaeotsunamis and their generating mechanisms forced major societal responses. Given the unquestioned impacts of recent tsunamis on human societies, it is reasonable to suggest that past societal responses can be used as proxies for contemporaneous environmental forcing in those parts of the world where independent evidence of the effects of these events is still being gathered. In the Pacific there are a range of responses that extend well beyond the abandonment of long distance sea-voyaging such as the outbreak of region-wide conflict and the associated abandonment of settlements in exposed (coastal) locations. The contemporaneity of these effects across a vast region requires a driver that is external to particular island groups. Given that this must have impacted coastal resources severely and enduringly, the only possibility is that this driver was of oceanic origin. This hypothesis is compelling when considered alongside the growing database of more conventional lines of evidence. The question therefore is how well are similar threshold responses recognised throughout the World? Are there similar region-wide responses that have been pigeonholed under the

  1. Enhancement by platelets of oxygen radical responses of human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

    1986-03-01

    When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O-/sub 2/ and H/sub 2/O/sub 2/. This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O-/sub 2/ generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O-/sub 2/ responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils.

  2. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    Science.gov (United States)

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening.

  3. Influences of hydration on post-exercise cardiovascular control in humans.

    Science.gov (United States)

    Charkoudian, Nisha; Halliwill, John R; Morgan, Barbara J; Eisenach, John H; Joyner, Michael J

    2003-10-15

    Dehydration is known to decrease orthostatic tolerance and cause tachycardia, but little is known about the cardiovascular control mechanisms involved. To test the hypothesis that arterial baroreflex sensitivity increases during exercise-induced dehydration, we assessed arterial baroreflex responsiveness in 13 healthy subjects (protocol 1) at baseline (PRE-EX) and 1 h after (EX-DEH) 90 min of exercise to cause dehydration, and after subsequent intravenous rehydration with saline (EX-REH). Six of these subjects were studied a second time (protocol 2) with intravenous saline during exercise to prevent dehydration. We measured heart rate, central venous pressure and arterial pressure during all trials, and muscle sympathetic nerve activity (MSNA) during the post-exercise trials. Baroreflex responses were assessed using sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). After exercise in protocol 1 (EX-DEH), resting blood pressure was decreased and resting heart rate was increased. Cardiac baroreflex gain, assessed as the responsiveness of heart rate or R-R interval to changes in systolic pressure, was diminished in the EX-DEH condition (9.17 +/- 1.06 ms mmHg-1 vs. PRE-EX: 18.68 +/- 2.22 ms mmHg-1, P exercise did not alter the increase in HR post-exercise or the decrease in baroreflex gain (EX-REH: 10.20 +/- 1.43 ms mmHg-1; P > 0.10 vs. EX-DEH). Saline infusion during exercise (protocol 2) resulted in less of a post-exercise decrease in blood pressure and a smaller change in cardiac baroreflex sensitivity. Saline infusion caused a decrease in MSNA in protocol 1. We conclude that exercise-induced dehydration causes post-exercise changes in the baroreflex control of blood pressure that may contribute to, rather than offset, orthostatic intolerance.

  4. Baroreflex control of heart rate in man awake and during enflurane and enflurane--nitrous oxide anesthesia.

    Science.gov (United States)

    Morton, M; Duke, P C; Ong, B

    1980-03-01

    Baroreflex control of heart rate was assessed by means of a pressor test in two groups of subjects while awake and at two levels of anesthesia with enflurane (Group I) and enflurane-nitrous oxide (Group II). In the awake control situation, calculated mean slopes (+/- SD) were 23 +/- 8 (Group I) and 25 +/- 11 (Group II). There was no significant difference between the groups. During enflurane anesthesia (Group I) mean slopes were significantly depressed to 5 +/- 5 at 1 MAC and 6 +/- 6 at 0.8 MAC. During enflurane-nitrous oxide anesthesia (Group II), slopes were significantly depressed to 5 +/- 3 at 1 MAC and 6 +/- 4 at 0.9 MAC. There was no significant difference between the extents of depression in the two groups. It is concluded that both enflurane anesthesia and enflurane-nitrous oxide anesthesia at 1 MAC produce significant depression of baroreflex control of heart rate in man.

  5. Quantifying human response capabilities towards tsunami threats at community level

    Science.gov (United States)

    Post, J.; Mück, M.; Zosseder, K.; Wegscheider, S.; Taubenböck, H.; Strunz, G.; Muhari, A.; Anwar, H. Z.; Birkmann, J.; Gebert, N.

    2009-04-01

    Decision makers at the community level need detailed information on tsunami risks in their area. Knowledge on potential hazard impact, exposed elements such as people, critical facilities and lifelines, people's coping capacity and recovery potential are crucial to plan precautionary measures for adaptation and to mitigate potential impacts of tsunamis on society and the environment. A crucial point within a people-centred tsunami risk assessment is to quantify the human response capabilities towards tsunami threats. Based on this quantification and spatial representation in maps tsunami affected and safe areas, difficult-to-evacuate areas, evacuation target points and evacuation routes can be assigned and used as an important contribution to e.g. community level evacuation planning. Major component in the quantification of human response capabilities towards tsunami impacts is the factor time. The human response capabilities depend on the estimated time of arrival (ETA) of a tsunami, the time until technical or natural warning signs (ToNW) can be received, the reaction time (RT) of the population (human understanding of a tsunami warning and the decision to take appropriate action), the evacuation time (ET, time people need to reach a safe area) and the actual available response time (RsT = ETA - ToNW - RT). If RsT is larger than ET, people in the respective areas are able to reach a safe area and rescue themselves. Critical areas possess RsT values equal or even smaller ET and hence people whin these areas will be directly affected by a tsunami. Quantifying the factor time is challenging and an attempt to this is presented here. The ETA can be derived by analyzing pre-computed tsunami scenarios for a respective area. For ToNW we assume that the early warning center is able to fulfil the Indonesian presidential decree to issue a warning within 5 minutes. RT is difficult as here human intrinsic factors as educational level, believe, tsunami knowledge and experience

  6. Nuclear responses to depletion of mitochondrial DNA in human cells.

    Science.gov (United States)

    Li, K; Neufer, P D; Williams, R S

    1995-11-01

    The derivation of human cell lines devoid of mitochondrial (mt) DNA (rho 0) provides an opportunity to study nuclear responses to a chronic impairment of mitochondrial oxidative phosphorylation. Expression of several nuclear genes is induced in human rho 0 cells, including those encoding integral proteins of the mitochondrial inner membrane, intermediate filaments, and ribosomes. In contrast to conditions in which mitochondrial respiration is altered acutely, expression of heat shock proteins and immediate early genes is not induced. Mitochondria from rho 0 cells maintain a transmembrane electrochemical potential and are distributed within the cytoplasm of these cells in a manner indistinguishable from that of wild-type cells. We conclude that a chronic deficiency of mitochondrial oxidative phosphorylation produced by elimination of mtDNA is associated with a different pattern of gene induction than that provoked by other acute or subacute conditions that impair mitochondrial respiration or create energy demands in excess of mitochondrial respiratory capacity.

  7. Human responses to bright light of different durations.

    Science.gov (United States)

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

    2012-07-01

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

  8. Transcriptional responses of human epidermal keratinocytes to Oncostatin-M.

    Science.gov (United States)

    Finelt, Nika; Gazel, Alix; Gorelick, Steven; Blumenberg, Miroslav

    2005-08-21

    Oncostatin-M (OsM) plays an important role in inflammatory and oncogenic processes in skin, including psoriasis and Kaposi sarcoma. However, the molecular responses to OsM in keratinocytes have not been explored in depth. Here we show the results of transcriptional profiling in OsM-treated primary human epidermal keratinocytes, using high-density DNA microarrays. We find that OsM strongly and specifically affects the expression of many genes, in particular those involved with innate immunity, angiogenesis, adhesion, motility, tissue remodeling, cell cycle and transcription. The timing of the responses to OsM comprises two waves, early at 1h, and late at 48 h, with much fewer genes regulated in the intervening time points. Secreted cytokines and growth factors and their receptors, as well as nuclear transcription factors, are primary targets of OsM regulation, and these, in turn, effect the secondary changes.

  9. Monitoring human melanocytic cell responses to piperine using multispectral imaging

    Science.gov (United States)

    Samatham, Ravikant; Phillips, Kevin G.; Sonka, Julia; Yelma, Aznegashe; Reddy, Neha; Vanka, Meenakshi; Thuillier, Philippe; Soumyanath, Amala; Jacques, Steven

    2011-03-01

    Vitiligo is a depigmentary disease characterized by melanocyte loss attributed most commonly to autoimmune mechanisms. Currently vitiligo has a high incidence (1% worldwide) but a poor set of treatment options. Piperine, a compound found in black pepper, is a potential treatment for the depigmentary skin disease vitiligo, due to its ability to stimulate mouse epidermal melanocyte proliferation in vitro and in vivo. The present study investigates the use of multispectral imaging and an image processing technique based on local contrast to quantify the stimulatory effects of piperine on human melanocyte proliferation in reconstructed epidermis. We demonstrate the ability of the imaging method to quantify increased pigmentation in response to piperine treatment. The quantization of melanocyte stimulation by the proposed imaging technique illustrates the potential use of this technology to quickly assess therapeutic responses of vitiligo tissue culture models to treatment non-invasively.

  10. Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

    Science.gov (United States)

    Castellani, John W; Young, Andrew J

    2016-04-01

    Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration.

  11. The effect of music on the human stress response.

    Directory of Open Access Journals (Sweden)

    Myriam V Thoma

    Full Text Available BACKGROUND: Music listening has been suggested to beneficially impact health via stress-reducing effects. However, the existing literature presents itself with a limited number of investigations and with discrepancies in reported findings that may result from methodological shortcomings (e.g. small sample size, no valid stressor. It was the aim of the current study to address this gap in knowledge and overcome previous shortcomings by thoroughly examining music effects across endocrine, autonomic, cognitive, and emotional domains of the human stress response. METHODS: Sixty healthy female volunteers (mean age = 25 years were exposed to a standardized psychosocial stress test after having been randomly assigned to one of three different conditions prior to the stress test: 1 relaxing music ('Miserere', Allegri (RM, 2 sound of rippling water (SW, and 3 rest without acoustic stimulation (R. Salivary cortisol and salivary alpha-amylase (sAA, heart rate (HR, respiratory sinus arrhythmia (RSA, subjective stress perception and anxiety were repeatedly assessed in all subjects. We hypothesized that listening to RM prior to the stress test, compared to SW or R would result in a decreased stress response across all measured parameters. RESULTS: The three conditions significantly differed regarding cortisol response (p = 0.025 to the stressor, with highest concentrations in the RM and lowest in the SW condition. After the stressor, sAA (p=0.026 baseline values were reached considerably faster in the RM group than in the R group. HR and psychological measures did not significantly differ between groups. CONCLUSION: Our findings indicate that music listening impacted the psychobiological stress system. Listening to music prior to a standardized stressor predominantly affected the autonomic nervous system (in terms of a faster recovery, and to a lesser degree the endocrine and psychological stress response. These findings may help better understanding the

  12. The Effect of Music on the Human Stress Response

    Science.gov (United States)

    Thoma, Myriam V.; La Marca, Roberto; Brönnimann, Rebecca; Finkel, Linda; Ehlert, Ulrike; Nater, Urs M.

    2013-01-01

    Background Music listening has been suggested to beneficially impact health via stress-reducing effects. However, the existing literature presents itself with a limited number of investigations and with discrepancies in reported findings that may result from methodological shortcomings (e.g. small sample size, no valid stressor). It was the aim of the current study to address this gap in knowledge and overcome previous shortcomings by thoroughly examining music effects across endocrine, autonomic, cognitive, and emotional domains of the human stress response. Methods Sixty healthy female volunteers (mean age = 25 years) were exposed to a standardized psychosocial stress test after having been randomly assigned to one of three different conditions prior to the stress test: 1) relaxing music (‘Miserere’, Allegri) (RM), 2) sound of rippling water (SW), and 3) rest without acoustic stimulation (R). Salivary cortisol and salivary alpha-amylase (sAA), heart rate (HR), respiratory sinus arrhythmia (RSA), subjective stress perception and anxiety were repeatedly assessed in all subjects. We hypothesized that listening to RM prior to the stress test, compared to SW or R would result in a decreased stress response across all measured parameters. Results The three conditions significantly differed regarding cortisol response (p = 0.025) to the stressor, with highest concentrations in the RM and lowest in the SW condition. After the stressor, sAA (p=0.026) baseline values were reached considerably faster in the RM group than in the R group. HR and psychological measures did not significantly differ between groups. Conclusion Our findings indicate that music listening impacted the psychobiological stress system. Listening to music prior to a standardized stressor predominantly affected the autonomic nervous system (in terms of a faster recovery), and to a lesser degree the endocrine and psychological stress response. These findings may help better understanding the

  13. The effect of music on the human stress response.

    Science.gov (United States)

    Thoma, Myriam V; La Marca, Roberto; Brönnimann, Rebecca; Finkel, Linda; Ehlert, Ulrike; Nater, Urs M

    2013-01-01

    Music listening has been suggested to beneficially impact health via stress-reducing effects. However, the existing literature presents itself with a limited number of investigations and with discrepancies in reported findings that may result from methodological shortcomings (e.g. small sample size, no valid stressor). It was the aim of the current study to address this gap in knowledge and overcome previous shortcomings by thoroughly examining music effects across endocrine, autonomic, cognitive, and emotional domains of the human stress response. Sixty healthy female volunteers (mean age = 25 years) were exposed to a standardized psychosocial stress test after having been randomly assigned to one of three different conditions prior to the stress test: 1) relaxing music ('Miserere', Allegri) (RM), 2) sound of rippling water (SW), and 3) rest without acoustic stimulation (R). Salivary cortisol and salivary alpha-amylase (sAA), heart rate (HR), respiratory sinus arrhythmia (RSA), subjective stress perception and anxiety were repeatedly assessed in all subjects. We hypothesized that listening to RM prior to the stress test, compared to SW or R would result in a decreased stress response across all measured parameters. The three conditions significantly differed regarding cortisol response (p = 0.025) to the stressor, with highest concentrations in the RM and lowest in the SW condition. After the stressor, sAA (p=0.026) baseline values were reached considerably faster in the RM group than in the R group. HR and psychological measures did not significantly differ between groups. Our findings indicate that music listening impacted the psychobiological stress system. Listening to music prior to a standardized stressor predominantly affected the autonomic nervous system (in terms of a faster recovery), and to a lesser degree the endocrine and psychological stress response. These findings may help better understanding the beneficial effects of music on the human body.

  14. Neural response to emotional stimuli during experimental human endotoxemia.

    Science.gov (United States)

    Kullmann, Jennifer S; Grigoleit, Jan-Sebastian; Lichte, Philipp; Kobbe, Philipp; Rosenberger, Christina; Banner, Christina; Wolf, Oliver T; Engler, Harald; Oberbeck, Reiner; Elsenbruch, Sigrid; Bingel, Ulrike; Forsting, Michael; Gizewski, Elke R; Schedlowski, Manfred

    2013-09-01

    Increases in peripheral cytokines during acute inflammation may affect various neuropsychological functions. The aim of this functional magnetic resonance imaging (fMRI) study was to investigate the effects of acute endotoxemia on mood and the neural response to emotionally aversive visual stimuli in healthy human subjects. In a double-blind, randomized crossover study, 18 healthy males received a bolus injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline. Plasma levels of pro- and anti-inflammatory cytokines and cortisol as well as mood ratings were analyzed together with the blood-oxygen-level dependent (BOLD) response during the presentation of aversive versus neutral pictures. Endotoxin administration induced pronounced transient increases in plasma levels of TNF-α, IL-1ra, IL-6, IL-10, and cortisol. Positive mood was decreased and state anxiety increased. In addition, activation of right inferior orbitofrontal cortex (OFC) in response to emotional visual stimuli was significantly increased in the LPS condition. Increased prefrontal activation during the presentation of emotional material may reflect enhanced cognitive regulation of emotions as an adaptive response during an acute inflammation. These findings may have implications for the putative role of inflammatory processes in the pathophysiology of depression.

  15. Linearity of dose-response relationships for human carcinogenic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.H. (Univ. of California, Berkeley (USA))

    The shape of dose-response relationships is a critical factor in considering cancer risks for the work place and environmental exposure to carcinogens. Markedly different risk estimates result from assumptions of linearity versus sublinear and threshold assumptions. This paper presents evidence that the relationship between the relative risk of development of cancer and the dose rate to carcinogenic exposures is frequently linear with no evidence for thresholds. Dose-response relationships from four studies of asbestos and lung cancer were examined, all of which were consistent with a linear relationship. Analysis of the relationship between the relative risk of lung cancer and exposure to nickel in a smelter study, selected because of relatively good exposure data, demonstrated a close agreement with a linear relationship. The relationship between the level of arsenic in drinking wter and the prevalence of skin cancer also was linear for males in the highest prevalence age group in Taiwan, although there was some evidence of sublinearity for females and younger persons. Also, the relationships between the number of cigarettes smoked per day and the relative risk of lung cancer was very close to linear in many studies. The analysis of these and other studies involving human exposure to carcinogens provides empirical evidence for linearity when the response variable is a rate ratio measure, rather than a risk difference measure. Linearity in dose-response is biologically plausible, without invoking a one-hit model. Except in special circumstances. the epidemiological evidence supports linear extrapolation of cancer relative risks.

  16. The low frequency power of heart rate variability is neither a measure of cardiac sympathetic tone nor of baroreflex sensitivity.

    Science.gov (United States)

    Martelli, Davide; Silvani, Alessandro; McAllen, Robin M; May, Clive N; Ramchandra, Rohit

    2014-10-01

    The lack of noninvasive approaches to measure cardiac sympathetic nerve activity (CSNA) has driven the development of indirect estimates such as the low-frequency (LF) power of heart rate variability (HRV). Recently, it has been suggested that LF HRV can be used to estimate the baroreflex modulation of heart period (HP) rather than cardiac sympathetic tone. To test this hypothesis, we measured CSNA, HP, blood pressure (BP), and baroreflex sensitivity (BRS) of HP, estimated with the modified Oxford technique, in conscious sheep with pacing-induced heart failure and in healthy control sheep. We found that CSNA was higher and systolic BP and HP were lower in sheep with heart failure than in control sheep. Cross-correlation analysis showed that in each group, the beat-to-beat changes in HP correlated with those in CSNA and in BP, but LF HRV did not correlate significantly with either CSNA or BRS. However, when control sheep and sheep with heart failure were considered together, CSNA correlated negatively with HP and BRS. There was also a negative correlation between CSNA and BRS in control sheep when considered alone. In conclusion, we demonstrate that in conscious sheep, LF HRV is neither a robust index of CSNA nor of BRS and is outperformed by HP and BRS in tracking CSNA. These results do not support the use of LF HRV as a noninvasive estimate of either CSNA or baroreflex function, but they highlight a link between CSNA and BRS.

  17. Is the Money Responsible? : Financial institutions’ human rights responsibilities along a supply chain.

    OpenAIRE

    Wikström, Linnea

    2016-01-01

    Corporate Social Responsibility (CSR) is a topic of rising importance in the current human rights discussion. As multinational supply chains have a growing impact on people’ lives, both in more developed and developing countries the question of how to regulate the behaviour of the companies that engage in these supply chains becomes increasingly important. States have tried to do this through both national and international law, by introducing hard law regulations as well as voluntary framewo...

  18. Human Macrophage Response to L. (Viannia) panamensis: Microarray Evidence for an Early Inflammatory Response

    Science.gov (United States)

    Rojas, Ricardo; Ettinger, Nicholas A.; Tikhonova, Irina; Alexander, Neal D.; Valderrama, Liliana; Hager, Janet; Wilson, Mary E.; Lin, Aiping; Zhao, Hongyu; Saravia, Nancy G.; McMahon-Pratt, Diane

    2012-01-01

    Background Previous findings indicate that susceptibility to Leishmania (Viannia) panamensis infection of monocyte-derived macrophages from patients and asymptomatically infected individuals were associated with the adaptive immune response and clinical outcome. Methodology/Principal Findings To understand the basis for this difference we examined differential gene expression of human monocyte-derived macrophages following exposure to L. (V.) panamensis. Gene activation profiles were determined using macrophages from healthy volunteers cultured with or without stationary phase promastigotes of L. (V.) panamensis. Significant changes in expression (>1.5-fold change; p<0.05; up- or down-regulated) were identified at 0.5, 4 and 24 hours. mRNA abundance profiles varied over time, with the highest level of activation occurring at earlier time points (0.5 and 4 hrs). In contrast to observations for other Leishmania species, most significantly changed mRNAs were up- rather than down-regulated, especially at early time points. Up-regulated transcripts over the first 24 hours belonged to pathways involving eicosanoid metabolism, oxidative stress, activation of PKC through G protein coupled receptors, or mechanism of gene regulation by peroxisome proliferators via PPARα. Additionally, a marked activation of Toll-receptor mediated pathways was observed. Comparison with published microarray data from macrophages infected with L. (Leishmania) chagasi indicate differences in the regulation of genes involved in signaling, motility and the immune response. Conclusions Results show that the early (0.5 to 24 hours) human monocyte-derived macrophage response to L. (Viannia) panamensis is not quiescent, in contrast to published reports examining later response times (48–96 hours). Early macrophage responses are important for the developing cellular response at the site of infection. The kinetics and the mRNA abundance profiles induced by L. (Viannia) panamensis illustrate the

  19. Behavioral responses associated with a human-mediated predator shelter.

    Directory of Open Access Journals (Sweden)

    Graeme Shannon

    Full Text Available Human activities in protected areas can affect wildlife populations in a similar manner to predation risk, causing increases in movement and vigilance, shifts in habitat use and changes in group size. Nevertheless, recent evidence indicates that in certain situations ungulate species may actually utilize areas associated with higher levels of human presence as a potential refuge from disturbance-sensitive predators. We now use four-years of behavioral activity budget data collected from pronghorn (Antilocapra americana and elk (Cervus elephus in Grand Teton National Park, USA to test whether predictable patterns of human presence can provide a shelter from predatory risk. Daily behavioral scans were conducted along two parallel sections of road that differed in traffic volume--with the main Teton Park Road experiencing vehicle use that was approximately thirty-fold greater than the River Road. At the busier Teton Park Road, both species of ungulate engaged in higher levels of feeding (27% increase in the proportion of pronghorn feeding and 21% increase for elk, lower levels of alert behavior (18% decrease for pronghorn and 9% decrease for elk and formed smaller groups. These responses are commonly associated with reduced predatory threat. Pronghorn also exhibited a 30% increase in the proportion of individuals moving at the River Road as would be expected under greater exposure to predation risk. Our findings concur with the 'predator shelter hypothesis', suggesting that ungulates in GTNP use human presence as a potential refuge from predation risk, adjusting their behavior accordingly. Human activity has the potential to alter predator-prey interactions and drive trophic-mediated effects that could ultimately impact ecosystem function and biodiversity.

  20. Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

    Directory of Open Access Journals (Sweden)

    Alessandra da Silva Dantas

    2015-02-01

    Full Text Available Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS, such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen.

  1. Brain connectivity reflects human aesthetic responses to music.

    Science.gov (United States)

    Sachs, Matthew E; Ellis, Robert J; Schlaug, Gottfried; Loui, Psyche

    2016-06-01

    Humans uniquely appreciate aesthetics, experiencing pleasurable responses to complex stimuli that confer no clear intrinsic value for survival. However, substantial variability exists in the frequency and specificity of aesthetic responses. While pleasure from aesthetics is attributed to the neural circuitry for reward, what accounts for individual differences in aesthetic reward sensitivity remains unclear. Using a combination of survey data, behavioral and psychophysiological measures and diffusion tensor imaging, we found that white matter connectivity between sensory processing areas in the superior temporal gyrus and emotional and social processing areas in the insula and medial prefrontal cortex explains individual differences in reward sensitivity to music. Our findings provide the first evidence for a neural basis of individual differences in sensory access to the reward system, and suggest that social-emotional communication through the auditory channel may offer an evolutionary basis for music making as an aesthetically rewarding function in humans. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Effects of Morphine, Fentanyl and Tramadol on Human Immune Response

    Institute of Scientific and Technical Information of China (English)

    LIU Zhihen; GAO Feng; TIAN Yuke

    2006-01-01

    Morphine has been reported to suppress human immune response. We aimed to observe the effects of morphine, fentanyl and tramadol on NF- κ B and IL-2 from both laboratory and clinical perspective. Jurkat cells were incubated with ten times clinically relevant concentrations of morphine,fentanyl and tramadol before being stimulated with PMA. NF- κ B binding activity and IL-2 levels were measured. In the clinical study, 150 consenting patients were randomized into 3 groups according to the analgesics used in them, namely, group morphine (M), group fentanyl (F) and group tramadol (T). IL-2 was measured preoperatively and 1, 3 and 24 h after operation. Consequently, NF-κ B activation was suppressed by morphine and fentanyl but not by tramadol. IL-2 was significantly decreased by morphine and fentanyl but not by tramadol in vitro. In the PCA patients, IL-2 was decreased in group M and increased in group F postoperatively. Whereas in group T, IL-2 was unchanged 1 h after operation but was significantly elevated 3 and 24 h after operation. Our results showed that the inhibition of morphine on IL-2 was most probably related to its suppression on NF-κ B. Fentanyl had different effects on human immune response in vitro and in vivo. Tramadol may have immune enhancing effect.

  3. Oxidized DNA induces an adaptive response in human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Kostyuk, Svetlana V., E-mail: svet.kostyuk@gmail.com [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Tabakov, Viacheslav J.; Chestkov, Valerij V.; Konkova, Marina S.; Glebova, Kristina V.; Baydakova, Galina V.; Ershova, Elizaveta S.; Izhevskaya, Vera L. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Baranova, Ancha, E-mail: abaranov@gmu.edu [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Center for the Study of Chronic Metabolic Diseases, School of System Biology, George Mason University, Fairfax, VA 22030 (United States); Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation)

    2013-07-15

    Highlights: • We describe the effects of gDNAOX on human fibroblasts cultivated in serum withdrawal conditions. • gDNAOX evokes an adaptive response in human fibroblasts. • gDNAOX increases the survival rates in serum starving cell populations. • gDNAOX enhances the survival rates in cell populations irradiated at 1.2 Gy dose. • gDNAOX up-regulates NRF2 and inhibits NF-kappaB-signaling. - Abstract: Cell-free DNA (cfDNA) released from dying cells contains a substantial proportion of oxidized nucleotides, thus, forming cfDNA{sup OX}. The levels of cfDNA{sup OX} are increased in the serum of patients with chronic diseases. Oxidation of DNA turns it into a stress signal. The samples of genomic DNA (gDNA) oxidized by H{sub 2}O{sub 2}in vitro (gDNA{sup OX}) induce effects similar to that of DNA released from damaged cells. Here we describe the effects of gDNA{sup OX} on human fibroblasts cultivated in the stressful conditions of serum withdrawal. In these cells, gDNA{sup OX} evokes an adaptive response that leads to an increase in the rates of survival in serum starving cell populations as well as in populations irradiated at the dose of 1.2 Gy. These effects are not seen in control populations of fibroblasts treated with non-modified gDNA. In particular, the exposure to gDNA{sup OX} leads to a decrease in the expression of the proliferation marker Ki-67 and an increase in levels of PSNA, a decrease in the proportion of subG1- and G2/M cells, a decrease in proportion of cells with double strand breaks (DSBs). Both gDNA{sup OX} and gDNA suppress the expression of DNA sensors TLR9 and AIM2 and up-regulate nuclear factor-erythroid 2 p45-related factor 2 (NRF2), while only gDNA{sup OX} inhibits NF-κB signaling. gDNA{sup OX} is a model for oxidized cfDNA{sup OX} that is released from the dying tumor cells and being carried to the distant organs. The systemic effects of oxidized DNA have to be taken into account when treating tumors. In particular, the damaged DNA

  4. Dynamic control of maximal ventricular elastance via the baroreflex and force-frequency relation in awake dogs before and after pacing-induced heart failure

    Science.gov (United States)

    Chen, Xiaoxiao; Sala-Mercado, Javier A.; Hammond, Robert L.; Ichinose, Masashi; Soltani, Soroor; Mukkamala, Ramakrishna

    2010-01-01

    We investigated to what extent maximal ventricular elastance (Emax) is dynamically controlled by the arterial baroreflex and force-frequency relation in conscious dogs and to what extent these mechanisms are attenuated after the induction of heart failure (HF). We mathematically analyzed spontaneous beat-to-beat hemodynamic variability. First, we estimated Emax for each beat during a baseline period using the ventricular unstressed volume determined with the traditional multiple beat method during vena cava occlusion. We then jointly identified the transfer functions (system gain value and time delay per frequency) relating beat-to-beat fluctuations in arterial blood pressure (ABP) to Emax (ABP→Emax) and beat-to-beat fluctuations in heart rate (HR) to Emax (HR→Emax) to characterize the dynamic properties of the arterial baroreflex and force-frequency relation, respectively. During the control condition, the ABP→Emax transfer function revealed that ABP perturbations caused opposite direction Emax changes with a gain value of −0.023 ± 0.012 ml−1, whereas the HR→Emax transfer function indicated that HR alterations caused same direction Emax changes with a gain value of 0.013 ± 0.005 mmHg·ml−1·(beats/min)−1. Both transfer functions behaved as low-pass filters. However, the ABP→Emax transfer function was more sluggish than the HR→Emax transfer function with overall time constants (indicator of full system response time to a sudden input change) of 11.2 ± 2.8 and 1.7 ± 0.5 s (P < 0.05), respectively. During the HF condition, the ABP→Emax and HR→Emax transfer functions were markedly depressed with gain values reduced to −0.0002 ± 0.007 ml−1 and −0.001 ± 0.004 mmHg·ml−1·(beats/min)−1 (P < 0.1). Emax is rapidly and significantly controlled at rest, but this modulation is virtually abolished in HF. PMID:20435845

  5. Injury Response of Resected Human Brain Tissue In Vitro.

    Science.gov (United States)

    Verwer, Ronald W H; Sluiter, Arja A; Balesar, Rawien A; Baaijen, Johannes C; de Witt Hamer, Philip C; Speijer, Dave; Li, Yichen; Swaab, Dick F

    2015-07-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by resection (interruption of the circulation) and aggravated by the preparation of slices (severed neuronal and glial processes and blood vessels) reflect the reaction of human brain tissue to severe injury. We investigated this process using immunocytochemical markers, reverse transcriptase quantitative polymerase chain reaction and Western blot analysis. Essential features were rapid shrinkage of neurons, loss of neuronal marker expression and proliferation of reactive cells that expressed Nestin and Vimentin. Also, microglia generally responded strongly, whereas the response of glial fibrillary acidic protein-positive astrocytes appeared to be more variable. Importantly, some reactive cells also expressed both microglia and astrocytic markers, thus confounding their origin. Comparison with post-mortem human brain tissue obtained at rapid autopsies suggested that the reactive process is not a consequence of epilepsy. © 2014 International Society of Neuropathology.

  6. Human influenza viruses and CD8(+) T cell responses.

    Science.gov (United States)

    Grant, Emma J; Quiñones-Parra, Sergio M; Clemens, E Bridie; Kedzierska, Katherine

    2016-02-01

    Influenza A viruses (IAVs) cause significant morbidity and mortality worldwide, despite new strain-specific vaccines being available annually. As IAV-specific CD8(+) T cells promote viral control in the absence of neutralizing antibodies, and can mediate cross-reactive immunity toward distinct IAVs to drive rapid recovery from both mild and severe influenza disease, there is great interest in developing a universal T cell vaccine. However, despite detailed studies in mouse models of influenza virus infection, there is still a paucity of data on human epitope-specific CD8(+) T cell responses to IAVs. This review focuses on our current understanding of human CD8(+) T cell immunity against distinct IAVs and discusses the possibility of achieving a CD8(+) T cell mediated-vaccine that protects against multiple, distinct IAV strains across diverse human populations. We also review the importance of CD8(+) T cell immunity in individuals highly susceptible to severe influenza infection, including those hospitalised with influenza, the elderly and Indigenous populations.

  7. Glucocorticoids boost stimulus-response memory formation in humans.

    Science.gov (United States)

    Guenzel, Friederike M; Wolf, Oliver T; Schwabe, Lars

    2014-07-01

    Stress affects memory beyond hippocampus-dependent spatial or episodic memory processes. In particular, stress may influence also striatum-dependent stimulus-response (S-R) memory processes. Rodent studies point to an important role of glucocorticoids in the modulation of S-R memory. However, whether glucocorticoids influence S-R memory processes in humans is still unknown. Therefore, we examined in the current experiment the impact of glucocorticoids on the formation of S-R memories in humans. For this purpose, healthy men and women received either hydrocortisone or a placebo 45 min before completing an S-R association learning task and an S-R navigation task. In addition, participants performed also a virtual spatial navigation task and a spatial navigation task in a real environment. Memory of all four learning tasks was tested one week later. Our data showed that hydrocortisone before learning enhanced memory of the S-R association learning task. Moreover, hydrocortisone enhanced the memory of the virtual spatial navigation task, mainly in women. Memory performance in the other tasks remained unaffected by hydrocortisone. These findings provide first evidence that glucocorticoids may facilitate S-R memory formation processes in humans.

  8. Human Responses to Climate Variability: The Case of South Africa

    Science.gov (United States)

    Oppenheimer, M.; Licker, R.; Mastrorillo, M.; Bohra-Mishra, P.; Estes, L. D.; Cai, R.

    2014-12-01

    Climate variability has been associated with a range of societal and individual outcomes including migration, violent conflict, changes in labor productivity, and health impacts. Some of these may be direct responses to changes in mean temperature or precipitation or extreme events, such as displacement of human populations by tropical cyclones. Others may be mediated by a variety of biological, social, or ecological factors such as migration in response to long-term changes in crops yields. Research is beginning to elucidate and distinguish the many channels through which climate variability may influence human behavior (ranging from the individual to the collective, societal level) in order to better understand how to improve resilience in the face of current variability as well as future climate change. Using a variety of data sets from South Africa, we show how climate variability has influenced internal (within country) migration in recent history. We focus on South Africa as it is a country with high levels of internal migration and dramatic temperature and precipitation changes projected for the 21st century. High poverty rates and significant levels of rain-fed, smallholder agriculture leave large portions of South Africa's population base vulnerable to future climate change. In this study, we utilize two complementary statistical models - one micro-level model, driven by individual and household level survey data, and one macro-level model, driven by national census statistics. In both models, we consider the effect of climate on migration both directly (with gridded climate reanalysis data) and indirectly (with agricultural production statistics). With our historical analyses of climate variability, we gain insights into how the migration decisions of South Africans may be influenced by future climate change. We also offer perspective on the utility of micro and macro level approaches in the study of climate change and human migration.

  9. Acute Exercise Modulates Feature-selective Responses in Human Cortex.

    Science.gov (United States)

    Bullock, Tom; Elliott, James C; Serences, John T; Giesbrecht, Barry

    2017-04-01

    An organism's current behavioral state influences ongoing brain activity. Nonhuman mammalian and invertebrate brains exhibit large increases in the gain of feature-selective neural responses in sensory cortex during locomotion, suggesting that the visual system becomes more sensitive when actively exploring the environment. This raises the possibility that human vision is also more sensitive during active movement. To investigate this possibility, we used an inverted encoding model technique to estimate feature-selective neural response profiles from EEG data acquired from participants performing an orientation discrimination task. Participants (n = 18) fixated at the center of a flickering (15 Hz) circular grating presented at one of nine different orientations and monitored for a brief shift in orientation that occurred on every trial. Participants completed the task while seated on a stationary exercise bike at rest and during low- and high-intensity cycling. We found evidence for inverted-U effects; such that the peak of the reconstructed feature-selective tuning profiles was highest during low-intensity exercise compared with those estimated during rest and high-intensity exercise. When modeled, these effects were driven by changes in the gain of the tuning curve and in the profile bandwidth during low-intensity exercise relative to rest. Thus, despite profound differences in visual pathways across species, these data show that sensitivity in human visual cortex is also enhanced during locomotive behavior. Our results reveal the nature of exercise-induced gain on feature-selective coding in human sensory cortex and provide valuable evidence linking the neural mechanisms of behavior state across species.

  10. Glucocorticoids enhance the in vivo migratory response of human monocytes.

    Science.gov (United States)

    Yeager, Mark P; Pioli, Patricia A; Collins, Jane; Barr, Fiona; Metzler, Sara; Sites, Brian D; Guyre, Paul M

    2016-05-01

    Glucocorticoids (GCs) are best known for their potent anti-inflammatory effects. However, an emerging model for glucocorticoid (GC) regulation of in vivo inflammation also includes a delayed, preparatory effect that manifests as enhanced inflammation following exposure to an inflammatory stimulus. When GCs are transiently elevated in vivo following exposure to a stressful event, this model proposes that a subsequent period of increased inflammatory responsiveness is adaptive because it enhances resistance to a subsequent stressor. In the present study, we examined the migratory response of human monocytes/macrophages following transient in vivo exposure to stress-associated concentrations of cortisol. Participants were administered cortisol for 6h to elevate in vivo cortisol levels to approximate those observed during major systemic stress. Monocytes in peripheral blood and macrophages in sterile inflammatory tissue (skin blisters) were studied before and after exposure to cortisol or placebo. We found that exposure to cortisol induced transient upregulation of monocyte mRNA for CCR2, the receptor for monocyte chemotactic protein-1 (MCP-1/CCL2) as well as for the chemokine receptor CX3CR1. At the same time, mRNA for the transcription factor IκBα was decreased. Monocyte surface expression of CCR2 but not CX3CR1 increased in the first 24h after cortisol exposure. Transient exposure to cortisol also led to an increased number of macrophages and neutrophils in fluid derived from a sterile inflammatory site in vivo. These findings suggest that the delayed, pro-inflammatory effects of cortisol on the human inflammatory responses may include enhanced localization of effector cells at sites of in vivo inflammation.

  11. Psychophysiological responses to pain identify reproducible human clusters.

    Science.gov (United States)

    Farmer, Adam D; Coen, Steven J; Kano, Michiko; Paine, Peter A; Shwahdi, Mustafa; Jafari, Jafar; Kishor, Jessin; Worthen, Sian F; Rossiter, Holly E; Kumari, Veena; Williams, Steven C R; Brammer, Michael; Giampietro, Vincent P; Droney, Joanne; Riley, Julia; Furlong, Paul L; Knowles, Charles H; Lightman, Stafford L; Aziz, Qasim

    2013-11-01

    Pain is a ubiquitous yet highly variable experience. The psychophysiological and genetic factors responsible for this variability remain unresolved. We hypothesised the existence of distinct human pain clusters (PCs) composed of distinct psychophysiological and genetic profiles coupled with differences in the perception and the brain processing of pain. We studied 120 healthy subjects in whom the baseline personality and anxiety traits and the serotonin transporter-linked polymorphic region (5-HTTLPR) genotype were measured. Real-time autonomic nervous system parameters and serum cortisol were measured at baseline and after standardised visceral and somatic pain stimuli. Brain processing reactions to visceral pain were studied in 29 subjects using functional magnetic resonance imaging (fMRI). The reproducibility of the psychophysiological responses to pain was assessed at year. In group analysis, visceral and somatic pain caused an expected increase in sympathetic and cortisol responses and activated the pain matrix according to fMRI studies. However, using cluster analysis, we found 2 reproducible PCs: at baseline, PC1 had higher neuroticism/anxiety scores (P ≤ 0.01); greater sympathetic tone (Ppain, less stimulus was tolerated (P ≤ 0.01), and there was an increase in parasympathetic tone (P ≤ 0.05). The 5-HTTLPR short allele was over-represented (P ≤ 0.005). PC2 had the converse profile at baseline and during pain. Brain activity differed (P ≤ 0.001); greater activity occurred in the left frontal cortex in PC1, whereas PC2 showed greater activity in the right medial/frontal cortex and right anterior insula. In health, 2 distinct reproducible PCs exist in humans. In the future, PC characterization may help to identify subjects at risk for developing chronic pain and may reduce variability in brain imaging studies.

  12. The Principle of Responsibility towards the Human Non-Presence or the Non-Human Presence

    Directory of Open Access Journals (Sweden)

    Loredana TEREC-VLAD

    2016-12-01

    Full Text Available The responsibility towards oneself and towards each other was analysed by philosophers such as Heidegger, Jonas, etc., and is based on care. If Heidegger brings forward the concept of caring for each other, Jonas believes that the prospective ethics based on responsibility should guide the behaviour of present individuals for the future generation. In the context of new technologies in genetic engineering, molecular biology and genetic editing, we consider it appropriate to bring into discussion that a new form of Kant’s categorical imperative is needed to guide the behaviour of all, to ensure the welfare planet-wide, not only for the human generations to come, but also of the non-human generations.

  13. T-cell responses to dengue virus in humans.

    Science.gov (United States)

    Kurane, Ichiro; Matsutani, Takaji; Suzuki, Ryuji; Takasaki, Tomohiko; Kalayanarooj, Siripen; Green, Sharone; Rothman, Alan L; Ennis, Francis A

    2011-12-01

    Dengue virus (DENV) is a leading cause of morbidity and mortality in most tropical and subtropical areas of the world. Dengue virus infection induces specific CD4+CD8- and CD8+CD4- T cells in humans. In primary infection, T-cell responses to DENV are serotype cross-reactive, but the highest response is to the serotype that caused the infection. The epitopes recognized by DENV-specific T cells are located in most of the structural and non-structural proteins, but NS3 is the protein that is most dominantly recognized. In patients with dengue hemorrhagic fever (DHF) caused by secondary DENV infection, T cells are highly activated in vivo. These highly activated T cells are DENV-specific and oligoclonal. Multiple kinds of lymphokines are produced by the activated T cells, and it has been hypothesized that these lymphokines are responsible for induction of plasma leakage, one of the most characteristic features of DHF. Thus, T-cells play important roles in the pathogenesis of DHF and in the recovery from DENV infection.

  14. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  15. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  16. The immune response of the human brain to abdominal surgery.

    Science.gov (United States)

    Forsberg, Anton; Cervenka, Simon; Jonsson Fagerlund, Malin; Rasmussen, Lars S; Zetterberg, Henrik; Erlandsson Harris, Helena; Stridh, Pernilla; Christensson, Eva; Granström, Anna; Schening, Anna; Dymmel, Karin; Knave, Nina; Terrando, Niccolò; Maze, Mervyn; Borg, Jacqueline; Varrone, Andrea; Halldin, Christer; Blennow, Kaj; Farde, Lars; Eriksson, Lars I

    2017-04-01

    Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [(11) C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Patients showed a global downregulation of gray matter [(11) C]PBR28 binding of 26 ± 26% (mean ± standard deviation) at 3 to 4 days postoperatively compared to baseline (p = 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-α in blood displayed a reduction (41 ± 39%) on the 3rd to 4th postoperative day, corresponding to changes in [(11) C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [(11) C]PBR28 binding (p = 0.027). This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. Ann Neurol 2017;81:572-582. © 2017 American Neurological Association.

  17. Cytokine response of human THP-1 macrophages to Trichomonas tenax.

    Science.gov (United States)

    Govro, Emily J; Stuart, Melissa K

    2016-10-01

    Trichomonas tenax is a protozoan that inhabits the oral cavity of humans, most often those with poor oral hygiene. Although T. tenax is widely considered a commensal, recent studies have suggested a pathogenic role for the protozoan in persons with periodontitis. Here we investigated the capacity of T. tenax to induce pro-inflammatory cytokine secretion in human macrophages, with the idea that elicitation of inflammation may be one mechanism by which T. tenax contributes to oral pathology. Human THP-1 cells differentiated to the macrophage phenotype (dTHP-1) were incubated with live or sonicated T. tenax at trophozoite:dTHP-1 ratios of 1:5, 1:10, and 1:20. Culture media removed from the wells after 4, 8, and 16 h of stimulation were assayed by ELISA for tumor necrosis factor alpha, interleukin-1 beta, interleukin-8, and the immunoregulatory cytokine interleukin-10. Live T. tenax trophozoites failed to induce production of any of the cytokines tested, regardless of trophozoite:dTHP-1 cell ratio or length of co-incubation. T. tenax lysates stimulated interleukin-8 synthesis, but only after 16 h of incubation at the 1:5 trophozoite:dTHP-1 cell ratio. These results suggest that pro-inflammatory cytokine synthesis by human macrophages in direct response to T. tenax contributes little to oral pathology. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Health and Human Rights: New challenges for social responsiveness

    Directory of Open Access Journals (Sweden)

    Leslie London

    2009-11-01

    . Finally, it is shown how the portfolio of social responsiveness activities in the health and human rights envelope has offered significant and novel mutual benefits to the University and the community.

  19. Human immune system mice: current potential and limitations for translational research on human antibody responses.

    Science.gov (United States)

    Vuyyuru, Raja; Patton, John; Manser, Tim

    2011-12-01

    It has recently become possible to generate chimeric mice durably engrafted with many components of the human immune system (HIS mice). We have characterized the maturation and function of the B cell compartment of HIS mice. The antibody response of HIS mice to T cell-dependent B cell antigens is limited, and contributing factors may be the general immaturity of the B cell compartment, infrequent helper T cells selected on human MHC class II antigens, and incomplete reconstitution of secondary lymphoid organs and their microenvironments. In contrast, HIS mice generate protective antibody responses to the bacterium Borrelia hermsii, which acts as a T cell-independent antigen in mice, but do not respond to purified polysaccharide antigens (PPS). We speculate that the anti-B. hermsii response of HIS mice is derived from an abundant B cell subset that may be analogous to B1 B cells in mice. We suggest that failure of HIS mice to respond to PPS is due to the lack of a B cell subset that may originate from adult bone marrow and is highly dependent on human interleukin-7 for development.

  20. Characterization of human antiviral adaptive immune responses during hepatotropic virus infection in HLA-transgenic human immune system mice.

    Science.gov (United States)

    Billerbeck, Eva; Horwitz, Joshua A; Labitt, Rachael N; Donovan, Bridget M; Vega, Kevin; Budell, William C; Koo, Gloria C; Rice, Charles M; Ploss, Alexander

    2013-08-15

    Humanized mice have emerged as a promising model to study human immunity in vivo. Although they are susceptible to many pathogens exhibiting an almost exclusive human tropism, human immune responses to infection remain functionally impaired. It has recently been demonstrated that the expression of HLA molecules improves human immunity to lymphotropic virus infections in humanized mice. However, little is known about the extent of functional human immune responses in nonlymphoid tissues, such as in the liver, and the role of HLA expression in this context. Therefore, we analyzed human antiviral immunity in humanized mice during a hepatotropic adenovirus infection. We compared immune responses of conventional humanized NOD SCID IL-2Rγ-deficient (NSG) mice to those of a novel NOD SCID IL-2Rγ-deficient strain transgenic for both HLA-A*0201 and a chimeric HLA-DR*0101 molecule. Using a firefly luciferase-expressing adenovirus and in vivo bioluminescence imaging, we demonstrate a human T cell-dependent partial clearance of adenovirus-infected cells from the liver of HLA-transgenic humanized mice. This correlated with liver infiltration and activation of T cells, as well as the detection of Ag-specific humoral and cellular immune responses. When infected with a hepatitis C virus NS3-expressing adenovirus, HLA-transgenic humanized mice mounted an HLA-A*0201-restricted hepatitis C virus NS3-specific CD8(+) T cell response. In conclusion, our study provides evidence for the generation of partial functional antiviral immune responses against a hepatotropic pathogen in humanized HLA-transgenic mice. The adenovirus reporter system used in our study may serve as simple in vivo method to evaluate future strategies for improving human intrahepatic immune responses in humanized mice.

  1. The fractional viscoelastic response of human breast tissue cells

    Science.gov (United States)

    Carmichael, B.; Babahosseini, H.; Mahmoodi, S. N.; Agah, M.

    2015-07-01

    The mechanical response of a living cell is notoriously complicated. The complex, heterogeneous characteristics of cellular structure introduce difficulties that simple linear models of viscoelasticity cannot overcome, particularly at deep indentation depths. Herein, a nano-scale stress-relaxation analysis performed with an atomic force microscope reveals that isolated human breast cells do not exhibit simple exponential relaxation capable of being modeled by the standard linear solid (SLS) model. Therefore, this work proposes the application of the fractional Zener (FZ) model of viscoelasticity to extract mechanical parameters from the entire relaxation response, improving upon existing physical techniques to probe isolated cells. The FZ model introduces a new parameter that describes the fractional time-derivative dependence of the response. The results show an exceptional increase in conformance to the experimental data compared to that predicted by the SLS model, and the order of the fractional derivative (α) is remarkably homogeneous across the populations, with a median value of 0.48 ± 0.06 for the malignant population and 0.51 ± 0.07 for the benign. The cells’ responses exhibit power-law behavior and complexity not associated with simple relaxation (SLS, α = 1) that supports the application of a fractional model. The distributions of some of the FZ parameters also preserve the distinction between the malignant and benign sample populations seen from the linear model and previous results while including the contribution of fast-relaxation behavior. The resulting viscosity, measured by a composite relaxation time, exhibits considerably less dispersion due to residual error than the distribution generated by the linear model and therefore serves as a more powerful marker for cell differentiation.

  2. Human papillomavirus typing of warts and response to cryotherapy.

    Science.gov (United States)

    Tomson, N; Sterling, J; Ahmed, I; Hague, J; Berth-Jones, J

    2011-09-01

    Cutaneous warts are common and caused by a number of different types of human papillomaviruses (HPVs). The aim of this study was to investigate the HPV types causing common warts and to determine any association between the HPV type and the duration of warts and response to cryotherapy. Eighty wart samples from 76 immunocompetent patients were taken from warts by paring prior to cryotherapy and analysed by in situ hybridization (ISH) with HPV probes specific to HPV 1, 2, 3, 4, 7, 10 and 57 and PCR analysis using degenerate cutaneous HPV primers with subsequent DNA sequencing. Each patient's details, including site, duration and response of the wart to cryotherapy were recorded. Cryotherapy was performed at 2 week intervals for a maximum of 12 weeks. An HPV type was identified in 65 samples. The majority of warts (58 samples) were typed as HPV 2/27/57 by ISH and/or PCR. Three of the 18 samples that were HPV negative with ISH were HPV positive by PCR. Response to treatment did not correlate with HPV type, duration or location. In the 21 wart parings taken from patients aged 16 and under, response to treatment did not correlate with HPV type but warts of shorter duration were more likely to resolve with cryotherapy treatment than longer standing lesions. This study demonstrates that HPV type can be determined from wart parings. HPV-2 related viruses are the prevalent HPV types causing common warts on the hands and feet in this population. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

  3. Incorporating Human Rights into the Sustainability Agenda: A Commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It"

    Science.gov (United States)

    Andrew, Jane

    2013-01-01

    In her commentary of McPhail's 2013 article "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It: Incorporating Human Rights into the Sustainability Agenda," Jane Andrew begins by highlighting a number of McPhail's primary arguments. She points out that McPhail sets out to achieve two things…

  4. Incorporating Human Rights into the Sustainability Agenda: A Commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It"

    Science.gov (United States)

    Andrew, Jane

    2013-01-01

    In her commentary of McPhail's 2013 article "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It: Incorporating Human Rights into the Sustainability Agenda," Jane Andrew begins by highlighting a number of McPhail's primary arguments. She points out that McPhail sets out to achieve two things…

  5. Mu suppression and human movement responses to the Rorschach test.

    Science.gov (United States)

    Pineda, Jaime A; Giromini, Luciano; Porcelli, Piero; Parolin, Laura; Viglione, Donald J

    2011-03-30

    Electroencephalographic μ wave suppression was investigated using all 10 static, ambiguous Rorschach stimuli. In an earlier study using four Rorschach stimuli, the two stimuli that elicited feelings of movement were associated with μ suppression. In this study, we replicated this relationship using all 10 Rorschach stimuli while overcoming a number of other earlier limitations. The results strongly support the hypothesis that internal representation of the feeling of movement is sufficient to suppress the μ rhythm even when minimal external cues are present. This outcome increases the generalizability and ecological validity of this approach and gives support to the traditional interpretation of the Rorschach human movement responses as being associated with cognitive functioning, empathy, and social cognition.

  6. Medial olivocochlear efferent reflex inhibition of human cochlear nerve responses.

    Science.gov (United States)

    Lichtenhan, J T; Wilson, U S; Hancock, K E; Guinan, J J

    2016-03-01

    Inhibition of cochlear amplifier gain by the medial olivocochlear (MOC) efferent system has several putative roles: aiding listening in noise, protection against damage from acoustic overexposure, and slowing age-induced hearing loss. The human MOC reflex has been studied almost exclusively by measuring changes in otoacoustic emissions. However, to help understand how the MOC system influences what we hear, it is important to have measurements of the MOC effect on the total output of the organ of Corti, i.e., on cochlear nerve responses that couple sounds to the brain. In this work we measured the inhibition produced by the MOC reflex on the amplitude of cochlear nerve compound action potentials (CAPs) in response to moderate level (52-60 dB peSPL) clicks from five, young, normal hearing, awake, alert, human adults. MOC activity was elicited by 65 dB SPL, contralateral broadband noise (CAS). Using tympanic membrane electrodes, approximately 10 h of data collection were needed from each subject to yield reliable measurements of the MOC reflex inhibition on CAP amplitudes from one click level. The CAS produced a 16% reduction of CAP amplitude, equivalent to a 1.98 dB effective attenuation (averaged over five subjects). Based on previous reports of efferent effects as functions of level and frequency, it is possible that much larger effective attenuations would be observed at lower sound levels or with clicks of higher frequency content. For a preliminary comparison, we also measured MOC reflex inhibition of DPOAEs evoked from the same ears with f2's near 4 kHz. The resulting effective attenuations on DPOAEs were, on average, less than half the effective attenuations on CAPs.

  7. Trichothecene mycotoxins activate inflammatory response in human macrophages.

    Science.gov (United States)

    Kankkunen, Päivi; Rintahaka, Johanna; Aalto, Annika; Leino, Marina; Majuri, Marja-Leena; Alenius, Harri; Wolff, Henrik; Matikainen, Sampsa

    2009-05-15

    Damp building-related illnesses have caused concern for years in many countries. Although the problem is extensive, the knowledge of the immunological reactions behind damp building-related illnesses is still quite limited. Trichothecene mycotoxins form one major group of toxins, which possibly contribute to the illnesses. Stachybotrys chartarum is a well-known, but also controversial damp building mold and many strains of this mold are capable of producing trichothecenes. In this report, we have examined the effect of S. chartarum and trichothecene mycotoxins on the proinflammatory cytokine response in human macrophages. As a result, satratoxin-positive S. chartarum activated inflammasome-associated caspase-1, which is needed for proteolytic processing of IL-1beta and IL-18. Furthermore, purified trichothecene mycotoxins, roridin A, verrucarin A, and T-2 toxin activated caspase-1, and these mycotoxins also strongly enhanced LPS-dependent secretion of IL-1beta and IL-18. The satratoxin-positive strain of S. chartarum and the trichothecenes also triggered the activation of caspase-3, which is an effector caspase of apoptosis. Satratoxin-negative S. chartarum was not able to activate either caspase-1 or caspase-3. In conclusion, our results indicate that human macrophages sense trichothecene mycotoxins as a danger signal, which activates caspase-1, and further enables the secretion of IL-1beta and IL-18 from the LPS-primed cells.

  8. The suppression of innate immune response by human rhinovirus C.

    Science.gov (United States)

    Pang, Li-Li; Yuan, Xin-Hui; Shao, Chang-Sheng; Li, Mao-Zhong; Wang, Ying; Wang, Hui-Min; Xie, Guang-Cheng; Xie, Zhi-Ping; Yuan, Yue; Zhou, Dong-Mei; Sun, Xiao-Man; Zhang, Qing; Xin, Yan; Li, Dan-di; Duan, Zhao-Jun

    2017-08-12

    Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-β mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-β activation was ascribed to 3C(pro) of RV-C, and the 40-His site of 3C(pro) played an important role. Furthermore, RIG-I was degraded by 3C(pro) in a caspase-dependent manner and 3C(pro) cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells. Copyright © 2017. Published by Elsevier Inc.

  9. Lactic acid delays the inflammatory response of human monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peter, Katrin, E-mail: katrin.peter@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Rehli, Michael, E-mail: michael.rehli@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Singer, Katrin, E-mail: katrin.singer@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Renner-Sattler, Kathrin, E-mail: kathrin.renner-sattler@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Kreutz, Marina, E-mail: marina.kreutz@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany)

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors.

  10. Alterations in the Medullary Endocannabinoid System Contribute to Age-related Impairment of Baroreflex Sensitivity.

    Science.gov (United States)

    Schaich, Chris L; Shaltout, Hossam A; Grabenauer, Megan; Thomas, Brian F; Gallagher, Patricia E; Howlett, Allyn C; Diz, Debra I

    2015-05-01

    As they age, Sprague-Dawley (SD) rats develop elevated systolic blood pressure associated with impaired baroreflex sensitivity (BRS) for control of heart rate. We previously demonstrated in young hypertensive (mRen2)27 rats that impaired BRS is restored by CB1 cannabinoid receptor blockade in the solitary tract nucleus (NTS), consistent with elevated content of the endocannabinoid 2-arachidonoylglycerol (2-AG) in dorsal medulla relative to normotensive SD rats. There is no effect of CB1 receptor blockade in young SD rats. We now report in older SD rats that dorsal medullary 2-AG levels are 2-fold higher at 70 versus 15 weeks of age (4.22 ± 0.61 vs. 1.93 ± 0.22 ng/mg tissue; P < 0.05). Furthermore, relative expression of CB1 receptor messenger RNA is significantly lower in aged rats, whereas CB2 receptor messenger RNA is significantly higher. In contrast to young adult SD rats, microinjection of the CB1 receptor antagonist SR141716A (36 pmole) into the NTS of older SD rats normalized BRS in animals exhibiting impaired baseline BRS (0.56 ± 0.06 baseline vs. 1.06 ± 0.05 ms/mm Hg after 60 minutes; P < 0.05). Therefore, this study provides evidence for alterations in the endocannabinoid system within the NTS of older SD rats that contribute to age-related impairment of BRS.

  11. Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas Disease

    Directory of Open Access Journals (Sweden)

    Astrid Meireles Santos

    2014-07-01

    Full Text Available Background: Sudden death is the leading cause of death in Chagas disease (CD, even in patients with preserved ejection fraction (EF, suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation contribute to its occurrence. Objective: To determine baroreflex sensitivity (BRS in patients with undetermined CD (GI, arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT (GII and CD with spontaneous sustained ventricular tachycardia (STV (GIII, to evaluate its association with the occurrence and complexity of arrhythmias. Method: Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor. The following were determined: BRS (phenylephrine method; heart rate variability (HRV on 24-h Holter; and EF (echocardiogram. Results: GIII had lower BRS (6.09 ms/mm Hg as compared to GII (11.84 and GI (15.23. The difference was significant between GI and GIII (p = 0.01. Correlating BRS with the density of ventricular extrasystoles (VE, low VE density ( 10/h had preserved BRS (p = 0.003. Patients with depressed BRS had higher VE density (p = 0.01, regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028. Conclusion: The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias.

  12. Aging process on spectrally determined spontaneous baroreflex sensitivity: a 5-year prospective study.

    Science.gov (United States)

    Fauvel, Jean-Pierre; Cerutti, Catherine; Mpio, Ignace; Ducher, Michel

    2007-09-01

    The interindividual age-related decrease in baroreflex sensitivity (BRS) was reported in many cross-sectional studies. However, the long-term intraindividual decrease in BRS has never been confirmed by longitudinal studies. Data obtained from a 5-year prospective study designed to assess the 5-year stress effects on blood pressure (BP) provided the opportunity to assess longitudinal aging process on spectrally determined BRS (S-BRS) using the cross spectral analysis. This analysis was carried out in 205 men aged between 18 and 50 years who had 2 valid beat to beat BP recordings (Finapress) at a mean 5-year interval. At inclusion and at end of follow-up, S-BRS was significantly correlated with age (r=-0.50, P<0.001, r=-0.33, P<0.001 respectively). Interestingly, the slopes and the intercepts were not significantly different at a 5-year interval. This result is in favor of the good reproducibility of S-BRS. The attenuation with age of S-BRS was calculated at 3.6% a year. This decrease was slightly higher than the one obtained with the baseline data (2.3% per year). This longitudinal study provided, for the first time, an estimate of the slope of the age-related physiological S-BRS decrease in a mid-aged healthy male population. Our findings reinforce the interest of evaluating spontaneous BRS reported to predict hypertension and cardiovascular events in various populations.

  13. Inhibition of cortisol production with metyrapone prevents mental stress-induced endothelial dysfunction and baroreflex impairment.

    Science.gov (United States)

    Broadley, Andrew J M; Korszun, Ania; Abdelaal, Eltigani; Moskvina, Valentina; Jones, Christopher J H; Nash, Gerard B; Ray, Clare; Deanfield, John; Frenneaux, Michael P

    2005-07-19

    This study was designed to investigate the role of cortisol in stress-induced endothelial dysfunction and impaired baroreflex sensitivity (BRS) by blocking cortisol production with metyrapone before subjecting healthy volunteers to mental stress. Mental stress raises cortisol levels and is associated with increased coronary heart disease (CHD) morbidity and mortality, especially from sudden cardiac death. It also causes endothelial dysfunction and impaired BRS. We measured brachial artery flow-mediated dilation (FMD), a measure of endothelial function, and BRS in 36 subjects without CHD risk factors who were then randomized in a double-blind fashion to oral metyrapone 750 mg x 2 or placebo. Five hours later we subjected subjects to mental stress and then remeasured endothelial function and BRS. Prestress cortisol levels were significantly higher in the placebo group at 270.5 (30.9) nmol/l versus 89.1 (11.8) nmol/l (p = 0.01), and the increase with stress was higher at 57.9 (17.9) nmol/l versus 11.2 (2.2) nmol/l (p Analysis of covariation showed a significant effect of metyrapone on change in both FMD (p = 0.009) and BRS (p = 0.024). Stress-related endothelial dysfunction and BRS impairment can be prevented by blocking cortisol production with metyrapone, demonstrating a direct or facilitative role for cortisol in these phenomena and suggesting mechanisms by which stress contributes to CHD and sudden cardiac death.

  14. Baroreflex sensitivity in children and adolescents: physiology, hypertension, obesity, diabetes mellitus.

    Science.gov (United States)

    Honzíková, N; Závodná, E

    2016-12-13

    The increased prevalence of obesity in children and its complications have led to a greater interest in studying baroreflex sensitivity (BRS) in children. This review of BRS in children and adolescents includes subtopics on: 1. Resting values of BRS and their reproducibility, 2. Genetics of BRS, 3. The role of a primarily low BRS and obesity in the development of hypertension, and 4. Association of diabetes mellitus, BRS, and obesity. The conclusions specific to this age follow from this review: 1. The mean heart rate (HR) influences the measurement of BRS. Since the mean HR decreases during adolescence, HR should be taken into account. 2. A genetic dependency of BRS was found. 3. Low BRS values may precede pathological blood-pressure elevation in children with white-coat hypertension. We hypothesize that low BRS plays an active role in the emergence of hypertension in youth. A contribution of obesity to the development of hypertension was also found. We hypothesize that both factors, a primarily low BRS and obesity, are partially independent risk factors for hypertension in youths. 4. In diabetics, a low BRS compared to healthy children can be associated with insulin resistance. A reversibility of the BRS values could be possible after weight loss.

  15. Analysis of baroreflex sensitivity during undulation pump ventricular assist device support.

    Science.gov (United States)

    Liu, Hongjian; Shiraishi, Yasuyuki; Zhang, Xiumin; Song, Hojin; Saijo, Yoshifumi; Baba, Atsushi; Yambe, Tomoyuki; Abe, Yusuke; Imachi, Kou

    2009-07-01

    The aim of this study was to examine the baroreflex sensitivity (BRS), which involves the autonomic nervous system, in a goat with a chronically implanted undulation pump ventricular assist device (UPVAD). The UPVAD involved transforming the rotation of a brushless DC motor into an undulating motion by a disc attached via a special linking mechanism, and a jellyfish valve in the outflow cannula to prevent diastolic backflow. The pump was implanted into the thoracic cavity of a goat by a left thoracotomy, and the inflow and outflow cannulae were sutured to the apex of the left ventricle and to the descending aorta, respectively. The driving cable was wired percutaneously to an external controller. Electrocardiogram and hemodynamic waveforms were recorded at a sampling frequency of 1 kHz. BRS was determined when awake by the slope of the linear regression of R-R interval against mean arterial pressure changes, which were induced by the administration of methoxamine hydrochloride, both with continuous driving of the UPVAD as well as without assistance. BRS values during the UPVAD support and without assistance were 1.60 +/- 0.30 msec/mm Hg and 0.98 +/- 0.22 msec/mm Hg (n = 5, P < 0.05), respectively. BRS was significantly improved during left ventricular assistance. Therefore, UPVAD support might decrease sympathetic nerve activity and increase parasympathetic nerve activity to improve both microcirculation and organ function.

  16. Comparison of Biodynamic Responses in Standing and Seated Human Bodies

    Science.gov (United States)

    MATSUMOTO, Y.; GRIFFIN, M. J.

    2000-12-01

    The dynamic responses of the human body in a standing position and in a sitting position have been compared. The apparent mass and transmissibilities to the head, six locations along the spine, and the pelvis were measured with eight male subjects exposed to vertical whole-body vibration. In both postures, the principal resonance in the apparent mass occurred in the range 5-6 Hz, with slightly higher frequencies and lower apparent mass in the standing posture. There was greater transmission of vertical vibration to the pelvis and the lower spine and greater relative motion within the lower spine in the standing posture than in the sitting posture at the principal resonance and at higher frequencies. Transmissibilities from the supporting surface (floor or seat) to the thoracic region had similar magnitudes for both standing and sitting subjects. The lumbar spine has less lordosis and may be more compressed and less flexible in the sitting posture than in the standing posture. This may have reduced the relative motions between lumbar vertebrae and both the supporting vibrating surface and the other vertebrae in the sitting posture. The characteristics of the vibration transmitted to the pelvis may have differed in the two postures due to different transmission paths. Increased forward rotation of the pelvis in the standing posture may have caused the differences in responses of the pelvis and the lower spine that were observed between the two postures.

  17. Cardiovascular responses to voluntary and nonvoluntary static exercise in humans.

    Science.gov (United States)

    Friedman, D B; Peel, C; Mitchell, J H

    1992-11-01

    We have measured the cardiovascular responses during voluntary and nonvoluntary (electrically induced) one-leg static exercise in humans. Eight normal subjects were studied at rest and during 5 min of static leg extension at 20% of maximal voluntary contraction performed voluntarily and nonvoluntarily in random order. Heart rate (HR), mean arterial pressure (MAP), and cardiac output (CO) were determined, and peripheral vascular resistance (PVR) and stroke volume (SV) were calculated. HR increased from approximately 65 +/- 3 beats/min at rest to 80 +/- 4 and 78 +/- 6 beats/min (P voluntary and nonvoluntary contractions, respectively. CO increased from 5.1 +/- 0.7 to 6.0 +/- 0.8 and 6.2 +/- 0.8 l/min (P voluntary and nonvoluntary contractions, respectively. PVR and SV did not change significantly during voluntary or nonvoluntary contractions. Thus the cardiovascular responses were not different between voluntary and electrically induced contractions. These results suggest that the increases in CO, HR, SV, MAP, and PVR during 5 min of static contractions can be elicited without any contribution from a central neural mechanism (central command). However, central command could still have an important role during voluntary static exercise.

  18. Human arm posture prediction in response to isometric endpoint forces.

    Science.gov (United States)

    Davoudabadi Farahani, Saeed; Andersen, Michael Skipper; de Zee, Mark; Rasmussen, John

    2015-11-26

    The ability to predict the musculoskeletal response to external loads has multiple applications for the design of machines with a human interface and for the prediction of outcomes of musculoskeletal interventions. In this study, we applied an inverse-inverse dynamics technique to investigate its ability to predict arm posture in response to isometric hand forces. For each subject, we made a three-dimensional musculoskeletal model using the AnyBody Modelling System (AMS). Then, we had each subject-specific model hold a weight anteriorly to the right shoulder joint at a distance of half of the arm length. We selected the glenohumeral abduction angle (GHAA) as the only free parameter. Subsequently, we used inverse-inverse dynamics to find the optimal GHAA that minimised a performance criterion with physiological constraints. In this study, we investigated the performance of two different objective functions: summation of squared muscle activity (SSMA) and summation of squared normalised joint torques (SSNJT). To validate the simulation results, arm posture responses to different isometric downward hand forces were measured for six healthy male subjects. Five trials were performed for each loading condition. The results showed that, with an increase in hand load, there was a reduced GHAA in all subjects. Another interesting finding was that self-selected postures for lighter tasks varied more than postures for heavier tasks for all subjects. To understand this, we investigated the curvature of the objective function as a function of the load and observed an increased curvature with increased load. This may explain the reduced intra-subject variations observed for increasing loads.

  19. Human auditory steady state responses to binaural and monaural beats.

    Science.gov (United States)

    Schwarz, D W F; Taylor, P

    2005-03-01

    Binaural beat sensations depend upon a central combination of two different temporally encoded tones, separately presented to the two ears. We tested the feasibility to record an auditory steady state evoked response (ASSR) at the binaural beat frequency in order to find a measure for temporal coding of sound in the human EEG. We stimulated each ear with a distinct tone, both differing in frequency by 40Hz, to record a binaural beat ASSR. As control, we evoked a beat ASSR in response to both tones in the same ear. We band-pass filtered the EEG at 40Hz, averaged with respect to stimulus onset and compared ASSR amplitudes and phases, extracted from a sinusoidal non-linear regression fit to a 40Hz period average. A 40Hz binaural beat ASSR was evoked at a low mean stimulus frequency (400Hz) but became undetectable beyond 3kHz. Its amplitude was smaller than that of the acoustic beat ASSR, which was evoked at low and high frequencies. Both ASSR types had maxima at fronto-central leads and displayed a fronto-occipital phase delay of several ms. The dependence of the 40Hz binaural beat ASSR on stimuli at low, temporally coded tone frequencies suggests that it may objectively assess temporal sound coding ability. The phase shift across the electrode array is evidence for more than one origin of the 40Hz oscillations. The binaural beat ASSR is an evoked response, with novel diagnostic potential, to a signal that is not present in the stimulus, but generated within the brain.

  20. IMMEDIATE HUMAN PULP RESPONSE TO ETHANOL-WET BONDING TECHNIQUE

    Science.gov (United States)

    Scheffel, Débora Lopes Salles; Sacono, Nancy Tomoko; Ribeiro, Ana Paula Dias; Soares, Diana Gabriela; Basso, Fernanda Gonçalves; Pashley, David Henry; Costa, Carlos Alberto de Souza; Hebling, Josimeri

    2016-01-01

    Objective To evaluate the short-term response of human pulps to ethanol-wet bonding technique associated with an etch-and-rinse adhesive system. Methods Deep class V cavities were prepared on the buccal surface of 17 sound premolars scheduled for extraction for orthodontics. The teeth were assigned into three groups: Ethanol-wet bonding (G1), water-wet bonding (G2) and calcium hydroxide (G3, control). Two teeth were used as intact control. After acid-etching, the cavities from G1 were filled with 100% ethanol for 60s and blot-dried before the application of Single Bond 2. In G2, the cavities were filled with distilled water for 60s previously to adhesive application and in G3, the cavity floor was lined with calcium hydroxide before etching and bonding. All cavities were restored with resin composite. The teeth were extracted 48h after the clinical procedures. From each tooth 6 μm-thick serial sections were obtained and stained with hematoxylin and eosin (H/E) and Masson's trichrome. Bacteria microleakage was assessed using Brown & Brenn. All sections were blindly evaluated and scored for five histological features. Results Mean remaining dentin thickness was 463±65μm (G1); 425±184μm (G2); and 348±194μm (G3). Similar pulp reactions followed ethanol- or water-wet bonding techniques. Slight inflammatory responses and disruption of the odontoblast layer related to the cavity floor were seen in all groups. Stained bacteria were not detected in any cavities. Normal pulp tissue was observed in G3 except for one case. Conclusions After 48 h, ethanol-wet bonding technique applied on deep cavities prepared in vital teeth does not increase pulpal damage compared to water-wet bonding technique. Clinical significance Ethanol-wet bonding has been considered an experimental technique that may increase resin-dentin bond durability. This study reported the in vivo response of human pulp tissue when 100% ethanol was applied previously to an etch-and-rinse simplified adhesive

  1. Amniotic fluid elicits appetitive responses in human newborns: fatty acids and appetitive responses.

    Science.gov (United States)

    Contreras, Carlos M; Gutiérrez-García, Ana G; Mendoza-López, Remedios; Rodríguez-Landa, Juan Francisco; Bernal-Morales, Blandina; Díaz-Marte, Cynthia

    2013-04-01

    In humans, maternal cues guide newborns to the maternal breast, and transitional cues may be present in maternal-fetal fluids. The aim of the present study was to determine the consistent presence of sensorial cues in three maternal-fetal fluids--amniotic fluid, colostrum, and milk--and test the ability of these cues to produce appetitive responses in newborns. In the analytical study, gas chromatography-mass spectrometry (GC-MS) detected eight fatty acids consistently present in the amniotic fluid, colostrum, and milk from 12 healthy volunteers, but we do not find a mammalian pheromone, identified in another mammalian species (rabbits), in another 30 volunteers. In the behavioral study, we explored the ability of amniotic fluid or its fatty acids to produce appetitive responses in 19 human newborns fluid or an artificial fatty acid mixture produced a longer duration of facial reactions that suggested appetitive (sucking) movements compared with respective vehicles (i.e., propylene glycol or centrifuged amniotic fluid with a low fatty acid content verified by GC-MS). We conclude that the fatty acids contained in amniotic fluid may constitute a transitional sensorial cue that guides newborns to the maternal breast.

  2. 24 CFR 7.14 - Responsibilities of the Office of Human Resources.

    Science.gov (United States)

    2010-04-01

    ... Human Resources. 7.14 Section 7.14 Housing and Urban Development Office of the Secretary, Department of... Reprisal Responsibilities § 7.14 Responsibilities of the Office of Human Resources. In accordance with guidelines issued by the Assistant Secretary for Administration, Human Resources Officers shall: (a)...

  3. Resolution of outcome-induced response conflict by humans after extended training

    NARCIS (Netherlands)

    de Wit, S.; Ridderinkhof, K.R.; Fletcher, P.C.; Dickinson, A.

    2013-01-01

    Studies of incongruent discrimination learning, where the outcome event of one response acts as the discriminative stimulus for the opposite response, suggest that humans rely on habitual stimulus-response (S-R) associations when outcome-response (O-R) associations would cause response conflict. Her

  4. Activated human neutrophil response to perfluorocarbon nanobubbles: oxygen-dependent and -independent cytotoxic responses.

    Science.gov (United States)

    Hwang, Tsong-Long; Fang, Chia-Lang; Al-Suwayeh, Saleh A; Yang, Li-Jia; Fang, Jia-You

    2011-06-10

    Nanobubbles, a type of nanoparticles with acoustically active properties, are being utilized as diagnostic and therapeutic nanoparticles to better understand, detect, and treat human diseases. The objective of this work was to prepare different nanobubble formulations and investigate their physicochemical characteristics and toxic responses to N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated human neutrophils. The nanobubbles were prepared using perfluoropentane and coconut oil as the respective core and shell, with soybean phosphatidylcholine (SPC) and/or cationic surfactants as the interfacial layers. The cytotoxic effect of the nanobubbles on neutrophils was determined by extracellular O₂(.)⁻ release, intracellular reactive oxygen species (ROS), lactate dehydrogenase (LDH), and elastase release. Particle sizes of the nanobubbles with different percentages of perfluorocarbon, oil, and surfactants in ranged 186-432 nm. The nanobubbles were demonstrated to inhibit the generation of superoxide and intracellular ROS. The cytotoxicity of nanobubbles may be mainly associated with membrane damage, as indicated by the high LDH leakage. Systems with Forestall (FE), a cationic surfactant, or higher SPC contents exhibited the greatest LDH release by 3-fold compared to the control. The further addition of an oil component reduced the cytotoxicity induced by the nanobubbles. Exposure to most of the nanobubble formulations upregulated elastase release by activated neutrophils. Contrary to this result, stearylamine (SA)-containing systems slightly but significantly suppressed elastase release. FE and SA in a free form caused stronger responses by neutrophils than when they were incorporated into nanobubbles. In summary, exposure to nanobubbles resulted in a formulation-dependent toxicity toward human neutrophils that was associated with both oxygen-dependent and -independent pathways. Clinicians should therefore exercise caution when using nanobubbles in patients

  5. Human rhinovirus induced cytokine/chemokine responses in human airway epithelial and immune cells.

    Directory of Open Access Journals (Sweden)

    Devi Rajan

    Full Text Available Infections with human rhinovirus (HRV are commonly associated with acute upper and lower respiratory tract disease and asthma exacerbations. The role that HRVs play in these diseases suggests it is important to understand host-specific or virus-specific factors that contribute to pathogenesis. Since species A HRVs are often associated with more serious HRV disease than species B HRVs, differences in immune responses they induce should inform disease pathogenesis. To identify species differences in induced responses, we evaluated 3 species A viruses, HRV 25, 31 and 36 and 3 species B viruses, HRV 4, 35 and 48 by exposing human PBMCs to HRV infected Calu-3 cells. To evaluate the potential effect of memory induced by previous HRV infection on study responses, we tested cord blood mononuclear cells that should be HRV naïve. There were HRV-associated increases (significant increase compared to mock-infected cells for one or more HRVs for IP-10 and IL-15 that was unaffected by addition of PBMCs, for MIP-1α, MIP-1β, IFN-α, and HGF only with addition of PBMCs, and for ENA-78 only without addition of PBMCs. All three species B HRVs induced higher levels, compared to A HRVs, of MIP-1α and MIP-1β with PBMCs and ENA-78 without PBMCs. In contrast, addition of CBMCs had less effect and did not induce MIP-1α, MIP-1β, or IFN-α nor block ENA-78 production. Addition of CBMCs did, however, increase IP-10 levels for HRV 35 and HRV 36 infection. The presence of an effect with PBMCs and no effect with CBMCs for some responses suggest differences between the two types of cells possibly because of the presence of HRV memory responses in PBMCs and not CBMCs or limited response capacity for the immature CBMCs relative to PBMCs. Thus, our results indicate that different HRV strains can induce different patterns of cytokines and chemokines; some of these differences may be due to differences in memory responses induced by past HRV infections, and other differences

  6. Lactic acid delays the inflammatory response of human monocytes.

    Science.gov (United States)

    Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. The cellular inflammatory response in human spinal cords after injury.

    Science.gov (United States)

    Fleming, Jennifer C; Norenberg, Michael D; Ramsay, David A; Dekaban, Gregory A; Marcillo, Alexander E; Saenz, Alvaro D; Pasquale-Styles, Melissa; Dietrich, W Dalton; Weaver, Lynne C

    2006-12-01

    Spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord but also may contribute to its repair. Anti-inflammatory treatment of human SCI and its timing must be based on knowledge of the types of cells participating in the inflammatory response, the time after injury when they appear and then decrease in number, and the nature of their actions. Using post-mortem spinal cords, we evaluated the time course and distribution of pathological change, infiltrating neutrophils, monocytes/macrophages and lymphocytes, and microglial activation in injured spinal cords from patients who were 'dead at the scene' or who survived for intervals up to 1 year after SCI. SCI caused zones of pathological change, including areas of inflammation and necrosis in the acute cases, and cystic cavities with longer survival (Zone 1), mantles of less severe change, including axonal swellings, inflammation and Wallerian degeneration (Zone 2) and histologically intact areas (Zone 3). Zone 1 areas increased in size with time after injury whereas the overall injury (size of the Zones 1 and 2 combined) remained relatively constant from the time (1-3 days) when damage was first visible. The distribution of inflammatory cells correlated well with the location of Zone 1, and sometimes of Zone 2. Neutrophils, visualized by their expression of human neutrophil alpha-defensins (defensin), entered the spinal cord by haemorrhage or extravasation, were most numerous 1-3 days after SCI, and were detectable for up to 10 days after SCI. Significant numbers of activated CD68-immunoreactive ramified microglia and a few monocytes/macrophages were in injured tissue within 1-3 days of SCI. Activated microglia, a few monocytes/macrophages and numerous phagocytic macrophages were present for weeks to months after SCI. A few CD8(+) lymphocytes were in the injured cords throughout the sampling intervals. Expression by the inflammatory cells of the oxidative

  8. Trigonometric regressive spectral analysis reliably maps dynamic changes in baroreflex sensitivity and autonomic tone: the effect of gender and age.

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    Manja Reimann

    Full Text Available BACKGROUND: The assessment of baroreflex sensitivity (BRS has emerged as prognostic tool in cardiology. Although available computer-assisted methods, measuring spontaneous fluctuations of heart rate and blood pressure in the time and frequency domain are easily applicable, they do not allow for quantification of BRS during cardiovascular adaption processes. This, however, seems an essential criterion for clinical application. We evaluated a novel algorithm based on trigonometric regression regarding its ability to map dynamic changes in BRS and autonomic tone during cardiovascular provocation in relation to gender and age. METHODOLOGY/PRINCIPAL FINDINGS: We continuously recorded systemic arterial pressure, electrocardiogram and respiration in 23 young subjects (25+/-2 years and 22 middle-aged subjects (56+/-4 years during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head-up tilt. Baroreflex- and spectral analysis was performed using the algorithm of trigonometric regressive spectral analysis. There was an age-related decline in spontaneous BRS and high frequency oscillations of RR intervals. Changes in autonomic tone evoked by cardiovascular provocation were observed as shifts in the ratio of low to high frequency oscillations of RR intervals and blood pressure. Respiration at 0.1 Hz elicited an increase in BRS while head-up tilt and Valsalva manoeuvre resulted in a downregulation of BRS. The extent of autonomic adaption was in general more pronounced in young individuals and declined stronger with age in women than in men. CONCLUSIONS/SIGNIFICANCE: The trigonometric regressive spectral analysis reliably maps age- and gender-related differences in baroreflex- and autonomic function and is able to describe adaption processes of baroreceptor circuit during cardiovascular stimulation. Hence, this novel algorithm may be a useful screening tool to detect abnormalities in cardiovascular adaption processes even when

  9. Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats.

    Science.gov (United States)

    Lopes, P R; Moreira, M C S; Marques, S M; Pinto, I S J; Macedo, L M; Silva, C C; Freiria-Oliveira, A H; Rebelo, A C S; Reis, A A S; Rosa, D A; Ferreira-Neto, M L; Castro, C H; Pedrino, G R

    2016-08-01

    The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280-350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50-60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

  10. Influence of Fragrances on Human Psychophysiological Activity: With Special Reference to Human Electroencephalographic Response

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    Kandhasamy Sowndhararajan

    2016-11-01

    Full Text Available The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. A fragrance consists of volatile chemicals with a molecular weight of less than 300 Da that humans perceive through the olfactory system. In humans, about 300 active olfactory receptor genes are devoted to detecting thousands of different fragrance molecules through a large family of olfactory receptors of a diverse protein sequence. The sense of smell plays an important role in the physiological effects of mood, stress, and working capacity. Electrophysiological studies have revealed that various fragrances affected spontaneous brain activities and cognitive functions, which are measured by an electroencephalograph (EEG. The EEG is a good temporal measure of responses in the central nervous system and it provides information about the physiological state of the brain both in health and disease. The EEG power spectrum is classified into different frequency bands such as delta (0.5–4 Hz, theta (4–8 Hz, alpha (8–13 Hz, beta (13–30 Hz and gamma (30–50 Hz, and each band is correlated with different features of brain states. A quantitative EEG uses computer software to provide the topographic mapping of the brain activity in frontal, temporal, parietal and occipital brain regions. It is well known that decreases of alpha and beta activities and increases of delta and theta activities are associated with brain pathology and general cognitive decline. In the last few decades, many scientific studies were conducted to investigate the effect of inhalation of aroma on human brain functions. The studies have suggested a significant role for olfactory stimulation in the alteration of cognition, mood, and social behavior. This review aims to evaluate the available literature regarding the influence of fragrances on the

  11. Hsp60 response in experimental and human temporal lobe epilepsy.

    Science.gov (United States)

    Marino Gammazza, Antonella; Colangeli, Roberto; Orban, Gergely; Pierucci, Massimo; Di Gennaro, Giancarlo; Lo Bello, Margherita; D'Aniello, Alfredo; Bucchieri, Fabio; Pomara, Cristoforo; Valentino, Mario; Muscat, Richard; Benigno, Arcangelo; Zummo, Giovanni; de Macario, Everly Conway; Cappello, Francesco; Di Giovanni, Giuseppe; Macario, Alberto J L

    2015-03-24

    The mitochondrial chaperonin Hsp60 is a ubiquitous molecule with multiple roles, constitutively expressed and inducible by oxidative stress. In the brain, Hsp60 is widely distributed and has been implicated in neurological disorders, including epilepsy. A role for mitochondria and oxidative stress has been proposed in epileptogenesis of temporal lobe epilepsy (TLE). Here, we investigated the involvement of Hsp60 in TLE using animal and human samples. Hsp60 immunoreactivity in the hippocampus, measured by Western blotting and immunohistochemistry, was increased in a rat model of TLE. Hsp60 was also increased in the hippocampal dentate gyrus neurons somata and neuropil and hippocampus proper (CA3, CA1) of the epileptic rats. We also determined the circulating levels of Hsp60 in epileptic animals and TLE patients using ELISA. The epileptic rats showed circulating levels of Hsp60 higher than controls. Likewise, plasma post-seizure Hsp60 levels in patients were higher than before the seizure and those of controls. These results demonstrate that Hsp60 is increased in both animals and patients with TLE in affected tissues, and in plasma in response to epileptic seizures, and point to it as biomarker of hippocampal stress potentially useful for diagnosis and patient management.

  12. CORPORATE SOCIAL RESPONSIBILITY IMPACTS ON SUSTAINABLE HUMAN DEVELOPMENT

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    Kerstin Anstätt

    2016-06-01

    Full Text Available The goal of this article is to critically analyze the findings of the first, recently published, studies about Corporate Social Responsibility (CSR impacts on Sustainable Human Development (SHD. We aim at deriving conclusions for effective CSR strategies and at identifying consequences for management and research. As CSR claims to create value for corporations and for society, we argue that the people-centered Capability Approach (CA is promising to provide neglected and much needed insights how corporate activities affect individuals and communities. Based on a survey of recent literature addressing CSR impacts on SHD, we highlight CSR potentials to improve average well-being in multiple dimensions of SHD. Moreover, we critically assess challenges and limitations of CSR as a strategy to preserve and foster SHD. For instance, studies have shown that, despite CSR-driven well-being increases, social capital, relational capabilities and collective agency may become challenged by corporate strategies. Moreover, corporate environmental impacts have been found to be less often addressed by both, companies and SHD researchers. Resulting inequality and fairness issues have been identified as causes of violence against corporations even in the presence of total well-being improvements. We conclude that companies should strategically take into account a comprehensive range of factors driving and hampering SHD to account for their whole portfolio of corporate opportunities and risks. This requires evaluating CSR impacts instead of only focusing on CSR inputs and outputs. Thereby, corporations can mitigate their risks, improve their stakeholder trust and strengthen their competitiveness.

  13. Studying the immune response to human viral infections using zebrafish.

    Science.gov (United States)

    Goody, Michelle F; Sullivan, Con; Kim, Carol H

    2014-09-01

    Humans and viruses have a long co-evolutionary history. Viral illnesses have and will continue to shape human history: from smallpox, to influenza, to HIV, and beyond. Animal models of human viral illnesses are needed in order to generate safe and effective antiviral medicines, adjuvant therapies, and vaccines. These animal models must support the replication of human viruses, recapitulate aspects of human viral illnesses, and respond with conserved immune signaling cascades. The zebrafish is perhaps the simplest, most commonly used laboratory model organism in which innate and/or adaptive immunity can be studied. Herein, we will discuss the current zebrafish models of human viral illnesses and the insights they have provided. We will highlight advantages of early life stage zebrafish and the importance of innate immunity in human viral illnesses. We will also discuss viral characteristics to consider before infecting zebrafish with human viruses as well as predict other human viruses that may be able to infect zebrafish.

  14. COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

    Science.gov (United States)

    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  15. Modulation of baroreflex sensitivity by walnuts versus cashew nuts in subjects with metabolic syndrome.

    Science.gov (United States)

    Schutte, Aletta E; Van Rooyen, Johannes M; Huisman, Hugo W; Mukuddem-Petersen, Janine; Oosthuizen, Welma; Hanekom, Susanna M; Jerling, Johann C

    2006-06-01

    Impaired baroreflex sensitivity (BRS) is associated with cardiovascular diseases and the metabolic syndrome. Because lipid abnormalities have been associated with impaired BRS, this study aimed to determine whether diets known to improve the lipid profile, namely a diet high in polyunsaturated fatty acids (walnuts) or monounsaturated fatty acids (cashew nuts), would improve BRS in subjects with metabolic syndrome (MS). A controlled feeding trial with a randomized, controlled, parallel study design was undertaken, which involved 62 subjects with MS. Subjects were stratified according to gender and age and were randomized into three groups receiving a control diet, or a diet high (20% energy) in walnuts or unsalted cashew nuts for 8 weeks while maintaining body weight. The BRS, C-reactive protein (CRP), and MS components were measured before and after the intervention. After the intervention, BRS in the walnut-fed study group decreased (P = .038) and that in the cashew-fed study group increased (P = .036), but the BRS in the control group did not change (P = .56). The percent change of the walnut versus cashew group differed (P = .019). Body mass index, waist circumference, blood pressure, high-density lipoprotein cholesterol, and triacylglycerol did not change. The fasting glucose concentrations of the cashew group increased (P = .03). The significant improvements in BRS obtained by a diet rich in cashew nuts underline the beneficial cardiovascular effects of nuts. However, the opposite result was obtained with a diet rich in walnuts. These significant changes observed might indicate that BRS is particularly sensitive and influenced by changes in diet without changes in obesity.

  16. Coconut oil supplementation and physical exercise improves baroreflex sensitivity and oxidative stress in hypertensive rats.

    Science.gov (United States)

    Alves, Naiane F B; Porpino, Suênia K P; Monteiro, Matheus M O; Gomes, Enéas R M; Braga, Valdir A

    2015-04-01

    The hypothesis that oral supplementation with virgin coconut oil (Cocos nucifera L.) and exercise training would improve impaired baroreflex sensitivity (BRS) and reduce oxidative stress in spontaneously hypertensive rats (SHR) was tested. Adult male SHR and Wistar Kyoto rats (WKY) were divided into 5 groups: WKY + saline (n = 8); SHR + saline (n = 8); SHR + coconut oil (2 mL·day(-1), n = 8); SHR + trained (n = 8); and SHR + trained + coconut oil (n = 8). Mean arterial pressure (MAP) was recorded and BRS was tested using phenylephrine (8 μg/kg, intravenous) and sodium nitroprusside (25 μg·kg(-1), intravenous). Oxidative stress was measured using dihydroethidium in heart and aorta. SHR + saline, SHR + coconut oil, and SHR + trained group showed higher MAP compared with WKY + saline (175 ± 6, 148 ± 6, 147 ± 7 vs. 113 ± 2 mm Hg; p coconut oil, SHR + trained group, and SHR + trained + coconut oil groups presented lower MAP compared with SHR + saline group (148 ± 6, 147 ± 7, 134 ± 8 vs. 175 ± 6 mm Hg; p Coconut oil combined with exercise training improved BRS in SHR compared with SHR + saline group (-2.47 ± 0.3 vs. -1.39 ± 0.09 beats·min(-1)·mm Hg(-1); p coconut oil group presented reduced oxidative stress compared with SHR + saline in heart (622 ± 16 vs. 774 ± 31 AU, p coconut oil reduced oxidative stress in SHR compared with SHR + saline group (454 ± 33 vs. 689 ± 29 AU, p coconut oil combined with exercise training improved impaired BRS and reduced oxidative stress in SHR.

  17. Rehabilitation: Periodic somatosensory stimulation increases arterial baroreflex sensitivity in chronic heart failure patients.

    Science.gov (United States)

    Gademan, Maaike G J; Sun, Yiping; Han, Liming; Valk, Vanessa J; Schalij, Martin J; van Exel, Henk J; Lucas, Carolien M H B; Maan, Arie C; Verwey, Harriette F; van de Vooren, Hedde; Pinna, Gian D; Maestri, Roberto; La Rovere, Maria Teresa; van der Wall, Ernst E; Swenne, Cees A

    2011-10-20

    One of the beneficial effects of exercise training in chronic heart failure (CHF) is an improvement in baroreflex sensitivity (BRS), a prognostic index in CHF. In our hypothesis-generating study we propose that at least part of this effect is mediated by neural afferent information, and more specifically, by exercise-induced somatosensory nerve traffic. To compare the effects of periodic electrical somatosensory stimulation on BRS in patients with CHF with the effects of exercise training and with usual care. We compared in stable CHF patients the effect of transcutaneous electrical nerve stimulation (TENS, N = 23, LVEF 30 ± 9%) with the effects of bicycle exercise training (EXTR, N = 20, LVEF 32 ± 7%). To mimic exercise-associated somatosensory ergoreceptor stimulation, we applied periodic (2/s, marching pace) burst TENS to both feet. TENS and EXTR sessions were held during two successive days. BRS, measured prior to the first intervention session and one day after the second intervention session, increased by 28% from 3.07 ± 2.06 to 4.24 ± 2.61 ms/mmHg in the TENS group, but did not change in the EXTR group (baseline: 3.37 ± 2.53 ms/mmHg; effect: 3.26 ± 2.54 ms/mmHg) (P(TENS vs EXTR) = 0.02). Heart rate and systolic blood pressure did not change in either group. We demonstrated that periodic somatosensory input alone is sufficient and efficient in increasing BRS in CHF patients. This concept constitutes a basis for studies towards more effective exercise training regimens in the diseased/impaired, in whom training aimed at BRS improvement should possibly focus more on the somatosensory aspect. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  18. Additive Effects of Heating and Exercise on Baroreflex Control of Heart Rate in Healthy Males.

    Science.gov (United States)

    Peçanha, Tiago; Forjaz, Claudia Lucia de Moraes; Low, David Andrew

    2017-08-31

    This study assessed the additive effects of passive heating and exercise on cardiac baroreflex sensitivity (cBRS) and heart rate variability (HRV). Twelve healthy young men (25±1 yrs, 23.8±0.5 kg/m(2)) randomly underwent two experimental sessions: heat stress (HS; whole-body heat stress using a tube-lined suit to increase core temperature by ~1°C) and normothermia (NT). Each session was composed of a: pre-intervention rest (REST1); HS or NT interventions; post-intervention rest (REST2); and 14 min of cycling exercise [7 min at 40%HRreserve (EX1) and 7 min at 60%HRreserve (EX2)]. Heart rate and finger blood pressure were continuously recorded. cBRS was assessed using the sequence (cBRSSEQ) and transfer function (cBRSTF) methods. HRV was assessed using the indices SDNN (standard deviation of RR intervals) and RMSSD (root mean square of successive RR intervals). cBRS and HRV were not different between sessions during EX1 and EX2 (i.e. matched heart rate conditions: EX1=116±3 vs. 114±3, EX2=143±4 vs. 142±3 bpm; but different workloads: EX1=50±9 vs. 114±8, EX2=106±10 vs. 165±8 Watts; for HS and NT, respectively; Pheart rates), cBRS and HRV were significantly reduced in HS (cBRSSEQ = 1.6±0.3 vs. 0.6±0.1 ms/mmHg, Pexercise does not affect cBRS and HRV. Alternatively, in workload-matched conditions, the addition of heat to exercise results in reduced cBRS and HRV compared to exercise in normothermia. Copyright © 2017, Journal of Applied Physiology.

  19. Human surrogate neck response to +Gz vertical impact

    NARCIS (Netherlands)

    Rooij, L. van; Uittenbogaard, J.

    2011-01-01

    For the evaluation of impact scenarios with a substantial vertical component, the performance of current human surrogates - the RID 3D hardware dummy and two numerical human models - was evaluated. Volunteer tests with 10G and 6G pulses were compared to reconstructed tests with human surrogates.

  20. Human surrogate neck response to +Gz vertical impact

    NARCIS (Netherlands)

    Rooij, L. van; Uittenbogaard, J.

    2011-01-01

    For the evaluation of impact scenarios with a substantial vertical component, the performance of current human surrogates - the RID 3D hardware dummy and two numerical human models - was evaluated. Volunteer tests with 10G and 6G pulses were compared to reconstructed tests with human surrogates. Add

  1. Reindeer and caribou (Rangifer tarandus response towards human activities

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    Eigil Reimers

    2009-01-01

    Full Text Available We address the question of how human activities and infrastructure influence reindeer/caribou’s (Rangifer tarandus behaviour and habitat use and review studies based on current methodologies. Anthropogenic activities have a direct affect on Rangifer behaviour through the senses hearing, sight and smell, and all of these are important tools for behavioural risk assessment. Short term indirect responses, such as habituation, sensitisation, avoidance, and displacement, develop through neutral, positive or negative associations towards stimulus in terms of Rangifer’s ability to experience, learn, and remember. Long term behavioural responses develop through interaction with predators and, for reindeer, also domestication. A survey of the literature dealing with behavioural studies reveals that although Rangifer in most cases retreat from anthropogenic activities, comfort distances (i.e. distances beyond which animal behaviour or activity are not influenced are relatively short. In most cases, energetic implications appear moderate and small compared to other natural, biotic influences such as disturbance (and death caused by insect and/or predator harassment. Unless obstructing access, physical constructions of various kinds apparently have limited effects on Rangifer behaviour or habitat use. On the other hand, constructions that do obstruct or limit access and recreational or other motorized and non-motorized activities appear to have stronger impacts on avoidance and redistribution of Rangifer. Behavioural effects that might decrease survival and reproduction include retreat from favourable habitat near disturbance sources and reduction of time spent feeding with resulting energy depletion over time. Rangifer habitat use, habitat avoidance, and feeding preferences are governed by a complexity of natural interacting factors. Domestication, habituation and sensitisation are essential in shaping Rangifer’s adaptability, and should be included

  2. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

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    King Nicholas JC

    2006-05-01

    Full Text Available Abstract Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM. We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. Methods HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. Results RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-κB + AP-1 in the non-asthmatic HASM cells. Conclusion This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations.

  3. Current human immunodeficiency virus epidemic and its response in China

    Institute of Scientific and Technical Information of China (English)

    KANG Lai-Yi

    2012-01-01

    The first patient with acquired immunodeficiency syndrome (AIDS) was identified in 1985; since then, as of October 31, 2010, a total accumulative number of 370 000 patients with human immunodeficiency virus (HIV)/AIDS have been reported. The estimated number of patients living with HIV (PLHIV) in China was 740 000 in 2009. Although China is still a low-HIV prevalence region (rate of 0.057%), the epidemic has spread more widely from the high-risk groups to the general population. This paper covers five topics of importance, i.e., current trends of the HIV epidemic; HIV-1 subtype diversity; emergence of HIV drug resistance (HIVDR); the country's response to the disease; and future challenges and additional actions needed. This paper emphasizes sexual transmission as the predominant route of transmission and it being spread more frequently among men who have sex with men; the epidemic being concentrated over particular areas in China. We also discuss the fact that diverse HIV-1 subtypes have been found throughout the entire country and that recombinant subtypes became predominant. We also explore other topics such as the possibility of HIVDR, including primary and secondary resistance, with the use of free highly active anti-retroviral therapy (HAART); the integrated strategy of HIVDR surveillance and individual clinical HIVDR testing as a new attempt in China. For many years both policy-makers and professionals (including non-governmental organizations) have expressed strong commitment to prevention, control, and care of HIV/sexual transmission infection (STI), promoted the research and conducted different actions to slow the rising trend of the HIV epidemics. Although China is facing many challenges, its citizens need to be persistent on continuing the campaign of the State Council titled "Information of Strengthening Work on Prevention and Control of AIDS".

  4. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun [Division of heavy ion clinical research, Korea University, Seoul (Korea, Republic of); Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2012-11-15

    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy.

  5. Predicting Metapopulation Responses To Conservation In Human-Dominated Landscapes

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    Zachary S. Ladin

    2016-10-01

    Full Text Available Loss of habitat to urbanization is a primary cause of population declines as human-dominated landscapes expand at increasing rates. Understanding how the relative effects of different conservation strategies is important to slow population declines for species in urban landscapes. We studied the wood thrush Hylocichla mustelina, a declining forest-breeding Neotropical migratory species, and umbrella species for forest-breeding songbirds, within the urbanized mid-Atlantic United States. We integrated 40 years of demographic data with contemporary metapopulation model simulations of breeding wood thrushes to predict population responses to differing conservation scenarios. We compared four conservation scenarios over a 30-year time period (2014–2044 representing A current observed state (Null, B replacing impervious surface with forest (Reforest, C reducing brown-headed cowbird Molothrus ater parasitism pressure (Cowbird removal, and D simultaneous reforesting and cowbird removal. Compared to the Null scenario, the Reforest scenario increased mean annual population trends by 54 % , the Remove cowbirds scenario increased mean annual population trends by 38 %, and the scenario combining reforestation and cowbird removal increased mean annual population trends by 98 %. Mean annual growth rates (λ per site were greater in the Reforest (λ = 0.94 and Remove cowbirds (λ = 0.92 compared to the Null (λ = 0.88 model scenarios. However, only by combining the positive effects of reforestation and cowbird removal did wood thrush populations stop declining (λ = 1.00. Our results suggest that independently replacing impervious surface with forest habitat around forest patches and removing cowbirds may slow current negative population trends. Furthermore, conservation efforts that combine reforestation and cowbird removal may potentially benefit populations of wood thrushes and other similarly forest-breeding songbird species within urbanized fragmented

  6. Integrating human responses to climate change into conservation vulnerability assessments and adaptation planning.

    Science.gov (United States)

    Maxwell, Sean L; Venter, Oscar; Jones, Kendall R; Watson, James E M

    2015-10-01

    The impact of climate change on biodiversity is now evident, with the direct impacts of changing temperature and rainfall patterns and increases in the magnitude and frequency of extreme events on species distribution, populations, and overall ecosystem function being increasingly publicized. Changes in the climate system are also affecting human communities, and a range of human responses across terrestrial and marine realms have been witnessed, including altered agricultural activities, shifting fishing efforts, and human migration. Failing to account for the human responses to climate change is likely to compromise climate-smart conservation efforts. Here, we use a well-established conservation planning framework to show how integrating human responses to climate change into both species- and site-based vulnerability assessments and adaptation plans is possible. By explicitly taking into account human responses, conservation practitioners will improve their evaluation of species and ecosystem vulnerability, and will be better able to deliver win-wins for human- and biodiversity-focused climate adaptation.

  7. The Brain Renin-Angiotensin System and Mitochondrial Function: Influence on Blood Pressure and Baroreflex in Transgenic Rat Strains

    Directory of Open Access Journals (Sweden)

    Manisha Nautiyal

    2013-01-01

    Full Text Available Mitochondrial dysfunction is implicated in many cardiovascular diseases, including hypertension, and may be associated with an overactive renin-angiotensin system (RAS. Angiotensin (Ang II, a potent vasoconstrictor hormone of the RAS, also impairs baroreflex and mitochondrial function. Most deleterious cardiovascular actions of Ang II are thought to be mediated by NADPH-oxidase- (NOX- derived reactive oxygen species (ROS that may also stimulate mitochondrial oxidant release and alter redox-sensitive signaling pathways in the brain. Within the RAS, the actions of Ang II are counterbalanced by Ang-(1–7, a vasodilatory peptide known to mitigate against increased oxidant stress. A balance between Ang II and Ang-(1–7 within the brain dorsal medulla contributes to maintenance of normal blood pressure and proper functioning of the arterial baroreceptor reflex for control of heart rate. We propose that Ang-(1–7 may negatively regulate the redox signaling pathways activated by Ang II to maintain normal blood pressure, baroreflex, and mitochondrial function through attenuating ROS (NOX-generated and/or mitochondrial.

  8. Nitrosative Stress-Induced Disruption of Baroreflex Neural Circuits in a Rat Model of Hepatic Encephalopathy: A DTI Study

    Science.gov (United States)

    Tsai, Ching-Yi; Su, Chia-Hao; Chan, Julie Y. H.; Chan, Samuel H. H.

    2017-01-01

    The onset of hepatic encephalopathy (HE) in liver failure is associated with high mortality; the underlying mechanism is undecided. Here we report that in an acute liver failure model employing intraperitoneal administration of thioacetamide in Sprague-Dawley rats, diffusion weighted imaging revealed a progressive reduction in apparent diffusion coefficient in the brain stem. Diffusion tensor imaging further showed that the connectivity between nucleus tractus solitarii (NTS), the terminal site of baroreceptor afferents in brain stem and rostral ventrolateral medulla (RVLM), the origin of sympathetic innervation of blood vessels, was progressively disrupted until its disappearance, coincidental with the irreversible cessation of baroreflex-mediated sympathetic vasomotor tone signifying clinically the occurrence of brain death. In addition, superoxide, nitric oxide, peroxynitrite and ammonia levels in the NTS or RVLM were elevated, alongside swelling of astroctytes. A scavenger of peroxynitrite, but not an antioxidant, delivered intracisternally reversed all these events. We conclude that nitrosative stress because of augmented peroxynitrite related to accumulation of ammonia and swelling of astrocytes in the NTS or RVLM, leading to cytotoxic edema in the brain stem and severance of the NTS-RVLM connectivity, underpins the defunct baroreflex-mediated sympathetic vasomotor tone that accounts for the high mortality associated with HE. PMID:28079146

  9. SOD1 Overexpression Preserves Baroreflex Control of Heart Rate with an Increase of Aortic Depressor Nerve Function

    Science.gov (United States)

    Hatcher, Jeffrey; Gu, He; Cheng, Zixi (Jack)

    2016-01-01

    Overproduction of reactive oxygen species (ROS), such as the superoxide radical (O2∙−), is associated with diseases which compromise cardiac autonomic function. Overexpression of SOD1 may offer protection against ROS damage to the cardiac autonomic nervous system, but reductions of O2∙− may interfere with normal cellular functions. We have selected the C57B6SJL-Tg (SOD1)2 Gur/J mouse as a model to determine whether SOD1 overexpression alters cardiac autonomic function, as measured by baroreflex sensitivity (BRS) and aortic depressor nerve (ADN) recordings, as well as evaluation of baseline heart rate (HR) and mean arterial pressure (MAP). Under isoflurane anesthesia, C57 wild-type and SOD1 mice were catheterized with an arterial pressure transducer and measurements of HR and MAP were taken. After establishing a baseline, hypotension and hypertension were induced by injection of sodium nitroprusside (SNP) and phenylephrine (PE), respectively, and ΔHR versus ΔMAP were recorded as a measure of baroreflex sensitivity (BRS). SNP and PE treatment were administered sequentially after a recovery period to measure arterial baroreceptor activation by recording aortic depressor nerve activity. Our findings show that overexpression of SOD1 in C57B6SJL-Tg (SOD1)2 Gur/J mouse preserved the normal HR, MAP, and BRS but enhanced aortic depressor nerve function. PMID:26823951

  10. Heart rate variability biofeedback as a method for assessing baroreflex function: a preliminary study of resonance in the cardiovascular system.

    Science.gov (United States)

    Vaschillo, Evgeny; Lehrer, Paul; Rishe, Naphtali; Konstantinov, Mikhail

    2002-03-01

    This study describes the use of a biofeedback method for the noninvasive study of baroreflex mechanisms. Five previously untrained healthy male participants learned to control oscillations in heart rate using biofeedback training to modify their heart rate variability at specific frequencies. They were instructed to match computer-generated sinusoidal oscillations with oscillations in heart rate at seven frequencies within the range of 0.01-0.14 Hz. All participants successfully produced high-amplitude target-frequency oscillations in both heart rate and blood pressure. Stable and predictable transfer functions between heart rate and blood pressure were obtained in all participants. The highest oscillation amplitudes were produced in the range of 0.055-0.11 Hz for heart rate and 0.02-0.055 Hz for blood pressure. Transfer functions were calculated among sinusoidal oscillations in the target stimuli, heart rate, blood pressure, and respiration for frequencies at which subjects received training. High and low target-frequency oscillation amplitudes at specific frequencies could be explained by resonance among various oscillatory processes in the cardiovascular system. The exact resonant frequencies differed among individuals. Changes in heart rate oscillations could not be completely explained by changes in breathing. The biofeedback method also allowed us to quantity characteristics of inertia, delay, and speed sensitivity in baroreflex system. We discuss the implications of these findings for using heart rate variability biofeedback as an aid in diagnosing various autonomic and cardiovascular system disorders and as a method for treating these disorders.

  11. The effects of bupivacaine and ropivacaine on baroreflex sensitivity with or without respiratory acidosis and alkalosis in rats.

    Science.gov (United States)

    Watanabe, Y; Dohi, S; Iida, H; Ishiyama, T

    1997-02-01

    Systemic toxicity of local anesthetics causes cardiac and central nervous system (CNS) depression that could be enhanced in the presence of respiratory acidosis. We examined a potential suppression of baroreflex function with bupivacaine and ropivacaine during hypercapnic acidosis or hypocapnic alkalosis. Baroreflex sensitivity (BRS) was randomly tested in rats with one of 13 conditions during intravenous administration of saline (control), bupivacaine 1, 2, or 3 mg/kg, or ropivacaine 2, 4, or 6 mg/kg. The effects of bupivacaine (3 mg/kg) or ropivacaine (6 mg/kg) on BRS were also examined during hypercapnic acidosis or hypocapnic alkalosis. The BRS was assessed using a value of delta heart rate/ delta mean arterial pressure after infusion of phenylephrine (3 micrograms/kg). Both bupivacaine and ropivacaine (at the largest dose) significantly suppressed BRS. Acute respiratory acidosis (pHa 7.24 +/- 0.04, Paco2 63 +/- 4 mm Hg) enhanced BRS. The BRS enhanced during acidosis was also suppressed with bupivacaine and ropivacaine, but less so than in the absence of acidosis. The presence of hypocapnic alkalosis (pHa 7.55 +/- 0.03, Paco2 25 +/- 2 mm Hg) did not affect BRS and reversed BRS suppression caused by both drugs. Thus, bupivacaine and ropivacaine affect neuronal control mechanisms for maintaining cardiovascular stability, and acute changes of respiration could significantly modify such suppression.

  12. Plasmodium falciparum infection causes proinflammatory priming of human TLR responses.

    NARCIS (Netherlands)

    McCall, M.B.B.; Netea, M.G.; Hermsen, C.C.; Jansen, T.; Jacobs, L.; Golenbock, D.; Ven, A.J.A.M. van der; Sauerwein, R.W.

    2007-01-01

    TLRs are a major group of pattern recognition receptors that are crucial in initiating innate immune responses and are capable of recognizing Plasmodium ligands. We have investigated TLR responses during acute experimental P. falciparum (P.f.) infection in 15 malaria-naive volunteers. TLR-4 response

  13. The human rights responsibilities of multinational tobacco companies.

    Science.gov (United States)

    Crow, M E

    2005-08-01

    This article explores various strategies which could be used to hold the tobacco industry accountable for human rights violations precipitated by its conduct. First, a brief overview of the international human rights regime and the tobacco related jurisprudence issued by human rights treaty bodies is provided. The article then explains how tobacco control advocates could promote more systematic consideration of governments' tobacco related human rights violations by reconceptualising the Framework Convention on Tobacco Control in the language of rights. The feasibility of using the existing human rights framework to target the tobacco industry directly is analysed with the conclusion that this approach has serious limitations. Emerging human rights norms, which have greater potential to affect the industry's conduct, are presented. Finally, given the questionable authoritativeness of these norms, alternative ways that they could be employed to hold tobacco companies accountable for the rights related consequences of their activities are proposed.

  14. Worms under stress: C. elegans stress response and its relevance to complex human disease and aging

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.; Snoek, L.B.; Bono, de M.; Kammenga, J.E.

    2013-01-01

    Many organisms have stress response pathways, components of which share homology with players in complex human disease pathways. Research on stress response in the nematode worm Caenorhabditis elegans has provided detailed insights into the genetic and molecular mechanisms underlying complex human d

  15. Quantitative Methods in Toxicology for Human Dose-Response Assessment

    NARCIS (Netherlands)

    Kramer HJ; Jansen EHJM; Zeilmaker MJ; van Kranen HJ; Kroese ED; TOX; LCM

    1995-01-01

    Het proces van de humane risicoschatting kan verdeeld worden in risico-identificatie, vaststellen van dosis-respons relaties, vaststellen van blootstelling en risico-karakterisering. In de humane risicoschatting worden kwantitatieve methoden en modellen toegepast. Welk model dient te worden toegep

  16. MCF-7 human mammary adenocarcinoma cells exhibit augmented responses to human insulin on a collagen IV surface

    DEFF Research Database (Denmark)

    Listov-Saabye, Nicolai; Jensen, Marianne Blirup; Kiehr, Benedicte;

    2009-01-01

    was significantly more mitogenic than native insulin, validating the ability of the assay to identify hypermitogenic human insulin analogs. With MCF-7 cells on a collagen IV surface, the ranking of mitogens was maintained, but fold mitogenic responses and dynamic range and steepness of dose-response curves were...

  17. Genetic polymorphisms and lipid response to dietary changes in humans

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Ordovas, J.M.; Ramos-Galluzzi, J.; Katan, M.B.

    2001-01-01

    Previous studies on the effects of genetic polymorphisms on the serum cholesterol response to dietary treatments were often inconsistent and frequently involved small numbers of subjects. We studied the effect of 10 genetic polymorphisms on the responses of serum cholesterol to saturated and trans f

  18. Biotin deficiency enhances the inflammatory response of human dendritic cells

    National Research Council Canada - National Science Library

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-01-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism...

  19. Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It: Incorporating Human Rights into the Sustainability Agenda

    Science.gov (United States)

    McPhail, Ken

    2013-01-01

    The Preamble to the Universal Declaration on Human Rights (UNDHR) calls on every organ of society to teach and educate for the promotion of the rights it contains. However, few if any business schools have any systematic or critical human rights content in their accounting and business curricula. This oversight is increasingly problematic as…

  20. Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It: Incorporating Human Rights into the Sustainability Agenda

    Science.gov (United States)

    McPhail, Ken

    2013-01-01

    The Preamble to the Universal Declaration on Human Rights (UNDHR) calls on every organ of society to teach and educate for the promotion of the rights it contains. However, few if any business schools have any systematic or critical human rights content in their accounting and business curricula. This oversight is increasingly problematic as…

  1. Human rights responsibilities of pharmaceutical companies in relation to access to medicines.

    Science.gov (United States)

    Lee, Joo-Young; Hunt, Paul

    2012-01-01

    Although access to medicines is a vital feature of the right to the highest attainable standard of health ("right to health"), almost two billion people lack access to essential medicines, leading to immense avoidable suffering. While the human rights responsibility to provide access to medicines lies mainly with States, pharmaceutical companies also have human rights responsibilities in relation to access to medicines. This article provides an introduction to these responsibilities. It briefly outlines the new UN Guiding Principles on Business and Human Rights and places the human rights responsibilities of pharmaceutical companies in this context. The authors draw from the work of the first UN Special Rapporteur on the right to the highest attainable standard of health, in particular the Human Rights Guidelines for Pharmaceutical Companies in Relation to Access to Medicines that he presented to the UN General Assembly in 2008, and his UN report on GlaxoSmithKline (GSK). While the Guiding Principles on Business and Human Rights are general human rights standards applicable to all business entities, the Human Rights Guidelines for Pharmaceutical Companies consider the specific human rights responsibilities of one sector (pharmaceutical companies) in relation to one area of activity (access to medicines). The article signals the human rights responsibilities of all pharmaceutical companies, with particular attention to patent-holding pharmaceutical companies. Adopting a right-to-health "lens," the article discusses GSK and accountability. The authors argue that human rights should shape pharmaceutical companies' policies, and provide standards in relation to which pharmaceutical companies could, and should, be held accountable. They conclude that it is now crucial to devise independent, accessible, transparent, and effective mechanisms to monitor pharmaceutical companies and hold them publicly accountable for their human rights responsibilities.

  2. Association between nicotine withdrawal and reward responsiveness in humans and rats.

    Science.gov (United States)

    Pergadia, Michele L; Der-Avakian, Andre; D'Souza, Manoranjan S; Madden, Pamela A F; Heath, Andrew C; Shiffman, Saul; Markou, Athina; Pizzagalli, Diego A

    2014-11-01

    Reward-related disturbances after withdrawal from nicotine are hypothesized to contribute to relapse to tobacco smoking but mechanisms underlying and linking such processes remain largely unknown. To determine whether withdrawal from nicotine affects reward responsiveness (ie, the propensity to modulate behavior as a function of prior reinforcement experience) across species using translational behavioral assessments in humans and rats. Experimental studies used analogous reward responsiveness tasks in both humans and rats to examine whether reward responsiveness varied in (1) an ad libitum smoking condition compared with a 24-hour acute nicotine abstinence condition in 31 human smokers with (n = 17) or without (n = 14) a history of depression; (2) rats 24 hours after withdrawal from chronic nicotine (n = 19) or saline (n = 20); and (3) rats following acute nicotine exposure after withdrawal from either chronic nicotine or saline administration. Performance on a reward responsiveness task under nicotine and nonnicotine conditions. In both human smokers and nicotine-treated rats, reward responsiveness was significantly reduced after 24-hour withdrawal from nicotine (P responsiveness were greater in those with a history of depression. In rats previously exposed to chronic nicotine, acute nicotine reexposure long after withdrawal potentiated reward responsiveness (P responsiveness to natural rewards and to experience potentiated nicotine-induced reward responsiveness. Moreover, demonstration of behavioral homology across humans and rodents provides a strong translational framework for the investigation and development of clinical treatments targeting reward responsiveness deficits during early withdrawal of nicotine.

  3. Human responses to the geophysical daily, annual and lunar cycles.

    Science.gov (United States)

    Foster, Russell G; Roenneberg, Till

    2008-09-09

    Collectively the daily, seasonal, lunar and tidal geophysical cycles regulate much of the temporal biology of life on Earth. The increasing isolation of human societies from these geophysical cycles, as a result of improved living conditions, high-quality nutrition and 24/7 working practices, have led many to believe that human biology functions independently of them. Yet recent studies have highlighted the dominant role that our circadian clock plays in the organisation of 24 hour patterns of behaviour and physiology. Preferred wake and sleep times are to a large extent driven by an endogenous temporal program that uses sunlight as an entraining cue. The alarm clock can drive human activity rhythms but has little direct effect on our endogenous 24 hour physiology. In many situations, our biology and our society appear to be in serious opposition, and the damaging consequences to our health under these circumstances are increasingly recognised. The seasons dominate the lives of non-equatorial species, and until recently, they also had a marked influence on much of human biology. Despite human isolation from seasonal changes in temperature, food and photoperiod in the industrialised nations, the seasons still appear to have a small, but significant, impact upon when individuals are born and many aspects of health. The seasonal changes that modulate our biology, and how these factors might interact with the social and metabolic status of the individual to drive seasonal effects, are still poorly understood. Lunar cycles had, and continue to have, an influence upon human culture, though despite a persistent belief that our mental health and other behaviours are modulated by the phase of the moon, there is no solid evidence that human biology is in any way regulated by the lunar cycle.

  4. Human Bronchial Epithelial Cell Response to Heavy Particle Exposure

    Science.gov (United States)

    Story, Michael; Ding, Liang-Hao; Minna, John; Park, Seong-mi; Peyton, Michael; Larsen, Jill

    2012-07-01

    A battery of non-oncogenically immortalized human bronchial epithelial cells (HBECs) are being used to examine the molecular changes that lead to lung carcinogenesis after exposure to heavy particles found in the free space environment. The goal is to ultimately identify biomarkers of radioresponse that can be used for prediction of carcinogenic risk for fatal lung cancer. Our initial studies have focused on the cell line HBEC3 KT and the isogenic variant HBEC3 KTR53, which overexpresses the RASv12 mutant and where p53 has been knocked down by shRNA, and is considered to be a more oncogenically progressed variant. We have previously described the response of HBEC3 KT at the cellular and molecular level, however, the focus here is on the rate of cellular transformation after HZE radiation exposure and the molecular changes in transformed cells. When comparing the two cell lines we find that there is a maximum rate of cellular transformation at 0.25 Gy when cells are exposed to 1 GeV Fe particles, and, for the HBEC3 KTR53 there are multiple pathways upregulated that promote anchorage independent growth including the mTOR pathway, the TGF-1 pathway, RhoA signaling and the ERK/MAPK pathway as early as 2 weeks after radiation. This does not occur in the HBEC3 KT cell line. Transformed HBEC3 KT cells do not show any morphologic or phenotypic changes when grown as cell cultures. HBEC3 KTR53 cells on the other hand show substantial changes in morphology from a cobblestone epithelial appearance to a mesenchymal appearance with a lack of contact inhibition. This epithelial to mesenchymal change in morphology is accompanied by the expression of vimentin and a reduction in the expression of E-cadherin, which are hallmarks of epithelial to mesenchymal transition. Interestingly, for HBEC3 KT transformed cells there are no mutations in the p53 gene, 2 of 15 clones were found to be heterozygous for the RASV12 mutation, and 3 of 15 clones expressed high levels of BigH3, a TGFB-responsive

  5. Human operant learning under concurrent reinforcement of response variability

    NARCIS (Netherlands)

    Maes, J.H.R.; Goot, M.H. van der

    2006-01-01

    This study asked whether the concurrent reinforcement of behavioral variability facilitates learning to emit a difficult target response. Sixty students repeatedly pressed sequences of keys, with an originally infrequently occurring target sequence consistently being followed by positive feedback. T

  6. Innate immune interferon responses to human immunodeficiency virus-1 infection.

    Science.gov (United States)

    Hughes, Rose; Towers, Greg; Noursadeghi, Mahdad

    2012-07-01

    Type I interferon (IFN) responses represent the canonical host innate immune response to viruses, which serves to upregulate expression of antiviral restriction factors and augment adaptive immune defences. There is clear evidence for type I IFN activity in both acute and chronic HIV-1 infection in vivo, and plasmacytoid dendritic cells have been identified as one important source for these responses, through innate immune detection of viral RNA by Toll-like receptor 7. In addition, new insights into the molecular mechanisms that trigger induction of type I IFNs suggest innate immune receptors for viral DNA may also mediate these responses. It is widely recognised that HIV-1 restriction factors share the characteristic of IFN-inducible expression, and that the virus has evolved to counteract these antiviral mechanisms. However, in some target cells, such as macrophages, IFN can still effectively restrict virus. In this context, HIV-1 shows the ability to evade innate immune recognition and thereby avoid induction of type I IFN in order to successfully establish productive infection. The relative importance of evasion of innate immune detection and evasion of IFN-inducible restriction in the natural history of HIV-1 infection is not known, and the data suggest that type I IFN responses may play a role in both viral control and in the immunopathogenesis of progressive disease. Further study of the relationship between HIV-1 infection and type I IFN responses is required to unravel these issues and inform the development of novel therapeutics or vaccine strategies.

  7. Corporate social responsibility, social contract, corporate personhood and human rights law: understanding the emerging responsibilities of modern corporations

    OpenAIRE

    Amao, Olufemi

    2008-01-01

    Copyright @ 2008 Olufemi Amao. The social contract theory has been advanced as a theoretical basis for explaining the emerging practice of Corporate Social Responsibility (CSR) by corporations. Since the 17th century the social contract concept has also been used to justify human rights. The concept is the constitutional foundation of many western states starting with England, US and France. Business ethicists and philosophers have tried to construct and analyse the social responsibility o...

  8. Vertical torque responses to vestibular stimulation in standing humans.

    Science.gov (United States)

    Reynolds, Raymond F

    2011-08-15

    The effects of electrical vestibular stimulation upon movement and perception suggest two evoked sensations: head roll and inter-aural linear acceleration. The head roll vector causes walking subjects to turn in a direction dependent on head pitch, requiring generation of torque around a vertical axis. Here the effect of vestibular stimulation upon vertical torque (T(z)) was investigated during quiet stance. With the head tilted forward, square-wave stimuli applied to the mastoid processes evoked a polarity-specific T(z) response accompanied by trunk yaw. Stochastic vestibular stimulation (SVS) was used to investigate the effect of head pitch with greater precision; the SVS–T(z) cross-correlation displayed a modulation pattern consistent with the head roll vector and this was also reflected by changes in coherence at 2–3 Hz. However, a separate response at 7–8 Hz was unaffected by head pitch. Head translation (rather than rotation) had no effect upon this high frequency response either, suggesting it is not caused by a sense of body rotation induced by an inter-aural acceleration vector offset from the body. Instead, high coherence between medio-lateral shear force and T(z) at the same frequency range suggests it is caused by mechanical coupling to evoked medio-lateral sway. Consistent with this explanation, the 7–8 Hz response was attenuated by 90 deg head roll or yaw, both of which uncouple the inter-aural axis from the medio-lateral sway axis. These results demonstrate two vertical torque responses to electrical vestibular stimulation in standing subjects. The high frequency response can be attributed to mechanical coupling to evoked medio-lateral sway. The low frequency response is consistent with a reaction to a sensation of head roll, and provides a novel method for investigating proprioceptive-vestibular interactions during stance.

  9. Sustained CD8+ T-cell responses induced after acute parvovirus B19 infection in humans

    DEFF Research Database (Denmark)

    Norbeck, Oscar; Isa, Adiba; Pöhlmann, Christoph

    2005-01-01

    Murine models have suggested that CD8+ T-cell responses peak early in acute viral infections and are not sustained, but no evidence for humans has been available. To address this, we longitudinally analyzed the CD8+ T-cell response to human parvovirus B19 in acutely infected individuals. We...... observed striking CD8+ T-cell responses, which were sustained or even increased over many months after the resolution of acute disease, indicating that CD8+ T cells may play a prominent role in the control of parvovirus B19 and other acute viral infections of humans, including potentially those generated...

  10. Inter-specific variation in avian responses to human disturbance

    Science.gov (United States)

    Daniel T. Blumstein; Esteban Fernandez-Juricic; Patrick A. Zollner; Susan C. Garity

    2005-01-01

    1. Increasing urbanization and recreational activities around and within biodiversity hotspots require an understanding of how to reduce the impacts of human disturbance on more than a single species; however, we lack a general framework to study multiple species. One approach is to expand on knowledge about the theory of anti-predator behaviour to understand and...

  11. MURINE IMMUNE RESPONSES TO HUMAN SPERM ANTIGENS FOLLOWING DIFFERENT IMMUNIZATIONS

    Institute of Scientific and Technical Information of China (English)

    MALan; CAOXiao-Mei; BENKun-Long; CHENYun-Liang

    1989-01-01

    Clinical and experimental investigations have shown that secretory IgA antibodies to human sperm may bc one of the most important factors in immunological infertility. Studies on the effects of these antibodies on sperm function arc helpful to understand the role of

  12. Task-Dependent V1 Responses in Human Retinitis Pigmentosa

    OpenAIRE

    Masuda,Yoichiro; Horiguchi, Hiroshi; Dumoulin, Serge O.; Furuta, Ayumu; Miyauchi, Satoru; Nakadomari, Satoshi; Brian A Wandell

    2010-01-01

    The presence of large-scale reorganization in adult human V1 may have important implications for visual restoration therapy and rehabilitation. New measurements in patients with retinitis pigmentosa and prior data from patients with macular degeneration can be explained without assuming a large-scale reorganization that includes the development of new feed-forward connections.

  13. Human-Robot Emergency Response - Experimental Platform and Preliminary Dataset

    Science.gov (United States)

    2014-07-28

    Proceedings of the IEEE International Conference on Robotics and Automation, Leuven, Belgium, May 16–21 1998, pp. 3715–3720. [13] itseez, “ Opencv ,” http...function and camshift function in OpenCV [13]. In each image obtained form cameras, we first calculate back projection of a histogram model of a human. In

  14. Prokineticin 1 Induces Inflammatory Response in Human Myometrium

    Science.gov (United States)

    Gorowiec, Marta R.; Catalano, Rob D.; Norman, Jane E.; Denison, Fiona C.; Jabbour, Henry N.

    2011-01-01

    The infiltration of human myometrium and cervix with leukocytes and the formation of a pro-inflammatory environment within the uterus have been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labor. The expression of PROK1 receptor remains unchanged during labor and is abundantly expressed in the myometrium. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines, including IL-1β, chemokine C-C motif ligand 3, and colony-stimulating factor 3. In addition, we demonstrate that PROK1 increases the expression of chemokine C-C motif ligand 20, IL-6, IL-8, prostaglandin synthase 2, and prostaglandin E2 and F2α secretion. The treatment of myometrial explants with 100 ng/mL of lipopolysaccharide up-regulates the expression of PROK1, PROK1 receptor, and inflammatory mediators. The infection of myometrial explants with lentiviral microRNA targeting PROK1, preceding treatment with lipopolysaccharide, reduces the expression of inflammatory genes. We propose that PROK1 is a novel inflammatory mediator that can contribute to the onset of human parturition at term and partially mediate premature onset of inflammatory pathways during bacterial infection. PMID:21983634

  15. Connecting Corporate Human Rights Responsibilities and State Obligations under the UN Guiding Principles

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2017-01-01

    Taking its point of departure in the UN Guiding Principles on Business and Human Rights (UNGP), this chapter discusses the complementarity between Pillars One on the State Duty to Respect and Pillar Two the Corporate Responsibility to Respect Human Rights. It does this through HRDD and communicat......Taking its point of departure in the UN Guiding Principles on Business and Human Rights (UNGP), this chapter discusses the complementarity between Pillars One on the State Duty to Respect and Pillar Two the Corporate Responsibility to Respect Human Rights. It does this through HRDD...

  16. Antibody response to Salmonella typhi lw human Schistosomiasis mansoni

    Directory of Open Access Journals (Sweden)

    Maria Imaculada Muniz-Junqueira

    1996-10-01

    Full Text Available Antibody response to Salmonella typhi O and H antigens was evaluated in 24 individuals with either hepatointestinal or hepatosplenic schistosomiasis mansoni before and after typhoid vaccination, and compared with that of non-infected controls. Before vaccination, Schistosoma-infected patients showed a higher frequency of positive antibody to O antigen and the same frequency to H antigen when compared with that of healthy individuals. However, those with hepatosplenic schistosomiasis showed higher titres of antibody to H antigen than those with hepatointestinal disease or healthy individuals. Infected subjects, particularly those with hepatointestinal disease, showed a decreased response after typhoid vaccine. Tins diminished ability to mount an immune response towards typhoid antigens dining schistosomiasis may interfere ivith the clearance of the bacteria from blood stream and, therefore, play a role in the prolonged survival of salmonella as obsewed in some patients with chronic salmonellosis associated with schistosomiasis.

  17. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  18. Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

    Directory of Open Access Journals (Sweden)

    Sonya Hui

    Full Text Available We recently identified sphingosine-1-phosphate (S1P signaling and the cystic fibrosis transmembrane conductance regulator (CFTR as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i express critical S1P signaling elements, (ii constrict in response to S1P and (iii lose myogenic responsiveness following S1P receptor antagonism (JTE013. However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

  19. Reproduction of continuous flow left ventricular assist device experimental data by means of a hybrid cardiovascular model with baroreflex control.

    Science.gov (United States)

    Fresiello, Libera; Zieliński, Krzysztof; Jacobs, Steven; Di Molfetta, Arianna; Pałko, Krzysztof Jakub; Bernini, Fabio; Martin, Michael; Claus, Piet; Ferrari, Gianfranco; Trivella, Maria Giovanna; Górczyńska, Krystyna; Darowski, Marek; Meyns, Bart; Kozarski, Maciej

    2014-06-01

    Long-term mechanical circulatory assistance opened new problems in ventricular assist device-patient interaction, especially in relation to autonomic controls. Modeling studies, based on adequate models, could be a feasible approach of investigation. The aim of this work is the exploitation of a hybrid (hydronumerical) cardiovascular simulator to reproduce and analyze in vivo experimental data acquired during a continuous flow left ventricular assistance. The hybrid cardiovascular simulator embeds three submodels: a computational cardiovascular submodel, a computational baroreflex submodel, and a hydronumerical interface submodel. The last one comprises two impedance transformers playing the role of physical interfaces able to provide a hydraulic connection with specific cardiovascular sites (in this article, the left atrium and the ascending/descending aorta). The impedance transformers are used to connect a continuous flow pump for partial left ventricular support (Synergy Micropump, CircuLite, Inc., Saddlebrooke, NJ, USA) to the hybrid cardiovascular simulator. Data collected from five animals in physiological, pathological, and assisted conditions were reproduced using the hybrid cardiovascular simulator. All parameters useful to characterize and tune the hybrid cardiovascular simulator to a specific hemodynamic condition were extracted from experimental data. Results show that the simulator is able to reproduce animal-specific hemodynamic status both in physiological and pathological conditions, to reproduce cardiovascular left ventricular assist device (LVAD) interaction and the progressive unloading of the left ventricle for different pump speeds, and to investigate the effects of the LVAD on baroreflex activity. Results in chronic heart failure conditions show that an increment of LVAD speed from 20 000 to 22 000 rpm provokes a decrement of left ventricular flow of 35% (from 2 to 1.3 L/min). Thanks to its flexibility and modular structure, the

  20. The Changes of Baroreflex Sensitivity During Head -up Tilt Test and Its Clinical Significance in the Patients with Vasovagal Syncope

    Institute of Scientific and Technical Information of China (English)

    胡兆霆; 吕艳青; 杨钧国

    2001-01-01

    Objective To study the changes of baroreflex sensitivity (BRS) during head -up tilt test (HUT) in patients with vasovagal syncope (VS),and to examine the relationship between baroreflex sensitivity and neurohormonal factors. Furthermore, to investigate the effects of the changes of BRS on VS.Methods Forty- two patients with unexplained syncope (Among the 42 patients, there were 22 patients with positive HUT and 20 patients with negative HUT respectively) and 20 healthy volunteers (with negative HUT) underwent passive head-up tilt testing, Antecubital vein blood samples were taken before and after HUT, or at syncope. The fasting plasma endothelin ,serum nitric oxide (NO), serum NE were measured. The BRS was assessed on the basis of the linear regression slope the RR interval versus systolic arterial blood pressure during the increment in blood pressure after intravenous administration of phenylephrine. Results ( 1 )During the syncope, the BRS significantly reduced in HUT( + ) group than baseline. At the end of tilt, the level of plasma ET, serum NO in patients with positive HUT significantly increased compared with baseline or normal controls, and the plasma concentration of NE also had the trend of increase. ( 2 ) By multiple regression analysis, a significant negative correlation was found between baroreceptor sensitivity and the plasma ET, NO at the end of HUT in patients with positive HUT, but there was no relationship between BRS and NE. Conclusions During the syncope occure, the BRS in patients with VS decreased significantly compared with normal controls. The abnormal plasma ET, NO concentration might contribute to the mechanism of VS.

  1. Central exogenous nitric oxide decreases cardiac sympathetic drive and improves baroreflex control of heart rate in ovine heart failure.

    Science.gov (United States)

    Ramchandra, Rohit; Hood, Sally G; May, Clive N

    2014-08-01

    Heart failure (HF) is associated with increased cardiac and renal sympathetic drive, which are both independent predictors of poor prognosis. A candidate mechanism for the centrally mediated sympathoexcitation in HF is reduced synthesis of the inhibitory neuromodulator nitric oxide (NO), resulting from downregulation of neuronal NO synthase (nNOS). Therefore, we investigated the effects of increasing the levels of NO in the brain, or selectively in the paraventricular nucleus of the hypothalamus (PVN), on cardiac sympathetic nerve activity (CSNA) and baroreflex control of CSNA and heart rate in ovine pacing-induced HF. The resting level of CSNA was significantly higher in the HF than in the normal group, but the resting level of RSNA was unchanged. Intracerebroventricular infusion of the NO donor sodium nitroprusside (SNP; 500 μg · ml(-1)· h(-1)) in conscious normal sheep and sheep in HF inhibited CSNA and restored baroreflex control of heart rate, but there was no change in RSNA. Microinjection of SNP into the PVN did not cause a similar cardiac sympathoinhibition in either group, although the number of nNOS-positive cells was decreased in the PVN of sheep in HF. Reduction of endogenous NO with intracerebroventricular infusion of N(ω)-nitro-l-arginine methyl ester decreased CSNA in normal but not in HF sheep and caused no change in RSNA in either group. These findings indicate that endogenous NO in the brain provides tonic excitatory drive to increase resting CSNA in the normal state, but not in HF. In contrast, exogenously administered NO inhibited CSNA in both the normal and HF groups via an action on sites other than the PVN. Copyright © 2014 the American Physiological Society.

  2. Influence of a multideficient diet from northeastern Brazil on resting blood pressure and baroreflex sensitivity in conscious, freely moving rats

    Directory of Open Access Journals (Sweden)

    F.M.F. Monteiro

    2001-02-01

    Full Text Available The "regional basic diet" or RBD is a multideficient diet (providing 8% protein which is known to produce dietary deficiencies in some populations in northeastern Brazil. The present study investigated the effects of RBD-induced malnutrition on resting blood pressure and baroreflex sensitivity in conscious rats. Malnourished rats were obtained by feeding dams the RBD during mating and pregnancy (RBD-1 group or during nursing and a 10-day period after weaning (RBD-2 group. At 90 days of age, only RBD-2 rats weighed significantly (P<0.001 less than control rats born to dams fed a standard commercial diet (23% protein during pregnancy and nursing. Baseline mean arterial pressure and heart rate of both RBD-1 and RBD-2 rats were comparable to those of controls. The slopes for both reflex bradycardia and tachycardia (bpm/mmHg induced by intravenous phenylephrine and sodium nitroprusside, respectively, were unchanged in either RBD-1 (-2.08 ± 0.11 and -3.10 ± 0.43, respectively or RBD-2 (-2.32 ± 0.30 and -3.73 ± 0.53, respectively rats, when compared to controls (-2.09 ± 0.10 and -3.17 ± 0.33, respectively. This study shows that, after a prolonged period of nutritional recovery, the patterns of resting blood pressure and baroreflex sensitivity of both pre- and postnatally malnourished rats were similar to those of controls. The decreased body weight and the tendency to increased reflex tachycardia in RBD-2 rats may suggest that this type of maternal malnutrition during lactation is more critical than during pregnancy.

  3. Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness

    Science.gov (United States)

    Cajochen, C.; Zeitzer, J. M.; Czeisler, C. A.; Dijk, D. J.

    2000-01-01

    Light can elicit both circadian and acute physiological responses in humans. In a dose response protocol men and women were exposed to illuminances ranging from 3 to 9100 lux for 6.5 h during the early biological night after they had been exposed to dose response curve. Half of the maximum alerting response to bright light of 9100 lux was obtained with room light of approximately 100 lux. This sensitivity to light indicates that variations in illuminance within the range of typical, ambient, room light (90-180 lux) can have a significant impact on subjective alertness and its electrophysiologic concomitants in humans during the early biological night.

  4. Cerebrovascular response to acute metabolic acidosis in humans.

    NARCIS (Netherlands)

    Ven, M.T.P. van de; Colier, W.N.J.M.; Kersten, B.T.P.; Oeseburg, B.; Folgering, H.T.M.

    2003-01-01

    OBJECTIVES: Evaluation of the cerebrovascular response (delta CBV/delta PaCO2) during baseline metabolic conditions and acute metabolic acidosis. METHODS: 15 healthy subjects, 5 m, 10 f, 56 +/- 10 yrs were investigated. For acidification, NH4Cl was given orally. CBV was measured using Near Infrared

  5. Form and Space Diversity in Human Habitats: Perceptual Responses

    Science.gov (United States)

    Pyron, Bernard

    1971-01-01

    To test perceptual responses, 120 subjects viewed 12 experimental and one controlled housing environments. Three levels of building form diversity were combined with four levels of space diversity in the experimental environments. Results indicated that amount of visual coverage of the field of view increased significantly with increases in both…

  6. Physiological responses to exposure to carbon dioxide and human bioeffluents

    DEFF Research Database (Denmark)

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

    2015-01-01

    Present paper describes physiological responses as a result of exposures to CO2 (between 500 ppm to 3,000 ppm) with and without bioeffluents. Twenty-five subjects participated. They were exposed in the climate chamber for 255 minutes in groups of five at a time. During exposure, they performed di...

  7. Gravitational effects on human cardiovascular responses to isometric muscle contractions

    Science.gov (United States)

    Bonde-Petersen, Flemmig; Suzuki, Yoji; Sadamoto, Tomoko

    Isometric exercise induces profound cardiovascular adaptations increasing mean arterial pressure and heart rate. We investigated effects of simulated +Gz and -Gz respectively on the central and peripheral cardiovascular system. Sustained handgrip exercise was performed at 40% of maximum for 2 minutes in five subjects. This maneuver increased mean arterial pressure by 40-45 mm Hg both during head out water immersion which simulates weightlessness, as well as bedrest during -25, 0, and +25 degrees tilt from the horizontal. Lower body negative pressure (-60 mm Hg for 10 min) attenuated the response to handgrip exercise to 30 mm Hg. It also increased the heart rate minimally by about 20 beats per minute while the water immersion, as well as head up, head down and horizontal bedrest showed increments of about 50 beats per min. It was concluded that the response to isometric contraction is mediated through the high pressure baroreceptors, because similar responses were seen during stresses producing a wide variation in central venous pressure. During lower body negative pressure the increased sympathetic nervous activity itself increased resting heart rate and mean arterial pressure. The responses to static exercise were, therefore, weaker.

  8. Hemopexin activity is associated with angiotensin II responsiveness in humans

    NARCIS (Netherlands)

    Krikken, Jan A.; Lely, Anna T.; Borghuis, Theo; Faas, Marijke M.; van Goor, Harry; Navis, Gerjan; Bakker, Stephanus; Bakker, Willem

    2013-01-01

    Background: Hemopexin, an acute phase protein, can downregulate the angiotensin (ang) II type 1 receptor (AT1-R) in vitro. Whether hemopexin is involved in the responsiveness to ang II in vivo is unknown. Therefore, we tested whether variations in endogenous hemopexin activity are associated with th

  9. The science of human security: a response from political science.

    Science.gov (United States)

    Roberts, David

    2008-01-01

    The concept of human security has developed in significance in the last decade to the point that its meaning and validity is hotly contested in the field of international relations, security, and development studies. A key consideration relates to its ambiguity at best and its amorphousness at worst. Medical scholarship proposes approaches that may render more meaningful the concept. However, collaboration and co-operation between political scientists and medical practitioners offers even greater potential to this vital programme. The latter offer the technical and methodological skills and approaches lacking in political science, whilst the former develop political frameworks to shift the causal focus towards human, institutional and structural agency in mass avoidable global civilian mortality.

  10. Measuring Human Performance within Computer Security Incident Response Teams

    Energy Technology Data Exchange (ETDEWEB)

    McClain, Jonathan T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Silva, Austin Ray [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Avina, Glory Emmanuel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Forsythe, James C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-09-01

    Human performance has become a pertinen t issue within cyber security. However, this research has been stymied by the limited availability of expert cyber security professionals. This is partly attributable to the ongoing workload faced by cyber security professionals, which is compound ed by the limited number of qualified personnel and turnover of p ersonnel across organizations. Additionally, it is difficult to conduct research, and particularly, openly published research, due to the sensitivity inherent to cyber ope rations at most orga nizations. As an alternative, the current research has focused on data collection during cyb er security training exercises. These events draw individuals with a range of knowledge and experience extending from seasoned professionals to recent college gradu ates to college students. The current paper describes research involving data collection at two separate cyber security exercises. This data collection involved multiple measures which included behavioral performance based on human - machine transactions and questionnaire - based assessments of cyber security experience.

  11. Cortical depth-dependent temporal dynamics of the BOLD response in the human brain

    National Research Council Canada - National Science Library

    Siero, Jeroen CW; Petridou, Natalia; Hoogduin, Hans; Luijten, Peter R; Ramsey, Nick F

    2011-01-01

    .... In this study, we characterize the temporal dynamics of the hemodynamic response (HDR) across cortical depth in the human primary motor and visual cortex, at 7T and using very short stimuli and with high spatial and temporal resolution...

  12. A Study of the Characteristics of Human-Pilot Control Response to Simulated Aircraft Lateral Motions

    Science.gov (United States)

    Cheatham, Donald C

    1954-01-01

    Report presents the results of studies made in an attempt to provide information on the control operations of the human pilot. These studies included an investigation of the ability of pilots to control simulated unstable yawing oscillations, a study of the basic characteristics of human-pilot control response, and a study to determine whether and to what extent pilot control response can be represented in an analytical form.

  13. Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses

    Directory of Open Access Journals (Sweden)

    Claudia Palena

    2010-01-01

    Full Text Available Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression.

  14. Immunological Responses against SARS-Coronavirus Infection in Humans

    Institute of Scientific and Technical Information of China (English)

    Xiaojun Xu; Xiao-Ming Gao

    2004-01-01

    Since the outbreak of a SARS epidemic last year, significant advances have been made on our understanding of the mechanisms of interaction between the SARS coronavirus (CoV) and the immune system. Strong humoral responses have been found in most patients following SARS-CoV infection, with high titers of neutralizing Abspresent in their convalescent sera. The nucleocapsid (N) and spike (S) proteins of SARS-CoV appear to be the dominant antigens recognized by serum Abs. CD4+ T cell responses against the N protein have been observed in SARS patients and an HLA-A2-restricted cytotoxic T lymphocyte epitope in the S protein has been identified.It is likely that the immune responses induced by SARS-CoV infection could also cause pathological damage to the host, especially in the case of proinflammatory cytokines. There is also evidence suggesting that SARS-CoV might be able to directly invade cells of the immune system. Our understanding on the interaction between SARS-CoV, the immune system and local tissues is essential to future diagnosis, control and treatment of this very contagious disease.

  15. Immunological Responses against SARS-Coronavirus Infection in Humans

    Institute of Scientific and Technical Information of China (English)

    XiaojunXu; Xiao-MingGao

    2004-01-01

    Since the outbreak of a SARS epidemic last year, significant advances have been made on our understanding of the mechanisms of interaction between the SARS coronavirus (CoV) and the immune system. Strong humoral responses have been found in most patients following SARS-CoV infection, with high titers of neutralizing Abs present in their convalescent sera. The nucleocapsid (N) and spike (S) proteins of SARS-CoV appear to be the dominant antigens recognized by serum Abs. CD4+ T cell responses against the N protein have been observed in SARS patients and an HLA-A2-restricted cytotoxic T lymphocyte epitope in the S protein has been identified. It is likely that the immune responses induced by SARS-CoV infection could also cause pathological damage to the host, especially in the case of proinflammatory cytokines. There is also evidence suggesting that SARS-CoV might be able to directly invade cells of the immune system. Our understanding on the interaction between SARS-CoV, the immune system and local tissues is essential to future diagnosis, control and treatment of this very contagious disease. Cellular & Molecular Immunology. 2004;1(2):119-122.

  16. Cytokines and dysregulation of the immune response in human malaria

    Directory of Open Access Journals (Sweden)

    M. Fátima C. Alves

    1992-01-01

    Full Text Available The dysregulation of the immune response by malaria parasite has been considered as a possible constraint to the effectiveness of malaria vaccination. In spite of the important role interleukin-I (IL-1 in malaria are lacking. We found that only 2 out of 35 subjectswith acute malaria showed increased levels of serum IL-1 alpha by enzyme immunoassay. To assess whether IL-1 could interfere with T- lymphocyte responses, blood mononuclear cells from patients infected with Plasmodium falciparum, P. vivax, or healthy subjects were cultured with phytohemagglutinin, and lymphocyte proliferation measured 72h later by 3H-thymidine incorporation. Our data showed that T-lymphocyte responses are depressed both in P. falciparum (10,500 ñ 2,900 and P. vivax malaria (13,000 ñ 3,300, as compared to that of healthy individuals (27,000 ñ 3,000. Addition of IL-1 partially reserved depression of malaria lymphocytes, but had no effect on normal cells. On the other hand, T-lymphocytes from malaria infected-subjects presented a minimal decrease in proliferation, when cultured in the presence of exogenous PGE2. These data indicate the occurrence of two defects of immunoregulation in malaria: a deficiency of IL-1 production by monocytes/macrophages, and an increased resistance of lymphocytes to the antiproliferative effect of PGE2.

  17. The human antibody response to the surface of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Casey C Perley

    Full Text Available Vaccine-induced human antibodies to surface components of Haemophilus influenzae and Streptococcus pneumonia are correlated with protection. Monoclonal antibodies to surface components of Mycobacterium tuberculosis are also protective in animal models. We have characterized human antibodies that bind to the surface of live M. tuberculosis.Plasma from humans with latent tuberculosis (TB infection (n = 23, active TB disease (n = 40, and uninfected controls (n = 9 were assayed by ELISA for reactivity to the live M. tuberculosis surface and to inactivated M. tuberculosis fractions (whole cell lysate, lipoarabinomannan, cell wall, and secreted proteins.When compared to uninfected controls, patients with active TB disease had higher antibody titers to the surface of live M. tuberculosis (Δ = 0.72 log10, whole cell lysate (Δ = 0.82 log10, and secreted proteins (Δ = 0.62 log10, though there was substantial overlap between the two groups. Individuals with active disease had higher relative IgG avidity (Δ = 1.4 to 2.6 to all inactivated fractions. Surprisingly, the relative IgG avidity to the live M. tuberculosis surface was lower in the active disease group than in uninfected controls (Δ =  -1.53, p = 0.004. Patients with active disease had higher IgG than IgM titers for all inactivated fractions (ratios, 2.8 to 10.1, but equal IgG and IgM titers to the live M. tuberculosis surface (ratio, 1.1. Higher antibody titers to the M. tuberculosis surface were observed in active disease patients who were BCG-vaccinated (Δ = 0.55 log10, p = 0.008, foreign-born (Δ = 0.61 log10, p = 0.004, or HIV-seronegative (Δ = 0.60 log10, p = 0.04. Higher relative IgG avidity scores to the M. tuberculosis surface were also observed in active disease patients who were BCG-vaccinated (Δ = 1.12, p < 0.001 and foreign-born (Δ = 0.87, p = 0.01.Humans with active TB disease produce antibodies to the surface of M. tuberculosis with low avidity and with a low IgG/IgM ratio

  18. The Human Antibody Response to the Surface of Mycobacterium tuberculosis

    Science.gov (United States)

    Perley, Casey C.; Frahm, Marc; Click, Eva M.; Dobos, Karen M.; Ferrari, Guido; Stout, Jason E.; Frothingham, Richard

    2014-01-01

    Background Vaccine-induced human antibodies to surface components of Haemophilus influenzae and Streptococcus pneumonia are correlated with protection. Monoclonal antibodies to surface components of Mycobacterium tuberculosis are also protective in animal models. We have characterized human antibodies that bind to the surface of live M. tuberculosis. Methods Plasma from humans with latent tuberculosis (TB) infection (n = 23), active TB disease (n = 40), and uninfected controls (n = 9) were assayed by ELISA for reactivity to the live M. tuberculosis surface and to inactivated M. tuberculosis fractions (whole cell lysate, lipoarabinomannan, cell wall, and secreted proteins). Results When compared to uninfected controls, patients with active TB disease had higher antibody titers to the surface of live M. tuberculosis (Δ = 0.72 log10), whole cell lysate (Δ = 0.82 log10), and secreted proteins (Δ = 0.62 log10), though there was substantial overlap between the two groups. Individuals with active disease had higher relative IgG avidity (Δ = 1.4 to 2.6) to all inactivated fractions. Surprisingly, the relative IgG avidity to the live M. tuberculosis surface was lower in the active disease group than in uninfected controls (Δ = –1.53, p = 0.004). Patients with active disease had higher IgG than IgM titers for all inactivated fractions (ratios, 2.8 to 10.1), but equal IgG and IgM titers to the live M. tuberculosis surface (ratio, 1.1). Higher antibody titers to the M. tuberculosis surface were observed in active disease patients who were BCG-vaccinated (Δ = 0.55 log10, p = 0.008), foreign-born (Δ = 0.61 log10, p = 0.004), or HIV-seronegative (Δ = 0.60 log10, p = 0.04). Higher relative IgG avidity scores to the M. tuberculosis surface were also observed in active disease patients who were BCG-vaccinated (Δ = 1.12, p<0.001) and foreign-born (Δ = 0.87, p = 0.01). Conclusions/Significance Humans

  19. Paroxetine suppresses recombinant human P2X7 responses

    OpenAIRE

    Dao-Ung, Phuong; Skarratt, Kristen; Fuller, Stephen; Stokes, Leanne

    2015-01-01

    P2X7 receptor (P2X7) activity may link inflammation to depressive disorders. Genetic variants of human P2X7 have been linked with major depression and bipolar disorders, and the P2X7 knockout mouse has been shown to exhibit anti-depressive-like behaviour. P2X7 is an ATP-gated ion channel and is a major regulator of the pro-inflammatory cytokine interleukin 1β (IL-1β) secretion from monocytes and microglia. We hypothesised that antidepressants may elicit their mood enhancing effects in part vi...

  20. Response to "The Shaky Legal Foundations of the Global Human Rights Education Project"

    Science.gov (United States)

    Tibbitts, Felisa

    2015-01-01

    This article is a response to "The Shaky Legal Foundations of the Global Human Rights Education Project," an article written by Barend Vlaardingerbroek, in which Vlaardingerbroek characterizes current practices of human rights education (HRE) as having an overriding agenda of activism, one that can draw on an ideologically-driven…

  1. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    Science.gov (United States)

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  2. Analysis of rear-end impact response using mathematical human modeling and volunteer tests

    NARCIS (Netherlands)

    Meijer, R.; Hoof, J.F.A.M. van; Ono, K.; Kaneoka, K.

    2001-01-01

    At TNO multi-directional mathematical human body models have been developed. The objective of this study was to simulate the rigid seat and standard seat JARI rear-impact sled tests using the MADYMO 50th percentile male model. The head and neck response of this human model and the volunteers were co

  3. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    Science.gov (United States)

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  4. Human and animal studies: portals into the whole body and whole population response

    Science.gov (United States)

    Human and animal studies: portals into the whole body and whole population response Michael C. Madden1 and Brett Winters21US Environmental Protection Agency and 2University of North Carolina Human Studies Facility, Chapel Hill, North Carolina, USA Studies involving collection and...

  5. Human protein status modulates brain reward responses to food cues1–3

    NARCIS (Netherlands)

    Griffioen-Roose, S.; Smeets, P.A.M.; Heuvel, van den E.M.; Boesveldt, S.; Finlayson, G.; Graaf, de C.

    2014-01-01

    Background: Protein is indispensable in the human diet, and its intake appears tightly regulated. The role of sensory attributes of foods in protein intake regulation is far from clear. Objective: We investigated the effect of human protein status on neural responses to different food cues with the

  6. The Socio-ecological Fit of Human Responses to Environmental Degradation: An Integrated Assessment Methodology

    Science.gov (United States)

    Briassoulis, Helen

    2015-12-01

    The scientific and policy interest in the human responses to environmental degradation usually focuses on responses sensu stricto and `best practices' that potentially abate degradation in affected areas. The transfer of individual, discrete instruments and `best practices' to different contexts is challenging, however, because socio-ecological systems are complex and environmental degradation is contextual and contingent. To sensibly assess the effectiveness of formal and informal interventions to combat environmental degradation, the paper proposes an integrative, non-reductionist analytic, the `response assemblage', for the study of `responses-in-context,' i.e., products of human decisions to utilize environmental resources to satisfy human needs in socio-ecological systems. Response assemblages are defined as geographically and historically unique, provisional, open, territorial wholes, complex compositions emerging from processes of assembling biophysical and human components, including responses sensu stricto, from affected focal and other socio-ecological systems, to serve human goals, one of which may be combatting environmental degradation. The degree of match among the components, called the socio- ecological fit of the response assemblage, indicates how effectively their contextual and contingent interactions maintain the socio-ecological resilience, promote sustainable development, and secure the continuous provision of ecosystem services in a focal socio-ecological system. The paper presents a conceptual approach to the analysis of the socio-ecological fit of response assemblages and details an integrated assessment methodology synthesizing the resilience, assemblage, and `problem of fit' literature. Lastly, it summarizes the novelty, value, and policy relevance of conceptualizing human responses as response assemblages and of the integrated assessment methodology, reconsiders `best practices' and suggests selected future research directions.

  7. The Socio-ecological Fit of Human Responses to Environmental Degradation: An Integrated Assessment Methodology.

    Science.gov (United States)

    Briassoulis, Helen

    2015-12-01

    The scientific and policy interest in the human responses to environmental degradation usually focuses on responses sensu stricto and 'best practices' that potentially abate degradation in affected areas. The transfer of individual, discrete instruments and 'best practices' to different contexts is challenging, however, because socio-ecological systems are complex and environmental degradation is contextual and contingent. To sensibly assess the effectiveness of formal and informal interventions to combat environmental degradation, the paper proposes an integrative, non-reductionist analytic, the 'response assemblage', for the study of 'responses-in-context,' i.e., products of human decisions to utilize environmental resources to satisfy human needs in socio-ecological systems. Response assemblages are defined as geographically and historically unique, provisional, open, territorial wholes, complex compositions emerging from processes of assembling biophysical and human components, including responses sensu stricto, from affected focal and other socio-ecological systems, to serve human goals, one of which may be combatting environmental degradation. The degree of match among the components, called the socio-ecological fit of the response assemblage, indicates how effectively their contextual and contingent interactions maintain the socio-ecological resilience, promote sustainable development, and secure the continuous provision of ecosystem services in a focal socio-ecological system. The paper presents a conceptual approach to the analysis of the socio-ecological fit of response assemblages and details an integrated assessment methodology synthesizing the resilience, assemblage, and 'problem of fit' literature. Lastly, it summarizes the novelty, value, and policy relevance of conceptualizing human responses as response assemblages and of the integrated assessment methodology, reconsiders 'best practices' and suggests selected future research directions.

  8. DMPD: Differential responses of human monocytes and macrophages to IL-4 and IL-13. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534111 Differential responses of human monocytes and macrophages to IL-4 and IL-1...):575-8. (.png) (.svg) (.html) (.csml) Show Differential responses of human monocytes and macrophages to IL-...4 and IL-13. PubmedID 10534111 Title Differential responses of human monocytes an

  9. The commerce of human body parts: an Eastern Orthodox response.

    Science.gov (United States)

    Reardon, P H

    2000-08-01

    The Orthodox Church teaches that the bodies of those in Christ are to be regarded as sanctified by the hearing of the Word and faithful participation in the Sacraments, most particularly the Holy Eucharist; because of the indwelling of the Holy Spirit the consecrated bodies of Christians do not belong to them but to Christ; with respect to the indwelling Holy Spirit there is no difference between the bodies of Christians before and after death; whether before or after death, the Christian body is also to receive the same veneration; and notwithstanding the physical corruptions that the body endures by reason of death, there remains a strict continuity between the body in which the Christian dies and the body in which the Christian will rise again. That is to say, it is the very same reality that is sown in corruption and will be raised in incorruption. Given such consideration, the notion of "selling" and integral part of a human being is simply outside the realm of rational comprehension. Indeed, it is profoundly repugnant to those Orthodox Christian sentiments that are formed and nourished by the Church's sacramental teaching and liturgical worship. One does not sell or purchase that which has been consecrated in those solemn ways that the Church consecrates the human body.

  10. Human psychometric and taste receptor responses to steviol glycosides.

    Science.gov (United States)

    Hellfritsch, Caroline; Brockhoff, Anne; Stähler, Frauke; Meyerhof, Wolfgang; Hofmann, Thomas

    2012-07-11

    Steviol glycosides, the sweet principle of Stevia Rebaudiana (Bertoni) Bertoni, have recently been approved as a food additive in the EU. The herbal non-nutritive high-potency sweeteners perfectly meet the rising consumer demand for natural food ingredients in Europe. We have characterized the organoleptic properties of the most common steviol glycosides by an experimental approach combining human sensory studies and cell-based functional taste receptor expression assays. On the basis of their potency to elicit sweet and bitter taste sensations, we identified glycone chain length, pyranose substitution, and the C16 double bond as the structural features giving distinction to the gustatory profile of steviol glycosides. A comprehensive screening of 25 human bitter taste receptors revealed that two receptors, hTAS2R4 and hTAS2R14, mediate the bitter off-taste of steviol glycosides. For some test substances, e.g., stevioside, we observed a decline in sweet intensity at supra-maximum concentrations. This effect did not arise from allosteric modulation of the hTAS1R2/R3 sweet taste receptor but might be explained by intramolecular cross-modal suppression between the sweet and bitter taste component of steviol glycosides. These results might contribute to the production of preferentially sweet and least bitter tasting Stevia extracts by an optimization of breeding and postharvest downstream processing.

  11. An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection

    NARCIS (Netherlands)

    Vissers, M.; Habets, M.N.; Ahout, I.M.L.; Jans, J.; Jonge, M.I. de; Diavatopoulos, D.A.; Ferwerda, G.

    2013-01-01

    Human respiratory syncytial virus (HRSV) infections present a broad spectrum of disease severity, ranging from mild infections to life-threatening bronchiolitis. An important part of the pathogenesis of severe disease is an enhanced immune response leading to immunopathology. Here, we describe a

  12. An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection

    NARCIS (Netherlands)

    Vissers, M.; Habets, M.N.; Ahout, I.M.L.; Jans, J.; Jonge, M.I. de; Diavatopoulos, D.A.; Ferwerda, G.

    2013-01-01

    Human respiratory syncytial virus (HRSV) infections present a broad spectrum of disease severity, ranging from mild infections to life-threatening bronchiolitis. An important part of the pathogenesis of severe disease is an enhanced immune response leading to immunopathology. Here, we describe a pro

  13. Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways

    NARCIS (Netherlands)

    Baarlen, van P.; Troost, F.J.; Meer, van der C.; Hooiveld, G.J.E.J.; Boekschoten, M.V.; Brummer, R.J.; Kleerebezem, M.

    2011-01-01

    Probiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function through largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy

  14. Human longevity and variation in DNA damage response and repair

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette; Flachsbart, Friederike

    2014-01-01

    others. Data were applied on 592 SNPs from 77 genes involved in nine sub-processes: DNA-damage response, base excision repair (BER), nucleotide excision repair, mismatch repair, non-homologous end-joining, homologous recombinational repair (HRR), RecQ helicase activities (RECQ), telomere functioning...... and mitochondrial DNA processes. The study population was 1089 long-lived and 736 middle-aged Danes. A self-contained set-based test of all SNPs displayed association with longevity (P-value=9.9 × 10-5), supporting that the overall pathway could affect longevity. Investigation of the nine sub-processes using...

  15. Proneness to worry is negatively associated with blood pressure and baroreflex sensitivity: further evidence of the blood pressure emotional dampening hypothesis.

    Science.gov (United States)

    Delgado, Luis Carlos; Vila, Jaime; Reyes del Paso, Gustavo A

    2014-02-01

    This study analyzes differences in blood pressure (BP) and baroreflex sensitivity (BRS) in relation to trait worry. 36 high worry and 21 low worry females were selected from scores on the Penn State Worry Questionnaire. Cardiovascular parameters were obtained during rest, a self-induced worry period, and defense reflex to intense auditory stimulation. Low worry participants exhibited greater BP during baseline and greater BRS both during baseline and the self-induced worry period than high worry participants. During the defense reflex, low worries present a greater increase in BP. It is concluded that low proneness to worry is associated with greater BP and BRS. Increases in BP during aversive stimulation activated a negative feedback mechanism to inhibit distress and emotional reactivity to negative stimulation. These results support the BP-emotional dampening hypothesis and suggest that the baroreflex can be a relevant mechanism in mediating this effect.

  16. Diverting attention suppresses human amygdala responses to faces

    Directory of Open Access Journals (Sweden)

    Carmen eMorawetz

    2010-12-01

    Full Text Available Recent neuroimaging studies disagree as to whether the processing of emotion-laden visual stimuli is dependent upon the availability of attentional resources or entirely capacity-free. Two main factors have been proposed to be responsible for the discrepancies: the differences in the perceptual attentional demands of the tasks used to divert attentional resources from emotional stimuli and the spatial location of the affective stimuli in the visual field. To date, no neuroimaging report addressed these two issues in the same set of subjects. Therefore, the aim of the study was to investigate the effects of high and low attentional load as well as different stimulus locations on face processing in the amygdala using fMRI to provide further evidence for one of the two opposing theories. We were able for the first time to directly test the interaction of attentional load and spatial location. The results revealed a strong attenuation of amygdala activity when the attentional load was high. The eccentricity of the emotional stimuli did not affect responses in the amygdala and no interaction effect between attentional load and spatial location was found. We conclude that the processing of emotional stimuli in the amygdala is strongly dependent on the availability of attentional resources without a preferred processing of stimuli presented in the periphery and provide firm evidence for the concept of the attentional load theory of emotional processing in the amygdala.

  17. The human ocular torsion position response during yaw angular acceleration.

    Science.gov (United States)

    Smith, S T; Curthoys, I S; Moore, S T

    1995-07-01

    Recent results by Wearne [(1993) Ph.D. thesis] using the scleral search-coil method of measuring eye position indicate that changes in ocular torsion position (OTP) occur during yaw angular acceleration about an earth vertical axis. The present set of experiments, using an image processing method of eye movement measurement free from the possible confound of search coil slippage, demonstrates the generality and repeatability of this phenomenon and examines its possible causes. The change in torsion position is not a linear vestibulo-ocular reflex (LVOR) response to interaural linear acceleration stimulation of the otoliths, but rather the effect is dependent on the characteristics of the angular acceleration stimulus, commencing at the onset and decaying at the offset of the angular acceleration. In the experiments reported here, the magnitude of the angular acceleration stimulus was varied and the torsion position response showed corresponding variations. We consider that the change in torsion position observed during angular acceleration is most likely to be due to activity of the semicircular canals.

  18. Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation

    NARCIS (Netherlands)

    Spronk, D.B.; De Bruijn, E.R.; van Wel, J.H.; Ramaekers, J.G.; Verkes, R.J.

    2016-01-01

    Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impul

  19. Human T cell responses to the ESAT-6 antigen from Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Ravn, P; Demissie, A; Eguale, T;

    1999-01-01

    Human T cell responses to ESAT-6 and eight synthetic overlapping peptides were investigated in tuberculosis (TB) patients and control subjects from regions of high and low endemicity for TB. ESAT-6 was recognized by 65% of all tuberculin purified protein derivative-responsive TB patients, whereas...

  20. A Pilot Study of Phase-Evoked Acoustic Responses From the Ears of Human Subjects

    DEFF Research Database (Denmark)

    Christensen, Anders Tornvig; Dewey, James; Dhar, Sumitrajit

    2015-01-01

    cochlear excitation revealing properties of the nonlinearity responsible for OAE generation. To explore the temporal properties of OAEs further, we studied acoustic responses from the ears of nine young, normal-hearing human subjects to abrupt changes in the phase of pure tones. The measurement paradigm...

  1. Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

    2009-10-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

  2. Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus1

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A.; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M.; Sandman, Curt A.

    2009-01-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks’ GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks’ GA, females however, presented with a mature FHR startle response by 31 weeks’ GA. The results indicate that there are different rates of maturation in the male and female fetus that may have implications for sex-specific programming influences. PMID:19726143

  3. Human factors regulation in response to advanced reactor design trends

    Energy Technology Data Exchange (ETDEWEB)

    Innes, L.; Harrison, F. (Atomic Energy Control Board, Ottawa, Ontario (Canada)); Rhodes, W. (Rhodes Associates Inc., Willowdale, Ontario (Canada))

    1993-01-01

    This paper presents the direction being taken in the Canadian regulatory program to guide the incorporation of human factors principles, knowledge, information, and methods in activities such as those that address the design and implementation of the advanced control room (ACR) in nuclear power plants. Within the current activity in the international nuclear industry aimed at the development of ACR concepts, the steps that are being taken to develop design review guidelines for ACRs, such as the work sponsored by the U.S. Nuclear Regulatory Commission are filling an identified important need. The salient feature of most ACR projects is the increased use of digital technology for the analysis, synthesis, management, and display of information. The greatly increased functionality of the devices that can be introduced during such projects allows changes to be made at the design and implementation stages that are not necessarily based on prior function allocation or task analyses.

  4. Human response to ductless personalized ventilation coupled with displacement ventilation

    DEFF Research Database (Denmark)

    Dalewski, Mariusz; Veselý, Michal; Melikov, Arsen K.

    2012-01-01

    A human subject experiment was carried out to investigate the extent to which ductless personalized ventilation (DPV) in conjunction with displacement ventilation can improve perceived air quality (PAQ) and thermal comfort at elevated room air temperature in comparison with displacement ventilation...... alone. The experimental conditions comprised displacement ventilation alone (room air temperature of 23 °C, 26 °C, 29 °C) and DPV with displacement ventilation (26 °C, 29 °C), both operating at supply air temperatures 3, 5 or 6K lower than room air temperature, as well as mixing ventilation (23 °C, 3 K......). During one hour exposure participants answered questionnaires regarding PAQ and thermal comfort. PAQ was significantly better with DPV than without DPV at the same background conditions. Thermal comfort improved when DPV was used. Combining DPV with displacement ventilation showed the potential...

  5. Human monocyte differentiation stage affects response to arachidonic acid.

    Science.gov (United States)

    Escobar-Alvarez, Elizabeth; Pelaez, Carlos A; García, Luis F; Rojas, Mauricio

    2010-01-01

    AA-induced cell death mechanisms acting on human monocytes and monocyte-derived macrophages (MDM), U937 promonocytes and PMA-differentiated U937 cells were studied. Arachidonic acid induced apoptosis and necrosis in monocytes and U937 cells but only apoptosis in MDM and U937D cells. AA increased both types of death in Mycobacterium tuberculosis-infected cells and increased the percentage of TNFalpha+ cells and reduced IL-10+ cells. Experiments blocking these cytokines indicated that AA-mediated death was TNFalpha- and IL-10-independent. The differences in AA-mediated cell death could be explained by high ROS, calpain and sPLA-2 production and activity in monocytes. Blocking sPLA-2 in monocytes and treatment with antioxidants favored M. tuberculosis control whereas AA enhanced M. tuberculosis growth in MDM. Such evidence suggested that AA-modulated effector mechanisms depend on mononuclear phagocytes' differentiation stage.

  6. Sequence features responsible for intron retention in human

    Directory of Open Access Journals (Sweden)

    Sakabe Noboru

    2007-02-01

    Full Text Available Abstract Background One of the least common types of alternative splicing is the complete retention of an intron in a mature transcript. Intron retention (IR is believed to be the result of intron, rather than exon, definition associated with failure of the recognition of weak splice sites flanking short introns. Although studies on individual retained introns have been published, few systematic surveys of large amounts of data have been conducted on the mechanisms that lead to IR. Results TTo understand how sequence features are associated with or control IR, and to produce a generalized model that could reveal previously unknown signals that regulate this type of alternative splicing, we partitioned intron retention events observed in human cDNAs into two groups based on the relative abundance of both isoforms and compared relevant features. We found that a higher frequency of IR in human is associated with individual introns that have weaker splice sites, genes with shorter intron lengths, higher expression levels and lower density of both a set of exon splicing silencers (ESSs and the intronic splicing enhancer GGG. Both groups of retained introns presented events conserved in mouse, in which the retained introns were also short and presented weaker splice sites. Conclusion Although our results confirmed that weaker splice sites are associated with IR, they showed that this feature alone cannot explain a non-negligible fraction of events. Our analysis suggests that cis-regulatory elements are likely to play a crucial role in regulating IR and also reveals previously unknown features that seem to influence its occurrence. These results highlight the importance of considering the interplay among these features in the regulation of the relative frequency of IR.

  7. Antibody response to Salmonella typhi lw human Schistosomiasis mansoni

    Directory of Open Access Journals (Sweden)

    Maria Imaculada Muniz-Junqueira

    1996-10-01

    Full Text Available Antibody response to Salmonella typhi O and H antigens was evaluated in 24 individuals with either hepatointestinal or hepatosplenic schistosomiasis mansoni before and after typhoid vaccination, and compared with that of non-infected controls. Before vaccination, Schistosoma-infected patients showed a higher frequency of positive antibody to O antigen and the same frequency to H antigen when compared with that of healthy individuals. However, those with hepatosplenic schistosomiasis showed higher titres of antibody to H antigen than those with hepatointestinal disease or healthy individuals. Infected subjects, particularly those with hepatointestinal disease, showed a decreased response after typhoid vaccine. Tins diminished ability to mount an immune response towards typhoid antigens dining schistosomiasis may interfere ivith the clearance of the bacteria from blood stream and, therefore, play a role in the prolonged survival of salmonella as obsewed in some patients with chronic salmonellosis associated with schistosomiasis.A resposta de anticorpos para os antígenos O e H da Salmonella typhi foi avaliada em 24 indivíduos com esquistossomose hepatointestinal ou hepatoesplênica antes e apôs vacinação antitifoídica, e comparada com a resposta de indivíduos controles normais. Antes da vacinação, pacientes esquistossomóticos mostraram uma maior frequência de anticoipos positivos para o antígeno O e a mesma frequência de anticoipos positivos para o antígeno H quando comparada com aquela de indivíduos controles normais. Porém, aqueles com esquistossomose hepatoesplênica mostraram títulos maiores de anticoipos para o antígeno H do que aqueles com a forma hepatointestinal da doença ou os indivíduos controles normais. Pacientes esquistossomóticos, particularmente aqueles com a forma hepatointestinal, mostraram uma menor resposta após a vacinação antitifoídica. Esta menor capacidade para apresentar uma resposta imune para ant

  8. Bystander T cells in human immune responses to dengue antigens

    Directory of Open Access Journals (Sweden)

    Suwannasaen Duangchan

    2010-09-01

    Full Text Available Abstract Background Previous studies of T cell activation in dengue infection have focused on restriction of specific T cell receptors (TCRs and classical MHC molecules. However, bystander T cell activation, which is TCR independent, occurs via cytokines in other viral infections, both in vitro and in vivo, and enables T cells to bypass certain control checkpoints. Moreover, clinical and pathological evidence has pointed to cytokines as the mediators of dengue disease severity. Therefore, we investigated bystander T cell induction by dengue viral antigen. Results Whole blood samples from 55 Thai schoolchildren aged 13-14 years were assayed for in vitro interferon-gamma (IFN-γ induction in response to inactivated dengue serotype 2 antigen (Den2. The contribution of TCR-dependent and independent pathways was tested by treatment with cyclosporin A (CsA, which inhibits TCR-dependent activation of T cells. ELISA results revealed that approximately 72% of IFN-γ production occurred via the TCR-dependent pathway. The major IFN-γ sources were natural killer (NK (mean ± SE = 55.2 ± 3.3, CD4+T (24.5 ± 3.3 and CD8+T cells (17.9 ± 1.5, respectively, as demonstrated by four-color flow cytometry. Interestingly, in addition to these cells, we found CsA-resistant IFN-γ producing T cells (CD4+T = 26.9 ± 3.6% and CD8+T = 20.3 ± 2.1% implying the existence of activated bystander T cells in response to dengue antigen in vitro. These bystander CD4+ and CD8+T cells had similar kinetics to NK cells, appeared after 12 h and were inhibited by anti-IL-12 neutralization indicating cytokine involvement. Conclusions This study described immune cell profiles and highlighted bystander T cell activation in response to dengue viral antigens of healthy people in an endemic area. Further studies on bystander T cell activation in dengue viral infection may reveal the immune mechanisms that protect or enhance pathogenesis of secondary dengue infection.

  9. THE ROLE OF HUMAN RESOURCES IN PROMOTING THE CORPORATE SOCIAL RESPONSABILITY

    OpenAIRE

    IOAN PASTOR; CAMELIA-OLIVIA ILIES

    2011-01-01

    In a global economy, organizations have the responsibility to demonstrate and promote corporate social responsibility. Long-term sustainability demands that organizations rethink their business goals and objectives from focusing on making a profit to corporate citizenship. Human resource managers play a critical role – that of leading and educating their companies regarding the importance of corporate social responsability while at the same time strategically implementing healthy management p...

  10. Strain-Related Differences in the Immune Response: Relevance to Human Stroke.

    Science.gov (United States)

    Becker, Kyra J

    2016-08-01

    There are significant differences in the immune response and in the susceptibility to autoimmune diseases among rodent strains. It would thus be expected that the contribution of the immune response to cerebral ischemic injury would also differ among rodent strains. More importantly, there are significant differences between the immune responses of rodents and humans. All of these factors are likely to impact the successful translation of immunomodulatory therapies from experimental rodent models to patients with stroke.

  11. Neural Markers of Responsiveness to the Environment in Human Sleep

    DEFF Research Database (Denmark)

    Andrillon, Thomas; Poulsen, Andreas Trier; Hansen, Lars Kai

    2016-01-01

    could be related to modulation in sleep depth. InREMsleep, however, this relationship was reversed.Wetherefore propose that, in REM sleep, endogenously generated processes compete with the processing of external input. Sleep can thus be seen as a self-regulated process in which external information can......Sleep is characterized by a loss of behavioral responsiveness. However, recent research has shown that the sleeping brain is not completely disconnected from its environment. How neural activity constrains the ability to process sensory information while asleep is yet unclear. Here, we instructed...... by Lempel-Ziv complexity (LZc), a measure shown to track arousal in sleep and anesthesia. Neural activity related to the semantic content of stimuli was conserved in light non-rapid eye movement (NREM) sleep. However, these processes were suppressed in deep NREM sleep and, importantly, also in REM sleep...

  12. Humanity and Social Responsibility, Solidarity, and Social Rights.

    Science.gov (United States)

    Ahola-Launonen, Johanna

    2016-04-01

    This article discusses the suggestion of having the notion of solidarity as the foundational value for welfare scheme reforms. Solidarity is an emerging concept in bioethical deliberations emphasizing the need for value-oriented discussion in revising healthcare structures, and the notion has been contrasted with liberal justice and rights. I suggest that this contrast is unnecessary, flawed, and potentially counterproductive. As necessary as the sense of solidarity is in a society, it is an insufficient concept to secure the goals related to social responsibility. The discussion on solidarity is also based on a questionable sense of nostalgia. Furthermore, solidarity and liberal justice share essential objectives concerning welfare schemes; therefore, the question arises whether the proper comparison should in the first place be within justice and solidarity.

  13. Hallucinogenic drugs attenuate the subjective response to alcohol in humans.

    Science.gov (United States)

    Barrett, Sean P; Archambault, Jennifer; Engelberg, Marla J; Pihl, Robert O

    2000-10-01

    This study investigated possible interactions between alcohol and hallucinogens in 22 lysergic acid diethylamide (LSD) and/or psilocybin users through retrospective structured interviews. Of those who had used LSD with alcohol, 86;7 per cent reported a complete blockade of subjective alcohol effects, while the remaining cases reported a diminished response. In addition, 60 per cent of respondents who had used alcohol and psilocybin together reported a partial antagonism of subjective alcohol effects.T-test analyses revealed that LSD's antagonism of alcohol effects were significantly greater than those associated with psilocybin. It is proposed that LSD's effect on alcohol intoxication may involve interactions with various serotonergic and/or dopaminergic receptor systems. Copyright 2000 John Wiley & Sons, Ltd.

  14. Is human hepatocellular carcinoma a hormone-responsive tumor?

    Institute of Scientific and Technical Information of China (English)

    Massimo Di Maio; Bruno Daniele; Sandra Pignata; Ciro Gallo; Ermelinda De Maio; Alessandro Morabito; Maria Carmela Piccirillo; Francesco Perrone

    2008-01-01

    Before the positive results recently obtained with multitarget tyrosine kinase inhibitor sorafenib, there was no standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC). Sex hormones receptors are expressed in a significant proportion of HCC samples. Following preclinical and epidemiological studies supporting a relationship between sex hormones and HCC tumorigenesis, several randomized controlled trials (RCTs) tested the efficacy of the anti-estrogen tamoxifen as systemic treatment. Largest among these trials showed no survival advantage from the administration of tamoxifen, and the recent Cochrane systematic review produced a completely negative result. This questions the relevance of estrogen receptor-mediated pathways in HCC. However, a possible explanation for these disappointing results is the lack of proper patients selection according to sex hormones receptors expression, but unfortunately the interaction between this expression and efficacy of tamoxifen has not been studied adequately. It has been also proposed that negative results might be explained if tamoxifen acts in HCC via an estrogen receptor-independent pathway, that requires higher doses than those usually administered, but an Asian RCT conducted to assess dose-response effect was completely negative. Interesting, preliminaryresults have been obtained when hormonal treatment (tamoxifen or megestrol) has been selected according to the presence of wild-type or variant estrogen receptors respectively, but no large RCTs are available to support this strategy. Negative results have been obtained also with anti-androgen therapy. In conclusion, there is no robust evidence to consider HCC a hormone-responsive tumor. Hormonal treatments should not be part of the current management of HCC.

  15. Gastroenteric hormone responses to hedonic eating in healthy humans.

    Science.gov (United States)

    Monteleone, Palmiero; Scognamiglio, Pasquale; Monteleone, Alessio Maria; Perillo, Donato; Canestrelli, Benedetta; Maj, Mario

    2013-08-01

    Hedonic eating differentiates from homeostatic eating on two main aspects: the first one is that eating occurs when there is no need for calorie ingestion and the second one is that the food is consumed exclusively for its gustatory and rewarding properties. Gastroeneteric hormones such as ghrelin, colecystokinin-33 (CCK) and peptide YY3-36 (PYY3-36) are known to play a pivotal role in the homeostatic control of food intake. To the contrary, their role in hedonic eating has been never investigated. Here we report peripheral responses of CCK, PYY3-36 and ghrelin to the consumption of food for pleasure in well-nourished satiated healthy subjects. Plasma levels of CCK, PYY3-36 and ghrelin were measured in 7 satiated healthy subjects before and after ad libitum consumption of both a highly pleasurable food (hedonic eating) and an isoenergetic non-pleasurable food (non-hedonic eating). The consumption of food for pleasure was associated to a significantly increased production of the hunger hormone ghrelin and a significantly decreased secretion of the satiety hormone CCK. No significant changes in plasma PYY3-36 levels occurred in the two eating conditions. These preliminary data demonstrate that in hedonic eating the peripheral hunger signal represented by ghrelin secretion is enhanced while the satiety signal of CCK production is decreased. This could be responsible for the persistence of peripheral cues allowing a continued eating as well as for the activation of endogenous reward mechanisms, which can drive food consumption in spite of no energy need, only for reward. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. The Human Sympathetic Nervous System Response to Spaceflight

    Science.gov (United States)

    Ertl, Andrew C.; Diedrich, Andre; Paranjape, Sachin Y.; Biaggioni, Italo; Robertson, Rose Marie; Lane, Lynda D.; Shiavi, Richard; Robertson, David

    2003-01-01

    The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

  17. Human Adolescent Phase Response Curves to Bright White Light.

    Science.gov (United States)

    Crowley, Stephanie J; Eastman, Charmane I

    2017-08-01

    Older adolescents are particularly vulnerable to circadian misalignment and sleep restriction, primarily due to early school start times. Light can shift the circadian system and could help attenuate circadian misalignment; however, a phase response curve (PRC) to determine the optimal time for receiving light and avoiding light is not available for adolescents. We constructed light PRCs for late pubertal to postpubertal adolescents aged 14 to 17 years. Participants completed 2 counterbalanced 5-day laboratory sessions after 8 or 9 days of scheduled sleep at home. Each session included phase assessments to measure the dim light melatonin onset (DLMO) before and after 3 days of free-running through an ultradian light-dark (wake-sleep) cycle (2 h dim [~20 lux] light, 2 h dark). In one session, intermittent bright white light (~5000 lux; four 20-min exposures) was alternated with 10 min of dim room light once per day for 3 consecutive days. The time of light varied among participants to cover the 24-h day. For each individual, the phase shift to bright light was corrected for the free-run derived from the other laboratory session with no bright light. One PRC showed phase shifts in response to light start time relative to the DLMO and another relative to home sleep. Phase delay shifts occurred around the hours corresponding to home bedtime. Phase advances occurred during the hours surrounding wake time and later in the afternoon. The transition from delays to advances occurred at the midpoint of home sleep. The adolescent PRCs presented here provide a valuable tool to time bright light in adolescents.

  18. Scale dependent behavioral responses to human development by a large predator, the puma.

    Science.gov (United States)

    Wilmers, Christopher C; Wang, Yiwei; Nickel, Barry; Houghtaling, Paul; Shakeri, Yasaman; Allen, Maximilian L; Kermish-Wells, Joe; Yovovich, Veronica; Williams, Terrie

    2013-01-01

    The spatial scale at which organisms respond to human activity can affect both ecological function and conservation planning. Yet little is known regarding the spatial scale at which distinct behaviors related to reproduction and survival are impacted by human interference. Here we provide a novel approach to estimating the spatial scale at which a top predator, the puma (Puma concolor), responds to human development when it is moving, feeding, communicating, and denning. We find that reproductive behaviors (communication and denning) require at least a 4× larger buffer from human development than non-reproductive behaviors (movement and feeding). In addition, pumas give a wider berth to types of human development that provide a more consistent source of human interference (neighborhoods) than they do to those in which human presence is more intermittent (arterial roads with speeds >35 mph). Neighborhoods were a deterrent to pumas regardless of behavior, while arterial roads only deterred pumas when they were communicating and denning. Female pumas were less deterred by human development than males, but they showed larger variation in their responses overall. Our behaviorally explicit approach to modeling animal response to human activity can be used as a novel tool to assess habitat quality, identify wildlife corridors, and mitigate human-wildlife conflict.

  19. Appropriate control time constant in relation to characteristics of the baroreflex vascular system in 1/R control of the total artificial heart.

    Science.gov (United States)

    Mizuta, Sora; Saito, Itsuro; Isoyama, Takashi; Hara, Shintaro; Yurimoto, Terumi; Li, Xinyang; Murakami, Haruka; Ono, Toshiya; Mabuchi, Kunihiko; Abe, Yusuke

    2017-05-17

    1/R control is a physiological control method of the total artificial heart (TAH) with which long-term survival was obtained with animal experiments. However, 1/R control occasionally diverged in the undulation pump TAH (UPTAH) animal experiment. To improve the control stability of the 1/R control, appropriate control time constant in relation to characteristics of the baroreflex vascular system was investigated with frequency analysis and numerical simulation. In the frequency analysis, data of five goats in which the UPTAH was implanted were analyzed with first Fourier transform technique to examine the vasomotion frequency. The numerical simulation was carried out repeatedly changing baroreflex parameters and control time constant using the elements-expanded Windkessel model. Results of the frequency analysis showed that the 1/R control tended to diverge when very low frequency band that was an indication of the vasomotion frequency was relative high. In numerical simulation, divergence of the 1/R control could be reproduced and the boundary curves between the divergence and convergence of the 1/R control varied depending on the control time constant. These results suggested that the 1/R control tended to be unstable when the TAH recipient had high reflex speed in the baroreflex vascular system. Therefore, the control time constant should be adjusted appropriately with the individual vasomotion frequency.

  20. Global changes in biogeochemical cycles in response to human activities

    Science.gov (United States)

    Moore, Berrien, III; Melillo, Jerry

    1994-01-01

    The main objective of our research was to characterize biogeochemical cycles at continental and global scales in both terrestrial and aquatic ecosystems. This characterization applied to both natural ecosystems and those disturbed by human activity. The primary elements of interest were carbon and nitrogen and the analysis sought to quantify standing stocks and dynamic cycling processes. The translocation of major nutrients from the terrestrial landscape to the atmosphere (via trace gases) and to fluvial systems (via leaching, erosional losses, and point source pollution) were of particular importance to this study. Our aim was to develop the first generation of Earth System Models. Our research was organized around the construction and testing of component biogeochemical models which treated terrestrial ecosystem processes, aquatic nutrient transport through drainage basins, and trace gas exchanges at the continental and global scale. A suite of three complementary models were defined within this construct. The models were organized to operate at a 1/2 degree latitude by longitude level of spatial resolution and to execute at a monthly time step. This discretization afforded us the opportunity to understand the dynamics of the biosphere down to subregional scales, while simultaneously placing these dynamics into a global context.

  1. Introduction: Human response to environmental decline at the forest frontier

    Directory of Open Access Journals (Sweden)

    Keith Alger

    2006-11-01

    Full Text Available Scientific insights about the places where the greatest environmental costs (and human welfare losses might be avoided has too frequently been misperceived as knowledge about which policy interventions are effective in the extremely varied contexts where these losses can occur. This forum demonstrates the behavioral consequences that can occur when protected areas are expanded to slow deforestation and highlights a need to better understand the behavioral changes that deforestation, infrastructure development, and malaria emergence prompt in tropical areas. Facilitation of this awareness will require the integration of rigorous social and ecological science in an interdisciplinary context. This work should be aimed at understanding the opportunity costs of economic drivers, such as soybean expansion, logging, mining, hunting, and wildlife trade, in order to scale the countervailing incentives that are incorporated into common property institutions or economic instruments. To get ahead of the curve of worsening environmental degradation and the poverty traps that occur at the forest edge requires special attention to the scientific evaluation of policies that create incentives for environmental stewardship in the varied contexts of the tropical forest frontier.

  2. Response of human rheumatoid arthritis osteoblasts and osteoclasts to adiponectin.

    Science.gov (United States)

    Krumbholz, Grit; Junker, Susann; Meier, Florian M P; Rickert, Markus; Steinmeyer, Jürgen; Rehart, Stefan; Lange, Uwe; Frommer, Klaus W; Schett, Georg; Müller-Ladner, Ulf; Neumann, Elena

    2017-01-01

    Adiponectin is an effector molecule in the pathophysiology of rheumatoid arthritis, e.g. by inducing cytokines and matrix degrading enzymes in synovial fibroblasts. There is growing evidence that adiponectin affects osteoblasts and osteoclasts although the contribution to the aberrant bone metabolism in rheumatoid arthritis is unclear. Therefore, the adiponectin effects on rheumatoid arthritis-derived osteoblasts and osteoclasts were evaluated. Adiponectin and its receptors were examined in bone tissue. Primary human osteoblasts and osteoclasts were stimulated with adiponectin and analysed using realtime polymerase chain-reaction and immunoassays. Effects on matrix-production by osteoblasts and differentiation and resorptive activity of osteoclasts were examined. Immunohistochemistry of rheumatoid arthritis bone tissue showed adiponectin expression in key cells of bone remodelling. Adiponectin altered gene expression and cytokine release in osteoblasts and increased IL-8 secretion by osteoclasts. Adiponectin inhibited osterix and induced osteoprotegerin mRNA in osteoblasts. In osteoclasts, MMP-9 and tartrate resistant acid phosphatase expression was increased. Accordingly, mineralisation capacity of osteoblasts decreased whereas resorptive activity of osteoclasts increased. The results confirm the proinflammatory potential of adiponectin and support the idea that adiponectin influences rheumatoid arthritis bone remodelling through alterations in osteoblast and osteoclast.

  3. Transcriptional Analysis of Normal Human Fibroblast Responses to Microgravity Stress

    Institute of Scientific and Technical Information of China (English)

    Yongqing Liu; Eugenia Wang

    2008-01-01

    To understand the molecular mechanism (s) of how spaceflight affects cellular signaling pathways, quiescent normal human WI-38 fibroblasts were flown on the STS-93 space shuttle mission. Subsequently, RNA samples from the space flown and ground-control cells were used to construct two cDNA libraries, which were then processed for suppression subtractive hybridization (SSH) to identify spaceflight-specific gene expression. The SSH data show that key genes related to oxidative stress, DNA repair, and fatty acid oxidation are activated by spaceflight, suggesting the induction of cellular oxidative stress. This is further substantiated by the up-regulation of neuregulin 1 and the calcium-binding protein calmodulin 2. Another obvious stress sign is that spaceflight evokes the Ras/mitogen-activated protein kinase and phosphatidylinositol-3 kinase signaling pathways, along with up-regulating several G1-phase cell cycle traverse genes. Other genes showing up regulation of expression are involved in protein synthesis and pro-apoptosis, as well as pro-survival. Interactome analysis of functionally related genes shows that c-Myc is the "hub" for those genes showing significant changes. Hence, our results suggest that microgravity travel may impact changes in gene expression mostly associated with cellular stress signaling, directing cells to either apoptotic death or premature senescence.

  4. Bridging the species divide: transgenic mice humanized for type-I interferon response.

    Directory of Open Access Journals (Sweden)

    Daniel Harari

    Full Text Available We have generated transgenic mice that harbor humanized type I interferon receptors (IFNARs enabling the study of type I human interferons (Hu-IFN-Is in mice. These "HyBNAR" (Hybrid IFNAR mice encode transgenic variants of IFNAR1 and IFNAR2 with the human extracellular domains being fused to transmembrane and cytoplasmic segments of mouse sequence. B16F1 mouse melanoma cells harboring the HyBNAR construct specifically bound Hu-IFN-Is and were rendered sensitive to Hu-IFN-I stimulated anti-proliferation, STAT1 activation and activation of a prototypical IFN-I response gene (MX2. HyBNAR mice were crossed with a transgenic strain expressing the luciferase reporter gene under the control of the IFN-responsive MX2 promoter (MX2-Luciferase. Both the HyBNAR and HyBNAR/MX2-Luciferase mice were responsive to all Hu-IFN-Is tested, inclusive of IFNα2A, IFNβ, and a human superagonist termed YNSα8. The mice displayed dose-dependent pharmacodynamic responses to Hu-IFN-I injection, as assessed by measuring the expression of IFN-responsive genes. Our studies also demonstrated a weak activation of endogenous mouse interferon response, especially after high dose administration of Hu-IFNs. In sharp contrast to data published for humans, our pharmacodynamic readouts demonstrate a very short-lived IFN-I response in mice, which is not enhanced by sub-cutaneous (SC injections in comparison to other administration routes. With algometric differences between humans and mice taken into account, the HyBNAR mice provides a convenient non-primate pre-clinical model to advance the study of human IFN-Is.

  5. Fractional Diffusion Based Modelling and Prediction of Human Brain Response to External Stimuli

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2015-01-01

    Full Text Available Human brain response is the result of the overall ability of the brain in analyzing different internal and external stimuli and thus making the proper decisions. During the last decades scientists have discovered more about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research, there were fewer efforts which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling and prediction of the human EEG signal, as an alert state of overall human brain activity monitoring, upon receiving external stimuli, based on fractional diffusion equations. The results of this modeling show very good agreement with the real human EEG signal and thus this model can be used for many types of applications such as prediction of seizure onset in patient with epilepsy.

  6. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.

    Science.gov (United States)

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a 'wildlife photographer', resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds.

  7. What is human in humans? Responses from biology, anthropology, and philosophy.

    Science.gov (United States)

    Bibeau, Gilles

    2011-08-01

    Genomics has brought biology, medicine, agriculture, psychology, anthropology, and even philosophy to a new threshold. In this new context, the question about "what is human in humans" may end up being answered by geneticists, specialists of technoscience, and owners of biotech companies. The author defends, in this article, the idea that humanity is at risk in our age of genetic engineering, biotechnologies, and market-geared genetic research; he also argues that the values at the very core of our postgenomic era bring to its peak the science-based ideology that has developed since the time of Galileo, Newton, Descartes, and Harvey; finally, it shows that the bioindustry has invented a new genomythology that goes against the scientific evidence produced by the research in human sciences in which life is interpreted as a language.

  8. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

    NARCIS (Netherlands)

    Oliver, Brian G G; Johnston, Sebastian L; Baraket, Melissa; Burgess, Janette K; King, Nicholas J C; Roth, Michael; Lim, Sam; Black, Judith L

    2006-01-01

    BACKGROUND: Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV) are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscl

  9. Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.

    Science.gov (United States)

    Hartmann, Boris M; Thakar, Juilee; Albrecht, Randy A; Avey, Stefan; Zaslavsky, Elena; Marjanovic, Nada; Chikina, Maria; Fribourg, Miguel; Hayot, Fernand; Schmolke, Mirco; Meng, Hailong; Wetmur, James; García-Sastre, Adolfo; Kleinstein, Steven H; Sealfon, Stuart C

    2015-10-01

    Influenza viruses continue to present global threats to human health. Antigenic drift and shift, genetic reassortment, and cross-species transmission generate new strains with differences in epidemiology and clinical severity. We compared the temporal transcriptional responses of human dendritic cells (DC) to infection with two pandemic (A/Brevig Mission/1/1918, A/California/4/2009) and two seasonal (A/New Caledonia/20/1999, A/Texas/36/1991) H1N1 influenza viruses. Strain-specific response differences included stronger activation of NF-κB following infection with A/New Caledonia/20/1999 and a unique cluster of genes expressed following infection with A/Brevig Mission/1/1918. A common antiviral program showing strain-specific timing was identified in the early DC response and found to correspond with reported transcript changes in blood during symptomatic human influenza virus infection. Comparison of the global responses to the seasonal and pandemic strains showed that a dramatic divergence occurred after 4 h, with only the seasonal strains inducing widespread mRNA loss. Continuously evolving influenza viruses present a global threat to human health; however, these host responses display strain-dependent differences that are incompletely understood. Thus, we conducted a detailed comparative study assessing the immune responses of human DC to infection with two pandemic and two seasonal H1N1 influenza strains. We identified in the immune response to viral infection both common and strain-specific features. Among the stain-specific elements were a time shift of the interferon-stimulated gene response, selective induction of NF-κB signaling by one of the seasonal strains, and massive RNA degradation as early as 4 h postinfection by the seasonal, but not the pandemic, viruses. These findings illuminate new aspects of the distinct differences in the immune responses to pandemic and seasonal influenza viruses. Copyright © 2015, American Society for Microbiology. All

  10. Match mismatch processes underlie human hippocampal responses to associative novelty.

    Science.gov (United States)

    Kumaran, Dharshan; Maguire, Eleanor A

    2007-08-08

    The hippocampus has long been proposed to play a critical role in novelty detection through its ability to act as a comparator between past and present experience. A recent study provided evidence for this hypothesis by characterizing hippocampal responses to sequence novelty, a type of associative novelty where familiar items appear in a new temporal order. Here, we ask whether a hippocampal match-mismatch (i.e., comparator) mechanism operates selectively to identify the violation of predictions within the temporal domain or instead also underlies the processing of associative novelty in other domains (e.g., spatial). We used functional magnetic resonance imaging and a repetition paradigm in which subjects viewed sequences of objects presented in distinct locations on the screen and performed an incidental target detection task. The left hippocampus exhibited a pattern of activity consistent with that of an associative match-mismatch detector, with novelty signals generated only in conditions where one contextual component was novel and the other repeated. In contrast, right hippocampal activation signaled the presence of objects in familiar locations. Our results suggest that hippocampal match-mismatch computations constitute a general mechanism underpinning the processing of associative novelty. These findings support a model in which hippocampal mismatch signals rely critically on the recall of previous experience, a process that only occurs when novel sensory inputs overlap significantly with stored representations. More generally, the current study also offers insights into how the hippocampus automatically represents the spatiotemporal context of our experiences, a function that may relate to its role in episodic memory.

  11. Plasma matrix metalloproteinase-9 response to downhill running in humans.

    Science.gov (United States)

    Welsh, M C; Allen, D L; Byrnes, W C

    2014-05-01

    Matrix metalloproteinase-9 is a proteolytic enzyme capable of degrading proteins of the muscle extracellular matrix. Systemic levels of MMP-9 or its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), have the potential to serve as blood markers of exercise-induced muscle damage. The purpose of this study was to determine if an eccentrically-dominated task, downhill running (DHR), produces changes in plasma MMP-9 or TIMP-1 and examine the relationship between MMP-9/TIMP-1 levels and indirect indicators of muscle damage. Subjects were sedentary (SED, n=12) or had a history of concentrically-biased training (CON, n=9). MMP-9 and TIMP-1 were measured before (Pre-Ex), immediately after (Post-Ex), and 1-, 2-, 4-, and 7-days post-DHR (-10°), and compared to discomfort ratings, creatine kinase activity and strength loss. At 1-day Post-Ex, discomfort increased (5.6 ± 7.8 to 45.5 ± 19.9 mm; 0-100 mm scale), strength decreased (-6.9 ± 1.6%) and CK increased (162.9 ± 177.2%). MMP-9 was modestly but significantly increased at Post-Ex in both CONC and SED (32.7 ± 33.6%) and at 4-days in SED (66.9 ± 88.1%), Individual responses were variable, however. There were no correlations between MMPs and discomfort ratings, plasma CK or strength. While plasma MMP-9 changes may be detectable in the systemic circulation after DHR, they are small and do not correspond to other markers of damage. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Are drug companies living up to their human rights responsibilities? Moving toward assessment.

    Directory of Open Access Journals (Sweden)

    Sofia Gruskin

    2010-09-01

    Full Text Available BACKGROUND TO THE DEBATE: The human rights responsibilities of drug companies have been considered for years by nongovernmental organizations, but were most sharply defined in a report by the UN Special Rapporteur on the right to health, submitted to the United Nations General Assembly in August 2008. The "Human Rights Guidelines for Pharmaceutical Companies in relation to Access to Medicines" include responsibilities for transparency, management, monitoring and accountability, pricing, and ethical marketing, and against lobbying for more protection in intellectual property laws, applying for patents for trivial modifications of existing medicines, inappropriate drug promotion, and excessive pricing. Two years after the release of the Guidelines, the PLoS Medicine Debate asks whether drug companies are living up to their human rights responsibilities. Sofia Gruskin and Zyde Raad from the Harvard School of Public Health say more assessment is needed of such responsibilities; Geralyn Ritter, Vice President of Global Public Policy and Corporate Responsibility at Merck & Co. argues that multiple stakeholders could do more to help States deliver the right to health; and Paul Hunt and Rajat Khosla introduce Mr. Hunt's work as the UN Special Rapporteur on the right to the highest attainable standard of health, regarding the human rights responsibilities of pharmaceutical companies and access to medicines.

  13. Are drug companies living up to their human rights responsibilities? The Merck perspective.

    Directory of Open Access Journals (Sweden)

    Geralyn S Ritter

    2010-09-01

    Full Text Available BACKGROUND TO THE DEBATE: The human rights responsibilities of drug companies have been considered for years by nongovernmental organizations, but were most sharply defined in a report by the UN Special Rapporteur on the right to health, submitted to the United Nations General Assembly in August 2008. The "Human Rights Guidelines for Pharmaceutical Companies in relation to Access to Medicines" include responsibilities for transparency, management, monitoring and accountability, pricing, and ethical marketing, and against lobbying for more protection in intellectual property laws, applying for patents for trivial modifications of existing medicines, inappropriate drug promotion, and excessive pricing. Two years after the release of the Guidelines, the PLoS Medicine Debate asks whether drug companies are living up to their human rights responsibilities. Sofia Gruskin and Zyde Raad from the Harvard School of Public Health say more assessment is needed of such responsibilities; Geralyn Ritter, Vice President of Global Public Policy and Corporate Responsibility at Merck & Co. argues that multiple stakeholders could do more to help States deliver the right to health; and Paul Hunt and Rajat Khosla introduce Mr. Hunt's work as the UN Special Rapporteur on the right to the highest attainable standard of health, regarding the human rights responsibilities of pharmaceutical companies and access to medicines.

  14. Actin-myosin contractility is responsible for the reduced viability of dissociated human embryonic stem cells.

    Science.gov (United States)

    Chen, Guokai; Hou, Zhonggang; Gulbranson, Daniel R; Thomson, James A

    2010-08-06

    Human ESCs are the pluripotent precursor of the three embryonic germ layers. Human ESCs exhibit basal-apical polarity, junctional complexes, integrin-dependent matrix adhesion, and E-cadherin-dependent cell-cell adhesion, all characteristics shared by the epiblast epithelium of the intact mammalian embryo. After disruption of epithelial structures, programmed cell death is commonly observed. If individualized human ESCs are prevented from reattaching and forming colonies, their viability is significantly reduced. Here, we show that actin-myosin contraction is a critical effector of the cell death response to human ESC dissociation. Inhibition of myosin heavy chain ATPase, downregulation of myosin heavy chain, and downregulation of myosin light chain all increase survival and cloning efficiency of individualized human ESCs. ROCK inhibition decreases phosphorylation of myosin light chain, suggesting that inhibition of actin-myosin contraction is also the mechanism through which ROCK inhibitors increase cloning efficiency of human ESCs.

  15. Human T cell responses induced by vaccination with Mycobacterium bovis bacillus Calmette-Guérin

    DEFF Research Database (Denmark)

    Ravn, P; Boesen, H; Pedersen, B K

    1997-01-01

    depending on the prevaccination sensitivity to PPD. Previously sensitized donors mounted a potent and highly accelerated recall response within the first week of BCG vaccination. Nonsensitized donors, in contrast, exhibited a gradually increasing responsiveness to mycobacterial Ags, reaching maximal levels...... have studied in vitro cell-mediated immune responses primed by BCG vaccination in 22 healthy Danish donors with different levels of in vitro purified protein derivative (PPD) reactivity before vaccination. The study demonstrated a markedly different development of reactivity to mycobacterial Ags...... important data on potentially protective immune responses in humans and suggest a careful evaluation of prevaccination sensitivity when investigating vaccine-induced immunity....

  16. Medullary Endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression.

    Science.gov (United States)

    Schaich, Chris L; Grabenauer, Megan; Thomas, Brian F; Shaltout, Hossam A; Gallagher, Patricia E; Howlett, Allyn C; Diz, Debra I

    2016-01-01

    CB1 cannabinoid receptors are expressed on vagal afferent fibers and neurons within the solitary tract nucleus (NTS), providing anatomical evidence for their role in arterial baroreflex modulation. To better understand the relationship between the brain renin-angiotensin system (RAS) and endocannabinoid expression within the NTS, we measured dorsal medullary endocannabinoid tissue content and the effects of CB1 receptor blockade at this brain site on cardiac baroreflex sensitivity (BRS) in ASrAOGEN rats with low glial angiotensinogen, normal Sprague-Dawley rats and (mRen2)27 rats with upregulated brain RAS expression. Mass spectrometry revealed higher levels of the endocannabinoid 2-arachidonoylglycerol in (mRen2)27 compared to ASrAOGEN rats (2.70 ± 0.28 vs. 1.17 ± 0.09 ng/mg tissue; P < 0.01), while Sprague-Dawley rats had intermediate content (1.85 ± 0.27 ng/mg tissue). Microinjection of the CB1receptor antagonist SR141716A (36 pmol) into the NTS did not change cardiac BRS in anesthetized Sprague-Dawley rats (1.04 ± 0.05 ms/mmHg baseline vs. 1.17 ± 0.11 ms/mmHg after 10 min). However, SR141716A in (mRen2)27 rats dose-dependently improved BRS in this strain: 0.36 pmol of SR141716A increased BRS from 0.43 ± 0.03 to 0.71 ± 0.04 ms/mmHg (P < 0.001), and 36 pmol of SR141716A increased BRS from 0.47 ± 0.02 to 0.94 ± 0.10 ms/mmHg (P < 0.01). In contrast, 0.36 pmol (1.50 ± 0.12 vs. 0.86 ± 0.08 ms/mmHg; P < 0.05) and 36 pmol (1.38 ± 0.16 vs. 0.46 ± 0.003 ms/mmHg; P < 0.01) of SR141716A significantly reduced BRS in ASrAOGEN rats. These observations reveal differential dose-related effects of the brain endocannabinoid system that influence cardiovagal BRS in animals with genetic alterations in the brain RAS.

  17. Influence of cigarette smoking on human autonomic function

    Science.gov (United States)

    Niedermaier, O. N.; Smith, M. L.; Beightol, L. A.; Zukowska-Grojec, Z.; Goldstein, D. S.; Eckberg, D. L.

    1993-01-01

    BACKGROUND. Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control. METHODS AND RESULTS. We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change. CONCLUSIONS. In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.

  18. Immunoproteomic analysis of human serological antibody responses to vaccination with whole-cell pertussis vaccine (WCV.

    Directory of Open Access Journals (Sweden)

    Yong-Zhang Zhu

    Full Text Available BACKGROUND: Pertussis (whooping cough caused by Bordetella pertussis (B.p, continues to be a serious public health threat. Vaccination is the most economical and effective strategy for preventing and controlling pertussis. However, few systematic investigations of actual human immune responses to pertussis vaccines have been performed. Therefore, we utilized a combination of two-dimensional electrophoresis (2-DE, immunoblotting, and mass spectrometry to reveal the entire antigenic proteome of whole-cell pertussis vaccine (WCV targeted by the human immune system as a first step toward evaluating the repertoire of human humoral immune responses against WCV. METHODOLOGY/PRINCIPAL FINDINGS: Immunoproteomic profiling of total membrane enriched proteins and extracellular proteins of Chinese WCV strain 58003 identified a total of 30 immunoreactive proteins. Seven are known pertussis antigens including Pertactin, Serum resistance protein, chaperonin GroEL and two OMP porins. Sixteen have been documented to be immunogenic in other pathogens but not in B.p, and the immunogenicity of the last seven proteins was found for the first time. Furthermore, by comparison of the human and murine immunoproteomes of B.p, with the exception of four human immunoreactive proteins that were also reactive with mouse immune sera, a unique group of antigens including more than 20 novel immunoreactive proteins that uniquely reacted with human immune serum was confirmed. CONCLUSIONS/SIGNIFICANCE: This study is the first time that the repertoire of human serum antibody responses against WCV was comprehensively investigated, and a small number of previously unidentified antigens of WCV were also found by means of the classic immunoproteomic strategy. Further research on these newly identified predominant antigens of B.p exclusively against humans will not only remarkably accelerate the development of diagnostic biomarkers and subunit vaccines but also provide detailed insight

  19. A Return to the Human in Humanism: A Response to Hansen's Humanistic Vision

    Science.gov (United States)

    Lemberger, Matthew E.

    2012-01-01

    In his extension of the humanistic vision, Hansen (2012) recommends that counseling practitioners and scholars adopt operations that are consistent with his definition of a multiple-perspective philosophy. Alternatively, the author of this article believes that Hansen has reduced the capacity of the human to interpret meaning through quantitative…

  20. Human infant faces provoke implicit positive affective responses in parents and non-parents alike.

    Directory of Open Access Journals (Sweden)

    Vincenzo Paolo Senese

    Full Text Available Human infants' complete dependence on adult caregiving suggests that mechanisms associated with adult responsiveness to infant cues might be deeply embedded in the brain. Behavioural and neuroimaging research has produced converging evidence for adults' positive disposition to infant cues, but these studies have not investigated directly the valence of adults' reactions, how they are moderated by biological and social factors, and if they relate to child caregiving. This study examines implicit affective responses of 90 adults toward faces of human and non-human (cats and dogs infants and adults. Implicit reactions were assessed with Single Category Implicit Association Tests, and reports of childrearing behaviours were assessed by the Parental Style Questionnaire. The results showed that human infant faces represent highly biologically relevant stimuli that capture attention and are implicitly associated with positive emotions. This reaction holds independent of gender and parenthood status and is associated with ideal parenting behaviors.

  1. Antibody-Independent Function of Human B Cells Contributes to Antifungal T Cell Responses.

    Science.gov (United States)

    Li, Rui; Rezk, Ayman; Li, Hulun; Gommerman, Jennifer L; Prat, Alexandre; Bar-Or, Amit

    2017-03-08

    Fungal infections (e.g., Candida albicans) can manifest as serious medical illnesses, especially in the elderly and immune-compromised hosts. T cells are important for Candida control. Whether and how B cells are involved in antifungal immunity has been less clear. Although patients with agammaglobulinemia exhibit normal antifungal immunity, increased fungal infections are reported following B cell-depleting therapy, together pointing to Ab-independent roles of B cells in controlling such infections. To test how human B cells may contribute to fungal-associated human T cell responses, we developed a novel Ag-specific human T cell/B cell in vitro coculture system and found that human B cells could induce C. albicans-associated, MHC class II-restricted responses of naive T cells. Activated B cells significantly enhanced C. albicans-mediated Th1 and Th17 T cell responses, which were both strongly induced by CD80/CD86 costimulation. IL-6(+)GM-CSF(+) B cells were the major responding B cell subpopulation to C. albicans and provided efficient costimulatory signals to the T cells. In vivo B cell depletion in humans resulted in reduced C. albicans-associated T responses. Of note, the decreased Th17, but not Th1, responses could be reversed by soluble factors from B cells prior to depletion, in an IL-6-dependent manner. Taken together, our results implicate an Ab-independent cytokine-defined B cell role in human antifungal T cell responses. These findings may be particularly relevant given the prospects of chronic B cell depletion therapy use in lymphoma and autoimmune disease, as patients age and are exposed to serial combination therapies.

  2. To what degree could responsible mining play a role to prevent human rights violations arising from the industry? : A human rights law perspective

    OpenAIRE

    Nguyen, Mai

    2012-01-01

    The study primarily aims to address the legal consequences of the rise of responsible mining and responsible mining itself to international human rights law in regulating the mining industry. Firstly, the thesis describes the rise of responsible mining in the context of considerable power of the industry and mining companies. Secondly, the thesis explains how international human rights law governs the mining industry and whereabouts responsible mining could be in the system. Thirdly, the t...

  3. Species-specific responses of Late Quaternary megafauna to climate and humans

    DEFF Research Database (Denmark)

    Lorenzen, Eline D; Nogués-Bravo, David; Orlando, Ludovic

    2011-01-01

    the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human...... signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change....

  4. Radiation response of mesenchymal stem cells derived from bone marrow and human pluripotent stem cells

    OpenAIRE

    Islam, Mohammad S; Stemig, Melissa E.; Takahashi, Yutaka; Hui, Susanta K.

    2014-01-01

    Mesenchymal stem cells (MSCs) isolated from human pluripotent stem cells are comparable with bone marrow-derived MSCs in their function and immunophenotype. The purpose of this exploratory study was comparative evaluation of the radiation responses of mesenchymal stem cells derived from bone marrow- (BMMSCs) and from human embryonic stem cells (hESMSCs). BMMSCs and hESMSCs were irradiated at 0 Gy (control) to 16 Gy using a linear accelerator commonly used for cancer treatment. Cells were harv...

  5. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds

    OpenAIRE

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J.

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breedin...

  6. Cephalic Phase Pancreatic Polypeptide Responses to Liquid and Solid Stimuli in Humans

    OpenAIRE

    TEFF, KAREN L.

    2009-01-01

    The hormone, pancreatic polypeptide (PP) is postulated to be involved in body weight regulation. PP release is dependent on vagal activation and is a marker of vagal efferent activity. Because vagal activity plays a role in glucose homeostasis, elucidating the conditions of activation has important implications for nutrient metabolism. In humans, modified sham-feeding is known to elicit vagally-mediated hormonal responses. We present results of 3 studies in which healthy human subjects tasted...

  7. Electrophysiological and hemodynamic mismatch responses in rats listening to human speech syllables

    Science.gov (United States)

    Dehaene-Lambertz, Ghislaine; Wallois, Fabrice

    2017-01-01

    Speech is a complex auditory stimulus which is processed according to several time-scales. Whereas consonant discrimination is required to resolve rapid acoustic events, voice perception relies on slower cues. Humans, right from preterm ages, are particularly efficient to encode temporal cues. To compare the capacities of preterms to those observed in other mammals, we tested anesthetized adult rats by using exactly the same paradigm as that used in preterm neonates. We simultaneously recorded neural (using ECoG) and hemodynamic responses (using fNIRS) to series of human speech syllables and investigated the brain response to a change of consonant (ba vs. ga) and to a change of voice (male vs. female). Both methods revealed concordant results, although ECoG measures were more sensitive than fNIRS. Responses to syllables were bilateral, but with marked right-hemispheric lateralization. Responses to voice changes were observed with both methods, while only ECoG was sensitive to consonant changes. These results suggest that rats more effectively processed the speech envelope than fine temporal cues in contrast with human preterm neonates, in whom the opposite effects were observed. Cross-species comparisons constitute a very valuable tool to define the singularities of the human brain and species-specific bias that may help human infants to learn their native language. PMID:28291832

  8. CORPORATE SOCIAL RESPONSIBILITY AS A COMPETITIVE STRATEGY: THE CASE OF HUMAN COMPANY

    Directory of Open Access Journals (Sweden)

    Daniela Castro Murillo

    2013-07-01

    Full Text Available Human Company, a 100% Costa Rican business, through its brand Eco Sunrise has achieved to produce biodegradable goods under a socially responsible approach. This paper is aimed at evaluating how these practices influence the Company’s competitiveness levels using the PRISMA method and the CINBAGE matrix. Therefore, the general objective is to determine whether Corporate Social Responsibility (CSR is a competitive strategy for Human Company, for which the Company must identify advantages and obstacles faced by SMEs in regards to CSR, evaluate each of the areas comprising the Company’s CSR, quantify the Company´s competitiveness, and determine how CSR influences competitiveness.

  9. Histologic Evaluation of Human Pulp Response to Total Etch and Self Etch Adhesive Systems

    OpenAIRE

    Malekipour, Mohammad Reza; Razavi, Sayed Mohammad; Khazaei, Saber; Kazemi, Shantia; Behnamanesh, Maryam; Shirani, Farzaneh

    2013-01-01

    Background To investigate pulp response to the application of two types adhesive systems (total-etch and self-etch) in human premolar teeth. Materials and Methods Cavities limited to enamel walls in all margins with 2.5 mm depth were prepared on buccal surfaces of thirty three human premolars. The cavities were treated with the following adhesive. Single Bond (SB) and Prompt L-Pop (PLP). The teeth were extracted after 30 days and prepared due to histological technique. Results Pulp responses ...

  10. Integrative genomic analysis of the human immune response to influenza vaccination

    Science.gov (United States)

    Franco, Luis M; Bucasas, Kristine L; Wells, Janet M; Niño, Diane; Wang, Xueqing; Zapata, Gladys E; Arden, Nancy; Renwick, Alexander; Yu, Peng; Quarles, John M; Bray, Molly S; Couch, Robert B; Belmont, John W; Shaw, Chad A

    2013-01-01

    Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits. DOI: http://dx.doi.org/10.7554/eLife.00299.001 PMID:23878721

  11. Discrimination of human and dog faces and inversion responses in domestic dogs (Canis familiaris).

    Science.gov (United States)

    Racca, Anaïs; Amadei, Eleonora; Ligout, Séverine; Guo, Kun; Meints, Kerstin; Mills, Daniel

    2010-05-01

    Although domestic dogs can respond to many facial cues displayed by other dogs and humans, it remains unclear whether they can differentiate individual dogs or humans based on facial cues alone and, if so, whether they would demonstrate the face inversion effect, a behavioural hallmark commonly used in primates to differentiate face processing from object processing. In this study, we first established the applicability of the visual paired comparison (VPC or preferential looking) procedure for dogs using a simple object discrimination task with 2D pictures. The animals demonstrated a clear looking preference for novel objects when simultaneously presented with prior-exposed familiar objects. We then adopted this VPC procedure to assess their face discrimination and inversion responses. Dogs showed a deviation from random behaviour, indicating discrimination capability when inspecting upright dog faces, human faces and object images; but the pattern of viewing preference was dependent upon image category. They directed longer viewing time at novel (vs. familiar) human faces and objects, but not at dog faces, instead, a longer viewing time at familiar (vs. novel) dog faces was observed. No significant looking preference was detected for inverted images regardless of image category. Our results indicate that domestic dogs can use facial cues alone to differentiate individual dogs and humans and that they exhibit a non-specific inversion response. In addition, the discrimination response by dogs of human and dog faces appears to differ with the type of face involved.

  12. Review on modeling heat transfer and thermoregulatory responses in human body.

    Science.gov (United States)

    Fu, Ming; Weng, Wenguo; Chen, Weiwang; Luo, Na

    2016-12-01

    Several mathematical models of human thermoregulation have been developed, contributing to a deep understanding of thermal responses in different thermal conditions and applications. In these models, the human body is represented by two interacting systems of thermoregulation: the controlling active system and the controlled passive system. This paper reviews the recent research of human thermoregulation models. The accuracy and scope of the thermal models are improved, for the consideration of individual differences, integration to clothing models, exposure to cold and hot conditions, and the changes of physiological responses for the elders. The experimental validated methods for human subjects and manikin are compared. The coupled method is provided for the manikin, controlled by the thermal model as an active system. Computational Fluid Dynamics (CFD) is also used along with the manikin or/and the thermal model, to evaluate the thermal responses of human body in various applications, such as evaluation of thermal comfort to increase the energy efficiency, prediction of tolerance limits and thermal acceptability exposed to hostile environments, indoor air quality assessment in the car and aerospace industry, and design protective equipment to improve function of the human activities.

  13. Human cytomegalovirus induces a distinct innate immune response in the maternal-fetal interface.

    Science.gov (United States)

    Weisblum, Yiska; Panet, Amos; Zakay-Rones, Zichria; Vitenshtein, Alon; Haimov-Kochman, Ronit; Goldman-Wohl, Debra; Oiknine-Djian, Esther; Yamin, Rachel; Meir, Karen; Amsalem, Hagai; Imbar, Tal; Mandelboim, Ofer; Yagel, Simcha; Wolf, Dana G

    2015-11-01

    The initial interplay between human cytomegalovirus (HCMV) and innate tissue response in the human maternal-fetal interface, though crucial for determining the outcome of congenital HCMV infection, has remained unknown. We studied the innate response to HCMV within the milieu of the human decidua, the maternal aspect of the maternal-fetal interface, maintained ex vivo as an integral tissue. HCMV infection triggered a rapid and robust decidual-tissue innate immune response predominated by interferon (IFN)γ and IP-10 induction, dysregulating the decidual cytokine/chemokine environment in a distinctive fashion. The decidual-tissue response was already elicited during viral-tissue contact, and was not affected by neutralizing HCMV antibodies. Of note, IFNγ induction, reflecting immune-cell activation, was distinctive to the maternal decidua, and was not observed in concomitantly-infected placental (fetal) villi. Our studies in a clinically-relevant surrogate human model, provide a novel insight into the first-line decidual tissue response which could affect the outcome of congenital infection.

  14. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  15. Brazilian response to the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic among injection drug users.

    Science.gov (United States)

    Mesquita, Fábio; Doneda, Denise; Gandolfi, Denise; Nemes, Maria Inês Battistella; Andrade, Tarcísio; Bueno, Regina; Piconez e Trigueiros, Daniela

    2003-12-15

    The Brazilian response to the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic is being observed all over the world because of its success. Understanding the role of injection drug users (IDUs) in the epidemic and the political response thereto is a key factor in the control of the epidemic in Brazil. This paper summarizes some of the most important analyses of the Brazilian response to the HIV/AIDS epidemic among and from IDUs. Key elements of the response include the support of the Brazilian Universal Public Health System, the provision of universal access to highly active antiretroviral therapy, and the creation of harm reduction projects that are politically and financially supported by the federal government. The response among and from IDUs is a key element in overall control of the HIV/AIDS epidemic. The response to the epidemic among and from IDUs has been headed in the correct direction since its beginning and is now being intensively expanded.

  16. Lipoproteins are Major Targets of the Polyclonal Human T-cell Response to M. tuberculosis1

    OpenAIRE

    2012-01-01

    Most vaccines and basic studies of T cell epitopes in M. tuberculosis emphasize water soluble proteins that are secreted into the extracellular space and presented in the context of MHC Class II. Much less is known about the role of antigens retained within the cell wall. We used polyclonal T cells from infected humans to probe for responses to immunodominant antigens in the M. tuberculosis cell wall. We found that the magnitude of response to secreted or cell wall intrinsic compounds was sim...

  17. A Unified Probabilistic Framework for Dose–Response Assessment of Human Health Effects

    OpenAIRE

    Chiu, Weihsueh A.; Slob, Wout

    2015-01-01

    Background When chemical health hazards have been identified, probabilistic dose–response assessment (“hazard characterization”) quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. Objectives We developed a unified framework for probabilistic dose–response assessment. Methods We established a framework based on four principles: a) indiv...

  18. Human response and adaptation to drought in the arid zone: lessons from southern Africa

    OpenAIRE

    W. R.J. Dean; S. J. Milton; P.J. O'Farrell; P. M.L. Anderson

    2009-01-01

    Human adaptation and response to drought is primarily through evasion or endurance. A review of historical agricultural practices in southern Africa demonstrates evidence of drought evasion response strategies in well-established transhumance routes, where herders move livestock on a seasonal basis in order to exploit resources subject to different climatic regimes. European settlers to the arid regions of South Africa quickly recognised the necessity of these evasion options to survive droug...

  19. Inter-Individual Variability in Human Response to Low-Dose Ionizing Radiation, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Rocke, David [Univ. of California, Davis, CA (United States)

    2016-08-01

    In order to investigate inter-individual variability in response to low-dose ionizing radiation, we are working with three models, 1) in-vivo irradiated human skin, for which we have a realistic model, but with few subjects, all from a previous project, 2) ex-vivo irradiated human skin, for which we also have a realistic model, though with the limitations involved in keeping skin pieces alive in media, and 3) MatTek EpiDermFT skin plugs, which provides a more realistic model than cell lines, which is more controllable than human samples.

  20. Characterising the mucosal and systemic immune responses to experimental human hookworm infection.

    Directory of Open Access Journals (Sweden)

    Soraya Gaze

    2012-02-01

    Full Text Available The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13 and regulatory (IL-10 and TGF-β response, with some evidence of a Th1 (IFN-γ and IL-2 response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17 response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases.

  1. Teaching baroreflex physiology to medical students: a comparison of quiz-based and conventional teaching strategies in a laboratory exercise.

    Science.gov (United States)

    Berg, Ronan M G; Plovsing, Ronni R; Damgaard, Morten

    2012-06-01

    Quiz-based and collaborative teaching strategies have previously been found to be efficient for the improving meaningful learning of physiology during lectures. These approaches have, however, not been investigated during laboratory exercises. In the present study, we compared the impact of solving quizzes individually and in groups with conventional teaching on the immediate learning during a laboratory exercise. We implemented two quizzes in a mandatory 4-h laboratory exercise on baroreflex physiology. A total of 155 second-year medical students were randomized to solve quizzes individually (intervention group I, n = 57), in groups of three to four students (intervention group II, n = 56), or not to perform any quizzes (control; intervention group III, n = 42). After the laboratory exercise, all students completed an individual test, which encompassed two recall questions, two intermediate questions, and two integrated questions. The integrated questions were of moderate and advanced difficulty, respectively. Finally, students completed an evaluation form. Intervention group I reached the highest total test scores and proved best at answering the integrated question of advanced difficulty. Moreover, there was an overall difference between groups for student evaluations of the quality of the teaching, which was highest for intervention group II. In conclusion, solving quizzes individually during a laboratory exercise may enhance learning, whereas solving quizzes in groups is associated with higher student satisfaction.

  2. Blood pressure, baroreflex sensitivity, and end organ damage in hybrid offspring of spontaneously hypertensive rats and Sprague-Dawley rats

    Institute of Scientific and Technical Information of China (English)

    He-hui XIE; Fu-ming SHEN; Chao-yu MIAO; Ding-feng SU

    2005-01-01

    Aim: To investigate the blood pressure (BP), baroreflex sensitivity (BRS), and organ damage in hybrids of spontaneously hypertensive rats and Sprague-Dawley rats. Methods: Spontaneously hypertensive rats and Sprague-Dawley rats were crossbred, and the F1 hybrids were inbred randomly to produce an F2 generation.At the age of 52 weeks, the F1 and F2 hybrids were tested to determine BP and BRS in a conscious state. Histopathological examinations were carried out after BP recording and BRS studies. Results: BP and BRS were not different in F1 and F2 hybrids. BRS was inversely related to systolic BP (SBP) in male, female, or whole populations of hybrids. Quantitatively, BRS values were one-third determined by SBP level (the determinant coefficient was 0.326). The indexes for left ventricular hypertrophy, aortic hypertrophy, and renal damage were all positively related to BP, and negatively related to BRS. In multiple-regression analysis, left ventricular and aortic hypertrophy and glomerulosclerosis score were all most significantly associated with lower BRS and higher systolic BP. The contribution of BRS to left ventricular and aortic hypertrophy and glomerulosclerosis was greater than that of SBP. Conclusion: The present work with hybrid rats demonstrated quantitatively that the BRS value was one-third determined by SBP level. Both BP level and BRS value contributed greatly to the hypertensive organ damage. However,the contribution of BRS to the hypertensive organ damage was greater than that of BP level in these rats.

  3. Thermoregulatory responses in exercising rats: methodological aspects and relevance to human physiology.

    Science.gov (United States)

    Wanner, Samuel Penna; Prímola-Gomes, Thales Nicolau; Pires, Washington; Guimarães, Juliana Bohnen; Hudson, Alexandre Sérvulo Ribeiro; Kunstetter, Ana Cançado; Fonseca, Cletiana Gonçalves; Drummond, Lucas Rios; Damasceno, William Coutinho; Teixeira-Coelho, Francisco

    2015-01-01

    Rats are used worldwide in experiments that aim to investigate the physiological responses induced by a physical exercise session. Changes in body temperature regulation, which may affect both the performance and the health of exercising rats, are evident among these physiological responses. Despite the universal use of rats in biomedical research involving exercise, investigators often overlook important methodological issues that hamper the accurate measurement of clear thermoregulatory responses. Moreover, much debate exists regarding whether the outcome of rat experiments can be extrapolated to human physiology, including thermal physiology. Herein, we described the impact of different exercise intensities, durations and protocols and environmental conditions on running-induced thermoregulatory changes. We focused on treadmill running because this type of exercise allows for precise control of the exercise intensity and the measurement of autonomic thermoeffectors associated with heat production and loss. Some methodological issues regarding rat experiments, such as the sites for body temperature measurements and the time of day at which experiments are performed, were also discussed. In addition, we analyzed the influence of a high body surface area-to-mass ratio and limited evaporative cooling on the exercise-induced thermoregulatory responses of running rats and then compared these responses in rats to those observed in humans. Collectively, the data presented in this review represent a reference source for investigators interested in studying exercise thermoregulation in rats. In addition, the present data indicate that the thermoregulatory responses of exercising rats can be extrapolated, with some important limitations, to human thermal physiology.

  4. Potent innate immune response to pathogenic leptospira in human whole blood.

    Directory of Open Access Journals (Sweden)

    Marga G A Goris

    Full Text Available BACKGROUND: Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. Not much is known about the innate immune response to leptospires during haematogenous dissemination. Previous work showed that a human THP-1 cell line recognized heat-killed leptospires and leptospiral LPS through TLR2 instead of TLR4. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the host response and killing of virulent and non-virulent Leptospira of different serovars by human THP-1 cells, human PBMC's and human whole blood. Virulence of each leptospiral strain was tested in a well accepted standard guinea pig model. Virulent leptospires displayed complement resistance in human serum and whole blood while in-vitro attenuated non-virulent leptospires were rapidly killed in a complement dependent manner. In vitro stimulation of THP-1 and PBMC's with heat-killed and living leptospires showed differential serovar and cell type dependence of cytokine induction. However, at low, physiological, leptospiral dose, living virulent complement resistant strains were consistently more potent in whole blood stimulations than the corresponding non-virulent complement sensitive strains. At higher dose living virulent and non-virulent leptospires were equipotent in whole blood. Inhibition of different TLRs indicated that both TLR2 and TLR4 as well as TLR5 play a role in the whole blood cytokine response to living leptospires. CONCLUSIONS/SIGNIFICANCE: Thus, in a minimally altered system as human whole blood, highly virulent Leptospira are potent inducers of the cytokine response.

  5. Human and laboratory rodent low response to alcohol: is better consilience possible?

    Science.gov (United States)

    Crabbe, John C; Bell, Richard L; Ehlers, Cindy L

    2010-04-01

    If people are brought into the laboratory and given alcohol, there are pronounced differences among individuals in many responses to the drug. Some participants in alcohol challenge protocols show a cluster of 'low level of responses to alcohol' determined by observing post-drinking-related changes in subjective, motor and physiological effects at a given dose level. Those individuals characterized as having low level of response (LR) to alcohol have been shown to be at increased risk for a lifetime diagnosis of alcohol dependence (AD), and this relationship between low LR and AD appears to be in part genetic. LR to alcohol is an area where achieving greater consilience between the human and the rodent phenotypes would seem to be highly likely. However, despite extensive data from both human and rodent studies, few attempts have been made to evaluate the human and animal data systematically in order to understand which aspects of LR appear to be most directly comparable across species and thus the most promising for further study. We review four general aspects of LR that could be compared between humans and laboratory animals: (1) behavioral measures of subjective intoxication; (2) body sway; (3) endocrine responses; and (4) stimulant, autonomic and electrophysiological responses. None of these aspects of LR provide completely face-valid direct comparisons across species. Nevertheless, one of the most replicated findings in humans is the low subjective response, but, as it may reflect either aversively valenced and/or positively valenced responses to alcohol as usually assessed, it is unclear which rodent responses are analogous. Stimulated heart rate appears to be consistent in animal and human studies, although at-risk subjects appear to be more rather than less sensitive to alcohol using this measure. The hormone and electrophysiological data offer strong possibilities of understanding the neurobiological mechanisms, but the rodent data in particular are rather

  6. Brain response to a humanoid robot in areas implicated in the perception of human emotional gestures.

    Directory of Open Access Journals (Sweden)

    Thierry Chaminade

    Full Text Available BACKGROUND: The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents. METHODOLOGY: Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted. PRINCIPAL FINDINGS: Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca's area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance. CONCLUSIONS: Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions. SIGNIFICANCE: Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions.

  7. Barcoding heat shock proteins to human diseases : looking beyond the heat shock response

    NARCIS (Netherlands)

    Kakkar, Vaishali; Meister-Broekema, Melanie; Minoia, Melania; Carra, Serena; Kampinga, Harm H.

    There are numerous human diseases that are associated with protein misfolding and the formation of toxic protein aggregates. Activating the heat shock response (HSR) - and thus generally restoring the disturbed protein homeostasis associated with such diseases - has often been suggested as a

  8. Ingested human insulin inhibits the mosquito NF-¿B-dependent immune response to Plasmodium falciparum

    Science.gov (United States)

    We showed previously that ingested human insulin activates the insulin/IGF-1 signaling pathway in Anopheles stephensi and increases the susceptibility of these mosquitoes to Plasmodium falciparum. In other organisms insulin can alter immune responsiveness through regulation of NF-kB transcription fa...

  9. The Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M;

    2015-01-01

    CA following lipopolysaccharide (LPS) infusion, a human-experimental model of the systemic inflammatory response during early sepsis. The dCA in eight healthy males was examined prior to and during an intended noradrenaline-induced MAP increase of approximately 30 mmHg. This was performed at baseline...... neuroprotective effect by enhancing dCA in patients with early sepsis....

  10. Earthworms and Humans in Vitro: Characterizing Evolutionarily Conserved Stress and Immune Responses to Silver Nanoparticles

    DEFF Research Database (Denmark)

    Hayashi, Yuya; Engelmann, Péter; Foldbjerg, Rasmus

    2012-01-01

    Little is known about the potential threats of silver nanoparticles (AgNPs) to ecosystem health, with no detailed report existing on the stress and immune responses of soil invertebrates. Here we use earthworm primary cells, cross-referencing to human cell cultures with a particular emphasis on t...

  11. Grassroots Responsiveness to Human Rights Abuse: History of the Washtenaw Interfaith Coalition for Immigrant Rights

    Science.gov (United States)

    Sanders, Laura; Martinez, Ramiro; Harner, Margaret; Harner, Melanie; Horner, Pilar; Delva, Jorge

    2013-01-01

    The purpose of this article is to discuss how a community agency based in Washtenaw County, the Washtenaw Interfaith Coalition for Immigration Rights (WICIR), emerged in response to increasing punitive immigration practices and human rights abuses toward the Latino community. The article discusses how WICIR is engaged in advocacy, community…

  12. CargoVibes: human response to vibration due to freight rail traffic

    NARCIS (Netherlands)

    Waddington, D.; Woodcock, J.; Smith, M.G.; Janssen, S.A.; Persson Waye, K.

    2015-01-01

    The aim of this paper is to present an overview of the research concerning human response to vibration conducted in the EU FP7 CargoVibes project. The European Union-funded project CargoVibes involved 10 partners from 8 nations and ran from April 2011 to April 2014. The project was concerned with ra

  13. Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans

    DEFF Research Database (Denmark)

    Asghar, Mohammed Sohail; Hansen, Adam E; Pedersen, Simon;

    2011-01-01

    To examine the effect of acetazolamide, known to increase cerebral blood flow (CBF) and glyceryl trinitrate (GTN), known to increase cerebral blood volume (CBV) on the blood oxygenation level-dependent (BOLD) response in humans using 3 T magnetic resonance imaging (MRI), and to evaluate how...

  14. Response of growth and myogenic factors in human skeletal muscle to strength training

    NARCIS (Netherlands)

    Liu, Y.; Heinichen, M.; Wirth, K.; Schmidtbleicher, D.; Steinacker, J. M.

    2008-01-01

    Objective: To investigate the response to different strength training techniques of growth and myogenic factors in human skeletal muscle, with particular emphasis on satellite cell (SC) activation. Methods: 24 volunteers were divided into two groups and performed a 6-week strength training (group A

  15. CargoVibes: human response to vibration due to freight rail traffic

    NARCIS (Netherlands)

    Waddington, D.; Woodcock, J.; Smith, M.G.; Janssen, S.A.; Persson Waye, K.

    2015-01-01

    The aim of this paper is to present an overview of the research concerning human response to vibration conducted in the EU FP7 CargoVibes project. The European Union-funded project CargoVibes involved 10 partners from 8 nations and ran from April 2011 to April 2014. The project was concerned with

  16. Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans

    DEFF Research Database (Denmark)

    Asghar, Mohammed Sohail; Hansen, Adam E; Pedersen, Simon;

    2011-01-01

    To examine the effect of acetazolamide, known to increase cerebral blood flow (CBF) and glyceryl trinitrate (GTN), known to increase cerebral blood volume (CBV) on the blood oxygenation level-dependent (BOLD) response in humans using 3 T magnetic resonance imaging (MRI), and to evaluate how pharm...... pharmacological agents may modulate cerebral hemodynamic and thereby possibly the BOLD signal....

  17. Grassroots Responsiveness to Human Rights Abuse: History of the Washtenaw Interfaith Coalition for Immigrant Rights

    Science.gov (United States)

    Sanders, Laura; Martinez, Ramiro; Harner, Margaret; Harner, Melanie; Horner, Pilar; Delva, Jorge

    2013-01-01

    The purpose of this article is to discuss how a community agency based in Washtenaw County, the Washtenaw Interfaith Coalition for Immigration Rights (WICIR), emerged in response to increasing punitive immigration practices and human rights abuses toward the Latino community. The article discusses how WICIR is engaged in advocacy, community…

  18. Learning Agreements and Socially Responsible Approaches to Professional and Human Resource Development in the United Kingdom

    Science.gov (United States)

    Wallis, Emma

    2008-01-01

    This article draws upon original qualitative data to present an initial assessment of the significance of learning agreements for the development of socially responsible approaches to professional and human resource development within the workplace. The article suggests that the adoption of a partnership-based approach to learning is more…

  19. Evaluation of on-farm veal calves' responses to unfamiliar humans and potential influencing factors

    NARCIS (Netherlands)

    Leruste, H.; Bokkers, E.A.M.; Heutinck, L.F.M.; Wolthuis-Fillerup, M.; Werf, van der J.T.N.; Brscic, M.; Cozzi, G.; Engel, B.; Reenen, van C.G.; Lensink, B.J.

    2012-01-01

    The human–animal relationship is an important component of the welfare of farm animals and for this reason animal responsiveness tests to humans are included in on-farm welfare assessment schemes that provide indicators for this. However, apart from the behaviour of stockpersons towards their

  20. Metabolomics for measuring phytochemicals, and assessing human and animal responses to phytochemicals, in food science.

    Science.gov (United States)

    McGhie, Tony K; Rowan, Daryl D

    2012-01-01

    Metabolomics, comprehensive metabolite analysis, is finding increasing application as a tool to measure and enable the manipulation of the phytochemical content of foods, to identify the measures of dietary intake, and to understand human and animal responses to phytochemicals in the diet. Recent applications of metabolomics directed toward understanding the role of phytochemicals in food and nutrition are reviewed.

  1. Human Response to Helicopter Noise: A Test of A-Weighting

    Science.gov (United States)

    1991-11-01

    34Environmental Quality Technology" Work Unit NN-TGO, "Department of Defense (DOD) Noise Source Human Response Characterization." Cosponsors of this research were...CH53E Indoo 50 CH5E Idoo92 dB Control SEL / O 4 0

  2. Environmentally responsive material to address human-system interaction in the automotive cockpit

    Science.gov (United States)

    Rehkopf, Jackie D.; Barbat, Saeed D.; Goldman, Neil M.; Samus, Marsha A.; Gold, Harris

    2001-06-01

    There is significant human-system interaction in an automotive cockpit, and for particular components this interaction can be ever-present while being transient in nature. It is envisioned that environmentally responsive materials can be used in some components to accommodate personal and transient differences in the desired human-system interaction. Systems containing responsive gels have been developed to provide user activation and adjustment of the physical properties of a particular interior automotive component. Proprietary reverse viscosification gel formulations were developed that are thermally responsive. Formulations were modified to adjust the dynamic modulus and viscosity in terms of magnitude, amount of change over the viscosification transition, and the temperature over which the transition occurs. Changes in the physical properties of two orders of magnitude and more were achieved over a narrow transition region. Preliminary human factors assessment indicates that this order of magnitude of change is desirable. As the system of responsive gel, encapsulating material and activation mechanism is developed further, additional human factors studies will refine the desired physical properties and thermal activation mechanism. Ultimately, this system will have to perform over the broad range of temperatures imposed on interior automotive components and exhibit long-term durability chemically, physically and mechanically.

  3. A System Dynamics Model to Predict the Human Monocyte Response to Endotoxins

    Directory of Open Access Journals (Sweden)

    Enrique Álvarez

    2017-08-01

    Full Text Available System dynamics is a powerful tool that allows modeling of complex and highly networked systems such as those found in the human immune system. We have developed a model that reproduces how the exposure of human monocytes to lipopolysaccharides (LPSs induces an inflammatory state characterized by high production of tumor necrosis factor alpha (TNFα, which is rapidly modulated to enter into a tolerant state, known as endotoxin tolerance (ET. The model contains two subsystems with a total of six states, seven flows, two auxiliary variables, and 14 parameters that interact through six differential and nine algebraic equations. The parameters were estimated and optimized to obtain a model that fits the experimental data obtained from human monocytes treated with various LPS doses. In contrast to publications on other animal models, stimulation of human monocytes with super-low-dose LPSs did not alter the response to a second LPSs challenge, neither inducing ET, nor enhancing the inflammatory response. Moreover, the model confirms the low production of TNFα and increased levels of C–C motif ligand 2 when monocytes exhibit a tolerant state similar to that of patients with sepsis. At present, the model can help us better understand the ET response and might offer new insights on sepsis diagnostics and prognosis by examining the monocyte response to endotoxins in patients with sepsis.

  4. Shared mental models of distributed human-robot teams for coordinated disaster responses

    NARCIS (Netherlands)

    Neerincx, M.A.; Greef, T. de; Smets, N.J.J.M.; Sam, M.P.

    2011-01-01

    Shared Mental Models (SSM) are crucial for adequate coordination of activities and resource deployment in disaster responses. Both human and robot are actors in the construction of such models. Based on a situated Cognitive Engineering (sCE) methodology, we identified the needs, functions and

  5. Attenuation of maternal psychophysiological stress responses and the maternal cortisol awakening response over the course of human pregnancy

    Science.gov (United States)

    ENTRINGER, SONJA; BUSS, CLAUDIA; SHIRTCLIFF, ELIZABETH A.; CAMMACK, ALISON L.; YIM, ILONA S.; CHICZ-DEMET, ALEKSANDRA; SANDMAN, CURT A.; WADHWA, PATHIK D.

    2010-01-01

    The effects of maternal stress during pregnancy may depend, in part, on the timing in gestation of the occurrence of stress. The aim of the present study was to examine the effect of stage of gestation on maternal psychophysiological responses to stress using a standardized laboratory paradigm and on the cortisol response to awakening (CAR). A longitudinal design was employed to quantify maternal psychophysiological stress reactivity [changes in heart rate (HR), blood pressure, salivary cortisol, and psychological distress in response to the trier social stress test (TSST)] and the CAR at approximately 17 and 31 weeks gestation in a sample of 148 women. To account for the possible effects of habituation when being exposed to the same stress protocol twice, a non-pregnant comparison group (CG, N = 36) also underwent these assessments at two time points, with a comparable time interval between the assessments. In both groups, the TSST elicited significant changes in maternal HR, mean arterial pressure, and psychological distress levels but not a significant increase in cortisol levels. Among the pregnant women (pregnant group(PG)), the stressor-induced increases in HR, blood pressure, and psychological distress were significantly lower at the second (31 weeks gestation) compared to the first (17 weeks gestation) assessment of pregnancy (all p < 0.01). The maternal CAR was also significantly attenuated in later compared to earlier gestation (p = 0.003). In the CG, there were no significant differences in psychophysiological stress responses and in the CAR across the two assessments. Among pregnant women there is a progressive attenuation of psychophysiological stress responses with advancing gestation. This attenuation is unlikely to be attributable to habituation. Individual differences in the degree of attenuation of stress responses over gestation may represent a novel marker of stress susceptibility in human pregnancy. PMID:20067400

  6. Attenuation of maternal psychophysiological stress responses and the maternal cortisol awakening response over the course of human pregnancy.

    Science.gov (United States)

    Entringer, Sonja; Buss, Claudia; Shirtcliff, Elizabeth A; Cammack, Alison L; Yim, Ilona S; Chicz-DeMet, Aleksandra; Sandman, Curt A; Wadhwa, Pathik D

    2010-05-01

    The effects of maternal stress during pregnancy may depend, in part, on the timing in gestation of the occurrence of stress. The aim of the present study was to examine the effect of stage of gestation on maternal psychophysiological responses to stress using a standardized laboratory paradigm and on the cortisol response to awakening (CAR). A longitudinal design was employed to quantify maternal psychophysiological stress reactivity [changes in heart rate (HR), blood pressure, salivary cortisol, and psychological distress in response to the trier social stress test (TSST)] and the CAR at approximately 17 and 31 weeks gestation in a sample of 148 women. To account for the possible effects of habituation when being exposed to the same stress protocol twice, a non-pregnant comparison group (CG, N = 36) also underwent these assessments at two time points, with a comparable time interval between the assessments. In both groups, the TSST elicited significant changes in maternal HR, mean arterial pressure, and psychological distress levels but not a significant increase in cortisol levels. Among the pregnant women (pregnant group(PG)), the stressor-induced increases in HR, blood pressure, and psychological distress were significantly lower at the second (31 weeks gestation) compared to the first (17 weeks gestation) assessment of pregnancy (all p stress responses and in the CAR across the two assessments. Among pregnant women there is a progressive attenuation of psychophysiological stress responses with advancing gestation. This attenuation is unlikely to be attributable to habituation. Individual differences in the degree of attenuation of stress responses over gestation may represent a novel marker of stress susceptibility in human pregnancy.

  7. [Affective behavioural responses by dogs to tactile human-dog interactions].

    Science.gov (United States)

    Kuhne, Franziska; Hössler, Johanna C; Struwe, Rainer

    2012-01-01

    The communication of dogs is based on complex, subtle body postures and facial expressions. Some social interaction between dogs includes physical contact. Humans generally use both verbal and tactile signals to communicate with dogs. Hence, interaction between humans and dogs might lead to conflicts because the behavioural responses of dogs to human-dog interaction may be misinterpreted and wrongly assessed. The behavioural responses of dogs to tactile human-dog interactions and human gestures are the focus of this study. The participating dogs (n = 47) were privately owned pets.They were of varying breed and gender.The test consisted of nine randomised test sequences (e. g. petting the dog's head or chest). A test sequence was performed for a period of 30 seconds. The inter-trial interval was set at 60 seconds and the test-retest interval was set at 10 minutes. The frequency and duration of the dogs'behavioural responses were recorded using INTERACT. To examine the behavioural responses of the dogs, a two-way analysis of variance within the linear mixed models procedure of IBM SPSS Statistics 19 was conducted. A significant influence of the test-sequenc order on the dogs' behaviour could be analysed for appeasement gestures (F8,137 = 2.42; p = 0.018), redirected behaviour (F8,161 = 6.31; p = 0.012) and socio-positive behaviour (F8,148 = 6.28; p = 0.012). The behavioural responses of the dogs, which were considered as displacement activities (F8,109 = 2.5; p = 0.014) differed significantly among the test sequences. The response of the dogs, measured as gestures of appeasement, redirected behaviours, and displacement activities, was most obvious during petting around the head and near the paws.The results of this study conspicuously indicate that dogs respond to tactile human-dog interactions with gestures of appeasement and displacement activities. Redirected behaviours, socio-positive behaviours as well displacement activities are behavioural responses which dogs

  8. Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.

    Science.gov (United States)

    Banchereau, Romain; Baldwin, Nicole; Cepika, Alma-Martina; Athale, Shruti; Xue, Yaming; Yu, Chun I; Metang, Patrick; Cheruku, Abhilasha; Berthier, Isabelle; Gayet, Ingrid; Wang, Yuanyuan; Ohouo, Marina; Snipes, LuAnn; Xu, Hui; Obermoser, Gerlinde; Blankenship, Derek; Oh, Sangkon; Ramilo, Octavio; Chaussabel, Damien; Banchereau, Jacques; Palucka, Karolina; Pascual, Virginia

    2014-10-22

    The mechanisms by which microbial vaccines interact with human APCs remain elusive. Herein, we describe the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Exposure of DCs to influenza, Salmonella enterica and Staphylococcus aureus allows us to build a modular framework containing 204 transcript clusters. We use this framework to characterize the responses of human monocytes, monocyte-derived DCs and blood DC subsets to 13 vaccines. Different vaccines induce distinct transcriptional programs based on pathogen type, adjuvant formulation and APC targeted. Fluzone, Pneumovax and Gardasil, respectively, activate monocyte-derived DCs, monocytes and CD1c+ blood DCs, highlighting APC specialization in response to vaccines. Finally, the blood signatures from individuals vaccinated with Fluzone or infected with influenza reveal a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, may guide the development of improved vaccines.

  9. Uncertain responses by humans and rhesus monkeys (Macaca mulatta) in a psychophysical same-different task

    Science.gov (United States)

    Shields, W. E.; Smith, J. D.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)

    1997-01-01

    The authors asked whether animals, like humans, use an uncertain response adaptively to escape indeterminate stimulus relations. Humans and monkeys were placed in a same-different task, known to be challenging for animals. Its difficulty was increased further by reducing the size of the stimulus differences, thereby making many same and different trials difficult to tell apart. Monkeys do escape selectively from these threshold trials, even while coping with 7 absolute stimulus levels concurrently. Monkeys even adjust their response strategies on short time scales according to the local task conditions. Signal-detection and optimality analyses confirm the similarity of humans' and animals' performances. Whereas associative interpretations account poorly for these results, an intuitive uncertainty construct does so easily. The authors discuss the cognitive processes that allow uncertainty's adaptive use and recommend further comparative studies of metacognition.

  10. A single exposure to acrolein desensitizes baroreflex responsiveness and increases cardiac arrhythmias in normotensive and hypertensive rats

    Science.gov (United States)

    Background – Short-term exposure to air pollutants has been linked to acute cardiovascular morbidity and mortality. Even in the absence of overt symptoms, pollutants can cause subtle disruptions of internal regulatory mechanisms, which maintain homeostatic balance, thereby reduci...

  11. The effect of feeding frequency on insulin and ghrelin responses in human subjects

    DEFF Research Database (Denmark)

    Solomon, Thomas; Chambers, Edward S; Jeukendrup, Asker E

    2008-01-01

    Recent work shows that increased meal frequency reduces ghrelin responses in sheep. Human research suggests there is an interaction between insulin and ghrelin. The effect of meal frequency on this interaction is unknown. Therefore, we investigated the effect of feeding frequency on insulin...... and ghrelin responses in human subjects. Five healthy male volunteers were recruited from the general population: age 24 (SEM 2)years, body mass 75.7 (SEM 3.2) kg and BMI 23.8 (SEM 0.8) kg/m(2). Volunteers underwent three 8-h feeding regimens: fasting (FAST); low-frequency(two) meal ingestion (LOFREQ(MEAL......)); high-frequency (twelve) meal ingestion (HIFREQ(MEAL)). Meals were equi-energetic within trials,consisting of 64% carbohydrate, 23% fat and 13% protein. Total energy intake was equal between feeding trials. Total area under the curve for serum insulin and plasma ghrelin responses did not differ between...

  12. Could be the swine responsible of transmission to the humans of Dientamoeba fragilis infection?

    Directory of Open Access Journals (Sweden)

    Daniele Crotti

    2011-03-01

    Full Text Available Dientamoeba fragilis, atypical protozoon because “flagellate without flagella” but amoeba-like, of whom we know only the trophozoitic stage (an so its brittleness outside intestinal tract, is a frequent responsible of intestinal human infections, worldwide, and some authors relate that D. fragilis is the most frequent protozoon and parasite that can infects humans. Actually we don’t know a sure potential “reservoir” in animals who are strictly in contact with humans, and it is difficult to understand its epidemiological chain, otherwise the transmissions to humans and from humans to humans. For all these reasons we performed another study on subjects of swine breedings, and among people who work in these breedings, that are in direct contact or not with pigs. Using standardized methodologies, we analyzed 224 faecal specimens of swine and 15 human specimens.We use for identification of D. fragilis the Giemsa stain.These were the results: D. fragilis was observed in 50.9% of pigs and 20% among humans (30% in workers strictly in contact with breedings and pigs, 0% in familiars or other without a closed contact with swines. Other commensal protozoa were observed with variable associations, but in this article we want to analyze the possible transmission from this pigs to humans (and for us this protozoon is undoubtedly a “reservoir” of D. fragilis for humans, and underline two aspects: for the research of this protozoon, standard procedures area mandatory, with a permanent stain, as Giemsa stain, is necessary, and in all humans with various intestinal infections or troubles, particularly “irritable bowel syndrome” (or similar ones, the specimens must be analyzed for D. fragilis. At least we think that in the near future molecular studies are important for confirming this our observations, and for verifying eventual and probable differences inside genotypes of this very suggestive protozoon, that until now present not rarely

  13. Dynamics of the transcriptome response of cultured human embryonic stem cells to ionizing radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sokolov, Mykyta V., E-mail: sokolovm@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Irina V., E-mail: ipanyutinv@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Panyutin, Igor G., E-mail: igorp@helix.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States); Neumann, Ronald D., E-mail: rneumann@mail.nih.gov [Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892 (United States)

    2011-05-10

    One of the key consequences of exposure of human cells to genotoxic agents is the activation of DNA damage responses (DDR). While the mechanisms underpinning DDR in fully differentiated somatic human cells have been studied extensively, molecular signaling events and pathways involved in DDR in pluripotent human embryonic stem cells (hESC) remain largely unexplored. We studied changes in the human genome-wide transcriptome of H9 hESC line following exposures to 1 Gy of gamma-radiation at 2 h and 16 h post-irradiation. Quantitative real-time PCR was performed to verify the expression data for a subset of genes. In parallel, the cell growth, DDR kinetics, and expression of pluripotency markers in irradiated hESC were monitored. The changes in gene expression in hESC after exposure to ionizing radiation (IR) are substantially different from those observed in somatic human cell lines. Gene expression patterns at 2 h post-IR showed almost an exclusively p53-dependent, predominantly pro-apoptotic, signature with a total of only 30 up-regulated genes. In contrast, the gene expression patterns at 16 h post-IR showed 354 differentially expressed genes, mostly involved in pro-survival pathways, such as increased expression of metallothioneins, ubiquitin cycle, and general metabolism signaling. Cell growth data paralleled trends in gene expression changes. DDR in hESC followed the kinetics reported for human somatic differentiated cells. The expression of pluripotency markers characteristic of undifferentiated hESC was not affected by exposure to IR during the time course of our analysis. Our data on dynamics of transcriptome response of irradiated hESCs may provide a valuable tool to screen for markers of IR exposure of human cells in their most naive state; thus unmasking the key elements of DDR; at the same time, avoiding the complexity of interpreting distinct cell type-dependent genotoxic stress responses of terminally differentiated cells.

  14. Hydrogen peroxide induces adaptive response and differential gene expression in human embryo lung fibroblast cells.

    Science.gov (United States)

    Wei, Qinzhi; Huang, Haiyan; Yang, Linqing; Yuan, Jianhui; Yang, Xiaohua; Liu, Yungang; Zhuang, Zhixiong

    2014-04-01

    Hydrogen peroxide (H2 O2 ), a substance involved in cellular oxidative stress, has been observed to induce an adaptive response, which is characterized by a protection against the toxic effect of H2 O2 at higher concentrations. However, the molecular mechanism for the adaptive response remains unclear. In particular, the existing reports on H2 O2 -induced adaptive response are limited to animal cells and human tumor cells, and relatively normal human cells have never been observed for an adaptive response to H2 O2 . In this study, a human embryo lung fibroblast (MRC-5) cell line was used to model an adaptive response to H2 O2 , and the relevant differential gene expressions by using fluoro mRNA differential display RT-PCR. The results showed significant suppression of cytotoxicity of H2 O2 (1100 μM, 1 h) after pretreatment of the cells with H2 O2 at lower concentrations (0.088-8.8 μM, 24 h), as indicated by cell survival, lactate dehydrogenase release, and the rate of apoptotic cells. Totally 60 mRNA components were differentially expressed compared to untreated cells, and five of them (sizing 400-600 bp) which demonstrated the greatest increase in expression were cloned and sequenced. They showed identity with known genes, such as BCL-2, eIF3S5, NDUFS4, and RPS10. Real time RT-PCR analysis of the five genes displayed a pattern of differential expression consistent with that by the last method. These five genes may be involved in the induction of adaptive response by H2 O2 in human cells, at least in this particular cell type. Copyright © 2012 Wiley Periodicals, Inc.

  15. cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells

    Science.gov (United States)

    Paijo, Jennifer; Döring, Marius; Spanier, Julia; Grabski, Elena; Nooruzzaman, Mohammed; Schmidt, Tobias; Witte, Gregor; Messerle, Martin; Hornung, Veit; Kaever, Volkhard; Kalinke, Ulrich

    2016-01-01

    Human cytomegalovirus (HCMV) infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS) senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING) and thus induces antiviral type I interferon (IFN-I) responses. We found that plasmacytoid dendritic cells (pDC) as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages. PMID:27058035

  16. Biomechanical modeling for the response of human thorax to blast waves

    Science.gov (United States)

    Zhou, Jie; Tao, Gang

    2015-08-01

    A simplified finite element model of a human thorax had been developed for probing into the mechanical response in simple and complex blast environments. The human thorax model was first created by CT images with blast loading applied via a coupled arbitrary Lagrangian-Eulerian method, allowing for a variety of loads to be considered. The goal is to analyze the maximum stress distributions of lung tissue and peak inward thorax wall velocity and to know the possible regions and levels of lung injury. In parallel, a mathematical model has been modified from the Lobdell model to investigate the detailed percentage of lung injury at each level. The blast loadings around the human thorax were obtained from the finite element model, and were then applied in the mathematical model as the boundary conditions to predict the normalized work of the human thorax lung. The present results are found in agreement with the modified Bowen curves and the results predicted by Axelsson's model.

  17. Methods of Assessing Human Tendon Metabolism and Tissue Properties in Response to Changes in Mechanical Loading

    DEFF Research Database (Denmark)

    Heinemeier, Katja M; Kjaer, Michael; Magnusson, S Peter

    2016-01-01

    In recent years a number of methodological developments have improved the opportunities to study human tendon. Microdialysis enables sampling of interstitial fluid in the peritendon tissue, while sampling of human tendon biopsies allows direct analysis of tendon tissue for gene- and protein...... expression as well as protein synthesis rate. Further the (14)C bomb-pulse method has provided data on long-term tissue turnover in human tendon. Non-invasive techniques allow measurement of tendon metabolism (positron emission tomography (PET)), tendon morphology (magnetic resonance imaging (MRI......)), and tendon mechanical properties (ultrasonography combined with force measurement during movement). Finally, 3D cell cultures of human tendon cells provide the opportunity to investigate cell-matrix interactions in response to various interventions....

  18. In vivo optical imaging of physiological responses to photostimulation in human photoreceptors

    CERN Document Server

    Hillmann, Dierck; Pfäffle, Clara; Sudkamp, Helge; Franke, Gesa; Hüttmann, Gereon

    2016-01-01

    Non-invasive functional imaging of molecular and cellular processes of vision is expected to have immense impact on research and clinical diagnostics. Although suitable intrinsic optical signals (IOS) have been observed ex vivo and in immobilized animals in vivo, it was so far not possible to obtain convincing IOS of photoreceptor activity in humans in vivo. Here, we observed spatially and temporally clearly resolved changes in the optical path length of the photoreceptor outer segment as response to an optical stimulus in living human. To obtain these changes, we evaluated phase data of a parallelized and computationally aberration-corrected optical coherence tomography (OCT) system. The non-invasive detection of optical path length changes shows the neuronal photoreceptor activity of single cones in living human retina, and, more importantly, it provides a new diagnostic option in ophthalmology and neurology and could give new insights into visual phototransduction in humans.

  19. Sex differences in baroreflex sensitivity, heart rate variability, and end organ damage in the TGR(mRen2)27 rat.

    Science.gov (United States)

    Johnson, Megan S; DeMarco, Vincent G; Heesch, Cheryl M; Whaley-Connell, Adam T; Schneider, Rebecca I; Rehmer, Nathan T; Tilmon, Roger D; Ferrario, Carlos M; Sowers, James R

    2011-10-01

    The aim of this investigation was to evaluate sex differences in baroreflex and heart rate variability (HRV) dysfunction and indexes of end-organ damage in the TG(mRen2)27 (Ren2) rat, a model of renin overexpression and tissue renin-angiotensin-aldosterone system overactivation. Blood pressure (via telemetric monitoring), blood pressure variability [BPV; SD of systolic blood pressure (SBP)], spontaneous baroreflex sensitivity, HRV [HRV Triangular Index (HRV-TI), standard deviation of the average NN interval (SDNN), low and high frequency power (LF and HF, respectively), and Poincaré plot analysis (SD1, SD2)], and cardiovascular function (pressure-volume loop analysis and proteinuria) were evaluated in male and female 10-wk-old Ren2 and Sprague Dawley rats. The severity of hypertension was greater in Ren2 males (R2-M) than in Ren2 females (R2-F). Increased BPV, suppression of baroreflex gain, decreased HRV, and associated end-organ damage manifested as cardiac dysfunction, myocardial remodeling, elevated proteinuria, and tissue oxidative stress were more pronounced in R2-M compared with R2-F. During the dark cycle, HRV-TI and SDNN were negatively correlated with SBP within R2-M and positively correlated within R2-F; within R2-M, these indexes were also negatively correlated with end-organ damage [left ventricular hypertrophy (LVH)]. Furthermore, within R2-M only, LVH was strongly correlated with indexes of HRV representing predominantly vagal (HF, SD1), but not sympathetic (LF, SD2), variability. These data demonstrated relative protection in females from autonomic dysfunction and end-organ damage associated with elevated blood pressure in the Ren2 model of hypertension.

  20. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients.

    NARCIS (Netherlands)

    Heusser, K.; Tank, J.; Engeli, S.; Diedrich, A.; Menne, J.; Eckert, S.; Peters, T.; Sweep, F.C.; Haller, H.; Pichlmaier, A.M.; Luft, F.C.; Jordan, J.

    2010-01-01

    In animals, electric field stimulation of carotid baroreceptors elicits a depressor response through sympathetic inhibition. We tested the hypothesis that the stimulation acutely reduces sympathetic vasomotor tone and blood pressure in patients with drug treatment-resistant arterial hypertension.

  1. Orienting asymmetries in dogs' responses to different communicatory components of human speech.

    Science.gov (United States)

    Ratcliffe, Victoria F; Reby, David

    2014-12-15

    It is well established that in human speech perception the left hemisphere (LH) of the brain is specialized for processing intelligible phonemic (segmental) content (e.g., [1-3]), whereas the right hemisphere (RH) is more sensitive to prosodic (suprasegmental) cues. Despite evidence that a range of mammal species show LH specialization when processing conspecific vocalizations, the presence of hemispheric biases in domesticated animals' responses to the communicative components of human speech has never been investigated. Human speech is familiar and relevant to domestic dogs (Canis familiaris), who are known to perceive both segmental phonemic cues and suprasegmental speaker-related and emotional prosodic cues. Using the head-orienting paradigm, we presented dogs with manipulated speech and tones differing in segmental or suprasegmental content and recorded their orienting responses. We found that dogs showed a significant LH bias when presented with a familiar spoken command in which the salience of meaningful phonemic (segmental) cues was artificially increased but a significant RH bias in response to commands in which the salience of intonational or speaker-related (suprasegmental) vocal cues was increased. Our results provide insights into mechanisms of interspecific vocal perception in a domesticated mammal and suggest that dogs may share ancestral or convergent hemispheric specializations for processing the different functional communicative components of speech with human listeners.

  2. Review of evoked and event-related delta responses in the human brain.

    Science.gov (United States)

    Güntekin, Bahar; Başar, Erol

    2016-05-01

    In the last decade, the brain's oscillatory responses have invaded the literature. The studies on delta (0.5-3.5Hz) oscillatory responses in humans upon application of cognitive paradigms showed that delta oscillations are related to cognitive processes, mainly in decision making and attentional processes. The present manuscript comprehensively reviews the studies on delta oscillatory responses upon cognitive stimulation in healthy subjects and in different pathologies, namely Alzheimer's disease, Mild Cognitive Impairment (MCI), bipolar disorder, schizophrenia and alcoholism. Further delta oscillatory response upon presentation of faces, facial expressions, and affective pictures are reviewed. The relationship between pre-stimulus delta activity and post-stimulus evoked and event-related responses and/or oscillations is discussed. Cross-frequency couplings of delta oscillations with higher frequency windows are also included in the review. The conclusion of this review includes several important remarks, including that delta oscillatory responses are involved in cognitive and emotional processes. A decrease of delta oscillatory responses could be a general electrophysiological marker for cognitive dysfunction (Alzheimer's disease, MCI, bipolar disorder, schizophrenia and alcoholism). The pre-stimulus activity (phase or amplitude changes in delta activity) has an effect on post-stimulus EEG responses. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Variable postpartum responsiveness among humans and other primates with "cooperative breeding": A comparative and evolutionary perspective.

    Science.gov (United States)

    Hrdy, Sarah B

    2016-01-01

    This article is part of a Special Issue "Parental Care".Until recently, evolutionists reconstructing mother-infant bonding among human ancestors relied on nonhuman primate models characterized by exclusively maternal care, overlooking the highly variable responsiveness exhibited by mothers in species with obligate reliance on allomaternal care and provisioning. It is now increasingly recognized that apes as large-brained, slow maturing, and nutritionally dependent for so long as early humans were, could not have evolved unless "alloparents" (group members other than genetic parents), in addition to parents, had helped mothers to care for and provision offspring, a rearing system known as "cooperative breeding." Here I review situation-dependent maternal responses ranging from highly possessive to permissive, temporarily distancing, rejecting, or infanticidal, documented for a small subset of cooperatively breeding primates. As in many mammals, primate maternal responsiveness is influenced by physical condition, endocrinological priming, prior experience and local environments (especially related to security). But mothers among primates who evolved as cooperative breeders also appear unusually sensitive to cues of social support. In addition to more "sapient" or rational decision-making, humankind's deep history of cooperative breeding must be considered when trying to understand the extremely variable responsiveness of human mothers.

  4. Dose-Response Curve of Chromosome Aberrations in Human Lymphocytes Induced by Gamma-Rays

    Directory of Open Access Journals (Sweden)

    Y. Lusiyanti

    2013-12-01

    Full Text Available Chromosome aberration is a biomarker to predict the level of cell damage caused by exposure to ionizing radiation on human body. Dicentric chromosome is a specific chromosome aberration caused by ionizing radiation and is used as a gold standard biodosimetry of individuals over exposed to ionizing radiation. In radiation accident the dicentric assays has been applied as biological dosimetry to estimate radiation absorbed dose and also to confirm the radiation dose received to radiation workers.The purpose of this study was to generate a dose response curve of chromosome aberration (dicentric in human lymphocyte induced by gamma radiation. Peripheral blood samples from three non smoking healthy volunteers aged between 25-48 years old with informed consent were irradiated with dose between 0.1-4.0 Gy and a control using gamma teletherapy source. The culture procedure was conducted following the IAEA standard procedures with slight modifications. Analysis of dose-response curves used was LQ model Y = a + αD + βD2. The result showed that α and β values of the curve obtained were 0.018 ± 0.006 and 0.013 ± 0.002, respectively. Dose response calibration curve for dicentric chromosome aberrations in human lymphocytes induced by gamma-radiation fitted to linear quadratic model. In order to apply the dose response curve of chromosome aberration disentric for biodosimetry, this standar curve still need to be validated.

  5. The human P-glycoprotein transporter enhances the type I interferon response to Listeria monocytogenes infection.

    Science.gov (United States)

    Sigal, Nadejda; Kaplan Zeevi, Millie; Weinstein, Shiri; Peer, Dan; Herskovits, Anat A

    2015-06-01

    Human multidrug efflux transporters are known for their ability to extrude antibiotics and toxic compounds out of cells, yet accumulating data indicate they have additional functions in diverse physiological processes not related to drug efflux. Here, we show that the human multidrug transporter P-glycoprotein (P-gp) (also named MDR1 and ABCB1) is transcriptionally induced in the monocytic cell line THP-1 upon infection with the human intracellular bacterial pathogen Listeria monocytogenes. Notably, we found that P-gp is important for full activation of the type I interferon response elicited against L. monocytogenes bacteria. Both inhibition of P-gp function by verapamil and inhibition of its transcription using mRNA silencing led to a reduction in the magnitude of the type I response in infected cells. This function of P-gp was specific to type I interferon cytokines elicited against cytosolic replicating bacteria and was not observed in response to cyclic di-AMP (c-di-AMP), a molecule that was shown to be secreted by L. monocytogenes during infection and to trigger type I interferons. Moreover, P-gp was not involved in activation of other proinflammatory cytokines, such as those triggered by vacuolar-restricted L. monocytogenes or lipopolysaccharide (LPS). Taken together, these findings demonstrate a role for P-gp in proper development of an innate immune response against intracellular pathogens, highlighting the complexity in employing therapeutic strategies that involve inhibition of multidrug resistance (MDR) efflux pumps.

  6. The behaviour of satellite cells in response to exercise: what have we learned from human studies?

    DEFF Research Database (Denmark)

    Kadi, Fawzi; Olsen, Steen Schytte

    2005-01-01

    Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards the underst......Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards...... the understanding of satellite cell behaviour in exercised human muscles. It is hypothesised currently that exercise in humans can induce (1) the activation of satellite cells without proliferation, (2) proliferation and withdrawal from differentiation, (3) proliferation and differentiation to provide myonuclei...... and (4) proliferation and differentiation to generate new muscle fibres or to repair segmental fibre injuries. In humans, the satellite cell pool can increase as early as 4 days following a single bout of exercise and is maintained at higher level following several weeks of training. Cessation...