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Sample records for subjects mechanical stimulation

  1. Anodal Transcranial Direct Current Stimulation Promotes Frontal Compensatory Mechanisms in Healthy Elderly Subjects

    Directory of Open Access Journals (Sweden)

    Jesús Cespón

    2017-12-01

    Full Text Available Recent studies have demonstrated that transcranial direct current stimulation (tDCS is potentially useful to improve working memory. In the present study, young and elderly subjects performed a working memory task (n-back task during an electroencephalogram recording before and after receiving anodal, cathodal, and sham tDCS over the left dorsolateral prefrontal cortex (DLPFC. We investigated modulations of behavioral performance and electrophysiological correlates of working memory processes (frontal and parietal P300 event-related potentials. A strong tendency to modulated working memory performance was observed after the application of tDCS. In detail, young, but not elderly, subjects benefited from additional practice in the absence of real tDCS, as indicated by their more accurate responses after sham tDCS. The cathodal tDCS had no effect in any group of participants. Importantly, anodal tDCS improved accuracy in elderly. Moreover, increased accuracy after anodal tDCS was correlated with a larger frontal P300 amplitude. These findings suggest that, in elderly subjects, improved working memory after anodal tDCS applied over the left DLPFC may be related to the promotion of frontal compensatory mechanisms, which are related to attentional processes.

  2. Infrastructure Development as a Condition for Improving the Mechanism of Innovative Activity Stimulation (on the Example of Southern Federal District Subjects

    Directory of Open Access Journals (Sweden)

    Nadezhda Nikolaevna Lebedeva

    2015-12-01

    Full Text Available The article discusses the concept of the mechanism of innovative activity stimulation, which represents a system consisting of actors with their goals; formal regulations (legislation; informal regulations and rules (business culture, adopted by the economic community; incentives and constraints (economic and non-economic in nature. The authors specify the understanding of infrastructure as a condition of the mechanism functioning, compare rating assessments (by the NAIDIT technique of innovation activity of subjects of the Southern Federal District (SFD and reveal significant inconsistencies. The comparative analysis of the main existing infrastructure elements of the innovation sphere (Krasnodar, Volgograd and Rostov regions let make conclusions about their sufficiency or insufficiency in different subjects of the macro-region. The negative trends of innovative infrastructure development include: the lack of a unified information and analytical database and system for the promotion and support of innovative projects; the lack of consolidated data to assess the development level of the regional innovative infrastructure in formal source; the failure and the need for development elements, such as clusters and science-technology parks, support funds and the creation of extensive networks of centers for collective use. Directions of improvement of innovation activity are presented on the basis of comparing its peculiar indicators as well as analyzing and identifying missing infrastructure elements of the innovation system (scientific and investment, information and analytical, organizational and communicative with the aim of increasing the efficiency of existing mechanisms of innovation stimulation in the regions. Scientific and practical significance of this work consists in the future use of its provisions and conclusions as additional theoretical and methodological substantiation of scientific developments in research of innovative activity

  3. Mechanisms of deep brain stimulation

    Science.gov (United States)

    Cheng, Jennifer J.; Eskandar, Emad N.

    2015-01-01

    Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders including obsessive-compulsive disorder. Rather than a single unifying mechanism, DBS likely acts via several, nonexclusive mechanisms including local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, and, potentially, neuroprotection and neurogenesis. These different mechanisms vary in importance depending on the condition being treated and the target being stimulated. Here we review each of these in turn and illustrate how an understanding of these mechanisms is inspiring next-generation approaches to DBS. PMID:26510756

  4. Mechanisms of deep brain stimulation

    National Research Council Canada - National Science Library

    Herrington, Todd M; Cheng, Jennifer J; Eskandar, Emad N

    2016-01-01

    Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders...

  5. Magnetic Vestibular Stimulation in Subjects with Unilateral Labyrinthine Disorders

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    Bryan Kevin Ward

    2014-03-01

    Full Text Available We recently discovered that static magnetic fields from high-strength MRI machines induce nystagmus in all normal humans, and that a magnetohydrodynamic (MHD Lorentz force, derived from ionic currents in the endolymph and pushing on the cupula, best explains this effect. Individuals with no labyrinthine function have no nystagmus. The influence of magnetic vestibular stimulation (MVS in individuals with unilateral loss of labyrinthine function is unknown and may provide insight into mechanism of MVS. These individuals should experience MVS, but with differences consistent with their residual labyrinthine function. We recorded eye movements in the static magnetic field of a 7T MRI machine in nine individuals with unilateral labyrinthine hypofunction, as determined by head impulse testing and vestibular-evoked myogenic potentials (VEMP. Eye movements were recorded using infrared videooculography. Static head positions were varied in pitch with the body supine, and slow-phase eye velocity (SPV was assessed. All subjects exhibited predominantly horizontal nystagmus after entering the magnet head-first, lying supine. The SPV direction reversed when entering feet-first. Pitching chin-to-chest caused subjects to reach a null point for horizontal SPV. Right unilateral vestibular hypofunction (UVH subjects developed slow-phase-up nystagmus and left UVH subjects, slow-phase-down nystagmus. Vertical and torsional components were consistent with superior semicircular canal excitation or inhibition, respectively, of the intact ear. These findings provide compelling support for the hypothesis that MVS is a result of a Lorentz force and suggest that the function of individual structures within the labyrinth can be assessed with MVS. As a novel method of comfortable and sustained labyrinthine stimulation, MVS can provide new insights into vestibular physiology and pathophysiology.

  6. Action-blindsight in healthy subjects after transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Christensen, Mark Schram; Kristiansen, Lasse; Rowe, James B.

    2008-01-01

    Clinical cases of blindsight have shown that visually guided movements can be accomplished without conscious visual perception. Here, we show that blindsight can be induced in healthy subjects by using transcranial magnetic stimulation over the visual cortex. Transcranial magnetic stimulation blo...

  7. Review: Bioelectrical mechanisms in spinal cord stimulation

    NARCIS (Netherlands)

    Holsheimer, J.; Buitenweg, Jan R.

    2015-01-01

    Objectives The aim of this review is to make specialists in a variety of disciplines familiar with basic aspects of spinal cord stimulation and the role of mathematical modeling in understanding its mechanisms of action and the solution of basic problems. Methods The paper is divided into five

  8. Uncovering the mechanism(s) of deep brain stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Li Gang; Yu Chao; Lin Ling; Lu, Stephen C-Y [Inspiring Technical Laboratory, College of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin 300072 (China)

    2005-01-01

    Deep brain stimulators, often called 'pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  9. Healthy subjects with a family history of alcoholism show increased stimulative subjective effects of alcohol.

    Science.gov (United States)

    Söderpalm Gordh, Anna H V; Söderpalm, Bo

    2011-08-01

    Research has shown that subjects with a family history positive (FHP) of alcoholism are at increased risk for alcoholism and that this group reacts differently to alcohol than family history negative (FHN) subjects. These different levels of sensitivity may make FHP persons more likely to consume alcohol. Here, we tested the hypothesis that subjects FHP for type 1 alcoholism (according to Cloninger) are more sensitive than control subjects to the stimulative, properties of alcohol following a single moderate dose of alcohol. Fifty-one healthy men and women (22 FHP and 29 FHN) participated in 2 laboratory sessions, in which they consumed a beverage containing ethanol (0.6 g/kg in juice) or placebo (juice alone) in a randomized order. Primary dependent measures were self-report questionnaires of mood states. Subjects with family history of type 1 alcoholism showed increased stimulative responses and an elevated positive mood state after ethanol compared to controls. At this moderate dose, ethanol increased stimulative subjective responses in individuals who were "family history positive." This enhanced sensitivity could motivate to exaggerated drinking and thereby increase the risk for developing alcoholism. Copyright © 2011 by the Research Society on Alcoholism.

  10. Comparison of the pedalling performance induced by magnetic and electrical stimulation cycle ergometry in able-bodied subjects.

    Science.gov (United States)

    Szecsi, J; Straube, A; Fornusek, C

    2014-04-01

    The purpose of the study was to compare the mechanical power and work generated by able-bodied subjects during functional magnetic stimulation (FMS) vs. functional electrical stimulation (FES) induced ergometer training conditions. Both stimulation methods were applied at a 30 Hz frequency to the quadriceps muscles of 22 healthy able-bodied subjects to induce cycling for 4× four minutes or until exhaustion. FMS was performed via large surface, cooled coils, while FES was applied with a typical stimulation setup used for cycling. Significantly more (pstimulation induced pain and fatigue mechanisms of the neuromuscular system. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

  11. Channeled Scaffolds for Engineering Myocardium with Mechanical Stimulation

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    Zhang, Ting; Wan, Leo Q.; Xiong, Zhuo; Marsano, Anna; Maidhof, Robert; Park, Miri; Yan, Yongnian; Vunjak-Novakovic, Gordana

    2011-01-01

    The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) are critically important for engineering functional myocardial tissue. We report the development of chitosan-collagen scaffolds with micro-pores and an array of parallel channels (~200 μm in diameter) that were specifically designed for cardiac tissue engineering with mechanical stimulation. The scaffolds were designed to have the structural and mechanical properties similar to those of the native human heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom-designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1–2 mm thick) consisted of metabolically active cells and started to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stresses promoted cell alignment, elongation, and the expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs. PMID:22081518

  12. Channelled scaffolds for engineering myocardium with mechanical stimulation.

    Science.gov (United States)

    Zhang, Ting; Wan, Leo Q; Xiong, Zhuo; Marsano, Anna; Maidhof, Robert; Park, Miri; Yan, Yongnian; Vunjak-Novakovic, Gordana

    2012-10-01

    The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) of the heart are important characteristics in the engineering of functional myocardial tissue. This study reports on the development of chitosan-collagen scaffolds with micropores and an array of parallel channels (~ 200 µm in diameter) that were specifically designed for cardiac tissue engineering using mechanical stimulation. The scaffolds were designed to have similar structural and mechanical properties of those of native heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1-2 mm thick) consisted of metabolically active cells that began to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stress promoted cell alignment, elongation, and expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs. Copyright © 2011 John Wiley & Sons, Ltd.

  13. Mechanics of composite material subjected to eigenstress

    DEFF Research Database (Denmark)

    Fuglsang Nielsen, L.

    In this SBI Bulletin a theory is presented dealing with the mechanical behavior of composites subjected to hygro-thermal actions such as shrinkage caused by moisture variations and expansion caused by temperature variations of freezing of water in pore systems. Special attention is given to the t......In this SBI Bulletin a theory is presented dealing with the mechanical behavior of composites subjected to hygro-thermal actions such as shrinkage caused by moisture variations and expansion caused by temperature variations of freezing of water in pore systems. Special attention is given...

  14. Mechanics of composite material subjected to eigenstress

    DEFF Research Database (Denmark)

    Fuglsang Nielsen, L.

    In this SBI Bulletin a theory is presented dealing with the mechanical behavior of composites subjected to hygro-thermal actions such as shrinkage caused by moisture variations and expansion caused by temperature variations of freezing of water in pore systems. Special attention is given to the t......In this SBI Bulletin a theory is presented dealing with the mechanical behavior of composites subjected to hygro-thermal actions such as shrinkage caused by moisture variations and expansion caused by temperature variations of freezing of water in pore systems. Special attention is given...... to the topic of frost resistance of wet building materials. Three computer algorithms are presented to facilitate the numerical analysis of the phenomenons considered....

  15. Mechanics of composite material subjected to eigenstress

    DEFF Research Database (Denmark)

    Fuglsang Nielsen, L.

    In this SBI Bulletin a theory is presented dealing with the mechanical behavior of composites subjected to hygro-thermal actions such as shrinkage caused by moisture variations and expansion caused by temperature variations of freezing of water in pore systems. Special attention is given...... to the topic of frost resistance of wet building materials. Three computer algorithms are presented to facilitate the numerical analysis of the phenomenons considered....

  16. Lipoic Acid Stimulates cAMP Production in Healthy Control and Secondary Progressive MS Subjects.

    Science.gov (United States)

    Fiedler, Sarah E; Yadav, Vijayshree; Kerns, Amelia R; Tsang, Catherine; Markwardt, Sheila; Kim, Edward; Spain, Rebecca; Bourdette, Dennis; Salinthone, Sonemany

    2017-11-15

    Lipoic acid (LA) exhibits antioxidant and anti-inflammatory properties; supplementation reduces disease severity and T lymphocyte migration into the central nervous system in a murine model of multiple sclerosis (MS), and administration in secondary progressive MS (SPMS) subjects reduces brain atrophy compared to placebo. The mechanism of action (MOA) of LA's efficacy in suppression of MS pathology is incompletely understood. LA stimulates production of the immunomodulator cyclic AMP (cAMP) in vitro. To determine whether cAMP could be involved in the MOA of LA in vivo, we performed a clinical trial to examine whether LA stimulates cAMP production in healthy control and MS subjects, and whether there are differences in the bioavailability of LA between groups. We administered 1200 mg of oral LA to healthy control, relapsing remitting MS (RRMS) and SPMS subjects, and measured plasma LA and cAMP levels in peripheral blood mononuclear cells (PBMCs). There were no significant differences between the groups in pharmacokinetic (PK) parameters. Healthy and SPMS subjects had increased cAMP at 2 and 4 h post-LA treatment compared to baseline, while RRMS subjects showed decreases in cAMP. Additionally, plasma concentrations of prostaglandin E2 (PGE2, a known cAMP stimulator) were significantly lower in female RRMS subjects compared to female HC and SPMS subjects 4 h after LA ingestion. These data indicate that cAMP could be part of the MOA of LA in SPMS, and that there is a divergent response to LA in RRMS subjects that may have implications in the efficacy of immunomodulatory drugs. This clinical trial, "Defining the Anti-inflammatory Role of Lipoic Acid in Multiple Sclerosis," NCT00997438, is registered at https://clinicaltrials.gov/ct2/show/record/NCT00997438 .

  17. Non-invasive brain stimulation: enhancing motor and cognitive functions in healthy old subjects

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    Maximo Zimerman

    2010-12-01

    Full Text Available Healthy aging is accompanied by changes in cognitive and motor functions that result in impairment of activities of daily living. This process involves a number of modifications in the brain and is associated with metabolic, structural and physiological changes; some of these serving as adaptive responses to the functional declines. Up to date there are no universally accepted strategies to ameliorate declining functions in this population. An essential basis to develop such strategies is a better understanding of neuroplastic changes during healthy aging. In this context, non-invasive brain stimulation techniques, such as transcranial direct current or transcranial magnetic stimulation, provide an attractive option to modulate cortical neuronal assemblies, even with subsequent changes in neuroplasticity. Thus, in the present review we discuss the use of these techniques as a tool to study underlying cortical mechanisms during healthy aging and as an interventional strategy to enhance declining functions and learning abilities in aged subjects.

  18. Nanoscale Mechanical Stimulation of Human Mesenchymal Stem Cells

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    H Nikukar

    2014-05-01

    We observed significant responses after 1 and 2-week stimulations in cell number, cell shapes and phenotypical markers. Microarray was performed for all groups. Cell count showed normal cell growth with stimulation. However, cell surface area, cell perimeter, and arboration after 1-week stimulation showed significant increases. Immunofluorescent studies have showed significant increase in osteocalcin production after stimulation. Conclusions: Nanoscale mechanical vibration showed significant changes in human mesenchymal stem cell behaviours. Cell morphology changed to become more polygonal and increased expression of the osteoblast markers were noted. These findings with gene regulation changes suggesting nanoscale mechanostimulation has stimulated osteoblastogenesis.  Keywords:  Mesenchymal, Nanoscale, Stem Cells.

  19. Interaction of transcranial magnetic stimulation and electrical transmastoid stimulation in human subjects

    DEFF Research Database (Denmark)

    Taylor, Janet L; Petersen, Nicolas Caesar; Butler, Jane E

    2002-01-01

    Transcranial magnetic stimulation activates corticospinal neurones directly and transsynaptically and hence, activates motoneurones and results in a response in the muscle. Transmastoid stimulation results in a similar muscle response through activation of axons in the spinal cord. This study......-wave, facilitation still occurred at ISIs of -6 and -5 ms and depression of the paired response at ISIs of 0, 1, 4 and 5 ms. The interaction of the response to transmastoid stimulation with the multiple descending volleys elicited by magnetic stimulation of the cortex is complex. However, depression of the response...

  20. Cellular Mechanisms of Transcranial Direct Current Stimulation

    Science.gov (United States)

    2016-07-14

    theory we call “functional targeting”. Report Sections This summary report is organized on chapters that approximated papers either published or in...Bikson M. Cellular Effects of Acute Direct Current Stimulation: Somatic and Synaptic Terminal Effects. Journal of Physiology 2013; 591.10: 2563- 2578...a finite element model of brain current flow, numerical simulations of neuronal activity, and a statistical theory of coincident activity predicts

  1. Cellular Mechanisms of Transcranial Direct Current Stimulation

    Science.gov (United States)

    2016-07-14

    enhanced synaptic efficacy. Understanding the cellular targets of tDCS is considered pre-requisite to rational electrotherapy design and optimization...quantifying transcranial electrotherapy dosage. Curr Treat Options Neurol 10:377-385. Bindman LJ, Lippold OC, Redfearn JW (1962) Long-lasting...transcutaneous DC stimulation for applications in drug delivery and electrotherapy , including tDCS. Journal of Neuroscience Methods 190:188-197

  2. Comparative Evaluation of Tactile Sensation by Electrical and Mechanical Stimulation.

    Science.gov (United States)

    Yem, Vibol; Kajimoto, Hiroyuki

    2017-01-01

    An electrotactile display is a tactile interface that provides tactile perception by passing electrical current through the surface of the skin. It is actively used instead of mechanical tactile displays for tactile feedback because of several advantages such as its small and thin size, light weight, and high responsiveness. However, the similarities and differences between these sensations is still not clear. This study directly compares the intensity sensation of electrotactile stimulation to that of mechanical stimulation, and investigates the characteristic sensation of anodic and cathodic stimulation. In the experiment, participants underwent a 30 pps electrotactile stimulus every one second to their middle finger, and were asked to match this intensity by adjusting the intensity of a mechanical tactile stimulus to an index finger. The results showed that anodic stimulation mainly produced vibration sensation, whereas cathodic sensation produced both vibration and pressure sensations. Relatively low pressure sensation was also observed for anodic stimulation but it remains low, regardless of the increasing of electrical intensity.

  3. Effects of Theta Burst Stimulation on Suprahyoid Motor Cortex Excitability in Healthy Subjects.

    Science.gov (United States)

    Lin, Tuo; Jiang, Lisheng; Dou, Zulin; Wu, Cheng; Liu, Feng; Xu, Guangqing; Lan, Yue

    Continuous theta burst stimulation (cTBS) and intermittent TBS (iTBS) are powerful patterns of repetitive transcranial magnetic stimulation (rTMS), with substantial potential for motor function rehabilitation post-stroke. However, TBS of suprahyoid motor cortex excitability has not been investigated. This study investigated TBS effects on suprahyoid motor cortex excitability and its potential mechanisms in healthy subjects. Thirty-five healthy subjects (23 females; mean age = 21.66 ± 1.66 years) completed three TBS protocols on separate days, separated by at least one week. A stereotaxic neuronavigation system facilitated accurate TMS positioning. Left and right suprahyoid motor evoked potentials (SMEP) were recorded using single-pulse TMS from the contralateral suprahyoid motor cortex before stimulation (baseline) and 0, 15, and 30 min after stimulation. The SMEP latency and amplitude were analyzed via repeated measures analysis of variance. cTBS suppressed ipsilateral suprahyoid motor cortex excitability and activated the contralateral suprahyoid motor cortex. iTBS facilitated ipsilateral suprahyoid motor cortex excitability; however, it did not affect the contralateral excitability. iTBS eliminated the inhibitory effect caused by cTBS applied to the contralateral suprahyoid motor cortex. TBS had no significant effect on the latencies of bilateral SMEP. TBS effects on suprahyoid motor cortex excitability lasted a minimum of 30 min. TBS effectively regulates suprahyoid motor cortex excitability. Suppression of excitability in one hemisphere leads to further activation of the corresponding contralateral motor cortex. iTBS reverses the inhibitory effect induced by cTBS of the contralateral suprahyoid motor cortex. Copyright © 2016. Published by Elsevier Inc.

  4. Electric-field-stimulated protein mechanics.

    Science.gov (United States)

    Hekstra, Doeke R; White, K Ian; Socolich, Michael A; Henning, Robert W; Šrajer, Vukica; Ranganathan, Rama

    2016-12-15

    The internal mechanics of proteins-the coordinated motions of amino acids and the pattern of forces constraining these motions-connects protein structure to function. Here we describe a new method combining the application of strong electric field pulses to protein crystals with time-resolved X-ray crystallography to observe conformational changes in spatial and temporal detail. Using a human PDZ domain (LNX2PDZ2) as a model system, we show that protein crystals tolerate electric field pulses strong enough to drive concerted motions on the sub-microsecond timescale. The induced motions are subtle, involve diverse physical mechanisms, and occur throughout the protein structure. The global pattern of electric-field-induced motions is consistent with both local and allosteric conformational changes naturally induced by ligand binding, including at conserved functional sites in the PDZ domain family. This work lays the foundation for comprehensive experimental study of the mechanical basis of protein function.

  5. Subject-controlled stimulation of dorsal genital nerve to treat neurogenic detrusor overactivity at home.

    Science.gov (United States)

    Opisso, Eloy; Borau, Albert; Rijkhoff, Nico J M

    2013-09-01

    To investigate the effects of subject controlled dorsal genital nerve (DGN) electrical stimulation on neurogenic detrusor overactivity (NDO) in subjects at home. Subjects underwent a 5-day study at home with DGN stimulation. Stimulation was provided with surface electrodes placed either on the dorsal penile shaft in males and on or close to the clitoris in females. The days 1 and 5 were with no stimulation whereas days 2-4 were with stimulation. Two urodynamic studies were performed at the beginning and at the end of the study. A bladder diary was obtained. Eleven subjects with NDO and with urge incontinence were included. One subject stopped the protocol before the end of the 5-day trial and two did not undergo the second urodynamic study. The subjects showed a statistically significant increase in bladder capacities compared to baseline (P = 0.047). Mean volume per day voided significantly increased over the study within the subjects. Differences between day 1 and day 5 were statistically significant (P = 0.028). The feasibility and the globally positive outcomes of the study indicate that the stimulation of the dorsal genital nerve can be an option for the treatment of the NDO. Copyright © 2012 Wiley Periodicals, Inc.

  6. Neural mechanisms underlying transcranial direct current stimulation in aphasia: A feasibility study.

    Directory of Open Access Journals (Sweden)

    Lena eUlm

    2015-10-01

    Full Text Available Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI. We employed a single subject, cross-over, sham-tDCS controlled design and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus (IFG and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioural stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS-effects on brain functions in aphasia.

  7. MUNIX and incremental stimulation MUNE in ALS patients and control subjects

    DEFF Research Database (Denmark)

    Furtula, Jasna; Johnsen, Birger; Christensen, Peter Broegger

    2013-01-01

    This study compares the new Motor Unit Number Estimation (MUNE) technique, MUNIX, with the more common incremental stimulation MUNE (IS-MUNE) with respect to reproducibility in healthy subjects and as potential biomarker of disease progression in patients with ALS.......This study compares the new Motor Unit Number Estimation (MUNE) technique, MUNIX, with the more common incremental stimulation MUNE (IS-MUNE) with respect to reproducibility in healthy subjects and as potential biomarker of disease progression in patients with ALS....

  8. Viscoelastic performance of dielectric elastomer subject to different voltage stimulation

    Science.gov (United States)

    Sheng, Junjie; Zhang, Yuqing; Liu, Lei; Li, Bo; Chen, Hualing

    2017-04-01

    Dielectric elastomer (DE) is capable of giant deformation subject to an electric field, and demonstrates significant advantages in the potentially application of soft machines with muscle-like characteristics. Due to an inherent property of all macromolecular materials, DE exhibits strong viscoelastic properties. Viscoelasticity could cause a time-dependent deformation and lower the response speed and energy conversion efficiency of DE based actuators, thus strongly affect its electromechanical performance and applications. Combining with the rheological model of viscoelastic relaxation, the viscoelastic performance of a VHB membrane in a circular actuator configuration undergoing separately constant, ramp and sinusoidal voltages are analyzed both theoretically and experimentally. The theoretical results indicated that DE could attain a big deformation under a small constant voltage with a longer time or under a big voltage with a shorter time. The model also showed that a higher critical stretch could be achieved by applying ramping voltage with a lower rate and the stretch magnitude under sinusoidal voltage is much larger at a relatively low frequency. Finally, experiments were designed to validate the simulation and show well consistent with the simulation results.

  9. Chaotic desynchronization as the therapeutic mechanism of deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Charles J Wilson

    2011-06-01

    Full Text Available High frequency deep-brain stimulation of the subthalamic nucleus (DBS relieves many of the symptoms of Parkinson's disease in humans and animal models. Although the treatment has seen widespread use, its therapeutic mechanism remains paradoxical. The subthalamic nucleus is excitatory, so its stimulation at rates higher than its normal firing rate should worsen the disease by increasing subthalamic excitation of the globus pallidus. The therapeutic effectiveness of DBS is also frequency and intensity sensitive, and the stimulation must be periodic; aperiodic stimulation at the same mean rate is ineffective. These requirements are not adequately explained by existing models, whether based on firing rate changes or on reduced bursting. Here we report modeling studies suggesting that high frequency periodic excitation of the subthalamic nucleus may act by desynchronizing the firing of neurons in the globus pallidus, rather than by changing the firing rate or pattern of individual cells. Globus pallidus neurons are normally desynchronized, but their activity becomes correlated in Parkinson's disease. Periodic stimulation may induce chaotic desynchronization by interacting with the intrinsic oscillatory mechanism of globus pallidus neurons. Our modeling results suggest a mechanism of action of deep brain stimulation and a pathophysiology of Parkinsonism in which synchrony, rather than firing rate, is the critical pathological feature.

  10. Effect of Low-Level Laser Stimulation on EEG Power in Normal Subjects with Closed Eyes

    Directory of Open Access Journals (Sweden)

    Jih-Huah Wu

    2013-01-01

    Full Text Available In a previous study, we found that the low-level laser (LLL stimulation at the palm with a frequency of 10 Hz was able to induce significant brain activation in normal subjects with opened eyes. However, the electroencephalography (EEG changes to LLL stimulation in subjects with closed eyes have not been studied. In the present study, the laser array stimulator was applied to deliver insensible laser stimulations to the palm of the tested subjects with closed eyes (the laser group. The EEG activities before, during, and after the laser stimulation were collected. The EEG amplitude powers of each EEG frequency band at 19 locations were calculated. These power data were then analyzed by SPSS software using repeated-measure ANOVAs and appropriate posthoc tests. We found a pronounced decrease in the EEG power in alpha-bandwidth during laser simulation and then less decrease in the EEG power in delta-bandwidth in normal subjects with laser stimulation. The EEG power in beta-bandwidth in the right occipital area also decreased significantly in the laser group. We suggest that LLL stimulation might be conducive to falling into sleep in patients with sleep problems.

  11. Physiological Mechanisms in Combined Electric-Acoustic Stimulation.

    Science.gov (United States)

    Sato, Mika; Baumhoff, Peter; Tillein, Jochen; Kral, Andrej

    2017-09-01

    Electrical stimulation is normally performed on ears that have no hearing function, i.e., lack functional hair cells. The properties of electrically-evoked responses in these cochleae were investigated in several previous studies. Recent clinical developments have introduced cochlear implantation (CI) in residually-hearing ears to improve speech understanding in noise. The present study documents the known physiological differences between electrical stimulation of hair cells and of spiral ganglion cells, respectively, and reviews the mechanisms of combined electric and acoustic stimulation in the hearing ears. Literature review from 1971 to 2016. Compared with pure electrical stimulation the combined electroacoustic stimulation provides additional low-frequency information and expands the dynamic range of the input. Physiological studies document a weaker synchronization of the evoked activity in electrically stimulated hearing ears compared with deaf ears that reduces the hypersynchronization of electrically-evoked activity. The findings suggest the possibility of balancing the information provided by acoustic and electric input using stimulus intensity. Absence of distorting acoustic-electric interactions allows exploiting these clinical benefits of electroacoustic stimulation.

  12. Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

    Science.gov (United States)

    Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

    2017-01-01

    Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Perception of electrical and mechanical stimulation of the skin: implications for electrotactile feedback

    Science.gov (United States)

    Marcus, Patrick L.; Fuglevand, Andrew J.

    2009-12-01

    Spinal cord injury is often accompanied by impaired tactile and proprioceptive sensations. Normally, somatosensensory information derived from such sensations is important in the formation of voluntary motor commands. Therefore, as a preliminary step toward the development of an electrotactile feedback system to restore somatosensation, psychophysical methods were used to characterize perceptual attributes associated with electrical stimulation of the skin on the back of the neck in human subjects. These data were compared to mechanical stimulation of the skin on the back of neck and on the distal pad of the index finger. Spatial acuity of the neck, evaluated using two-point thresholds, was not significantly different for electrical (37 ± 14 mm) or mechanical stimulation (39 ± 10 mm). The exponent (β) of the best fitting power function relating perceived intensity to applied stimulus strength was used to characterize perceptual sensitivity to mechanical and electrical stimuli. For electrical stimuli, both current amplitude-modulated and frequency-modulated trains of pulses were tested. Perceptual sensitivity was significantly greater for current amplitude modulation (β = 1.14 ± 0.37) compared to frequency modulation (β = 0.57 ± 0.24) and mechanical stimulation (0.51 ± 0.12). Finally, based on the data gathered here, we derive a transfer function that could be used in the future to convert mechanical stimuli detected with artificial sensors placed on the fingers into electrotactile signals that evoke perceptions similar to those arising from normal mechanical stimulation of the skin.

  14. Mechanisms of magnetic stimulation of central nervous system neurons.

    Directory of Open Access Journals (Sweden)

    Tamar Pashut

    2011-03-01

    Full Text Available Transcranial magnetic stimulation (TMS is a stimulation method in which a magnetic coil generates a magnetic field in an area of interest in the brain. This magnetic field induces an electric field that modulates neuronal activity. The spatial distribution of the induced electric field is determined by the geometry and location of the coil relative to the brain. Although TMS has been used for several decades, the biophysical basis underlying the stimulation of neurons in the central nervous system (CNS is still unknown. To address this problem we developed a numerical scheme enabling us to combine realistic magnetic stimulation (MS with compartmental modeling of neurons with arbitrary morphology. The induced electric field for each location in space was combined with standard compartmental modeling software to calculate the membrane current generated by the electromagnetic field for each segment of the neuron. In agreement with previous studies, the simulations suggested that peripheral axons were excited by the spatial gradients of the induced electric field. In both peripheral and central neurons, MS amplitude required for action potential generation was inversely proportional to the square of the diameter of the stimulated compartment. Due to the importance of the fiber's diameter, magnetic stimulation of CNS neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. Passive dendrites affect this process primarily as current sinks, not sources. The simulations predict that neurons with low current threshold are more susceptible to magnetic stimulation. Moreover, they suggest that MS does not directly trigger dendritic regenerative mechanisms. These insights into the mechanism of MS may be relevant for the design of multi-intensity TMS protocols, may facilitate the construction of magnetic stimulators, and may aid the interpretation of results of TMS of the CNS.

  15. Mechanism of Deep Brain Stimulation: Inhibition, Excitation, or Disruption?

    Science.gov (United States)

    Chiken, Satomi; Nambu, Atsushi

    2016-06-01

    Deep brain stimulation (DBS), applying high-frequency electrical stimulation to deep brain structures, has now provided an effective therapeutic option for treatment of various neurological and psychiatric disorders. DBS targeting the internal segment of the globus pallidus, subthalamic nucleus, and thalamus is used to treat symptoms of movement disorders, such as Parkinson's disease, dystonia, and tremor. However, the mechanism underlying the beneficial effects of DBS remains poorly understood and is still under debate: Does DBS inhibit or excite local neuronal elements? In this short review, we would like to introduce our recent work on the physiological mechanism of DBS and propose an alternative explanation: DBS dissociates input and output signals, resulting in the disruption of abnormal information flow through the stimulation site. © The Author(s) 2015.

  16. Whisking recovery after automated mechanical stimulation during facial nerve regeneration.

    NARCIS (Netherlands)

    Kleiss, I.J.; Knox, C.J.; Malo, J.S.; Marres, H.A.M.; Hadlock, T.A.; Heaton, J.T.

    2014-01-01

    IMPORTANCE Recovery from facial nerve transection is typically poor, but daily mechanical stimulation of the face in rats has been reported to remarkably enhance functional recovery after facial nerve transection and suture repair. This phenomenon needs additional investigation because of its

  17. Electrical and mechanical stimulation of cardiac cells and tissue constructs.

    Science.gov (United States)

    Stoppel, Whitney L; Kaplan, David L; Black, Lauren D

    2016-01-15

    The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. [Mechanisms and applications of transcutaneous electrical nerve stimulation in analgesia].

    Science.gov (United States)

    Tang, Zheng-Yu; Wang, Hui-Quan; Xia, Xiao-Lei; Tang, Yi; Peng, Wei-Wei; Hu, Li

    2017-06-25

    Transcutaneous electrical nerve stimulation (TENS), as a non-pharmacological and non-invasive analgesic therapy with low-cost, has been widely used to relieve pain in various clinical applications, by delivering current pulses to the skin area to activate the peripheral nerve fibers. Nevertheless, analgesia induced by TENS varied in the clinical practice, which could be caused by the fact that TENS with different stimulus parameters has different biological mechanisms in relieving pain. Therefore, to advance our understanding of TENS in various basic and clinical studies, we discussed (1) neurophysiological and biochemical mechanisms of TENS-induced analgesia; (2) relevant factors that may influence analgesic effects of TENS from the perspectives of stimulus parameters, including stimulated position, pulse parameters (current intensity, frequency, and pulse width), stimulus duration and used times in each day; and (3) applications of TENS in relieving clinical pain, including post-operative pain, chronic low back pain and labor pain. Finally, we propose that TENS may involve multiple and complex psychological neurophysiological mechanisms, and suggest that different analgesic effects of TENS with different stimulus parameters should be taken into consideration in clinical applications. In addition, to optimize analgesic effect, we recommend that individual-based TENS stimulation parameters should be designed by considering individual differences among patients, e.g., adaptively adjusting the stimulation parameters based on the dynamic ratings of patients' pain.

  19. Stimulation of Tissue Healing by Ultrasound: Physical Mechanisms of Action

    Science.gov (United States)

    Rodríguez, O.; Chong, J.; Monreal, R.

    2004-09-01

    Even though the use of ultrasound in medicine is better known by its results in diagnostic procedures, the employ of this type of mechanical energy with therapeutic purposes is been used in new and impressive applications. To obtain or to improve tissue healing in many ailments it is used a lot of approaches, from the employ of antibiotics when it is considered by the presence of an infection in the wound, to several types of physical stimulation. One of them is ultrasound. This paper consider some of the most important mechanisms of action of ultrasound in tissue that can be related whit the repair processes and specifies levels of activation of many paths of action. Especial emphasis has received the stimulation of bone repair by ultrasound.

  20. Directional migration and transcriptional analysis of oligodendrocyte precursors subjected to stimulation of electrical signal.

    Science.gov (United States)

    Li, Yongchao; Wang, Xinkun; Yao, Li

    2015-10-15

    Loss of oligodendrocytes as the result of central nervous system disease causes demyelination that impairs axon function. Effective directional migration of endogenous or grafted oligodendrocyte precursor cells (OPCs) to a lesion is crucial in the neural remyelination process. In this study, the migration of OPCs in electric fields (EFs) was investigated. We found that OPCs migrated anodally in applied EFs, and the directedness and displacement of anodal migration increased significantly when the EF strength increased from 50 to 200 mV/mm. However, EFs did not significantly affect the cell migration speed. The transcriptome of OPCs subjected to EF stimulation (100 and 200 mV/mm) was analyzed using RNA sequencing (RNA-Seq), and results were verified by the reverse transcription quantitative polymerase chain reaction. A Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the mitogen-activated protein kinase pathway that signals cell migration was significantly upregulated in cells treated with an EF of 200 mV/mm compared with control cells. Gene ontology enrichment analysis showed the downregulation of differentially expressed genes in chemotaxis. This study suggests that an applied EF is an effective cue to guiding OPC migration in neural regeneration and that transcriptional analysis contributes to the understanding of the mechanism of EF-guided cell migration. Copyright © 2015 the American Physiological Society.

  1. Mechanical Characteristics of Reflex Durign Upright Posture in Paralyzed Subjects

    Science.gov (United States)

    Kim, Yongchul; Youm, Youngil; Lee, Bumsuk; Kim, Youngho; Choi, Hyeonki

    The characteristics of flexor reflexes have been investigated in the previous studies with human subjects who were seated or supine position. However, researchers did not describe how the spinal circuits are used in different hip angles for paralyzed subjects, such as the standing position with walker or cane. In upright posture the compatibility between a flexor reflex of leg and body balance is a special problem for lower limb injured subjects. Therefore, the purpose of this study was to investigate the effects of hip angle change on the flexor reflex evoked in standing paralyzed subjects supported by walker. In this study, six spinal cord injured and four stroke subjects were recruited through the inpatient physical therapy clinics of Korea national rehabilitation hospital. A single axis electronic goniometer was mounted on the lateral side of the hip joint of the impaired limb to record movements in the sagittal plane at this joint. The electronic goniometer was connected to a data acquisition system, through amplifiers to a computer. Since subject' posture influenced characteristics of the flexion reflex response, the subjects were supported in an upright posture by the help of parallelogram walder. Two series of tests were performed on each leg. The first series of the tests investigated the influence of hip angle during stationary standing posture on flexion reflex response. The hip angle was adjusted by the foot plate. The second examined the effect of the voluntary action of subject on swing motion during the gait. The electrically induced flexion reflex simultaneously produced the flexion of the hip, knee and dorsiflexion of the ankle enabling the swing phase of walking. Form the experimental results we observed that the reflex response of hip joint was largerwith the hip in the extended position than in the flexed position during standing posture. Under voluntary movement on flexion reflex during gaint, the peak hip angle induced by stimulation was

  2. Temporal interactions during paired-electrode stimulation in two retinal prosthesis subjects.

    Science.gov (United States)

    Horsager, Alan; Boynton, Geoffrey M; Greenberg, Robert J; Fine, Ione

    2011-01-01

    Since 2002, six blind patients have undergone implantation of an epiretinal 4 × 4 electrode array designed to directly stimulate the remaining cells of the retina after severe photoreceptor degeneration due to retinitis pigmentosa. This study was conducted to investigate how the brightness of percepts is affected by pulse timing across electrodes in two of these patients. Subjects compared the perceived brightness of a standard stimulus (synchronous pulse trains presented across pairs of electrodes) to the perceived brightness of a test stimulus (pulse trains across the electrode pair phase shifted by 0.075, 0.375, 1.8, or 9 ms). The current amplitude necessary for each phase-shifted test stimulus to match the brightness of the standard was determined. Depending on the electrode pair, interactions between electrodes were either facilitatory (the perceived brightness produced by stimulating the pair of electrodes was greater than that produced by stimulating either electrode alone) or suppressive (the perceived brightness produced by stimulating the pair of electrodes was less than that produced by stimulating either electrode alone). The amount of interaction between electrodes decreased as a function of increased separation both in time (the phase-shift between pulse trains) and space (center-to-center distance between the electrode pair). For visual prostheses to represent visual scenes that are changing in both space and time requires the development of spatiotemporal models describing the effects of stimulation across multiple electrodes. During multielectrode stimulation, interactions between electrodes have a significant influence on subjective brightness that includes both facilitatory and suppressive effects, and these interactions can be described with a simple computational model. (ClinicalTrials.gov number, NCT00279500.).

  3. Bone conduction hearing sensitivity in normal-hearing subjects: transcutaneous stimulation at BAHA vs BCI position.

    Science.gov (United States)

    Reinfeldt, Sabine; Håkansson, Bo; Taghavi, Hamidreza; Eeg-Olofsson, Måns

    2014-06-01

    Bone conduction (BC) stimulation closer to the cochlea has previously been shown to give higher cochlear promontory acceleration measured by laser Doppler vibrometry (LDV). This study is investigating whether stimulation closer to the cochlea also gives improved hearing sensitivity. Furthermore, the study compares shifts in hearing sensitivity (BC thresholds) and ear-canal sound pressure (ECSP). BC hearing thresholds and ECSP have been measured for stimulation at two positions: the existing bone-anchored hearing aid (BAHA) position, and a new bone conduction implant (BCI) position that is located closer to the cochlea. The measurements were made on 20 normal-hearing subjects. Depending on frequency, the ipsilateral hearing threshold was 3-14 dB better, and the ipsilateral ECSP was 2-12 dB higher for the BCI than for the BAHA position, with no significant differences between threshold and ECSP shifts at group level for most frequencies, and individually only for some subjects. It was found that both the objective ECSP and the subjective hearing threshold measurements gave similar improvement as previous LDV measurements for stimulation closer to the cochlea. One exception was that the LDV measurements did not show the improved sensitivity for frequencies below 500 Hz found here.

  4. Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Hove, Jens D; Freiberg, Jacob

    2002-01-01

    The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure......, bicycle exercise test, electrocardiogram and echocardiography were studied [ P(coronary artery disease) ... rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion...

  5. Cortical hypermetabolism in MCI subjects: a compensatory mechanism?

    Energy Technology Data Exchange (ETDEWEB)

    Ashraf, A.; Fan, Z.; Brooks, D.J.; Edison, P. [Imperial College London, Neurology Imaging Unit, Division of Brain Sciences, London (United Kingdom)

    2014-09-30

    Alzheimer's disease (AD) is associated with amyloid accumulation that takes place decades before symptoms appear. Cognitive impairment in AD is associated with reduced glucose metabolism. However, neuronal plasticity/compensatory mechanisms might come into play before the onset of dementia. The aim of this study was to determine whether there is evidence of cortical hypermetabolism as a compensatory mechanism before amyloid deposition takes place in subjects with amnestic mild cognitive impairment (aMCI). Nine AD subjects and ten aMCI subjects had both [{sup 11}C]PIB and [{sup 18}F]FDG PET scans with arterial input in order to quantify the amyloid deposition and glucose metabolism in vivo in comparison with healthy control subjects who underwent either [{sup 11}C]PIB or [{sup 18}F]FDG PET scans. The [{sup 11}C]PIB PET scans were quantified using [{sup 11}C]PIB target region to cerebellum uptake ratio images created by integrating the activity collected from 60 to 90 min, and regional cerebral glucose metabolism was quantified using spectral analysis. In MCI subjects, cortical hypermetabolism was observed in four amyloid-negative subjects and one amyloid-positive subject, while hypometabolism was seen in five other MCI subjects with high amyloid load. Subjects with hypermetabolism and low amyloid did not convert to AD during clinical follow-up for 18 months in contrast to four amyloid-positive hypometabolic subjects who did convert to AD. This preliminary study suggests that compensatory hypermetabolism can occur in aMCI subjects, particularly in those who are amyloid-negative. The increase in metabolic rate in different cortical regions with predominance in the occipital cortex may be a compensatory response to the neuronal damage occurring early in the disease process. It may also reflect recruitment of relatively minimally affected cortical regions to compensate for reduced function in the temporoparietal cortical association areas. (orig.)

  6. A dual flow bioreactor with controlled mechanical stimulation for cartilage tissue engineering

    NARCIS (Netherlands)

    Spitters, Tim; Leijten, Jeroen Christianus Hermanus; Deus, F.D.; Costa, I.B.F.; van Apeldoorn, Aart A.; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2013-01-01

    In cartilage tissue engineering bioreactors can create a controlled environment to study chondrocyte behavior under mechanical stimulation or produce chondrogenic grafts of clinically relevant size. Here we present a novel bioreactor, which combines mechanical stimulation with a two compartment

  7. Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

    Science.gov (United States)

    Wang, Bo; Wang, Guangjun; To, Filip; Butler, J Ryan; Claude, Andrew; McLaughlin, Ronald M; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

    2013-09-03

    Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.

  8. A Novel bioreactor with mechanical stimulation for skeletal tissue engineering

    Directory of Open Access Journals (Sweden)

    M. Petrović

    2009-01-01

    Full Text Available The provision of mechanical stimulation is believed to be necessary for the functional assembly of skeletal tissues, which are normally exposed to a variety of biomechanical signals in vivo. In this paper, we present a development and validation of a novel bioreactor aimed for skeletal tissue engineering that provides dynamic compression and perfusion of cultivated tissues. Dynamic compression can be applied at frequencies up to 67.5 Hz and displacements down to 5 m thus suitable for the simulation of physiological conditions in a native cartilage tissue (0.1-1 Hz, 5-10 % strain. The bioreactor also includes a load sensor that was calibrated so to measure average loads imposed on tissue samples. Regimes of the mechanical stimulation and acquisition of load sensor outputs are directed by an automatic control system using applications developed within the LabView platform. In addition, perfusion of tissue samples at physiological velocities (10–100 m/s provides efficient mass transfer, as well as the possibilities to expose the cells to hydrodynamic shear and simulate the conditions in a native bone tissue. Thus, the novel bioreactor is suited for studies of the effects of different biomechanical signals on in vitro regeneration of skeletal tissues, as well as for the studies of newly formulated biomaterials and cell biomaterial interactions under in vivo-like settings.

  9. Mechanisms and Effects of Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Giordano, James; Bikson, Marom; Kappenman, Emily S; Clark, Vincent P; Coslett, H Branch; Hamblin, Michael R; Hamilton, Roy; Jankord, Ryan; Kozumbo, Walter J; McKinley, R Andrew; Nitsche, Michael A; Reilly, J Patrick; Richardson, Jessica; Wurzman, Rachel; Calabrese, Edward

    2017-01-01

    The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing research in the field of transcranial direct current stimulation (tDCS) and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical populations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising applications include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models) can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose-response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light) therapy, can be prudently leveraged.

  10. Mechanisms and Effects of Transcranial Direct Current Stimulation

    Directory of Open Access Journals (Sweden)

    James Giordano

    2017-02-01

    Full Text Available The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing research in the field of transcranial direct current stimulation (tDCS and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical populations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising applications include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose–response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light therapy, can be prudently leveraged.

  11. Synchronization of neuron population subject to steady DC electric field induced by magnetic stimulation.

    Science.gov (United States)

    Yu, Kai; Wang, Jiang; Deng, Bin; Wei, Xile

    2013-06-01

    Electric fields, which are ubiquitous in the context of neurons, are induced either by external electromagnetic fields or by endogenous electric activities. Clinical evidences point out that magnetic stimulation can induce an electric field that modulates rhythmic activity of special brain tissue, which are associated with most brain functions, including normal and pathological physiological mechanisms. Recently, the studies about the relationship between clinical treatment for psychiatric disorders and magnetic stimulation have been investigated extensively. However, further development of these techniques is limited due to the lack of understanding of the underlying mechanisms supporting the interaction between the electric field induced by magnetic stimulus and brain tissue. In this paper, the effects of steady DC electric field induced by magnetic stimulation on the coherence of an interneuronal network are investigated. Different behaviors have been observed in the network with different topologies (i.e., random and small-world network, modular network). It is found that the coherence displays a peak or a plateau when the induced electric field varies between the parameter range we defined. The coherence of the neuronal systems depends extensively on the network structure and parameters. All these parameters play a key role in determining the range for the induced electric field to synchronize network activities. The presented results could have important implications for the scientific theoretical studies regarding the effects of magnetic stimulation on human brain.

  12. Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects.

    Science.gov (United States)

    Ridding, M C; Ziemann, U

    2010-07-01

    The ability to induce cortical plasticity with non-invasive brain stimulation (NBS) techniques has provided novel and exciting opportunities for examining the role of the human cortex during a variety of behaviours. Additionally, and importantly, the induction of lasting changes in cortical excitability can, under some conditions, reversibly modify behaviour and interact with normal learning. Such findings have driven a large number of recent studies examining whether by using such approaches it might be possible to induce functionally significant changes in patients with a large variety of neurological and psychiatric conditions including stroke, Parkinson's disease and depression. However, even in neurologically normal subjects the variability in the neurophysiological and behavioural response to such brain stimulation techniques is high. This variability at present limits the therapeutic usefulness of these techniques. The cause of this variability is multifactorial and to some degree still unknown. However, a number of factors that can influence the induction of plasticity have been identified. This review will summarise what is known about the causes of variability in healthy subjects and propose additional factors that are likely to be important determinants. A greater understanding of these determinants is critical for optimising the therapeutic applications of non-invasive brain stimulation techniques.

  13. Cyclic mechanical deformation stimulates human lung fibroblast proliferation and autocrine growth factor activity.

    Science.gov (United States)

    Bishop, J E; Mitchell, J J; Absher, P M; Baldor, L; Geller, H A; Woodcock-Mitchell, J; Hamblin, M J; Vacek, P; Low, R B

    1993-08-01

    Cellular hypertrophy and hyperplasia and increased extracellular matrix deposition are features of tissue hypertrophy resulting from increased work load. It is known, for example, that mechanical forces play a critical role in lung development, cardiovascular remodeling following pressure overload, and skeletal muscle growth. The mechanisms involved in these processes, however, remain unclear. Here we examined the effect of mechanical deformation on fibroblast function in vitro. IMR-90 human fetal lung fibroblasts grown on collagen-coated silastic membranes were subjected to cyclical mechanical deformation (10% increase in culture surface area; 1 Hz) for up to 5 days. Cell number was increased by 39% after 2 days of deformation (1.43 +/- .01 x 10(5) cells/membrane compared with control, 1.03 +/- 0.02 x 10(5) cells; mean +/- SEM; P < 0.02) increasing to 163% above control by 4 days (2.16 +/- 0.16 x 10(5) cells compared with 0.82 +/- 0.03 x 10(5) cells; P < 0.001). The medium from mechanically deformed cells was mitogenic for IMR-90 cells, with maximal activity in the medium from cells mechanically deformed for 2 days (stimulating cell replication by 35% compared with media control; P < 0.002). These data suggest that mechanical deformation stimulates human lung fibroblast replication and that this effect is mediated by the release of autocrine growth factors.

  14. Ultrasonic stimulation of peripheral nervous tissue: an investigation into mechanisms

    Science.gov (United States)

    Wright, C. J.; Rothwell, J.; Saffari, N.

    2015-01-01

    Neuro-stimulation has wide ranging clinical and research potential but this is currently limited either by low resolution, penetration or by highly invasive procedures. It has been reported in previous studies that ultrasound is able to elicit a neuro-stimulatory effect at a higher resolution than other non-invasive approaches but both the underlying mechanism that makes this possible and the practical details of how it can be implemented are still poorly understood. The current study has identified the main issues that need to be resolved in the field, proposing several different approaches to tackling these areas. An isolated in vitro peripheral nerve bundle was chosen as a simple model to demonstrate and investigate the neuro-stimulatory effect after preliminary results showed successful stimulation in a skin-nerve preparation. Early results from the nerve bundle show successful neurostimulation, indicating that structures in the peripheral nerve axon are sensitive to ultrasound. Further research using this model should reveal more precisely what structures are being affected and how to optimise the effect, helping to inform the design of future procedures and devices used in in vivo applications.

  15. Effect of tone-based sound stimulation on balance performance of normal subjects: preliminary investigation.

    Science.gov (United States)

    Pagnacco, Guido; Klotzek, Adam S; Carrick, Frederick R; Wright, Cameron H G; Oggero, Elena

    2015-01-01

    Sound is known to affect the human brain, hence sound or music therapy is sometimes used to improve a subject's physicaland mental health. In this study, the effects sound stimulation has on balance were investigated by means of computerizeddynamic posturography tests performed with eyes closed on an unstable surface using a CAPS® system, exceeding theInternational Society for Posture and Gait Research (ISPGR) recommended metrological performance standards. Subjectswere tested without listening to any music (baseline), listening to “pure music”, and listening to the same music with differenttones embedded into it (one for each key). We found that different subjects react differently to different tones. Music alonedid not have a statistically significant effect on balance compared to the baseline, but the “best” tone significantly improvedbalance compared to the baseline or the “pure music” conditions. Furthermore, the “worst” tone reduced the balancecompared to “pure music”, but the reduction was not statistically significant relative to the baseline. The results thereforeindicate that, at least relative to balance performance, the tone-based sound stimulation we investigated is effective andinherently safe, but that tone selection depends on the individual subject.

  16. Transcranial Alternating Current Stimulation (tACS Mechanisms and Protocols

    Directory of Open Access Journals (Sweden)

    Amir V. Tavakoli

    2017-09-01

    Full Text Available Perception, cognition and consciousness can be modulated as a function of oscillating neural activity, while ongoing neuronal dynamics are influenced by synaptic activity and membrane potential. Consequently, transcranial alternating current stimulation (tACS may be used for neurological intervention. The advantageous features of tACS include the biphasic and sinusoidal tACS currents, the ability to entrain large neuronal populations, and subtle control over somatic effects. Through neuromodulation of phasic, neural activity, tACS is a powerful tool to investigate the neural correlates of cognition. The rapid development in this area requires clarity about best practices. Here we briefly introduce tACS and review the most compelling findings in the literature to provide a starting point for using tACS. We suggest that tACS protocols be based on functional brain mechanisms and appropriate control experiments, including active sham and condition blinding.

  17. High frequency somatosensory stimulation increases sensori-motor inhibition and leads to perceptual improvement in healthy subjects.

    Science.gov (United States)

    Rocchi, Lorenzo; Erro, Roberto; Antelmi, Elena; Berardelli, Alfredo; Tinazzi, Michele; Liguori, Rocco; Bhatia, Kailash; Rothwell, John

    2017-06-01

    High frequency repetitive somatosensory stimulation (HF-RSS), which is a patterned electric stimulation applied to the skin through surface electrodes, improves two-point discrimination, somatosensory temporal discrimination threshold (STDT) and motor performance in humans. However, the mechanisms which underlie these changes are still unknown. In particular, we hypothesize that refinement of inhibition might be responsible for the improvement in spatial and temporal perception. Fifteen healthy subjects underwent 45min of HF-RSS. Before and after the intervention several measures of inhibition in the primary somatosensory area (S1), such as paired-pulse somatosensory evoked potentials (pp-SEP), high-frequency oscillations (HFO), and STDT were tested, as well as tactile spatial acuity and short intracortical inhibition (SICI). HF-RSS increased inhibition in S1 tested by pp-SEP and HFO; these changes were correlated with improvement in STDT. HF-RSS also enhanced bumps detection, while there was no change in grating orientation test. Finally there was an increase in SICI, suggesting widespread changes in cortical sensorimotor interactions. These findings suggest that HF-RSS can improve spatial and temporal tactile abilities by increasing the effectiveness of inhibitory interactions in the somatosensory system. Moreover, HF-RSS induces changes in cortical sensorimotor interaction. HF-RSS is a repetitive electric stimulation technique able to modify the effectiveness of inhibitory circuitry in the somatosensory system and primary motor cortex. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

  18. Comparison of neuropathology in Parkinson's disease subjects with and without deep brain stimulation.

    Science.gov (United States)

    Pal, Gian D; Ouyang, Bichun; Serrano, Geidy; Shill, Holly A; Goetz, Christopher; Stebbins, Glenn; Metman, Leo Verhagen; Driver-Dunckley, Erika; Mehta, Shyamal H; Caviness, John N; Sabbagh, Marwan N; Adler, Charles H; Beach, Thomas G

    2017-02-01

    The aim of this postmortem study was to compare, in Parkinson's disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions. PD subjects were identified from the Arizona Study of Aging and Neurodegenerative Disorders database (STN-DBS = 11, non-DBS = 156). Pigmented neuron loss scores within the substantia nigra as well as alpha-synuclein density scores within the substantia nigra and 9 other brain regions were compared, the latter individually and in summary as the Lewy body brain load score. DBS subjects had higher alpha-synuclein density scores within the substantia nigra, olfactory bulb, and locus ceruleus, as well as higher total Lewy body brain load scores when compared with non-DBS subjects. No differences in substantia nigra pigmented neuron loss scores were found. STN-DBS subjects tend to have higher alpha-synuclein density scores, but do not have a differential loss of substantia nigra pigmented neurons. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  19. The effect of oscillatory mechanical stimulation on osteoblast attachment and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Aryaei, Ashkan [Department of Mechanical Engineering, College of Engineering, University of Toledo, Toledo, OH 43606 (United States); Jayasuriya, Ambalangodage C., E-mail: a.jayasuriya@utoledo.edu [Department of Orthopaedic Surgery, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614 (United States)

    2015-07-01

    The aim of this paper is to investigate the effect of the magnitude and duration of oscillatory mechanical stimulation on osteoblast attachment and proliferation as well as the time gap between seeding and applying the stimulation. Cells were exposed to three levels of speed at two different conditions. For the first group, mechanical shear stress was applied after 20 min of cell seeding. For the second group there was no time gap between cell seeding and applying mechanical stimulation. The total area subjected to shear stress was divided into three parts and for each part a comparative study was conducted at defined time points. Our results showed that both shear stress magnitude and the time gap between cell seeding and applying shear stress, are important in further cell proliferation and attachment. The effect of shear stress was not significant at lower speeds for both groups at earlier time points. However, a higher percentage of area was covered by cells at later time points under shear stress. In addition, the time gap can also improve osteoblast attachment. For the best rate of cell attachment and proliferation, the magnitude of shear stress and time gap should be optimized. The results of this paper can be utilized to improve cell attachment and proliferation in bioreactors. - Highlights: • The effect of oscillatory mechanical stimulation on osteoblast functions was studied. • Cells were exposed at three levels of speed to attach cells. • Shear stress magnitude and time gap are important for cell functions. • Cells start developing extracellular components at the early stage of seeding.

  20. Insulin-stimulated glucose transport in circulating mononuclear cells from nondiabetic and IDDM subjects.

    Science.gov (United States)

    Daneman, D; Zinman, B; Elliott, M E; Bilan, P J; Klip, A

    1992-02-01

    The objectives of this study were 1) to evaluate glucose transport and its regulation by insulin in easily accessible human cells, 2) to investigate the glucose transporter isoforms involved, and 3) to establish whether a defect in glucose transport is associated with peripheral insulin resistance, which is common in insulin-dependent diabetes mellitus (IDDM) patients. We measured 2-deoxyglucose (2-DG) uptake in circulating mononuclear cells from 23 nondiabetic adults, 16 adults with IDDM, and 10 children with IDDM. Circulating mononuclear cells were separated from whole blood by Ficoll gradients and incubated with +/- 1 nM insulin. 2-DG uptake was measured after incubation with [3H]2-DG and cell separation through corn oil-phthalate. Cytochalasin B-inhibitable 2-DG uptake (basal and insulin stimulated) was higher in control than in IDDM subjects (P less than 0.001). Insulin significantly increased 2-DG uptake or 3-O-methylglucose uptake in both groups. Basal and insulin-stimulated 2-DG uptake was similar for adults and children with IDDM and did not correlate with age or body mass index in any group or disease duration, insulin dosage, or HbA1c in IDDM. In separated monocytes and lymphocytes, 2-DG uptake increased in response to insulin only in the monocyte population. Insulin dose-response curves indicated maximal stimulation of hexose uptake at 1-2 nM insulin for both control and diabetic subjects and demonstrated a significant decrease in maximal insulin response in the latter. Immunoblotting with specific antibodies revealed that circulating mononuclear cells and separated monocytes express the GLUT1 but not the GLUT4 isoform of the glucose transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Effect of repetitive transcranial magnetic stimulation on mood in healthy subjects

    Directory of Open Access Journals (Sweden)

    Virginie Moulier

    2016-03-01

    Full Text Available Background: High frequency repetitive transcranial magnetic stimulation (rTMS of the left dorsolateral prefrontal cortex (DLPFC has shown significant efficiency in the treatment of resistant depression. However in healthy subjects, the effects of rTMS remain unclear. Objective: Our aim was to determine the impact of 10 sessions of rTMS applied to the DLPFC on mood and emotion recognition in healthy subjects. Design: In a randomised double-blind study, 20 subjects received 10 daily sessions of active (10 Hz frequency or sham rTMS. The TMS coil was positioned on the left DLPFC through neuronavigation. Several dimensions of mood and emotion processing were assessed at baseline and after rTMS with clinical scales, visual analogue scales (VASs, and the Ekman 60 faces test. Results: The 10 rTMS sessions targeting the DLPFC were well tolerated. No significant difference was found between the active group and the control group for clinical scales and the Ekman 60 faces test. Compared to the control group, the active rTMS group presented a significant improvement in their adaptation to daily life, which was assessed through VAS. Conclusion: This study did not show any deleterious effect on mood and emotion recognition of 10 sessions of rTMS applied on the DLPFC in healthy subjects. This study also suggested a positive effect of rTMS on quality of life.

  2. Neural correlates of transmeatal cochlear laser (TCL) stimulation in healthy human subjects.

    Science.gov (United States)

    Siedentopf, Christian M; Ischebeck, Anja; Haala, Ilka A; Mottaghy, Felix M; Schikora, Detlef; Verius, Michael; Koppelstaetter, Florian; Buchberger, Waltraud; Schlager, Andreas; Felber, Stephan R; Golaszewski, Stefan M

    2007-01-16

    Transmeatal cochlear laser (TCL) treatment has recently been proposed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. The aim of this study was to investigate whether TLC has any influence on the central nervous system using functional MRI with healthy young adults. The laser stimulation device was placed on the tympanic membrane of both ears. A laser stimulation run and a placebo run were performed in random order. The participants were unable to differentiate between verum and placebo stimulation. In the comparison of verum to placebo runs, we observed significant activations within the left superior frontal gyrus, the right middle and medial frontal gyrus, the right superior parietal lobule, the left superior occipital gyrus, the precuneus and cuneus bilaterally, the right anterior and the left and right middle and posterior cingulate gyrus and the left thalamus. This network of brain areas corresponds well to results from previous PET studies of patients with tinnitus. Though TCL seems to have a clinically measurable effect on the central nervous system the neurophysiological mechanism leading to the observed activated neuronal network remains unknown.

  3. Anorectal stimulation causes increased colonic motor activity in subjects with spinal cord injury.

    Science.gov (United States)

    Korsten, Mark A; Singal, Ashwani K; Monga, Amit; Chaparala, Geeta; Khan, Amir M; Palmon, Ron; Mendoza, John Reagan D; Lirio, Juan P; Rosman, Alan S; Spungen, Ann; Bauman, William A

    2007-01-01

    Difficulty with evacuation (DWE) is a major problem after spinal cord injury (SCI). Stimulation of the anal canal and lower rectum, accomplished using a gloved finger (so-called digital rectal stimulation or DRS) is often used as an adjunct to laxatives and enemas to facilitate bowel evacuation. However, the basis for the efficacy of DRS is not known. This study assessed the effect of DRS on colonic motility. Six subjects with SCI were studied several hours after a bowel care session. Colonic motility was assessed using a manometric catheter (affixed endoscopically to the splenic flexure) at baseline, during DRS, and after DRS. In addition, evacuation of barium oatmeal paste (with the consistency of stool and introduced into the rectum and descending colon) was assessed simultaneously using fluoroscopic techniques. The mean number (+/- SEM) of peristaltic waves per minute increased from 0 at baseline to 1.9 (+/- 0.5/min) during DRS and 1.5 (+/- 0.3/min) during the period immediately after cessation of DRS (P < 0.05). The mean amplitude (+/- SEM) of the peristaltic contractions was 43.4 (+/- 2.2) mmHg. The frequency of contractions, as well as amplitude of contractions, during or immediately after DRS was not significantly different. These manometric changes in response to DRS were accompanied by expulsion of barium oatmeal paste in every subject by the fifth DRS. DRS causes left-sided colonic activity in subjects with SCI. At least in part, an anorectal colonic reflex that results in enhanced contractions of the descending colon and rectum may contribute to bowel evacuation in individuals with SCI.

  4. Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid.

    Directory of Open Access Journals (Sweden)

    Jae Sung You

    Full Text Available Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70(s6k T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

  5. Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid.

    Science.gov (United States)

    You, Jae Sung; Frey, John W; Hornberger, Troy A

    2012-01-01

    Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA) may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70(s6k) T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

  6. Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Andersen, Birgit; Westlund, Barbro; Krarup, Christian

    2003-01-01

    During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique...... to control levels within 1 min and implies that a decreased number of spinal MNs were excited. Additional TST experiments after maximal and submaximal efforts showed that the decrease in size of the TST response was related to duration and strength of exercise. Motor evoked potentials (MEPs) after...... response depression. Overall, the results suggest that the outflow from the motor cortex could become insufficient to drive all spinal MNs to discharge when the muscle is fatigued and that complex interactions between failure of activation and compensatory mechanisms to maintain motor unit activation occur...

  7. Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Andersen, Birgit; Westlund, Barbro; Krarup, Christian

    2003-01-01

    response depression. Overall, the results suggest that the outflow from the motor cortex could become insufficient to drive all spinal MNs to discharge when the muscle is fatigued and that complex interactions between failure of activation and compensatory mechanisms to maintain motor unit activation occur......During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique...... to estimate the proportion of motor units activated by a transcranial magnetic stimulus. Following a sustained contraction of the abductor digiti minimi muscle at 50 % maximal force maintained to exhaustion there was an immediate reduction of the TST response from > 95 % to about 60 %. This effect recovered...

  8. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  9. Unraveling the cellular and molecular mechanisms of repetitive magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Florian eMüller-Dahlhaus

    2013-12-01

    Full Text Available Despite numerous clinical studies, which have investigated the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS in various brain diseases, our knowledge of the cellular and molecular mechanisms underlying rTMS-based therapies remains limited. Thus, a deeper understanding of rTMS-induced neural plasticity is required to optimize current treatment protocols. Studies in small animals or appropriate in vitro preparations (including models of brain diseases provide highly useful experimental approaches in this context. State-of-the-art electrophysiological and live-cell imaging techniques that are well established in basic neuroscience can help answering some of the major questions in the field, such as (i which neural structures are activated during TMS, (ii how does rTMS induce Hebbian plasticity, and (iii are other forms of plasticity (e.g., metaplasticity, structural plasticity induced by rTMS? We argue that data gained from these studies will support the development of more effective and specific applications of rTMS in clinical practice.

  10. When does mechanical plantar stimulation promote sensory re-weighing: standing on a firm or compliant surface?

    Science.gov (United States)

    Preszner-Domjan, Andrea; Nagy, Edit; Szíver, Edit; Feher-Kiss, Anna; Horvath, Gyöngyi; Kranicz, Janos

    2012-08-01

    The purpose of this study was to investigate the effect of different types of mechanical stimulation of the sole on standing postural stability in healthy, young adults. Fifty subjects (34 women, 16 men; mean age 23 ± 2 (mean ± SE)) stood barefoot on fixed force plates both with open and closed eyes on firm surface and then on compliant surface (foam). A modified clinical test of sensory interaction on balance protocol was employed to assess the center of gravity (COG) excursions along anteroposterior (AP) and mediolateral (ML) axes on each surface and visual condition. After the baseline measurement, a stimulation was applied with an elastic spiked layer topped to the firm and then foam surface, and the COG excursions were measured during the stimulation, and then at least 30 min after the stimulation of the spiked layer, we used 10 min of manual static and glide pressure applied to the plantar surface of both feet. Immediately after manual stimulation, static balance parameters were measured again. Results showed that after manual stimulation, the sway path with closed eyes decreased significantly on the AP and ML directions on firm surface conditions. The spiked layer caused significantly decreased sway path on firm platform in both directions, but it was ineffective on compliant surface. Our results established that the activation of plantar mechanoreceptors by 10-min manual stimulation can partially compensate subjects for the absence of visual input and the lack of accurate pressure information from the supporting surface, too.

  11. POSSIBLE MECHANISMS UNDERLYING THE THERAPEUTIC EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION

    Directory of Open Access Journals (Sweden)

    Alexander eChervyakov

    2015-06-01

    Full Text Available Transcranial magnetic stimulation (TMS is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson's disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation (LTP and long-term depression (LTD. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor (BDNF concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals. It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

  12. Subjective stimulant and sedative effects of alcohol during early drinking experiences predict alcohol involvement in treated adolescents.

    Science.gov (United States)

    Chung, Tammy; Martin, Christopher S

    2009-09-01

    Research on low subjective response to alcohol has focused primarily on alcohol's sedative effects during early drinking experiences. This study examined subjective response to both stimulant and sedative effects of alcohol during initial drinking experiences as predictors of treated adolescents' severity of alcohol involvement before treatment and over 1-year follow-up. Adolescents (N = 169) recruited from addictions treatment reported on the number of drinks needed to obtain stimulant and sedative effects of alcohol for early and heavy drinking periods. The number of drinks needed to obtain stimulant and sedative effects, as well as the degree of stimulant and sedative effect obtained, were examined as predictors of adolescents' alcohol involvement at baseline (before treatment) and 1-year follow-up. During early drinking experiences, females reported a greater degree of sedative effect compared with males; there was no gender difference in degree of stimulant effect reported during early drinking experiences. Both early subjective stimulant and sedative effects of alcohol predicted the usual number of drinks needed to become intoxicated and the maximum drinking quantity per day before treatment. However, at 1-year follow-up, only early sedative effects predicted 1-year outcomes. Study findings suggest potentially important roles for both early subjective stimulant and sedative effects of alcohol in relation to adolescent alcohol involvement.

  13. No Effect of Cathodal Transcranial Direct Current Stimulation on Fear Memory in Healthy Human Subjects

    Directory of Open Access Journals (Sweden)

    Aditya Mungee

    2016-11-01

    Full Text Available Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS of the right dorsolateral prefrontal cortex during fear reconsolidation in humans. Methods: Seventeen young, healthy subjects were randomly assigned to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal—cathodal, left supraorbital—anodal for 20 min at 1 mA, or sham stimulation. A day later, fear responses of both groups were compared. Results: On Day 3, during fear response assessment, there were no significant differences between the tDCS and sham group (p > 0.05. Conclusion: We conclude that cathodal tDCS of the right dorsolateral prefrontal cortex (right prefrontal—cathodal, left supraorbital—anodal did not influence fear memories.

  14. Effects of short and prolonged transcutaneous vagus nerve stimulation on heart rate variability in healthy subjects.

    Science.gov (United States)

    De Couck, M; Cserjesi, R; Caers, R; Zijlstra, W P; Widjaja, D; Wolf, N; Luminet, O; Ellrich, J; Gidron, Y

    2017-03-01

    The vagus nerve is strategically located in the body, and has multiple homeostatic and health-promoting effects. Low vagal activity predicts onset and progression of diseases. These are the reasons to activate this nerve. This study examined the effects of transcutaneous vagus nerve stimulation (t-VNS) on a main index of vagal activity, namely heart rate variability (HRV). In Study 1, we compared short (10min) left versus right ear t-VNS versus sham (no stimulation) in a within-subjects experimental design. Results revealed significant increases in only one HRV parameter (standard deviation of the RR intervals (SDNN)) following right-ear t-VNS. Study 2 examined the prolonged effects of t-VNS (1h) in the right ear. Compared to baseline, right-t-VNS significantly increased the LF and LF/HF components of HRV, and SDNN in women, but not in men. These results show limited effects of t-VNS on HRV, and are discussed in light of neuroanatomical and statistical considerations and future directions are proposed. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Transcutaneous mechanical nerve stimulation using perineal vibration: a novel method for the treatment of female stress urinary incontinence

    DEFF Research Database (Denmark)

    Sønksen, Jens; Ohl, Dana A; Bonde, Birthe

    2007-01-01

    We defined basic guidelines for transcutaneous mechanical nerve stimulation in modifying pelvic floor responses in women and determined the efficacy of transcutaneous mechanical nerve stimulation in treating stress urinary incontinence.......We defined basic guidelines for transcutaneous mechanical nerve stimulation in modifying pelvic floor responses in women and determined the efficacy of transcutaneous mechanical nerve stimulation in treating stress urinary incontinence....

  16. Effects of Potential and Mechanical Stimulation on Oxidation of Tantalum During Electrochemical Mechanical Polishing

    Science.gov (United States)

    Gao, F.; Liang, Hong

    2012-03-01

    Metal oxidation under stress plays a significant role in many industrial applications, particularly in chemical mechanical polishing (CMP). Here we report effects of mechanical stimulation on tantalum (Ta) oxidation during CMP. A tantalum surface was polished at various anodic potentials and under different mechanical forces. A potentiostat was used to measure the anodic reaction current during electrochemical mechanical polishing (ECMP). The material removal rate (MRR) measured using atomic force microscopy (AFM) was compared with that calculated using Faraday's law. Relationship was linked (or established) between the anodic potential and a mechanical force. The MRR was a second-order polynomial function of potential at constant mechanical force, followed by a logarithmic function. It was found that more suboxides were present at extreme potentials (low and high), while substantial pentoxide was generated under intermediate potentials. A model is proposed to explain the oxidation process of Ta during ECMP. The oxidation of Ta was a function of the anodic potential and mechanical force. The ex situ method used in this study fulfilled the in situ observation on Ta oxidation in polishing. Additionally, this technique can be used to investigate oxidation of other metals.

  17. Increased probability of repetitive spinal motoneuron activation by transcranial magnetic stimulation after muscle fatigue in healthy subjects

    DEFF Research Database (Denmark)

    Andersen, Birgit; Felding, Ulrik Ascanius; Krarup, Christian

    2012-01-01

    Triple stimulation technique (TST) has previously shown that transcranial magnetic stimulation (TMS) fails to activate a proportion of spinal motoneurons (MNs) during motor fatigue. The TST response depression without attenuation of the conventional motor evoked potential suggested increased prob...... the muscle is fatigued. Repetitive MN firing may provide an adaptive mechanism to maintain motor unit activation and task performance during sustained voluntary activity.......Triple stimulation technique (TST) has previously shown that transcranial magnetic stimulation (TMS) fails to activate a proportion of spinal motoneurons (MNs) during motor fatigue. The TST response depression without attenuation of the conventional motor evoked potential suggested increased...... probability of repetitive spinal MN activation during exercise even if some MNs failed to discharge by the brain stimulus. Here we used a modified TST (Quadruple stimulation; QuadS and Quintuple stimulation; QuintS) to examine the influence of fatiguing exercise on second and third MN discharges after...

  18. Bio imaging of intracellular NO production in single bone cells after mechanical stimulation

    NARCIS (Netherlands)

    Vatsa, A.; Mizuno, D.; Smit, T.H.; Schmidt, C.; Mac Kintosh, F.C.; Klein-Nulend, J.

    2006-01-01

    We show the intracellular upregulation of NO production after mechanical stimulation, an essential chemical signal in bone remodeling. This is done in real time using the fluorescent chromophore DAR-4M AM. Differences in cellular response to mechanical stimulation of different regions of a single

  19. Binaural hearing ability with mastoid applied bilateral bone conduction stimulation in normal hearing subjects.

    Science.gov (United States)

    Stenfelt, Stefan; Zeitooni, Mehrnaz

    2013-07-01

    The ability to use binaural cues when stimulation was by bilaterally applied bone conduction (BC) transducers was investigated in 20 normal hearing participants. The results with BC stimulation were compared with normal air conduction (AC) stimulation through earphones. The binaural hearing ability was tested by spatial release from masking, binaural intelligibility level difference (BILD), binaural masking level difference (BMLD) using chirp stimulation, and test of the precedence effect. In all tests, the participants revealed a benefit of bilateral BC stimulation indicating use of binaural cues. In the speech based tests, the binaural benefit for BC stimulation was approximately half that with AC stimulation. For the BC BMLD test with chirp stimulation, there were indications of superposition of the ipsilateral and contralateral pathways at the cochlear level affecting the results. The precedence effect test indicated significantly worse results for BC stimulation than for AC stimulation with low-frequency stimulation while they were close for high-frequency stimulation; broad-band stimulation gave results that were slightly worse than the high-frequency results.

  20. Gravity dependence of the effect of optokinetic stimulation on the subjective visual vertical.

    Science.gov (United States)

    Ward, Bryan K; Bockisch, Christopher J; Caramia, Nicoletta; Bertolini, Giovanni; Tarnutzer, Alexander Andrea

    2017-05-01

    Accurate and precise estimates of direction of gravity are essential for spatial orientation. According to Bayesian theory, multisensory vestibular, visual, and proprioceptive input is centrally integrated in a weighted fashion based on the reliability of the component sensory signals. For otolithic input, a decreasing signal-to-noise ratio was demonstrated with increasing roll angle. We hypothesized that the weights of vestibular (otolithic) and extravestibular (visual/proprioceptive) sensors are roll-angle dependent and predicted an increased weight of extravestibular cues with increasing roll angle, potentially following the Bayesian hypothesis. To probe this concept, the subjective visual vertical (SVV) was assessed in different roll positions (≤ ± 120°, steps = 30°, n = 10) with/without presenting an optokinetic stimulus (velocity = ± 60°/s). The optokinetic stimulus biased the SVV toward the direction of stimulus rotation for roll angles ≥ ± 30° (P integration when estimating direction of gravity with optokinetic stimulation. Visual input was weighted more when vestibular input became less reliable, i.e., at larger roll-tilt angles. However, according to Bayesian theory, the variability of combined cues is always lower than the variability of each source cue. If the observed increase in variability, although nonsignificant, is true, either it must depend on an additional source of variability, added after SVV computation, or it would conflict with the Bayesian hypothesis.NEW & NOTEWORTHY Applying a rotating optokinetic stimulus while recording the subjective visual vertical in different whole body roll angles, we noted the optokinetic-induced bias to correlate with the roll angle. These findings allow the hypothesis that the established optimal weighting of single-sensory cues depending on their reliability to estimate direction of gravity could be extended to a bias caused by visual self-motion stimuli. Copyright © 2017 the American Physiological

  1. Normative data of cortical excitability measurements obtained by transcranial magnetic stimulation in healthy subjects.

    Science.gov (United States)

    Cueva, Ana Sofia; Galhardoni, Ricardo; Cury, Rubens Gisbert; Parravano, Daniella Cardoso; Correa, Guilherme; Araujo, Haniel; Cecilio, Sofia Barros; Raicher, Irina; Toledo, Diego; Silva, Valquíria; Marcolin, Marco Antonio; Teixeira, Manoel Jacobsen; Ciampi de Andrade, Daniel

    2016-02-01

    The assessment of cortical excitability (CE) measurements has been increasingly used in neuropsychiatric research. However, there is scant information on the normative values of these measurements, as well as the possible effect of hemisphere laterality, gender and age on these variables. To obtain normative data for CE measurements by transcranial magnetic stimulation, to assess inter-/intra-investigator variability and the influence of sex, age and oral contraception use. A sample of 216 healthy volunteers matched according to age and gender was evaluated. Bilateral rest motor thresholds, motor evoked potentials (MEP), intracortical inhibition and facilitation were measured in the first dorsal interosseous muscle area representation of the primary motor cortex with a circular transcranial magnetic stimulation coil delivering biphasic pulses. Normative data were obtained for 200 participants (in a 1:1 male:female ratio) in a balanced proportion between five age groups (18-30; 31-40; 41-50; 51-60; >60 years). Inter/intra-investigator variability was assessed in 20 healthy volunteers in two sessions performed within a 30-minute interval. Measurements were also performed in a subgroup of 16 healthy female volunteers, using oral contraception and during the menstrual phase. Age had a dichotomous effect on CE measurements, providing significantly different normative data for subjects 50 years old, with smaller MEP's and intracortical inhibition in older individuals. There were no differences between genders or between left and right hemispheres. Also, CE parameters did not significantly differ with use of contraceptive treatment compared to the menstrual phase of the cycle. The inter-/intra-investigator reliability assessment showed some variability that may not be clinically significant. Age had a non-linear effect on CE. There were non-significant differences between genders, hemispheres or with use of oral contraceptives. There was good inter

  2. Nociceptive responses to thermal and mechanical stimulations in awake pigs

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo; Petersen, Lars Jelstrup; Herskin, Mette S

    2013-01-01

    BACKGROUND: Porcine skin exhibits a high degree of homology to human skin, and the pig has recently been used as a cutaneous pain model. However, before the full potential of this novel in vivo cutaneous pain model can be achieved, several methodological aspects related to the management of awake...... animal studies in a large species require further examination. This manuscript describes the initial development of a porcine model of cutaneous nociception and focuses on interactions between the sensory modality, body size and the anatomical location of the stimulation site. METHODS: Pigs of different......, small animals exhibited lower levels of individual variability between single stimulations. CONCLUSIONS: Our data indicate that this experimental approach may be valuable for use in studies that focus on porcine cutaneous nociception....

  3. Differential effects of painful and non-painful stimulation on tactile processing in fibromyalgia syndrome and subjects with masochistic behaviour.

    Directory of Open Access Journals (Sweden)

    Bettina Pollok

    Full Text Available BACKGROUND: In healthy subjects repeated tactile stimulation in a conditioning test stimulation paradigm yields attenuation of primary (S1 and secondary (S2 somatosensory cortical activation, whereas a preceding painful stimulus results in facilitation. METHODOLOGY/PRINCIPAL FINDINGS: Since previous data suggest that cognitive processes might affect somatosensory processing in S1, the present study aims at investigating to what extent cortical reactivity is altered by the subjective estimation of pain. To this end, the effect of painful and tactile stimulation on processing of subsequently applied tactile stimuli was investigated in patients with fibromyalgia syndrome (FMS and in subjects with masochistic behaviour (MB by means of a 122-channel whole-head magnetoencephalography (MEG system. Ten patients fulfilling the criteria for the diagnosis of FMS, 10 subjects with MB and 20 control subjects matched with respect to age, gender and handedness participated in the present study. Tactile or brief painful cutaneous laser stimuli were applied as conditioning stimulus (CS followed by a tactile test stimulus (TS 500 ms later. While in FMS patients significant attenuation following conditioning tactile stimulation was evident, no facilitation following painful stimulation was found. By contrast, in subjects with MB no attenuation but significant facilitation occurred. Attenuation as well as facilitation applied to cortical responses occurring at about 70 ms but not to early S1 or S2 responses. Additionally, in FMS patients the amount of attenuation was inversely correlated with catastrophizing tendency. CONCLUSION: The present results imply altered cortical reactivity of the primary somatosensory cortex in FMS patients and MB possibly reflecting differences of individual pain experience.

  4. Brain plasticity and cortical correlates of osseoperception revealed by punctate mechanical stimulation of osseointegrated oral implants during fMRI.

    Science.gov (United States)

    Habre-Hallage, Pascale; Dricot, Laurence; Jacobs, Reinhilde; van Steenberghe, Daniel; Reychler, Hervé; Grandin, Cecile B

    2012-01-01

    Our aim was to unveil the cortical neural correlates of osseoperception, i.e. the tactile sensation perceived when loading a bone-anchored implant, by taking oral implants as a model. This was performed in a cross-sectional observational study with 9 volunteering patients and 10 age-matched controls. For each patient, functional magnetic resonance imaging (fRMI) recordings were made during punctate mechanical stimulation of either teeth or osseointegrated implants in the maxillary incisor area. During fMRI recordings, 1 Hz punctate tactile stimuli were applied either on a maxillary left central incisor, canine tooth or central incisor implant. A block design paradigm was used to stimulate, in 9 patients, maxillary left central incisor implants (I21-p) and maxillary left canines (T23-p). In 10 control subjects, maxillary left central incisors and canines (T21-c, T23-c) were stimulated. Random effect group analyses were performed for each stimulated site, and differences in cortical activity elicited when loading teeth or implants were examined using ANOVA. As a group, patients activated somatosensory area S2 bilaterally for both I21 and T23, while controls activated S1 and S2 bilaterally for T21 and T23. At an individual level, S1 was activated by 4/9 implants, mainly on the ipsilateral side. The stimulated implants activated a larger bilateral cortical network outside the somatosensory areas: in parietal, frontal and insular lobes, the main clusters being located in the inferior frontal gyri. Stimulation of T23 in patients resulted in an activation pattern intermediate between that of the implants and that of natural teeth. This study demonstrates that punctate mechanical stimulation of oral implants activates both primary and secondary cortical somatosensory areas. It also suggests that brain plasticity occurs when extracted teeth are replaced by endosseous implants. This cortical activation may represent the underlying mechanism of osseoperception.

  5. Mechanical loading prevents the stimulating effect of IL-1{beta} on osteocyte-modulated osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kulkarni, Rishikesh N.; Bakker, Astrid D.; Everts, Vincent [Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Amsterdam (Netherlands); Klein-Nulend, Jenneke, E-mail: j.kleinnulend@acta.nl [Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Amsterdam (Netherlands)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Osteocyte incubation with IL-1{beta} stimulated osteocyte-modulated osteoclastogenesis. Black-Right-Pointing-Pointer Conditioned medium from IL-1{beta}-treated osteocytes increased osteoclastogenesis. Black-Right-Pointing-Pointer IL-1{beta} upregulated RANKL and downregulated OPG gene expression by osteocytes. Black-Right-Pointing-Pointer CYR61 is upregulated in mechanically stimulated osteocytes. Black-Right-Pointing-Pointer Mechanical loading of osteocytes may abolish IL-1{beta}-induced osteoclastogenesis. -- Abstract: Inflammatory diseases such as rheumatoid arthritis are often accompanied by higher plasma and synovial fluid levels of interleukin-1{beta} (IL-1{beta}), and by increased bone resorption. Since osteocytes are known to regulate bone resorption in response to changes in mechanical stimuli, we investigated whether IL-1{beta} affects osteocyte-modulated osteoclastogenesis in the presence or absence of mechanical loading of osteocytes. MLO-Y4 osteocytes were pre-incubated with IL-1{beta} (0.1-1 ng/ml) for 24 h. Cells were either or not subjected to mechanical loading by 1 h pulsating fluid flow (PFF; 0.7 {+-} 0.3 Pa, 5 Hz) in the presence of IL-1{beta} (0.1-1 ng/ml). Conditioned medium was collected after 1 h PFF or static cultures. Subsequently mouse bone marrow cells were seeded on top of the IL-1{beta}-treated osteocytes to determine osteoclastogenesis. Conditioned medium from mechanically loaded or static IL-1{beta}-treated osteocytes was added to co-cultures of untreated osteocytes and mouse bone marrow cells. Gene expression of cysteine-rich protein 61 (CYR61/CCN1), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) by osteocytes was determined immediately after PFF. Incubation of osteocytes with IL-1{beta}, as well as conditioned medium from static IL-1{beta}-treated osteocytes increased the formation of osteoclasts. However, conditioned medium from mechanically loaded IL

  6. Biophysical Stimuli: A Review of Electrical and Mechanical Stimulation in Hyaline Cartilage.

    Science.gov (United States)

    Vaca-González, Juan J; Guevara, Johana M; Moncayo, Miguel A; Castro-Abril, Hector; Hata, Yoshie; Garzón-Alvarado, Diego A

    2017-09-01

    Objective Hyaline cartilage degenerative pathologies induce morphologic and biomechanical changes resulting in cartilage tissue damage. In pursuit of therapeutic options, electrical and mechanical stimulation have been proposed for improving tissue engineering approaches for cartilage repair. The purpose of this review was to highlight the effect of electrical stimulation and mechanical stimuli in chondrocyte behavior. Design Different information sources and the MEDLINE database were systematically revised to summarize the different contributions for the past 40 years. Results It has been shown that electric stimulation may increase cell proliferation and stimulate the synthesis of molecules associated with the extracellular matrix of the articular cartilage, such as collagen type II, aggrecan and glycosaminoglycans, while mechanical loads trigger anabolic and catabolic responses in chondrocytes. Conclusion The biophysical stimuli can increase cell proliferation and stimulate molecules associated with hyaline cartilage extracellular matrix maintenance.

  7. Animal models of transcranial direct current stimulation: Methods and mechanisms.

    Science.gov (United States)

    Jackson, Mark P; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C; Bikson, Marom

    2016-11-01

    The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: (1) transcranial stimulation; (2) direct cortical stimulation in vivo and (3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching "quasi-uniform" assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the

  8. Animal Models of transcranial Direct Current Stimulation: Methods and Mechanisms

    Science.gov (United States)

    Jackson, Mark P.; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C.; Bikson, Marom

    2016-01-01

    The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: 1) transcranial stimulation; 2) direct cortical stimulation in vivo and 3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching “quasi-uniform” assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the

  9. Cognitive stimulation therapy (CST): neuropsychological mechanisms of change.

    Science.gov (United States)

    Hall, Louise; Orrell, Martin; Stott, Joshua; Spector, Aimee

    2013-03-01

    Cognitive stimulation therapy (CST) is an evidence-based psychosocial intervention for people with dementia consisting of 14 group sessions aiming to stimulate various areas of cognition. This study examined the effects of CST on specific cognitive domains and explored the neuropsychological processes underpinning any effects. A total of 34 participants with mild to moderate dementia were included. A one-group pretest-posttest design was used. Participants completed a battery of neuropsychological tests in the week before and after the manualised seven-week CST programme. There were significant improvement pre- to post-CST group on measures of delayed verbal recall (WMS III logical memory subtest - delayed), visual memory (WMS III visual reproduction subtest - delayed), orientation (WMS III information and orientation subscale), and auditory comprehension (Token Test). There were no significant changes on measures of naming (Boston Naming Test-2), attention (Trail Making Test A/Digit Span), executive function (DKEFS verbal fluency/Trail Making Test B), praxis (WMS III visual reproduction - immediate) or on a general cognitive screen (MMSE). Memory, comprehension of syntax, and orientation appear to be the cognitive domains most impacted by CST. One hypothesis is that the language-based nature of CST enhances neural pathways responsible for processing of syntax, possibly also aiding verbal recall. Another is that the reduction in negative self-stereotypes due to the de-stigmatising effect of CST may impact on language and memory, domains that are the primary focus of CST. Further research is required to substantiate these hypotheses.

  10. Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years

    Directory of Open Access Journals (Sweden)

    Piccirillo G

    2016-11-01

    Full Text Available Gianfranco Piccirillo,1 Cristina Ottaviani,2 Claudia Fiorucci,1 Nicola Petrocchi,2 Federica Moscucci,1 Claudia Di Iorio,1 Fabiola Mastropietri,1 Ilaria Parrotta,1 Matteo Pascucci,1 Damiano Magrì3 1Department of Cardiovascular, Respiratory, Nephrological, Anestesiological and Geriatric Sciences, “Sapienza” University, 2Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, 3Department of Clinical and Molecular Medicine, University of Rome “Sapienza”, Rome, Italy Background: Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS responses. Objective: The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. Subjects and methods: In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI, and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. Results: In the older group, the QTVI, low-frequency (LF power expressed in normalized units, the ratio between LF and high-frequency (HF power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P<0.05. Conclusion: In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity. Keywords: transcranial direct current stimulation, QT variability, heart rate variability

  11. A dual flow bioreactor with controlled mechanical stimulation for cartilage tissue engineering

    OpenAIRE

    Spitters, Tim; Leijten, Jeroen Christianus Hermanus; Deus, F.D.; Costa, I.B.F.; van Apeldoorn, Aart A.; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2013-01-01

    In cartilage tissue engineering bioreactors can create a controlled environment to study chondrocyte behavior under mechanical stimulation or produce chondrogenic grafts of clinically relevant size. Here we present a novel bioreactor, which combines mechanical stimulation with a two compartment system through which nutrients can be supplied solely by diffusion from opposite sides of a tissue engineered construct. This design is based on the hypothesis that creating gradients of nutrients, gro...

  12. Determinants of the induction of cortical plasticity by non‐invasive brain stimulation in healthy subjects

    National Research Council Canada - National Science Library

    Ridding, M. C; Ziemann, U

    2010-01-01

    The ability to induce cortical plasticity with non‐invasive brain stimulation (NBS) techniques has provided novel and exciting opportunities for examining the role of the human cortex during a variety of behaviours...

  13. Mechanism of attenuation of leptin signaling under chronic ligand stimulation

    Directory of Open Access Journals (Sweden)

    Bamberg-Lemper Simone

    2010-01-01

    Full Text Available Abstract Background Leptin is an adipocyte-derived hormone that acts via its hypothalamic receptor (LEPRb to regulate energy balance. A downstream effect essential for the weight-regulatory action of leptin is the phosphorylation and activation of the latent transcription factor STAT3 by LEPRb-associated Janus kinases (JAKs. Obesity is typically associated with chronically elevated leptin levels and a decreased ability of LEPRb to activate intracellular signal transduction pathways (leptin resistance. Here we have studied the roles of the intracellular tyrosine residues in the negative feedback regulation of LEPRb-signaling under chronic leptin stimulation. Results Mutational analysis showed that the presence of either Tyr985 and Tyr1077 in the intracellular domain of LEPRb was sufficient for the attenuation of STAT3 phosphorylation, whereas mutation of both tyrosines rendered LEPRb resistant to feedback regulation. Overexpression and RNA interference-mediated downregulation of suppressor of cytokine signaling 3 (SOCS3 revealed that both Tyr985 and Tyr1077 were capable of supporting the negative modulatory effect of SOCS3 in reporter gene assays. In contrast, the inhibitory effect of SOCS1 was enhanced by the presence of Tyr985 but not Tyr1077. Finally, the reduction of the STAT-phosphorylating activity of the LEPRb complex after 2 h of leptin stimulation was not accompanied by the dephosphorylation or degradation of LEPRb or the receptor-associated JAK molecule, but depended on Tyr985 and/or Tyr1077. Conclusions Both Tyr985 and Tyr1077 contribute to the negative regulation of LEPRb signaling. The inhibitory effects of SOCS1 and SOCS3 differ in the dependence on the tyrosine residues in the intracellular domain of LEPRb.

  14. Human brain activity associated with painful mechanical stimulation to muscle and bone.

    Science.gov (United States)

    Maeda, Lynn; Ono, Mayu; Koyama, Tetsuo; Oshiro, Yoshitetsu; Sumitani, Masahiko; Mashimo, Takashi; Shibata, Masahiko

    2011-08-01

    The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.

  15. Mechanical stimulation in the engineering of heart muscle.

    Science.gov (United States)

    Liaw, Norman Yu; Zimmermann, Wolfram-Hubertus

    2016-01-15

    Recreating the beating heart in the laboratory continues to be a formidable bioengineering challenge. The fundamental feature of the heart is its pumping action, requiring considerable mechanical forces to compress a blood filled chamber with a defined in- and outlet. Ventricular output crucially depends on venous loading of the ventricles (preload) and on the force generated by the preloaded ventricles to overcome arterial blood pressure (afterload). The rate of contraction is controlled by the spontaneously active sinus node and transmission of its electrical impulses into the ventricles. The underlying principles for these physiological processes are described by the Frank-Starling mechanism and Bowditch phenomenon. It is essential to consider these principles in the design and evaluation of tissue engineered myocardium. This review focuses on current strategies to evoke mechanical loading in hydrogel-based heart muscle engineering. Copyright © 2015. Published by Elsevier B.V.

  16. Subjectivity

    Directory of Open Access Journals (Sweden)

    Jesús Vega Encabo

    2015-11-01

    Full Text Available In this paper, I claim that subjectivity is a way of being that is constituted through a set of practices in which the self is subject to the dangers of fictionalizing and plotting her life and self-image. I examine some ways of becoming subject through narratives and through theatrical performance before others. Through these practices, a real and active subjectivity is revealed, capable of self-knowledge and self-transformation. 

  17. Modal Testing of Mechanical Structures Subject to Operational Excitation Forces

    DEFF Research Database (Denmark)

    Møller, N.; Brincker, Rune; Herlufsen, H.

    2000-01-01

    Operational Modal Analysis also known as Output Only Modal Analysis has in the recent years been used for extracting modal parameters of civil engineering structures and is now becoming popular for mechanical structures. The advantage of the method is that no artificial excitation need to be appl...

  18. Modal Testing of Mechanical Structures subject to Operational Excitation Forces

    DEFF Research Database (Denmark)

    Møller, N.; Brincker, Rune; Herlufsen, H.

    2001-01-01

    Operational Modal Analysis also known as Output Only Modal Analysis has in the recent years been used for extracting modal parameters of civil engineering structures and is now becoming popular for mechanical structures. The advantage of the method is that no artificial excitation need to be appl...

  19. Mechanical stimulation increases proliferation, differentiation and protein expression in culture

    DEFF Research Database (Denmark)

    Grossi, Alberto; Yadav, Kavita; Lawson, Moira Ann

    2007-01-01

    -induced signaling is now beginning to be understood as a factor which affects various signal transduction pathways, gene sequences and protein synthesis. One indication of which cells are competent to undergo the fusion process is their expression of two proteins, Myo-D and myogenin. The mechanism by which...

  20. Effects of exercise and electrical stimulation on lumbar stabilization in asymptomatic subjects: a comparative study.

    Science.gov (United States)

    Bilgin, Sevil; Temucin, Cagrı Mesut; Nurlu, Gulay; Kaya, Derya Ozer; Kose, Nezire; Gunduz, Arzu Guclu

    2013-01-01

    Segmental stabilization training and electrical stimulation are used as a treatment for patients with low back pain. There is limited information on the efficacy of two interventions in the literature. In this study, the efficacy of the two interventions on the multifidus muscle activation and fatigue, segmental stabilization training and electrical stimulation, were examined and compared. Our sample consists of 30 asymptomatic individuals, randomly assigned to one of three groups: the group that was given segmental stabilization training, the group that was given electrical stimulation and the control group that received no treatment. The muscle activity and fatigability of the multifidus were recorded by the surface electromyography before and after the intervention. No difference is detected for any of the multifidus muscle activation and fatigue characteristics either within or between groups. Both techniques did not improve multifidus activation capacity. An effort at submaximal and maximal level affects and increases the activity of multifidus.

  1. Tissue heterogeneity as a mechanism for localized neural stimulation by applied electric fields

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, P C [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Correia, L [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Salvador, R [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Basser, P J [Section on Tissue Biophysics and Biomimetics, NICHD, National Institutes of Health, Bethesda, MD 20892-1428 (United States)

    2007-09-21

    We investigate the heterogeneity of electrical conductivity as a new mechanism to stimulate excitable tissues via applied electric fields. In particular, we show that stimulation of axons crossing internal boundaries can occur at boundaries where the electric conductivity of the volume conductor changes abruptly. The effectiveness of this and other stimulation mechanisms was compared by means of models and computer simulations in the context of transcranial magnetic stimulation. While, for a given stimulation intensity, the largest membrane depolarization occurred where an axon terminates or bends sharply in a high electric field region, a slightly smaller membrane depolarization, still sufficient to generate action potentials, also occurred at an internal boundary where the conductivity jumped from 0.143 S m{sup -1} to 0.333 S m{sup -1}, simulating a white-matter-grey-matter interface. Tissue heterogeneity can also give rise to local electric field gradients that are considerably stronger and more focal than those impressed by the stimulation coil and that can affect the membrane potential, albeit to a lesser extent than the two mechanisms mentioned above. Tissue heterogeneity may play an important role in electric and magnetic 'far-field' stimulation.

  2. The efficiency of simultaneous binaural ocular vestibular evoked myogenic potentials: a comparative study with monaural acoustic stimulation in healthy subjects.

    Science.gov (United States)

    Kim, Min-Beom; Ban, Jae Ho

    2012-12-01

    To evaluate the test-retest reliability and convenience of simultaneous binaural acoustic-evoked ocular vestibular evoked myogenic potentials (oVEMP). Thirteen healthy subjects with no history of ear diseases participated in this study. All subjects underwent oVEMP test with both separated monaural acoustic stimulation and simultaneous binaural acoustic stimulation. For evaluating test-retest reliability, three repetitive sessions were performed in each ear for calculating the intraclass correlation coefficient (ICC) for both monaural and binaural tests. We analyzed data from the biphasic n1-p1 complex, such as latency of peak, inter-peak amplitude, and asymmetric ratio of amplitude in both ears. Finally, we checked the total time required to complete each test for evaluating test convenience. No significant difference was observed in amplitude and asymmetric ratio in comparison between monaural and binaural oVEMP. However, latency was slightly delayed in binaural oVEMP. In test-retest reliability analysis, binaural oVEMP showed excellent ICC values ranging from 0.68 to 0.98 in latency, asymmetric ratio, and inter-peak amplitude. Additionally, the test time was shorter in binaural than monaural oVEMP. oVEMP elicited from binaural acoustic stimulation yields similar satisfactory results as monaural stimulation. Further, excellent test-retest reliability and shorter test time were achieved in binaural than in monaural oVEMP.

  3. Mechanical Stimulation Modifies Canopy Architecture and Improves Volume Utilization Efficiency in Bell Pepper: Implications for Bioregenerative Life-support and Vertical Farming

    Directory of Open Access Journals (Sweden)

    Graham Thomas

    2017-02-01

    Full Text Available Mechanical stimuli or stress has been shown to induce characteristic morphogenic responses (thigmomorphogenesis in a range of crop species. The typical mechanically stimulated phenotype is shorter and more compact than non-mechanically stimulated plants. This dwarfing effect can be employed to help conform crop plants to the constraints of spaceflight and vertical agriculture crop production systems. Capsicum annum (cv. California Wonder plants were grown in controlled environment chambers and subjected to mechanical stimulation in the form of firm but gentle daily rubbing of internode tissue with a tightly wrapped cotton swab. Two studies were conducted, the first being a vegetative growth phase study in which plants were mechanically stimulated until anthesis. The second study carried the mechanical stimulation through to fruit set. The response during the vegetative growth experiment was consistent with other results in the literature, with a general reduction in all plant growth metrics and an increase in relative chlorophyll (SPAD content under mechanical stimulation. In the fruiting phase study, only height and stem thickness differed from the control plants. Using the data from the fruiting study, a rudimentary calculation of volume use efficiency (VUE improvements was conducted. Results suggest that VUE can be improved, particularly in terrestrial vertical agriculture systems that can take advantage of moderate height reductions by exploiting much greater vertical capacity in the production system. Mechanical stimulation can also improve VUE in spaceflight applications by reducing vertical system requirements or by expanding the species range that can be grown in a fixed production volume. Mechanical stimulation is also discussed as a microgravity countermeasure for crop plants.

  4. Suppression of EMG activity by transcranial magnetic stimulation in human subjects during walking

    DEFF Research Database (Denmark)

    Petersen, Nicolas Caesar; Butler, Jane E; Marchand-Pauvert, Veronique

    2001-01-01

    1. The involvement of the motor cortex during human walking was evaluated using transcranial magnetic stimulation (TMS) of the motor cortex at a variety of intensities. Recordings of EMG activity in tibialis anterior (TA) and soleus muscles during walking were rectified and averaged. 2. TMS of lo...

  5. Thyroid peroxidase antibodies, levels of thyroid stimulating hormone and development of hypothyroidism in euthyroid subjects

    NARCIS (Netherlands)

    Roos, A.; Links, T.P.; de Jong-van den Berg, L.T.; Gans, R.O.; Wolffenbuttel, B.H.; Bakker, S.J.

    2010-01-01

    Objective: Thyroid peroxidase antibodies (TPOAbs) have been found to be related to the levels of thyroid stimulating hormone (TSH) and to predict future development of thyroid failure in selected populations. We investigated these relations in a euthyroid general population. Design: Cross-sectional

  6. Modal Testing of Mechanical Structures Subject to Operational Excitation Forces

    DEFF Research Database (Denmark)

    Møller, N.; Brincker, Rune; Herlufsen, H.

    2000-01-01

    Operational Modal Analysis also known as Output Only Modal Analysis has in the recent years been used for extracting modal parameters of civil engineering structures and is now becoming popular for mechanical structures. The advantage of the method is that no artificial excitation need...... to the Operational Modal Analysis. For Operational Modal Analysis two different estimation techniques are used: a non-parametric technique based on Frequency Domain Decomposition (FDD), and a parametric technique working on the raw data in time domain, a data driven Stochastic Subspace Identification (SSI) algorithm....... These are compared to other methods such as traditional Modal Analysis....

  7. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Brady, Robert T. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); O' Brien, Fergal J. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Hoey, David A., E-mail: david.hoey@ul.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); The Centre for Applied Biomedical Engineering Research, University of Limerick (Ireland); Materials & Surface Science Institute, University of Limerick (Ireland)

    2015-03-27

    Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

  8. Modelling the thermal quenching mechanism in quartz based on time-resolved optically stimulated luminescence

    DEFF Research Database (Denmark)

    Pagonis, V.; Ankjærgaard, Christina; Murray, Andrew

    2010-01-01

    This paper presents a new numerical model for thermal quenching in quartz, based on the previously suggested Mott–Seitz mechanism. In the model electrons from a dosimetric trap are raised by optical or thermal stimulation into the conduction band, followed by an electronic transition from...... simulations are carried out of time-resolved optically stimulated luminescence (TR-OSL) experiments, in which the temperature dependence of luminescence lifetimes in quartz is studied as a function of the stimulation temperature. Good quantitative agreement is found between the simulation results and new...... experimental data obtained using a single-aliquot procedure on a sedimentary quartz sample....

  9. Response mechanisms of attached premixed flames subjected to harmonic forcing

    Science.gov (United States)

    Shreekrishna

    vicinity of typical screech frequencies in gas turbine combustors. The nonlinear response problem is exclusively studied in the case of equivalence ratio coupling. Various nonlinearity mechanisms are identified, amongst which the crossover mechanisms, viz., stoichiometric and flammability crossovers, are seen to be responsible in causing saturation in the overall heat release magnitude of the flame. The response physics remain the same across various preheat temperatures and reactant pressures. Finally, comparisons between the chemiluminescence transfer function obtained experimentally and the heat release transfer functions obtained from the reduced order model (ROM) are performed for lean, CH4/Air swirl-stabilized, axisymmetric V-flames. While the comparison between the phases of the experimental and theoretical transfer functions are encouraging, their magnitudes show disagreement at lower Strouhal number gains show disagreement.

  10. Mechanical ventilation in patients subjected to extracorporeal membrane oxygenation (ECMO).

    Science.gov (United States)

    López Sanchez, M

    2017-11-01

    Mechanical ventilation (MV) is a crucial element in the management of acute respiratory distress syndrome (ARDS), because there is high level evidence that a low tidal volume of 6ml/kg (protective ventilation) improves survival. In these patients with refractory respiratory insufficiency, venovenous extracorporeal membrane oxygenation (ECMO) can be used. This salvage technique improves oxygenation, promotes CO2 clearance, and facilitates protective and ultraprotective MV, potentially minimizing ventilation-induced lung injury. Although numerous trials have investigated different ventilation strategies in patients with ARDS, consensus is lacking on the optimal MV settings during venovenous ECMO. Although the concept of "lung rest" was introduced years ago, there are no evidence-based guidelines on its use in application to MV in patients supported by ECMO. How MV in ECMO patients can promote lung recovery and weaning from ventilation is not clear. The purpose of this review is to describe the ventilation strategies used during venovenous ECMO in clinical practice. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  11. Objective QbTest and subjective evaluation of stimulant treatment in adult attention deficit-hyperactivity disorder.

    Science.gov (United States)

    Bijlenga, D; Jasperse, M; Gehlhaar, S K; Sandra Kooij, J J

    2015-01-01

    To evaluate the QbTest as an objective measure versus self-reported ADHD Rating Scale (ADHD-RS) before and during stimulant treatment in adults with ADHD. We used the subjective ADHD Rating Scale (ADHD-RS), and the objective computerized QbTest, which is a 20-minute unconditional identical pairs test that measures attention, impulsivity, and also hyperactivity using a motion-tracking system. Patients were assessed before (baseline) and during medical treatment with stimulants (follow-up) in an observational study design. Data of n=145 patients at baseline and n=82 patients at follow-up were analyzed. There were significant symptom reductions on all symptom domains, but correlations between the tests were weak. Improvement on the QbTest was independent of the patient's age, gender, educational level, ADHD subtype, co-morbid disorders, and use of other medications. Patients with worst QbTest results at baseline showed most improvement at follow-up. The QbTest was more sensitive to medication effects than the ADHD-RS. QbTest objectified clinical significant medication effect in 54% of patients who subjectively did not report any clinical effects. Symptoms dimensions of objective and subjective tests refer to different psychological constructs. The QbTest is a valuable addition to existing subjective measures to assess medication effects in ADHD patients who have difficulties reporting treatment effects. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Characterising the effects of in vitro mechanical stimulation on morphogenesis of developing limb explants.

    Science.gov (United States)

    Chandaria, Vikesh V; McGinty, James; Nowlan, Niamh C

    2016-11-07

    Mechanical forces due to fetal movements play an important role in joint shape morphogenesis, and abnormalities of the joints relating to abnormal fetal movements can have long-term health implications. While mechanical stimulation during development has been shown to be important for joint shape, the relationship between the quantity of mechanical stimulation and the growth and shape change of developing cartilage has not been quantified. In this study, we culture embryonic chick limb explants in vitro in order to reveal how the magnitude of applied movement affects key aspects of the developing joint shape. We hypothesise that joint shape is affected by movement magnitude in a dose-dependent manner, and that a movement regime most representative of physiological fetal movements will promote characteristics of normal shape development. Chick hindlimbs harvested at seven days of incubation were cultured for six days, under either static conditions or one of three different dynamic movement regimes, then assessed for joint shape, cell survival and proliferation. We demonstrate that a physiological magnitude of movement in vitro promotes the most normal progression of joint morphogenesis, and that either under-stimulation or over-stimulation has detrimental effects. Providing insight into the optimal level of mechanical stimulation for cartilage growth and morphogenesis is pertinent to gaining a greater understanding of the etiology of conditions such as developmental dysplasia of the hip, and is also valuable for cartilage tissue engineering. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Mechanical stimulation evokes rapid increases in extracellular adenosine concentration in the prefrontal cortex

    Science.gov (United States)

    Ross, Ashley E.; Nguyen, Michael D.; Privman, Eve; Venton, B. Jill

    2014-01-01

    Mechanical perturbations can release ATP, which is broken down to adenosine. In this work, we used carbon-fiber microelectrodes and fast-scan cyclic voltammetry to measure mechanically-stimulated adenosine in the brain by lowering the electrode 50 μm. Mechanical stimulation evoked adenosine in vivo (average: 3.3 ± 0.6 μM) and in brain slices (average: 0.8 ± 0.1 μM) in the prefrontal cortex. The release was transient, lasting 18 ± 2 s. Lowering a 15 μm diameter glass pipette near the carbon-fiber microelectrode produced similar results as lowering the actual microelectrode. However, applying a small puff of artificial cerebral spinal fluid was not sufficient to evoke adenosine. Multiple stimulations within a 50 μm region of a slice did not significantly change over time or damage cells. Chelating calcium with EDTA or blocking sodium channels with tetrodotoxin (TTX) significantly decreased mechanically evoked adenosine, signifying that the release is activity-dependent. An alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), did not affect mechanically-stimulated adenosine; however, the nucleoside triphosphate diphosphohydrolase 1,2 and 3 (NTDPase) inhibitor POM-1 significantly reduced adenosine so a portion of adenosine is dependent on extracellular ATP metabolism. Thus, mechanical perturbations from inserting a probe in the brain cause rapid, transient adenosine signaling which might be neuroprotective. PMID:24606335

  14. Mechanisms for chelator stimulation of microbial Fe(III) -oxide reduction

    Science.gov (United States)

    Lovley, D.R.; Woodward, J.C.

    1996-01-01

    The mechanisms by which nitrilotriacetic acid (NTA) stimulated Fe(III) reduction in sediments from a petroleum-contaminated aquifer were investigated in order to gain insight into how added Fe(III) chelators stimulate the activity of hydrocarbon-degrading, Fe(III)-reducing microorganisms in these sediments, and how naturally occurring Fe(III) chelators might promote Fe(III) reduction in aquatic sediments. NTA solubilized Fe(III) from the aquifer sediments. NTA stimulation of microbial Fe(III) reduction did not appear to be the result of making calcium, magnesium, potassium, or trace metals more available to the microorganisms. Stimulation of Fe(III) reduction could not be attributed to NTA serving as a source of carbon or fixed nitrogen for Fe(III)-reducing bacteria as NTA was not degraded in the sediments. Studies with the Fe(III)-reducing microorganism, Geobacter metallireducens, and pure Fe(III)-oxide forms, demonstrated that NTA stimulated the reduction of a variety of Fe(III) forms, including highly crystalline Fe(III)-oxides such as goethite and hematite. The results suggest that NTA solubilization of insoluble Fe(III)-oxide is an important mechanism for the stimulation of Fe(III) reduction by NTA in aquifer sediments.

  15. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia

    DEFF Research Database (Denmark)

    Meier, J J; Gallwitz, B; Siepmann, N

    2003-01-01

    secretion under normoglycaemic conditions. METHODS: Ten healthy subjects (9 men, 1 woman; age 33+/-11; BMI 26.8+/-2.2 kg/m(2)) received three different doses of intravenous GIP (7, 20, and 60 pmol/kg body weight) and placebo. Venous blood samples were drawn over 30 min for glucagon and GIP concentrations...

  16. Substrate utilization and thermogenic responses to beta-adrenergic stimulation in obese subjects with NIDDM

    NARCIS (Netherlands)

    Blaak, E E; Saris, W H; Wolffenbuttel, B H

    OBJECTIVE: This study intended to investigate disturbances in beta-adrenergically-mediated substrate utilization and thermogenesis in obese subjects with mild non insulin-dependent diabetes mellitus (NIDDM). DESIGN: Following a baseline period of 30 min, the beta-agonist isoproterenol (ISO) was

  17. Building gyms for cells - development of combinatorial screening platforms for mechanical stimulation

    NARCIS (Netherlands)

    Sinha, Ravi

    2017-01-01

    This thesis describes the development and validation of medium throughput combinatorial screening platforms for mechanical stimulation of cells. The developed platforms allow for the simultaneous application of substrate strains and flow-induced shear stresses to cells and can test for 100

  18. Probing cell structure responses through a shear and stretching mechanical stimulation technique.

    Science.gov (United States)

    Steward, Robert L; Cheng, Chao-Min; Wang, Danny L; LeDuc, Philip R

    2010-04-01

    Cells are complex, dynamic systems that respond to various in vivo stimuli including chemical, mechanical, and scaffolding alterations. The influence of mechanics on cells is especially important in physiological areas that dictate what modes of mechanics exist. Complex, multivariate physiological responses can result from multi-factorial, multi-mode mechanics, including tension, compression, or shear stresses. In this study, we present a novel device based on elastomeric materials that allowed us to stimulate NIH 3T3 fibroblasts through uniaxial strip stretching or shear fluid flow. Cell shape and structural response was observed using conventional approaches such as fluorescent microscopy. Cell orientation and actin cytoskeleton alignment along the direction of applied force were observed to occur after an initial 3 h time period for shear fluid flow and static uniaxial strip stretching experiments although these two directions of alignment were oriented orthogonal relative to each other. This response was then followed by an increasingly pronounced cell and actin cytoskeleton alignment parallel to the direction of force after 6, 12, and 24 h, with 85% of the cells aligned along the direction of force after 24 h. These results indicate that our novel device could be implemented to study the effects of multiple modes of mechanical stimulation on living cells while probing their structural response especially with respect to competing directions of alignment and orientation under these different modes of mechanical stimulation. We believe that this will be important in a diversity of fields including cell mechanotransduction, cell-material interactions, biophysics, and tissue engineering.

  19. Dominant negative Bmp5 mutation reveals key role of BMPs in skeletal response to mechanical stimulation

    Directory of Open Access Journals (Sweden)

    Kingsley David M

    2008-04-01

    Full Text Available Abstract Background Over a hundred years ago, Wolff originally observed that bone growth and remodeling are exquisitely sensitive to mechanical forces acting on the skeleton. Clinical studies have noted that the size and the strength of bone increase with weight bearing and muscular activity and decrease with bed rest and disuse. Although the processes of mechanotransduction and functional response of bone to mechanical strain have been extensively studied, the molecular signaling mechanisms that mediate the response of bone cells to mechanical stimulation remain unclear. Results Here, we identify a novel germline mutation at the mouse Bone morphogenetic protein 5 (Bmp5 locus. Genetic analysis shows that the mutation occurs at a site encoding the proteolytic processing sequence of the BMP5 protein and blocks proper processing of BMP5. Anatomic studies reveal that this mutation affects the formation of multiple skeletal features including several muscle-induced skeletal sites in vivo. Biomechanical studies of osteoblasts from these anatomic sites show that the mutation inhibits the proper response of bone cells to mechanical stimulation. Conclusion The results from these genetic, biochemical, and biomechanical studies suggest that BMPs are required not only for skeletal patterning during embryonic development, but also for bone response and remodeling to mechanical stimulation at specific anatomic sites in the skeleton.

  20. Modification of electrical pain threshold by voluntary breathing-controlled electrical stimulation (BreEStim in healthy subjects.

    Directory of Open Access Journals (Sweden)

    Shengai Li

    Full Text Available BACKGROUND: Pain has a distinct sensory and affective (i.e., unpleasantness component. BreEStim, during which electrical stimulation is delivered during voluntary breathing, has been shown to selectively reduce the affective component of post-amputation phantom pain. The objective was to examine whether BreEStim increases pain threshold such that subjects could have improved tolerance of sensation of painful stimuli. METHODS: Eleven pain-free healthy subjects (7 males, 4 females participated in the study. All subjects received BreEStim (100 stimuli and conventional electrical stimulation (EStim, 100 stimuli to two acupuncture points (Neiguan and Weiguan of the dominant hand in a random order. The two different treatments were provided at least three days apart. Painful, but tolerable electrical stimuli were delivered randomly during EStim, but were triggered by effortful inhalation during BreEStim. Measurements of tactile sensation threshold, electrical sensation and electrical pain thresholds, thermal (cold sensation, warm sensation, cold pain and heat pain thresholds were recorded from the thenar eminence of both hands. These measurements were taken pre-intervention and 10-min post-intervention. RESULTS: There was no difference in the pre-intervention baseline measurement of all thresholds between BreEStim and EStim. The electrical pain threshold significantly increased after BreEStim (27.5±6.7% for the dominant hand and 28.5±10.8% for the non-dominant hand, respectively. The electrical pain threshold significantly decreased after EStim (9.1±2.8% for the dominant hand and 10.2±4.6% for the non-dominant hand, respectively (F[1, 10] = 30.992, p = .00024. There was no statistically significant change in other thresholds after BreEStim and EStim. The intensity of electrical stimuli was progressively increased, but no difference was found between BreEStim and EStim. CONCLUSION: Voluntary breathing controlled electrical stimulation

  1. Enhanced balance associated with coordination training with stochastic resonance stimulation in subjects with functional ankle instability: an experimental trial

    Directory of Open Access Journals (Sweden)

    Brown Cathleen N

    2007-12-01

    Full Text Available Abstract Background Ankle sprains are common injuries that often lead to functional ankle instability (FAI, which is a pathology defined by sensations of instability at the ankle and recurrent ankle sprain injury. Poor postural stability has been associated with FAI, and sports medicine clinicians rehabilitate balance deficits to prevent ankle sprains. Subsensory electrical noise known as stochastic resonance (SR stimulation has been used in conjunction with coordination training to improve dynamic postural instabilities associated with FAI. However, unlike static postural deficits, dynamic impairments have not been indicative of ankle sprain injury. Therefore, the purpose of this study was to examine the effects of coordination training with or without SR stimulation on static postural stability. Improving postural instabilities associated with FAI has implications for increasing ankle joint stability and decreasing recurrent ankle sprains. Methods This study was conducted in a research laboratory. Thirty subjects with FAI were randomly assigned to either a: 1 conventional coordination training group (CCT; 2 SR stimulation coordination training group (SCT; or 3 control group. Training groups performed coordination exercises for six weeks. The SCT group received SR stimulation during training, while the CCT group only performed coordination training. Single leg postural stability was measured after the completion of balance training. Static postural stability was quantified on a force plate using anterior/posterior (A/P and medial/lateral (M/L center-of-pressure velocity (COPvel, M/L COP standard deviation (COPsd, M/L COP maximum excursion (COPmax, and COP area (COParea. Results Treatment effects comparing posttest to pretest COP measures were highest for the SCT group. At posttest, the SCT group had reduced A/P COPvel (2.3 ± 0.4 cm/s vs. 2.7 ± 0.6 cm/s, M/L COPvel (2.6 ± 0.5 cm/s vs. 2.9 ± 0.5 cm/s, M/L COPsd (0.63 ± 0.12 cm vs. 0.73 ± 0

  2. Stimulation from Cochlear Implant Electrodes Assists with Recovery from Asymmetric Perceptual Tilt: Evidence from the Subjective Visual Vertical Test

    Directory of Open Access Journals (Sweden)

    Joshua J. Gnanasegaram

    2016-09-01

    Full Text Available Vestibular end organ impairment is highly prevalent in children who have sensorineural hearing loss (SNHL rehabilitated with cochlear implants (CIs. As a result, spatial perception is likely to be impacted in this population. Of particular interest is the perception of visual vertical because it reflects a perceptual tilt in the roll axis and is sensitive to an imbalance in otolith function. The objectives of the present study were thus to identify abnormalities in perception of the vertical plane in children with SNHL and determine whether such abnormalities could be resolved with stimulation from the CI. Participants included 53 children (15.2±4.0 years of age with SNHL and vestibular loss, confirmed with vestibular evoked myogenic potential testing. Testing protocol was validated in a sample of 9 young adults with normal hearing (28.8±7.7 years. Perception of visual vertical was assessed using the static Subjective Visual Vertical (SVV test performed with and without stimulation in the participants with cochleovestibular loss. Trains of electrical pulses were delivered by an electrode in the left and/or right ear. Asymmetric spatial orientation deficits were found in nearly half of the participants with CIs (24/53 [45%]. The abnormal perception in this cohort was exacerbated by visual tilts in the direction of their deficit. Electric pulse trains delivered using the CI shifted this abnormal perception towards centre (i.e., normal [p = 0.007]. Importantly, this benefit was realized regardless of which ear was stimulated. These results suggest a role for CI stimulation beyond the auditory system, in particular, for improving vestibular/balance function.

  3. The researcher as experimental subject: using self-experimentation to access experiences, understand social phenomena, and stimulate reflexivity.

    Science.gov (United States)

    Corti, Kevin; Reddy, Geetha; Choi, Ellen; Gillespie, Alex

    2015-06-01

    The current article argues that researcher-as-subject self-experimentation can provide valuable insight and systematic knowledge to social psychologists. This approach, the modus operandi of experimental psychology when the field was in its infancy, has been largely eclipsed by an almost exclusive focus on participant-as-subject other-experimentation. Drawing from the non-experimental first-person traditions of autoethnography, participant observation, and phenomenology, we argue that participating as both observer and subject within one's own social psychological experiment affords researchers at least three potential benefits: (1) access to "social qualia," that is, the subjective experience of social phenomena; (2) improved mental models of social phenomena, potentially stimulating new research questions; and (3) an enhanced ability to be reflexive about the given experiment. To support our position, we provide first-person self-reflections from researchers who have self-experimented with transformed social interactions involving Milgram's cyranoid method. We close by offering guidelines on how one might approach self-experimentation, and discuss a variety of first-person perspective ethnographic technologies that can be incorporated into the practice.

  4. Acylation stimulating protein, complement C3 and lipid metabolism in ketosis-prone diabetic subjects.

    Directory of Open Access Journals (Sweden)

    Yan Liu

    Full Text Available Ketosis-prone diabetes (KPDM is new-onset diabetic ketoacidosis without precipitating factors in non-type 1 diabetic patients; after management, some are withdrawn from exogenous insulin, although determining factors remain unclear.Twenty KPDM patients and twelve type 1 diabetic patients (T1DM, evaluated at baseline, 12 and 24 months with/without insulin maintenance underwent a standardized mixed-meal tolerance test (MMTT for 2 h.At baseline, triglyceride and C3 were higher during MMTT in KPDM vs. T1DM (p<0.0001 with no differences in non-esterified fatty acids (NEFA while Acylation Stimulating Protein (ASP tended to be higher. Within 12 months, 11 KPDM were withdrawn from insulin treatment (KPDM-ins, while 9 were maintained (KPDM+ins. NEFA was lower in KPDM-ins vs. KPDM+ins at baseline (p = 0.0006, 12 months (p<0.0001 and 24 months (p<0.0001 during MMTT. NEFA in KPDM-ins decreased over 30-120 minutes (p<0.05, but not in KPDM+ins. Overall, C3 was higher in KPDM-ins vs KPDM+ins at 12 months (p = 0.0081 and 24 months (p = 0.0019, while ASP was lower at baseline (p = 0.0024 and 12 months (p = 0.0281, with a decrease in ASP/C3 ratio.Notwithstanding greater adiposity in KPDM-ins, greater NEFA decreases and lower ASP levels during MMTT suggest better insulin and ASP sensitivity in these patients.

  5. Slip behaviour of carbonate-bearing faults subjected to fluid pressure stimulations

    Science.gov (United States)

    Collettini, Cristiano; Scuderi, Marco; Marone, Chris

    2017-04-01

    Earthquakes caused by fluid injection within reservoir have become an important topic of political and social discussion as new drilling and improved technologies enable the extraction of oil and gas from previously unproductive formations. During reservoir stimulation, the coupled interactions of frictional and fluid flow properties together with the stress state control both the onset of fault slip and fault slip behaviour. However, currently, there are no studies under controlled, laboratory conditions for which the effect of fluid pressure on fault slip behaviour can be deduced. To cover this gap, we have developed laboratory experiments where we monitor fault slip evolution at constant shear stress but with increasing fluid pressure, i.e. reducing the effective normal stress. Experiments have been conducted in the double direct shear configuration within a pressure vessel on carbonate fault gouge, characterized by a slightly velocity strengthening friction that is indicative of stable aseismic creep. In our experiments fault slip history can be divided in three main stages: 1) for high effective normal stress the fault is locked and undergoes compaction; 2) when the shear and effective normal stress reach the failure condition, accelerated creep is associated to fault dilation; 3) further pressurization leads to an exponential acceleration during fault compaction and slip localization. Our results indicate that fault weakening induced by fluid pressurization overcomes the velocity strengthening behaviour of calcite gouge, resulting in fast acceleration and earthquake slip. As applied to tectonic faults our results suggest that a larger number of crustal faults, including those slightly velocity strengthening, can experience earthquake slip due to fluid pressurization.

  6. Physical and Cognitive Stimulation Using an Exergame in Subjects with Normal Aging, Mild and Moderate Cognitive Impairment.

    Science.gov (United States)

    Ben-Sadoun, Grégory; Sacco, Guillaume; Manera, Valeria; Bourgeois, Jérémy; König, Alexandra; Foulon, Pierre; Fosty, Baptiste; Bremond, François; d'Arripe-Longueville, Fabienne; Robert, Philippe

    2016-06-30

    The use of Serious exerGames (SeG) as enriched environments (EE), which promotes cognitive simulation with physical activity in a positive emotional context, has been proposed to represent a powerful method to slow down the decline due to neurodegenerative diseases (ND), such as Alzheimer's disease (AD). However, so far, no SeG targeting EE has been tested in ND subjects. This study aimed at evaluating the usability and short-term training effects of X-Torp, an action SeG designed for elderly ND subjects with mild cognitive impairment (MCI) and AD. X-Torp is a SeG played using the Microsoft® Kinect™. 10 ND subjects and 8 healthy elderly controls (HEC) were enrolled in a 1-month program with three training sessions per week. Usability was evaluated through game time, game performance, the aerobic intensity level reached, perceived emotions, and perceived usability. All participants successfully completed the training program. ND subjects played less and had a lower game performance compared to HEC. During the sessions, ND subjects maintained a light intensity of aerobic activity, while HEC maintained a moderate intensity. Both groups experienced only positive emotions, and reported a 'moderate' to 'high' perceived competence, a 'moderate' game difficulty, and a 'high' interest in the game. Usability results suggest that X-Torp represents a usable EE for healthy subjects and persons with MCI and AD. However, in order to reach moderate or high intensity of aerobic activity, X-Torp control modes should be adapted to become more physically stimulating.

  7. Potential psychosocial mechanisms linking depression to immune function in elderly subjects

    NARCIS (Netherlands)

    Bouhuys, AL; Flentge, F; Oldehinkel, AJ; van den Berg, MD

    2004-01-01

    Although depression and immune changes in elderly subjects constitute a considerable health risk, mechanisms underlying the association between depression and immune function are unclear. The question of whether personality and social support can explain the variation in immune function during

  8. Recovery of corneal sensitivity to mechanical and chemical stimulation after laser in situ keratomileusis.

    Science.gov (United States)

    Gallar, Juana; Acosta, M Carmen; Moilanen, Jukka A O; Holopainen, Juha M; Belmonte, Carlos; Tervo, Timo M T

    2004-01-01

    To evaluate the time course of changes in corneal sensitivity to mechanical and chemical stimuli produced by laser in situ keratomileusis (LASIK) in humans. We performed a cross-sectional study of 17 LASIK-operated eyes (VisX S2, equipped with version 2.50-3.10 software) and 15 control eyes of 17 individuals to evaluate regeneration of corneal sensitivity after LASIK. Gas pulses of variable flow and compositions were applied to the cornea by a non-contact gas esthesiometer. Mechanical stimuli consisted of air puffs at flows from 0 to 200 ml/min. Chemical stimulation was made with gas pulses containing 0% to 80% CO2 in air at subthreshold flow. Mechanical and chemical thresholds and intensity-response curves for the evoked sensations were determined prior to surgery, and 7 to 9 days, 3 to 5 months, and 1.5 to 2.5 years after surgery. Corneal sensitivity to mechanical stimulation was enhanced 7 to 9 days after surgery but subsequently dropped markedly and remained significantly below control levels 3 to 5 months after LASIK. Sensitivity to both mechanical and chemical types of stimuli was close to normal 2 years postoperatively. Corneal sensitivity decreased immediately after LASIK but mechanical sensitivity showed a transient hyperesthesia 7 to 9 days afterward. Subsequently, a long-lasting and deep hypoesthesia to mechanical and chemical stimuli was observed. Gas esthesiometry revealed that disturbances of corneal sensation still exist at times when coarse mechanical sensitivity appeared to be normal.

  9. Identifying cancer subjects with acute respiratory failure at high risk for intubation and mechanical ventilation.

    Science.gov (United States)

    Lemiale, Virginie; Lambert, Jérôme; Canet, Emmanuel; Mokart, Djamel; Pène, Frederic; Rabbat, Antoine; Kouatchet, Achille; Vincent, François; Bruneel, Fabrice; Gruson, Didier; Chevret, Sylvie; Azoulay, Elie

    2014-10-01

    We sought to identify risk factors for mechanical ventilation in patients with malignancies and acute respiratory failure (ARF). We analyzed data from a previous randomized controlled trial in which nonintubated oncology and hematology subjects with ARF were randomized to early bronchoalveolar lavage or routine care in 16 ICUs in France. Consecutive patients with malignancies were admitted to the ICU for ARF in 2005 and 2006 with no intervention. During the study period, 219 patients were admitted to the ICU for ARF, and 8 patients were not included due to a nonintubation order. Data on the underlying disease, pulmonary involvement, and extrapulmonary organ dysfunctions were recorded at admission in the 211 remaining subjects. Ventilatory support included oxygen only (49 subjects), noninvasive ventilation (NIV) only (81 subjects), NIV followed by invasive mechanical ventilation (49 subjects), and first-line invasive mechanical ventilation (32 subjects). The 81 subjects who required invasive mechanical ventilation were compared with the 130 subjects who remained on oxygen or NIV. Factors associated with invasive mechanical ventilation by multivariate analysis were the oxygen flow required at ICU admission, the number of quadrants involved on chest x-ray, and hemodynamic dysfunction. Mortality rates for subjects who had NIV failure were 65.3% compared with 50% for subjects who were first-line intubated (P = .34). In cancer patients with ARF, hypoxemia, extent of pulmonary infiltration on chest x-ray, or hemodynamic dysfunction are risk factors for invasive mechanical ventilation. Mortality was not significantly different between NIV failure and first-line intubation. Copyright © 2014 by Daedalus Enterprises.

  10. Complex regional pain syndrome (CRPS) or continuous unilateral distal experimental pain stimulation in healthy subjects does not bias visual attention towards one hemifield.

    Science.gov (United States)

    Filippopulos, Filipp M; Grafenstein, Jessica; Straube, Andreas; Eggert, Thomas

    2015-11-01

    In natural life pain automatically draws attention towards the painful body part suggesting that it interacts with different attentional mechanisms such as visual attention. Complex regional pain syndrome (CRPS) patients who typically report on chronic distally located pain of one extremity may suffer from so-called neglect-like symptoms, which have also been linked to attentional mechanisms. The purpose of the study was to further evaluate how continuous pain conditions influence visual attention. Saccade latencies were recorded in two experiments using a common visual attention paradigm whereby orientating saccades to cued or uncued lateral visual targets had to be performed. In the first experiment saccade latencies of healthy subjects were measured under two conditions: one in which continuous experimental pain stimulation was applied to the index finger to imitate a continuous pain situation, and one without pain stimulation. In the second experiment saccade latencies of patients suffering from CRPS were compared to controls. The results showed that neither the continuous experimental pain stimulation during the experiment nor the chronic pain in CRPS led to an unilateral increase of saccade latencies or to a unilateral increase of the cue effect on latency. The results show that unilateral, continuously applied pain stimuli or chronic pain have no or only very limited influence on visual attention. Differently from patients with visual neglect, patients with CRPS did not show strong side asymmetries of saccade latencies or of cue effects on saccade latencies. Thus, neglect-like clinical symptoms of CRPS patients do not involve the allocation of visual attention.

  11. Sex differences in lipolysis-regulating mechanisms in overweight subjects: effect of exercise intensity.

    Science.gov (United States)

    Moro, Cédric; Pillard, Fabien; de Glisezinski, Isabelle; Crampes, François; Thalamas, Claire; Harant, Isabelle; Marques, Marie-Adeline; Lafontan, Max; Berlan, Michel

    2007-09-01

    To explore sex differences in the regulation of lipolysis during exercise, the lipid-mobilizing mechanisms in the subcutaneous adipose tissue (SCAT) of overweight men and women were studied using microdialysis. Subjects matched for age, BMI, and physical fitness performed two 30-minute exercise bouts in a randomized fashion: the first test at 30% and 50% of their individual maximal oxygen uptake (Vo(2max)) and the second test at 30% and 70% of their Vo(2max). In both groups, an exercise-dependent increment in extracellular glycerol concentration (EGC) was observed. Whatever the intensity, phentolamine [alpha-adrenergic receptor (AR) antagonist] added to a dialysis probe potentiated exercise-induced lipolysis only in men. In a probe containing phentolamine plus propranolol (beta-AR antagonist), no changes in EGC occurred when compared with the control probe when exercise was performed at 30% and 50% Vo(2max). A significant reduction of EGC (when compared with the control probe) was observed in women at 70% Vo(2max). At each exercise power, the plasma non-esterified fatty acid and glycerol concentrations were higher in women. Exercise-induced increase in plasma catecholamine levels was lower in women compared with men. Plasma insulin decreased and atrial natriuretic peptide increased similarly in both groups. Overweight women mobilize more lipids (assessed by glycerol) than men during exercise. alpha(2)-Anti-lipolytic effect was functional in SCAT of men only. The major finding is that during low-to-moderate exercise periods (30% and 50% Vo(2max)), lipid mobilization in SCAT relies less on catecholamine-dependent stimulation of beta-ARs than on an increase in plasma atrial natriuretic peptide concentrations and the decrease in plasma insulin.

  12. PUTATIVE PHYSIOLOGICAL MECHANISMS UNDERLYING ANALGESIC EFFECTS OF TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS

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    Helena eKnotkova

    2013-09-01

    Full Text Available Transcranial direct current stimulation (tDCS is a non-invasive neuromodulation technique that induces changes in excitability, and activation of brain neurons and neuronal circuits.It has been observed that beyond regional effects under the electrodes, tDCS also alters activity of remote interconnected cortical and subcortical areas. This makes the tDCS stimulation technique potentially promising for modulation of pain syndromes. Indeed, utilizing specific montages, tDCS resulted in analgesic effects in experimental settings, as well as in post-operative acute pain and chronic pain syndromes. The promising evidence of tDCS-induced analgesic effects raises the challenging and complex question of potential physiologic mechanisms that underlie/mediate the accomplished pain relief. Here we present hypotheses on how the specific montages and targets for stimulation may affect the pain processing network.

  13. Potential mechanisms supporting the value of motor cortex stimulation to treat chronic pain syndromes

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    Marcos Fabio DosSantos

    2016-02-01

    Full Text Available Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS, transcranial magnetic stimulation (TMS and transcranial direct current stimulation (tDCS have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary motor cortex stimulation to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1 modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g. glutamate, GABA and serotonin as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of motor cortex stimulation to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g. tDCS and TMS, which are analyzed comparatively.

  14. Differential and synergistic effects of mechanical stimulation and growth factor presentation on vascular wall function

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    Liang, Mao-Shih; Koobatian, Maxwell T.; Lei, Pedro; Swartz, Daniel D.; Andreadis, Stelios T.

    2013-01-01

    We investigated the hypothesis that immobilizing TGF-β1 within fibrin hydrogels may act in synergy with cyclic mechanical stimulation to enhance the properties of vascular grafts. To this end, we engineered a fusion TGF-β1 protein that can covalently anchor to fibrin during polymerization upon the action of factor XIII. We also developed a 24-well based bioreactor in which vascular constructs can be mechanically stimulated by distending the silastic mandrel in the middle of each well. TGF-β1 was either conjugated to fibrin or supplied in the culture medium and the fibrin based constructs were cultured statically for a week followed by cyclic distention for another week. The tissues were examined for myogenic differentiation, vascular reactivity, mechanical properties and ECM content. Our results showed that some aspects of vascular function were differentially affected by growth factor presentation vs. pulsatile force application, while others were synergistically enhanced by both. Overall, this two-prong biomimetic approach improved ECM secretion, vascular reactivity and mechanical properties of vascular constructs. These findings may be applied in other tissue engineering applications such as cartilage, tendon or cardiac regeneration where growth factors TGF-β1 and mechano-stimulation play critical roles. PMID:23810080

  15. Inhibitory mechanisms following electrical stimulation of tendon and cutaneous afferents in the lower limb.

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    Khan, Serajul I; Burne, John A

    2010-01-13

    Electrical stimulation of the Achilles tendon (TES) produced strong reflex depression (duration>250 ms) of a small background contraction in both heads of gastrocnemius (GA) via large diameter electrodes localized to the tendon. The inhibitory responses were produced without electrical (M wave) or mechanical (muscle twitch) signs of direct muscle stimulation. In this study, the contribution of presynaptic and postsynaptic mechanisms to the depression was investigated by studying conditioning effects of tendon afferent stimulation on the mechanical tendon reflex (TR) and magnetic motor evoked potential (MEP). TES completely inhibited the TR over an ISI of 300 ms that commenced before and continued during and after the period of voluntary EMG depression. Tendon afferent conditioning stimuli also partially inhibited the MEP, but over a short time course confined to the period of voluntary EMG depression. The strength and extended time course of tendon afferent conditioning of the TR and its failure to produce a similar depression of the MEP are consistent with a mechanism involving presynaptic inhibition of Ia terminals. Cutaneous (sural nerve) afferent conditioning partially inhibited the TR and MEP over a short time course (ISI origin of cutaneous inhibition of the motoneurons.

  16. Primary cilia expression in bone marrow in response to mechanical stimulation in explant bioreactor culture.

    Science.gov (United States)

    Coughlin, T R; Schiavi, J; Alyssa Varsanik, M; Voisin, M; Birmingham, E; Haugh, M G; McNamara, L M; Niebur, G L

    2016-07-19

    Bone marrow contains a multitude of mechanically sensitive cells that may participate in mechanotransduction. Primary cilia are sensory organelles expressed on mesenchymal stem cells (MSCs), osteoblasts, osteocytes, and other cell types that sense fluid flow in monolayer culture. In marrow, cilia could similarly facilitate the sensation of relative motion between adjacent cells or interstitial fluid. The goal of this study was to determine the response of cilia to mechanical stimulation of the marrow. Bioreactors were used to supply trabecular bone explants with low magnitude mechanical stimulation (LMMS) of 0.3 ×g at 30 Hz for 1 h/d, 5 d/week, inducing shear stresses in the marrow. Four groups were studied: unstimulated (UNSTIM), stimulated (LMMS), and with and without chloral hydrate (UNSTIM+CH and LMMS+CH, respectively), which was used to disrupt cilia. After 19 days of culture, immunohistochemistry for acetylated α-tubulin revealed that more cells expressed cilia in culture compared to in vivo controls. Stimulation decreased the number of cells expressing cilia in untreated explants, but not in CH-treated explants. MSCs represented a greater fraction of marrow cells in the untreated explants than CH-treated explants. MSCs harvested from the stimulated groups were more proliferative than in the unstimulated explants, but this effect was absent from CH treated explants. In contrast to the marrow, neither LMMS nor CH treatment affected bone formation as measured by mineralising surface. Computational models indicated that LMMS does not induce bone strain, and the reported effects were thus attributed to shear stress in the marrow. From a clinical perspective, genetic or pharmaceutical alterations of cilia expression may affect marrow health and function.

  17. Safety and Tolerability of Theta Burst Stimulation versus Single and Paired Pulse Transcranial Magnetic Stimulation: A Comparative Study of 165 Pediatric Subjects

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    Yaejee H Hong

    2015-02-01

    Full Text Available Background: Although single- and paired-pulse (sp/pp transcranial magnetic stimulation (TMS studies are considered minimal risk in adults and children, the safety profile for theta-burst TMS (TBS is unknown.Objective: In this comparative analysis, we explored the rate, severity, and specific symptoms of TMS-related adverse effects (AEs between sp/ppTMS and TBS in subjects between ages 6 and 18 years.Method: Data from 165 participants from 2009-2014 were analyzed. Assessment of AEs was performed based on baseline and post-TMS administration of a symptom-based questionnaire that rated AEs on a 5-level ordinal scale (minimal, mild, moderate, marked, severe. AE rates and severity were compared using Chi Square or Fisher’s Exact Test depending on data characteristics.Result: Overall, no seizures or severe-rated AEs were reported by 165 pediatric participants. The rate of AE in all TBS sessions was 10.5% (n=76, 95% CI: 4.7 - 19.7%, whereas the rate of AE in all sp/ppTMS sessions was 12.4% (n=89, 95% CI: 6.3 - 21.0%. There was no statistical difference in AE rates between TBS and sp/ppTMS (p=0.71. In all sp/ppTMS and TBS sessions, 20 subjects reported a total of 35 AEs, among these 31 (~88.6% were rated as minimal or mild. There was no difference in the severity of AE between TBS and sp/ppTMS (p=1.0. Only one of 76 TBS participants reported an AE rated as more than minimal/mild.Conclusion: Our comparative analysis showed that TBS appears to be as safe as sp/ppTMS in terms of AE rate and severity. This report supports further investigation of TBS in children.

  18. Mapping of cortical language function by functional magnetic resonance imaging and repetitive navigated transcranial magnetic stimulation in 40 healthy subjects.

    Science.gov (United States)

    Sollmann, Nico; Ille, Sebastian; Boeckh-Behrens, Tobias; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

    2016-07-01

    Functional magnetic resonance imaging (fMRI) is considered to be the standard method regarding non-invasive language mapping. However, repetitive navigated transcranial magnetic stimulation (rTMS) gains increasing importance with respect to that purpose. However, comparisons between both methods are sparse. We performed fMRI and rTMS language mapping of the left hemisphere in 40 healthy, right-handed subjects in combination with the tasks that are most commonly used in the neurosurgical context (fMRI: word-generation = WGEN task; rTMS: object-naming = ON task). Different rTMS error rate thresholds (ERTs) were calculated, and Cohen's kappa coefficient and the cortical parcellation system (CPS) were used for systematic comparison of the two techniques. Overall, mean kappa coefficients were low, revealing no distinct agreement. We found the highest agreement for both techniques when using the 2-out-of-3 rule (CPS region defined as language positive in terms of rTMS if at least 2 out of 3 stimulations led to a naming error). However, kappa for this threshold was only 0.24 (kappa of <0, 0.01-0.20, 0.21-0.40, 0.41-0.60, 0.61-0.80 and 0.81-0.99 indicate less than chance, slight, fair, moderate, substantial and almost perfect agreement, respectively). Because of the inherent differences in the underlying physiology of fMRI and rTMS, the different tasks used and the impossibility of verifying the results via direct cortical stimulation (DCS) in the population of healthy volunteers, one must exercise caution in drawing conclusions about the relative usefulness of each technique for language mapping. Nevertheless, this study yields valuable insights into these two mapping techniques for the most common language tasks currently used in neurosurgical practice.

  19. Animal Hairs as Water-stimulated Shape Memory Materials: Mechanism and Structural Networks in Molecular Assemblies

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    Xiao, Xueliang; Hu, Jinlian

    2016-05-01

    Animal hairs consisting of α-keratin biopolymers existing broadly in nature may be responsive to water for recovery to the innate shape from their fixed deformation, thus possess smart behavior, namely shape memory effect (SME). In this article, three typical animal hair fibers were first time investigated for their water-stimulated SME, and therefrom to identify the corresponding net-points and switches in their molecular and morphological structures. Experimentally, the SME manifested a good stability of high shape fixation ratio and reasonable recovery rate after many cycles of deformation programming under water stimulation. The effects of hydration on hair lateral size, recovery kinetics, dynamic mechanical behaviors and structural components (crystal, disulfide and hydrogen bonds) were then systematically studied. SME mechanisms were explored based on the variations of structural components in molecular assemblies of such smart fibers. A hybrid structural network model with single-switch and twin-net-points was thereafter proposed to interpret the water-stimulated shape memory mechanism of animal hairs. This original work is expected to provide inspiration for exploring other natural materials to reveal their smart functions and natural laws in animals including human as well as making more remarkable synthetic smart materials.

  20. A dual flow bioreactor with controlled mechanical stimulation for cartilage tissue engineering.

    Science.gov (United States)

    Spitters, Tim W G M; Leijten, Jeroen C H; Deus, Filipe D; Costa, Ines B F; van Apeldoorn, Aart A; van Blitterswijk, Clemens A; Karperien, Marcel

    2013-10-01

    In cartilage, tissue engineering bioreactors can create a controlled environment to study chondrocyte behavior under mechanical stimulation or produce chondrogenic grafts of clinically relevant size. Here we present a novel bioreactor that combines mechanical stimulation with a two compartment system through which nutrients can be supplied solely by diffusion from opposite sides of a tissue-engineered construct. This design is based on the hypothesis that creating gradients of nutrients, growth factors, and growth factor antagonists can aid in the generation of zonal tissue-engineered cartilage. Computational modeling predicted that the design facilitates the creation of a biologically relevant glucose gradient. This was confirmed by quantitative glucose measurements in cartilage explants. In this system, it is not only possible to create gradients of nutrients, but also of anabolic or catabolic factors. Therefore, the bioreactor design allows control over nutrient supply and mechanical stimulation useful for in vitro generation of cartilage constructs that can be used for the resurfacing of articulated joints or as a model for studying osteoarthritis disease progression.

  1. Neural mechanism of pupillary dilation elicited by electro-acupuncture stimulation in anesthetized rats.

    Science.gov (United States)

    Ohsawa, H; Yamaguchi, S; Ishimaru, H; Shimura, M; Sato, Y

    1997-06-06

    The neural mechanisms to reflex dilation elicited by electro-acupuncture stimulation were investigated in anesthetized rats. Two needles, with 160 microns diameter and about 5 mm apart, were inserted into the skin and underlying muscle of a hindpaw. Repetitive 20 Hz, 0.5 ms electrical pulses at various intensities were used for stimulation for 30s. The pupil size was magnified about 44 times via a microscope and was continuously recorded on a videotape. Electro-acupuncture stimulation at more than 0.5 up to 6 mA induced stimulus intensity-dependent pupil dilation. These responses were abolished by the severance of the sciatic and saphenous nerve of the stimulated hindlimb. Compound action potentials were recorded from the distal cut end of the tibial of a saphenous nerve following electro-acupuncture stimulation of the hindpaw. The mean threshold of the compound action potentials of the myelinated fibers in saphenous nerves was 0.18 mA, while that of unmyelinated fibers was 3.0 mA. The mean threshold of the compound action potentials of the myelinated fibers in the tibial nerve was 0.20 mA of unmyelinated fibers was 3.3 mA. Severance of bilateral trunks did not affect the response, while severance of the third cranial nerves abolished the responses. In conclusion, electro-acupuncture stimulation applied to the hindpaws of the anesthetized rats induced excitation of myelinated or of both myelinated and unmyelinated afferent fibers of the tibial and saphenous nerve, and involved a reflex response of pupil dilation through the third cranial parasympathetic efferent nerve.

  2. Pulse propagation and failure in the discrete FitzHugh-Nagumo model subject to high-frequency stimulation.

    Science.gov (United States)

    Ratas, Irmantas; Pyragas, Kestutis

    2012-10-01

    We investigate the effect of a homogeneous high-frequency stimulation (HFS) on a one-dimensional chain of coupled excitable elements governed by the FitzHugh-Nagumo equations. We eliminate the high-frequency term by the method of averaging and show that the averaged dynamics depends on the parameter A=a/ω equal to the ratio of the amplitude a to the frequency ω of the stimulating signal, so that for large frequencies an appreciable effect from the HFS is attained only at sufficiently large amplitudes. The averaged equations are analyzed by an asymptotic theory based on the different time scales of the recovery and excitable variables. As a result, we obtain the main characteristics of a propagating pulse as functions of the parameter A and derive an analytical criterion for the propagation failure. We show that depending on the parameter A, the HFS can either enhance or suppress pulse propagation and reveal the mechanism underlying these effects. The theoretical results are confirmed by numerical simulations of the original system with and without noise.

  3. Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons.

    Science.gov (United States)

    Li, Ai-Jun; Wang, Qing; Dinh, Thu T; Powers, Bethany R; Ritter, Sue

    2014-02-15

    Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component.

  4. Intraoperative hemidiaphragm electrical stimulation reduces oxidative stress and upregulates autophagy in surgery patients undergoing mechanical ventilation: exploratory study

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    Robert T. Mankowski

    2016-10-01

    Full Text Available Abstract Background Mechanical ventilation (MV during a cardio-thoracic surgery contributes to diaphragm muscle dysfunction that impairs weaning and can lead to the ventilator- induced diaphragm dysfunction. Especially, it is critical in older adults who have lower muscle reparative capacity following MV. Reports have shown that the intraoperative intermittent hemidiaphragm electrical stimulation can maintain and/or improve post-surgery diaphragm function. In particular, from a molecular point of view, intermittent electrical stimulation (ES may reduce oxidative stress and increase regulatory autophagy levels, and therefore improve diaphragm function in animal studies. We have recently shown in humans that intraoperative ES attenuates mitochondrial dysfunction and force decline in single diaphragm muscle fibers. The aim of this study was to investigate an effect of ES on oxidative stress, antioxidant status and autophagy biomarker levels in the human diaphragm during surgery. Methods One phrenic nerve was simulated with an external cardiac pacer in operated older subjects (62.4 ± 12.9 years (n = 8 during the surgery. The patients received 30 pulses per min every 30 min. The muscle biopsy was collected from both hemidiaphragms and frozen for further analyses. 4-hydroxynonenal (4-HNE, an oxidative stress marker, and autophagy marker levels (Beclin-1 and the ratio of microtubule-associated protein light chain 3, I and II-LC3 II/I protein concentrations were detected by the Western Blot technique. Antioxidant enzymatic activity copper-zinc (CuZnSOD and manganese (MnSOD superoxide dismutase were analyzed. Results Levels of lipid peroxidation (4-HNE were significantly lower in the stimulated side (p  0.05. Additionally, the protein concentrations of Beclin-1 and the LC3 II/I ratio were higher in the stimulated side (p < 0.05. Conclusion These results suggest that the intraoperative electrical stimulation decreases oxidative stress levels

  5. Transcranial alternating current stimulation: A review of the underlying mechanisms and modulation of cognitive processes

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    Christoph S Herrmann

    2013-06-01

    Full Text Available Brain oscillations of different frequencies have been associated with a variety of cognitive functions. Convincing evidence supporting those associations has been provided by studies using intracranial stimulation, pharmacological interventions and lesion studies. The emergence of novel non-invasive brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS and transcranial alternating current stimulation (tACS now allows to modulate brain oscillations directly. Particularly, tACS offers the unique opportunity to causally link brain oscillations of a specific frequency range to cognitive processes, because it uses sinusoidal currents that are bound to one frequency only. Using tACS allows to modulate brain oscillations and in turn to influence cognitive processes, thereby demonstrating the causal link between the two. Here, we review findings about the physiological mechanism of tACS and studies that have used tACS to modulate basic motor and sensory processes as well as higher cognitive processes like memory, ambiguous perception, and decision making.

  6. The influence of adrenergic stimulation on sex differences in left ventricular twist mechanics.

    Science.gov (United States)

    Williams, Alexandra M; Shave, Rob E; Cheyne, William S; Eves, Neil D

    2017-06-15

    Sex differences in left ventricular (LV) mechanics occur during acute physiological challenges; however, it is unknown whether sex differences in LV mechanics are fundamentally regulated by differences in adrenergic control. Using two-dimensional echocardiography and speckle tracking analysis, this study compared LV mechanics in males and females matched for LV length during post-exercise ischaemia (PEI) and β1 -adrenergic receptor blockade. Our data demonstrate that while basal rotation was increased in males, LV twist was not significantly different between the sexes during PEI. In contrast, during β1 -adrenergic receptor blockade, LV apical rotation, twist and untwisting velocity were reduced in males compared to females. Significant relationships were observed between LV twist and LV internal diameter and sphericity index in females, but not males. These findings suggest that LV twist mechanics may be more sensitive to alterations in adrenergic stimulation in males, but more highly influenced by ventricular structure and geometry in females. Sex differences in left ventricular (LV) mechanics exist at rest and during acute physiological stress. Differences in cardiac autonomic and adrenergic control may contribute to sex differences in LV mechanics and LV haemodynamics. Accordingly, this study aimed to investigate sex differences in LV mechanics with altered adrenergic stimulation achieved through post-handgrip-exercise ischaemia (PEI) and β1 -adrenergic receptor (AR) blockade. Twenty males (23 ± 5 years) and 20 females (22 ± 3 years) were specifically matched for LV length (males: 8.5 ± 0.5 cm, females: 8.2 ± 0.6 cm, P = 0.163), and two-dimensional speckle-tracking echocardiography was used to assess LV structure and function at baseline, during PEI and following administration of 5 mg bisoprolol (β1 -AR antagonist). During PEI, LV end-diastolic volume and stroke volume were increased in both groups (P mechanics are reduced in males

  7. Mechanisms of the Stimulation of Import Substitution in the Construction Industry

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    Svetlana Nikolayevna Kotlyarova

    2016-12-01

    Full Text Available The issues of the dependence on imports and import substitution are the major factors in the development of the domestic economy. The subject matter of the research is the dependence of construction industry on imports in the area of foreign technology, it is aimed at identifying the scope of the problem and justifying the mechanisms to overcome it. The article substantiates the relevance and importance of import substitution in the production of construction materials and equipment. Import substitution in the construction industry can be implemented in two main ways, requiring different approaches in supporting and encouraging. Firstly, there is the substitution of products used in construction, aimed at minimizing the risk of disruption of the supply of imported products for construction purposes and the predominant use of domestic analogues of imported products for construction purposes. Secondly, there is the substitution in the technologies of production of goods used in construction, focused on stimulating the development of the domestic production of competitive products and technological and managerial modernization of the construction materials industry, construction industry. The process of import substitution in the construction industry have a number of limitations. In this connection, the article discusses the opportunities and constraints for import substitution. A special attention is paid to the practice of the formation of regional construction clusters as a tool of implementing the policy of import substitution. The purposes and principles of the development of clusters, sources of initiatives, used systems of transfer and knowledge and innovations are considered critically. The conclusion is made about the need for the strategic development of new products for the construction market and domestic research and development projects within the framework of cross-sectoral clusters. The basic forms of state support required for the

  8. Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle

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    Zuyderduyn Suzanne

    2010-09-01

    Full Text Available Abstract Background Acetylcholine, the primary parasympathetic neurotransmitter in the airways, plays an important role in bronchoconstriction and mucus production. Recently, it has been shown that acetylcholine, by acting on muscarinic receptors, is also involved in airway inflammation and remodelling. The mechanism(s by which muscarinic receptors regulate inflammatory responses are, however, still unknown. Methods The present study was aimed at characterizing the effect of muscarinic receptor stimulation on cytokine secretion by human airway smooth muscle cells (hASMc and to dissect the intracellular signalling mechanisms involved. hASMc expressing functional muscarinic M2 and M3 receptors were stimulated with the muscarinic receptor agonist methacholine, alone, and in combination with cigarette smoke extract (CSE, TNF-α, PDGF-AB or IL-1β. Results Muscarinic receptor stimulation induced modest IL-8 secretion by itself, yet augmented IL-8 secretion in combination with CSE, TNF-α or PDGF-AB, but not with IL-1β. Pretreatment with GF109203X, a protein kinase C (PKC inhibitor, completely normalized the effect of methacholine on CSE-induced IL-8 secretion, whereas PMA, a PKC activator, mimicked the effects of methacholine, inducing IL-8 secretion and augmenting the effects of CSE. Similar inhibition was observed using inhibitors of IκB-kinase-2 (SC514 and MEK1/2 (U0126, both downstream effectors of PKC. Accordingly, western blot analysis revealed that methacholine augmented the degradation of IκBα and the phosphorylation of ERK1/2 in combination with CSE, but not with IL-1β in hASMc. Conclusions We conclude that muscarinic receptors facilitate CSE-induced IL-8 secretion by hASMc via PKC dependent activation of IκBα and ERK1/2. This mechanism could be of importance for COPD patients using anticholinergics.

  9. Mathematical modeling of calcium waves induced by mechanical stimulation in keratinocytes.

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    Yasuaki Kobayashi

    Full Text Available Recent studies have shown that the behavior of calcium in the epidermis is closely related to the conditions of the skin, especially the differentiation of the epidermal keratinocytes and the permeability barrier function, and therefore a correct understanding of the calcium dynamics is important in explaining epidermal homeostasis. Here we report on experimental observations of in vitro calcium waves in keratinocytes induced by mechanical stimulation, and present a mathematical model that can describe the experimentally observed wave behavior that includes finite-range wave propagation and a ring-shaped pattern. A mechanism of the ring formation hypothesized by our model may be related to similar calcium propagation patterns observed during the wound healing process in the epidermis. We discuss a possible extension of our model that may serve as a tool for investigating the mechanisms of various skin diseases.

  10. Myofascial trigger points in subjects presenting with mechanical neck pain: a blinded, controlled study.

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    Fernández-de-las-Peñas, C; Alonso-Blanco, C; Miangolarra, J C

    2007-02-01

    The aim of this study was to describe the differences in the presence of myofascial trigger points (TrPs) in the upper trapezius,sternocleidomastoid, levator scapulae and suboccipital muscles between patients presenting with mechanical neck pain and control healthy subjects. Twenty subjects with mechanical neck pain and 20 matched healthy controls participated in this study. TrPs were identified, by an assessor blinded to the subjects' condition, when there was a hypersensible tender spot in a palpable taut band, local twitch response elicited by the snapping palpation of the taut band, and reproduction of the referred pain typical of each TrP. The mean number of TrPs present on each neck pain patient was 4.3 (SD: 0.9), of which 2.5 (SD: 1.3) were latent and 1.8 (SD: 0.8) were active TrPs. Control subjects also exhibited TrPs (mean: 2; SD: 0.8). All were latent TrPs. Differences in the number of TrPs between both study groups were significant for active TrPs (P latent TrPs (P > 0.5). Moreover, differences in the distribution of TrPs within the analysed cervical muscles were also significant (P Active TrPs were more frequent in patients presenting with mechanical neck pain than in healthy subjects. ©2006 Elsevier Ltd.

  11. Sedation and memories of patients subjected to mechanical ventilation in an intensive care unit.

    Science.gov (United States)

    Costa, Jaquilene Barreto da; Marcon, Sonia Silva; Macedo, Claudia Rejane Lima de; Jorge, Amaury Cesar; Duarte, Péricles Almeida Delfino

    2014-01-01

    To investigate the relationship between sedation and the memories reported by patients subjected to mechanical ventilation following discharge from the intensive care unit. This prospective, observational, cohort study was conducted with individuals subjected to mechanical ventilation who remained in the intensive care unit for more than 24 hours. Clinical statistics and sedation records were extracted from the participants' clinical records; the data relative to the participants' memories were collected using a specific validated instrument. Assessment was performed three months after discharge from the intensive care unit. A total of 128 individuals were assessed, most of whom (84.4%) reported recollections from their stay in the intensive care unit as predominantly a combination of real and illusory events. The participants subjected to sedation (67.2%) at deep levels (Richmond Agitation-Sedation Scale [RASS] -4 and -5) for more than two days and those with psychomotor agitation (33.6%) exhibited greater susceptibility to occurrence of illusory memories (p>0.001). The probability of the occurrence of illusory memories was greater among the participants who were subjected to deep sedation. Sedation seems to be an additional factor that contributed to the occurrence of illusory memories in severely ill individuals subjected to mechanical ventilation.

  12. Models of intracellular mechanisms of plant bioelectrical potentials caused by combined stimulation

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    D. V. Chernetchenko

    2014-10-01

    Full Text Available This paper deals with bioelectrical potentials of the plants recorded during different types of stimuli and combined stimulus as well. All registrations were observed on the leaves of the corn. We used different stimuli, such as cold, heat, photo- and electrical stimulation, and certain combination of this stimuli. Hardware and software system for automated recording of bioelectrical potentials has been successfully used in this work. We proposed the universal pattern of bioelectrical potentials’ recording which allowed to detect the response of the biological object to different stimuli and various combinations of these stimuli. This pattern can be used for the deeper understanding of biological mechanisms of electrical potentials’ generation in cells and discovering of processes of accommodation of whole organisms to these stimuli. Integrated system of recording and biometrical processing was used for analysis of corn leaves electrical responses to the thermal stimuli. The dynamics of these potentials was studied, with the quantitative analysis of the potential level stabilization.We calculated the ratio of amplitude of response potentials to the first response amplitude. Mathematical models of the plant cell were used for studying of intracellular mechanisms of biopotentials gereration. As a result of modeling, we revealed that electrical response of the cells was based on selectiveconductivity of cell membrane for Н+ and Ca2+ ions. Therefore, we showed the biophysical relation of plant potentials to underlying intracellular biophysical mechanisms during thermal and combined stimulation.

  13. Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive-Compulsive Disorder

    OpenAIRE

    van Westen, Maarten; Rietveld, Erik; Figee, Martijn; Denys, D.

    2015-01-01

    Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients regain a normal quality of life (QoL) after DBS. Reviewing the literature of the last 4 years, we argue that the mechanisms of action of DBS are a combination of excitatory and inhibitory as well as ...

  14. Binaural Hearing Ability With Bilateral Bone Conduction Stimulation in Subjects With Normal Hearing: Implications for Bone Conduction Hearing Aids.

    Science.gov (United States)

    Zeitooni, Mehrnaz; Mäki-Torkko, Elina; Stenfelt, Stefan

    The purpose of this study is to evaluate binaural hearing ability in adults with normal hearing when bone conduction (BC) stimulation is bilaterally applied at the bone conduction hearing aid (BCHA) implant position as well as at the audiometric position on the mastoid. The results with BC stimulation are compared with bilateral air conduction (AC) stimulation through earphones. Binaural hearing ability is investigated with tests of spatial release from masking and binaural intelligibility level difference using sentence material, binaural masking level difference with tonal chirp stimulation, and precedence effect using noise stimulus. In all tests, results with bilateral BC stimulation at the BCHA position illustrate an ability to extract binaural cues similar to BC stimulation at the mastoid position. The binaural benefit is overall greater with AC stimulation than BC stimulation at both positions. The binaural benefit for BC stimulation at the mastoid and BCHA position is approximately half in terms of decibels compared with AC stimulation in the speech based tests (spatial release from masking and binaural intelligibility level difference). For binaural masking level difference, the binaural benefit for the two BC positions with chirp signal phase inversion is approximately twice the benefit with inverted phase of the noise. The precedence effect results with BC stimulation at the mastoid and BCHA position are similar for low frequency noise stimulation but differ with high-frequency noise stimulation. The results confirm that binaural hearing processing with bilateral BC stimulation at the mastoid position is also present at the BCHA implant position. This indicates the ability for binaural hearing in patients with good cochlear function when using bilateral BCHAs.

  15. Transcriptome analysis of Phelipanche aegyptiaca seed germination mechanisms stimulated by fluridone, TIS108, and GR24.

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    Ya Zhou Bao

    Full Text Available P. aegyptiaca is one of the most destructive root parasitic plants worldwide, causing serious damage to many crop species. Under natural conditions P. aegyptiaca seeds must be conditioned and then stimulated by host root exudates before germinating. However, preliminary experiments indicated that TIS108 (a triazole-type inhibitor of strigolactone and fluridone (FL, an inhibitor of carotenoid-biosynthesis both stimulated the germination of P. aegyptiaca seeds without a water preconditioning step (i.e. unconditioned seeds. The objective of this study was to use deep RNA sequencing to learn more about the mechanisms by which TIS108 and FL stimulate the germination of unconditioned P. aegyptiaca seeds. Deep RNA sequencing was performed to compare the mechanisms of germination in the following treatments: (i unconditioned P. aegyptiaca seeds with no other treatment, (ii unconditioned seeds treated with 100 mg/L TIS108, (iii unconditioned seeds treated with 100 mg/L FL + 100 mg/L GA3, (iv conditioned seeds treated with sterile water, and (v conditioned seeds treated with 0.03 mg/L GR24. The de novo assembled transcriptome was used to analyze transcriptional dynamics during seed germination. The key gene categories involved in germination were also identified. The results showed that only 119 differentially expressed genes were identified in the conditioned treatment vs TIS108 treatment. This indicated that the vast majority of conditions for germination were met during the conditioning stage. Abscisic acid (ABA and gibberellic acid (GA played important roles during P. aegyptiaca germination. The common pathway of TIS108, FL+GA3, and GR24 in stimulating P. aegyptiaca germination was the simultaneous reduction in ABA concentrations and increase GA concentrations. These results could potentially aid the identification of more compounds that are capable of stimulating P. aegyptiaca germination. Some potential target sites of TIS108 were also identified in

  16. Spontaneous Breathing Trials and Conservative Sedation Practices Reduce Mechanical Ventilation Duration in Subjects With ARDS.

    Science.gov (United States)

    Kallet, Richard H; Zhuo, Hanjing; Yip, Vivian; Gomez, Antonio; Lipnick, Michael S

    2018-01-01

    Spontaneous breathing trials (SBTs) and daily sedation interruptions (DSIs) reduce both the duration of mechanical ventilation and ICU length of stay (LOS). The impact of these practices in patients with ARDS has not previously been reported. We examined whether implementation of SBT/DSI protocols reduce duration of mechanical ventilation and ICU LOS in a retrospective group of subjects with ARDS at a large, urban, level-1 trauma center. All ARDS survivors from 2002 to 2016 (N = 1,053) were partitioned into 2 groups: 397 in the pre-SBT/DSI group (June 2002-December 2007) and 656 in the post-SBT/DSI group (January 2009-April 2016). Patients from 2008, during the protocol implementation period, were excluded. An additional SBT protocol database (2008-2010) was used to assess the efficacy of SBT in transitioning subjects with ARDS to unassisted breathing. Comparisons were assessed by either unpaired t tests or Mann-Whitney tests. Multiple comparisons were made using either one-way analysis of variance or Kruskal-Wallis and Dunn's tests. Linear regression modeling was used to determine variables independently associated with mechanical ventilation duration and ICU LOS; differences were considered statistically significant when P mechanical ventilation duration (14 [6-29] vs 9 [4-17] d, respectively, P mechanical ventilation duration and ICU LOS. Among subjects with ARDS in the SBT performance database, most achieved unassisted breathing with a median of 2 SBTs. Evidenced-based protocols governing weaning and sedation practices were associated with both reduced mechanical ventilation duration and ICU LOS in subjects with ARDS. However, higher respiratory system compliance in the SBT/DSI cohort also contributed to these improved outcomes. Copyright © 2018 by Daedalus Enterprises.

  17. Effect of transcutaneous electric nerve stimulation (TENS on hormones profile in subjects with primary dysmenorrhoea - a preliminary study

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    S. R. A. Akinbo

    2007-02-01

    Full Text Available Background & Objective: Primary dysmenorrhoea (PD is definedas the occurrence of painful menstrual cramps of uterine origin which occurs in the absence of any underlying disease. The pathogenesis is unclear, but uterine hyperactivity, elevated prostaglandin and leukotrienes levels, and hormonal level fluctuations have all been implicated. The objective of this study was to evaluate the effect of TENS on the hormones cortisol and prolactin in individuals with PD.Methods: Plasma levels of cortisol and prolactin were studied in twenty-one (21 subjects with PD by obtaining blood samples from each subject pre-and post-TENS therapy on the first day of menstruation. The mean age of subjects was 23 (+ 2 years.  The Visual Analogue Scale (VAS was used to assess the pre-and post-treatment pain intensity.  The TENS unit was applied for a duration of 30 minutes.Results: A paired t-test showed that there was an overall reduction in the mean cortisol and prolactin from  pre treatment values of 28.45µg/dl ((5.27 and 56.81ng/ml ((31.86 to post treatment values of 27.33µg/dl ((5.13 and 53.23ng/ml ((37.63 respectively. However, these differences were not statistically significant (P>0.05.  Pain intensity was significantly reduced comparing pre and post treatment VAS scores (P = 0.001.Conclusion: The probable mechanism by which TENS effected alterations in cortisol and prolactin levels and pain reduction in subjects with PD might be through the opioid-modulating analgesia system, which releases B-endorphins and other endogenous opiates in response to pain.  This is because there is a close relationship between B-endorphin, cortisol and neurons, which secrete dopamine into the hypothalamic-pituitary-portal system.

  18. Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through Multiple Mechanisms.

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    Marieke C Verweij

    2015-05-01

    Full Text Available Varicella zoster virus (VZV causes chickenpox in humans and, subsequently, establishes latency in the sensory ganglia from where it reactivates to cause herpes zoster. Infection of rhesus macaques with simian varicella virus (SVV recapitulates VZV pathogenesis in humans thus representing a suitable animal model for VZV infection. While the type I interferon (IFN response has been shown to affect VZV replication, the virus employs counter mechanisms to prevent the induction of anti-viral IFN stimulated genes (ISG. Here, we demonstrate that SVV inhibits type I IFN-activated signal transduction via the JAK-STAT pathway. SVV-infected rhesus fibroblasts were refractory to IFN stimulation displaying reduced protein levels of IRF9 and lacking STAT2 phosphorylation. Since previous work implicated involvement of the VZV immediate early gene product ORF63 in preventing ISG-induction we studied the role of SVV ORF63 in generating resistance to IFN treatment. Interestingly, SVV ORF63 did not affect STAT2 phosphorylation but caused IRF9 degradation in a proteasome-dependent manner, suggesting that SVV employs multiple mechanisms to counteract the effect of IFN. Control of SVV ORF63 protein levels via fusion to a dihydrofolate reductase (DHFR-degradation domain additionally confirmed its requirement for viral replication. Our results also show a prominent reduction of IRF9 and inhibition of STAT2 phosphorylation in VZV-infected cells. In addition, cells expressing VZV ORF63 blocked IFN-stimulation and displayed reduced levels of the IRF9 protein. Taken together, our data suggest that varicella ORF63 prevents ISG-induction both directly via IRF9 degradation and indirectly via transcriptional control of viral proteins that interfere with STAT2 phosphorylation. SVV and VZV thus encode multiple viral gene products that tightly control IFN-induced anti-viral responses.

  19. Diaphragmatic Dysfunction Is Characterized by Increased Duration of Mechanical Ventilation in Subjects With Prolonged Weaning.

    Science.gov (United States)

    Lu, Zhihua; Xu, Qiuping; Yuan, Yuehua; Zhang, Ge; Guo, Feng; Ge, Huiqing

    2016-10-01

    Diaphragmatic dysfunction is often underdiagnosed and is among the risk factors for failed weaning. The purpose of this study was to determine the prevalence of diaphragmatic dysfunction diagnosed by B-mode ultrasonography and to determine whether prolonged weaning subjects with diaphragmatic dysfunction have increased duration of mechanical ventilation compared with those without diaphragmatic dysfunction. This was a prospective observational study in mechanically ventilated subjects who failed ≥3 spontaneous breathing trials or required >7 d of weaning after the first spontaneous breathing trial. Diaphragm thickness was measured in the zone of apposition using a 6-13-MHz ultrasound transducer during a spontaneous breathing trial. The diaphragmatic thickening fraction was calculated as a percentage from the formula: (Thickness at peak inspiration - thickness at end expiration)/thickness at end expiration. Intra-observer and inter-observer reliability were also evaluated. Forty-one subjects (24 males; 62.2 ± 15.9 y old) were included in the study. Of these, the prevalence of ultrasonographic diaphragmatic dysfunction (defined as diaphragmatic thickening fraction of ventilation time after inclusion (293.4 ± 194.8 vs 145.1 ± 101.3 h, P = .02) and ICU stay (29.2 ± 11.4 vs 22.4 ± 7.7 d, P = .03) than subjects without diaphragmatic dysfunction. Diaphragmatic dysfunction as assessed by B-mode ultrasonography is common in subjects with prolonged weaning. Subjects with such diaphragmatic dysfunction show longer mechanical ventilation durations and ICU stays. Copyright © 2016 by Daedalus Enterprises.

  20. Quantitative analysis of iris changes following mydriasis in subjects with different mechanisms of angle closure.

    Science.gov (United States)

    Zhang, Ye; Li, Si Zhen; Li, Lei; He, Ming Guang; Thomas, Ravi; Wang, Ning Li

    2015-01-08

    We estimate and compare change in iris cross-sectional area (IA) after physiologic and pharmacologic mydriasis in subjects with different dominant mechanisms for primary angle closure. Anterior segment optical coherence tomography (AS-OCT) measurements in light, dark, and following pharmacologic dilation were obtained on primary angle closure suspects (PACS), primary angle closure (PAC), and primary angle closure glaucoma (PACG) examined during the 5-year follow-up of the Handan Eye Study. Subjects were categorized into three subgroups according to their dominant angle closure (AC) mechanisms as determined by AS-OCT: pupillary block (PB), plateau iris configuration (PIC), and thick peripheral iris roll (TPIR). The IA and other biometric parameters measured using the Zhongshan Angle Assessment Program in the right eyes of all subjects were analyzed. A total of 364 right eyes of subjects with PACS (333), and PAC/PACG (31) was included in the analysis. Significant differences in the change of IAs (P = 0.030), IA loss per mm pupil diameter (PD) increase (P = 0.001) in light versus pharmacologic dilation, and IA loss per mm PD increase (P = 0.011) from dark versus pharmacologic dilation were observed among the three groups. The smallest decrease occurred in the PB group. There are significant differences in IA and IA loss per mm of pupil change following physiologic or pharmacologic mydriasis in Chinese subjects with dissimilar dominant mechanisms for AC. Dynamic iris change may have a more important role in angle closure where PB is the dominant mechanism. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  1. Effects of Force Load, Muscle Fatigue, and Magnetic Stimulation on Surface Electromyography during Side Arm Lateral Raise Task: A Preliminary Study with Healthy Subjects

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    Liu Cao

    2017-01-01

    Full Text Available The aim of this study was to quantitatively investigate the effects of force load, muscle fatigue, and extremely low-frequency (ELF magnetic stimulation on surface electromyography (SEMG signal features during side arm lateral raise task. SEMG signals were recorded from 18 healthy subjects on the anterior deltoid using a BIOSEMI ActiveTwo system during side lateral raise task (with the right arm 90 degrees away from the body with three different loads on the forearm (0 kg, 1 kg, and 3 kg; their order was randomized between subjects. The arm maintained the loads until the subject felt exhausted. The first 10 s recording for each load was regarded as nonfatigue status and the last 10 s before the subject was exhausted was regarded as fatigue status. The subject was then given a five-minute resting between different loads. Two days later, the same experiment was repeated on every subject, and this time the ELF magnetic stimulation was applied to the subject’s deltoid muscle during the five-minute rest period. Three commonly used SEMG features, root mean square (RMS, median frequency (MDF, and sample entropy (SampEn, were analyzed and compared between different loads, nonfatigue/fatigue status, and ELF stimulation and no stimulation. Variance analysis results showed that the effect of force load on RMS was significant (p0.05. In comparison with nonfatigue status, for all the different force loads with and without ELF stimulation, RMS was significantly larger at fatigue (all p<0.001 and MDF and SampEn were significantly smaller (all p<0.001.

  2. The Impact of Ventilator-Associated Events in Critically Ill Subjects With Prolonged Mechanical Ventilation.

    Science.gov (United States)

    Kobayashi, Hidetsugu; Uchino, Shigehiko; Takinami, Masanori; Uezono, Shoichi

    2017-11-01

    The Centers for Disease Control and Prevention recently released a surveillance definition for respiratory complications in ventilated patients, ventilator-associated events (VAEs), to replace ventilator-associated pneumonia (VAP). VAEs consist of ventilator-associated conditions (VAC), infection-related ventilator-associated complications (IVAC), and possible VAP. A duration of mechanical ventilation of at least 4 d is required to diagnose VAE. However, the observed duration of mechanical ventilation was mechanical ventilation for ≥ 4 d. This single-center retrospective cohort study was conducted in the general ICU of an academic hospital. We included 407 adult subjects who were admitted to the ICU and required mechanical ventilation for at least 4 d. VAC and IVAC were identified from the electronic medical records. VAP was defined according to the Centers for Disease Control and Prevention 2008 criteria and was identified from the surveillance data of the infection control team of our hospital. Clinical outcomes were studied in the VAC, IVAC, and VAP groups. Possible VAP was not investigated. Higher mortality was seen in VAC and IVAC subjects, but not in VAP subjects, compared with those without VAEs and VAP. By multivariable hazard analysis for hospital mortality, IVAC was independently associated with hospital mortality (hazard ratio 2.42, 95% CI 1.39-4.20, P = .002). VAC also tended to show a similar association with hospital mortality (hazard ratio 1.45, 95% CI 0.97-2.18, P = .07). On the other hand, VAP did not increase a hazard of hospital death (hazard ratio 1.08, 95% CI 0.44-2.66, P = .87). We found that a VAE was related to hospital mortality in critically ill subjects with prolonged mechanical ventilation, and that VAP was not. Copyright © 2017 by Daedalus Enterprises.

  3. Mechanism of Interferon-Stimulated Gene Induction in HIV-1-Infected Macrophages.

    Science.gov (United States)

    Nasr, Najla; Alshehri, Abdullateef A; Wright, Thomas K; Shahid, Maryam; Heiner, Bonnie M; Harman, Andrew N; Botting, Rachel A; Helbig, Karla J; Beard, Michael R; Suzuki, Kazuo; Kelleher, Anthony D; Hertzog, Paul; Cunningham, Anthony L

    2017-10-15

    Viruses manipulate the complex interferon and interferon-stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells, many of which are antiviral. Here, we examine the mechanism of induction of ISGs and show this occurs in two phases. The first phase was transient (0 to 24 h postinfection [hpi]), induced mainly by extracellular vesicles and one of its component proteins, HSP90α, contained within the HIV inoculum. The second, dominant, and persistent phase (>48 hpi) was induced via newly transcribed HIV RNA and sensed via RIGI, as shown by the reduction in ISG expression after the knockdown of the RIGI adaptor, MAVS, by small interfering RNA (siRNA) and the inhibition of both the initiation and elongation of HIV transcription by short hairpin RNA (shRNA) transcriptional silencing. We further define the induction pathway, showing sequential HIV RNA stimulation via Tat, RIGI, MAVS, IRF1, and IRF7, also identified by siRNA knockdown. IRF1 also plays a key role in the first phase. We also show that the ISGs IFIT1 to -3 inhibit HIV production, measured as extracellular infectious virus. All induced antiviral ISGs probably lead to restriction of HIV replication in macrophages, contributing to a persistent, noncytopathic infection, while the inhibition of interferon facilitates spread to adjacent cells. Both may influence the size of macrophage HIV reservoirs in vivo Elucidating the mechanisms of ISG induction may help in devising immunotherapeutic strategies to limit the size of these reservoirs.IMPORTANCE HIV, like other viruses, manipulates the antiviral interferon and interferon-stimulated gene (ISG) system to facilitate its initial infection and establishment of viral reservoirs. HIV specifically inhibits all type I and III interferons in its target cells, including macrophages, dendritic cells, and T cells

  4. Inactivation of mechano-sensitive dilatation upon repetitive mechanical stimulation of the musculo-vascular network in the rabbit.

    Science.gov (United States)

    Turturici, M; Roatta, S

    2013-06-01

    Mechano-sensitivity of the vascular network is known to be implicated in the rapid dilatation at the onset of exercise, however, it is not known how this mechanism responds to repetitive mechanical stimulation. This study tests the hypothesis that the mechanically-induced hyperaemia undergoes some attenuation upon repetitive stimulation. Muscle blood flow was recorded from 9 masseteric arteries (5 right, 4 left) in 6 anesthetized rabbits. Two mechanical stimuli, masseter muscle compression (MC) and occlusion of the masseteric artery (AO), were provided in different combinations: A) repeated stimulation (0.5 Hz, for 40 s); B) single stimuli delivered at decreasing inter-stimulus interval (ISI) from 4 min to 2 s, C) single AO delivered before and immediately after a series of 20 MCs at 0.5 Hz, and vice-versa. Repetitive AO stimulation at 0.5 Hz produced a transient hyperaemia (378 ±189%) peaking at 4.5 ±1.4 s and then decaying before the end of stimulation. The hyperaemic response to individual AOs progressively decreased by 74 ±39% with decreasing ISI from 4 min to 2 s (p<0.01). Non significant differences were observed between AO and MC stimulation. Decreased response to AO was also provoked by previous repetitive MC stimulation, and vice-versa. The results provide evidence that the mechano-sensitivity of the vascular network is attenuated by previous mechanical stimulation. It is suggested that the mechano-sensitive dilatory mechanisms undergoes some inactivation whose recovery time is in the order of a few minutes.

  5. [Predictors of extubation failure and reintubation in newborn infants subjected to mechanical ventilation].

    Science.gov (United States)

    Costa, Ana Cristina de Oliveira; Schettino, Renata de Carvalho; Ferreira, Sandra Clecêncio

    2014-01-01

    To identify risk factors for extubation failure and reintubation in newborn infants subjected to mechanical ventilation and to establish whether ventilation parameters and blood gas analysis behave as predictors of those outcomes. Prospective study conducted at a neonatal intensive care unit from May to November 2011. A total of 176 infants of both genders subjected to mechanical ventilation were assessed after extubation. Extubation failure was defined as the need to resume mechanical ventilation within less than 72 hours. Reintubation was defined as the need to reintubate the infants any time after the first 72 hours. Based on the univariate analysis, the variables gestational age mechanical ventilation (days), potential of hydrogen (pH) and partial pressure of oxygen (pO₂) remained associated with extubation failure, and the five-minute Apgar score and age at extubation were associated with reintubation. Low five-minute Apgar scores, age at extubation, length of mechanical ventilation, acid-base disorders and hyperoxia exhibited associations with the investigated outcomes of extubation failure and reintubation.

  6. Characteristics and progression of children with acute viral bronchiolitis subjected to mechanical ventilation.

    Science.gov (United States)

    Ferlini, Roberta; Pinheiro, Flávia Ohlweiler; Andreolio, Cinara; Carvalho, Paulo Roberto Antonacci; Piva, Jefferson Pedro

    2016-01-01

    To analyze the characteristics of children with acute viral bronchiolitis subjected to mechanical ventilation for three consecutive years and to correlate their progression with mechanical ventilation parameters and fluid balance. Longitudinal study of a series of infants (mechanical ventilation for acute viral bronchitis from January 2012 to September 2014 in the pediatric intensive care unit. The children's clinical records were reviewed, and their anthropometric data, mechanical ventilation parameters, fluid balance, clinical progression, and major complications were recorded. Sixty-six infants (3.0 ± 2.0 months old and with an average weight of 4.7 ± 1.4kg) were included, of whom 62% were boys; a virus was identified in 86%. The average duration of mechanical ventilation was 6.5 ± 2.9 days, and the average length of stay in the pediatric intensive care unit was 9.1 ± 3.5 days; the mortality rate was 1.5% (1/66). The peak inspiratory pressure remained at 30cmH2O during the first four days of mechanical ventilation and then decreased before extubation (25 cmH2O; p mechanical ventilation day four was 402 ± 254mL, which corresponds to an increase of 9.0 ± 5.9% in body weight. Thirty-seven patients (56%) exhibited a weight gain of 10% or more, which was not significantly associated with the ventilation parameters on mechanical ventilation day four, extubation failure, duration of mechanical ventilation or length of stay in the pediatric intensive care unit. The rate of mechanical ventilation for acute viral bronchiolitis remains constant, being associated with low mortality, few adverse effects, and positive cumulative fluid balance during the first days. Better fluid control might reduce the duration of mechanical ventilation.

  7. Effect of a mechanical stimulation bioreactor on tissue engineered, scaffold-free cartilage.

    Science.gov (United States)

    Tran, Scott C; Cooley, Avery J; Elder, Steven H

    2011-06-01

    Achieving sufficient functional properties prior to implantation remains a significant challenge for the development of tissue engineered cartilage. Many studies have shown chondrocytes respond well to various mechanical stimuli, resulting in the development of bioreactors capable of transmitting forces to articular cartilage in vitro. In this study, we describe the production of sizeable, tissue engineered cartilage using a novel scaffold-free approach, and determine the effect of perfusion and mechanical stimulation from a C9-x Cartigen bioreactor on the properties of the tissue engineered cartilage. We created sizable tissue engineered cartilage from porcine chondrocytes using a scaffold-free approach by centrifuging a high-density chondrocyte cell-suspension onto an agarose layer in a 50 mL tube. The gross and histological appearances, biochemical content, and mechanical properties of constructs cultured in the bioreactor for 4 weeks were compared to constructs cultured statically. Mechanical properties were determined from unconfined uniaxial compression tests. Constructs cultured in the bioreactor exhibited an increase in total GAG content, equilibrium compressive modulus, and dynamic modulus versus static constructs. Our study demonstrates the C9-x CartiGen bioreactor is able to enhance the biomechanical and biochemical properties of scaffold-free tissue engineered cartilage; however, no additional enhancement was seen between loaded and perfused groups. Copyright © 2011 Wiley Periodicals, Inc.

  8. Cellular and molecular mechanisms triggered by Deep Brain Stimulation in depression: A preclinical and clinical approach.

    Science.gov (United States)

    Torres-Sanchez, S; Perez-Caballero, L; Berrocoso, E

    2017-02-06

    Deep Brain Stimulation (DBS) was originally developed as a therapeutic approach to manage movement disorders, in particular Parkinson's Disease. However, DBS also seems to be an effective treatment against refractory depression when patients fail to respond satisfactorily to conventional therapies. Thus, DBS targeting specific brain areas can produce an antidepressant response that improves depressive symptomatology, these areas including the subcallosal cingulate region, nucleus accumbens, ventral capsule/ventral striatum, medial forebrain bundle, the inferior thalamic peduncle and lateral habenula. Although the efficacy and safety of this therapy has been demonstrated in some clinical trials and preclinical studies, the intrinsic mechanisms underlying its antidepressant effect remain poorly understood. This review aims to provide a comprehensive overview of DBS, focusing on the molecular and cellular changes reported after its use that could shed light on the mechanisms underpinning its antidepressant effect. Several potential mechanisms of action of DBS are considered, including monoaminergic and glutamatergic neurotransmission, neurotrophic and neuroinflammatory mechanisms, as well as potential effects on certain intracellular signaling pathways. Although future studies will be necessary to determine the key molecular events underlying the antidepressant effect of DBS, the findings presented provide an insight into some of its possible modes of action. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Shock wave as biological therapeutic tool: From mechanical stimulation to recovery and healing, through mechanotransduction.

    Science.gov (United States)

    d'Agostino, M C; Craig, K; Tibalt, E; Respizzi, S

    2015-12-01

    Extracorporeal Shock Wave Therapy (ESWT) is a form of "mechanotherapy", that, from its original applications as urological lithotripsy, gained the field of musculo-skeletal diseases as Orthotripsy (mainly tendinopaties and bone regenerative disorders) and Regenerative Medicine as well. The mechanisms of action of Shock Waves (SW), when applied in non-urological indications, are not related to the direct mechanical effect, but to the different pathways of biological reactions, that derive from that acoustic stimulations, through "mechano-transduction". So, the "mechanical model" of urological lithotripsy has been substituted by a "biological model", also supported by current knowledge in "mechanobiology", the emerging multidisciplinary field of science that investigates how physical forces and changes in cell/tissue mechanics can influence the tissue development, physiology and diseases. Although some details are still under study, it is known that SW are able to relief pain, as well to positively regulate inflammation (probably as immunomodulator), to induce neoangiogenesis and stem cells activities, thus improving tissue regeneration and healing. ESWT can be nowadays considered an effective, safe, versatile, repeatable, noninvasive therapy for the treatment of many musculo-skeletal diseases, and for some pathological conditions where regenerative effects are desirable, especially when some other noninvasive/conservative therapies have failed. Moreover, based on the current knowledge in SW mechanobiology, it seems possible to foresee new interesting and promising applications in the fields of Regenerative Medicine, tissue engineering and cell therapies. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  10. Femtosecond stimulated Raman spectroscopy of the cyclobutane thymine dimer repair mechanism: a computational study.

    Science.gov (United States)

    Ando, Hideo; Fingerhut, Benjamin P; Dorfman, Konstantin E; Biggs, Jason D; Mukamel, Shaul

    2014-10-22

    Cyclobutane thymine dimer, one of the major lesions in DNA formed by exposure to UV sunlight, is repaired in a photoreactivation process, which is essential to maintain life. The molecular mechanism of the central step, i.e., intradimer C-C bond splitting, still remains an open question. In a simulation study, we demonstrate how the time evolution of characteristic marker bands (C═O and C═C/C-C stretch vibrations) of cyclobutane thymine dimer and thymine dinucleotide radical anion, thymidylyl(3'→5')thymidine, can be directly probed with femtosecond stimulated Raman spectroscopy (FSRS). We construct a DFT(M05-2X) potential energy surface with two minor barriers for the intradimer C₅-C₅' splitting and a main barrier for the C₆-C₆' splitting, and identify the appearance of two C₅═C₆ stretch vibrations due to the C₆-C₆' splitting as a spectroscopic signature of the underlying bond splitting mechanism. The sequential mechanism shows only absorptive features in the simulated FSRS signals, whereas the fast concerted mechanism shows characteristic dispersive line shapes.

  11. Mechanical stimulation of mesenchymal stem cells: Implications for cartilage tissue engineering.

    Science.gov (United States)

    Fahy, Niamh; Alini, Mauro; Stoddart, Martin J

    2017-08-01

    Articular cartilage is a load-bearing tissue playing a crucial mechanical role in diarthrodial joints, facilitating joint articulation, and minimizing wear. The significance of biomechanical stimuli in the development of cartilage and maintenance of chondrocyte phenotype in adult tissues has been well documented. Furthermore, dysregulated loading is associated with cartilage pathology highlighting the importance of mechanical cues in cartilage homeostasis. The repair of damaged articular cartilage resulting from trauma or degenerative joint disease poses a major challenge due to a low intrinsic capacity of cartilage for self-renewal, attributable to its avascular nature. Bone marrow-derived mesenchymal stem cells (MSCs) are considered a promising cell type for cartilage replacement strategies due to their chondrogenic differentiation potential. Chondrogenesis of MSCs is influenced not only by biological factors but also by the environment itself, and various efforts to date have focused on harnessing biomechanics to enhance chondrogenic differentiation of MSCs. Furthermore, recapitulating mechanical cues associated with cartilage development and homeostasis in vivo, may facilitate the development of a cellular phenotype resembling native articular cartilage. The goal of this review is to summarize current literature examining the effect of mechanical cues on cartilage homeostasis, disease, and MSC chondrogenesis. The role of biological factors produced by MSCs in response to mechanical loading will also be examined. An in-depth understanding of the impact of mechanical stimulation on the chondrogenic differentiation of MSCs in terms of endogenous bioactive factor production and signaling pathways involved, may identify therapeutic targets and facilitate the development of more robust strategies for cartilage replacement using MSCs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society

  12. Hypokinesia upon pallidal deep brain stimulation of dystonia: support of a GABAergic mechanism

    Directory of Open Access Journals (Sweden)

    Florian eAmtage

    2013-12-01

    Full Text Available In the past, many studies have documented the beneficial effects of deep brain stimulation (DBS in the globus pallidus internus for treatment of primary segmental or generalized dystonia. Recently however, several reports focused on DBS-induced hypokinesia or freezing of gait as a side effect in these patients. Here we report on two patients suffering from freezing of gait after successful treatment of their dystonic movement disorder with pallidal high frequency stimulation (HFS. Several attempts to reduce the freezing of gait resulted in worsening of the control of dystonia. In one patient levodopa treatment was initialized which was somewhat successful to relieve freezing of gait. We discuss the possible mechanisms of hypokinetic side effects of pallidal DBS which can be explained by the hypothesis of selective GABA release as the mode of action of HFS. Pallidal HFS is also effective in treating idiopathic Parkinson’s disease as a hypokinetic disorder which at first sight seems to be a paradox. In our view, however, the GABAergic hypothesis can explain this and other clinical observations.

  13. Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

    Science.gov (United States)

    Iriki, Atsushi; Isoda, Masaki

    2015-01-01

    Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

  14. Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism

    Science.gov (United States)

    The adaptive mechanisms that protect brain metabolism during and after hypoxia, for instance, during hypoxic preconditioning, are coordinated in part by nitric oxide (NO). We tested the hypothesis that acute transient hypoxia stimulates NO synthase (NOS)-activated mechanisms of m...

  15. No effects of slow oscillatory transcranial direct current stimulation (tDCS) on sleep-dependent memory consolidation in healthy elderly subjects.

    Science.gov (United States)

    Eggert, Torsten; Dorn, Hans; Sauter, Cornelia; Nitsche, Michael A; Bajbouj, Malek; Danker-Hopfe, Heidi

    2013-11-01

    Studies in young healthy volunteers provided evidence of a beneficial impact of an anodal time-varied transcranial direct current stimulation (tDCS) during early slow wave rich sleep on declarative memory but not on procedural memory. The present study investigated whether sleep-dependent memory consolidation can also be affected by slow oscillating tDCS in a population of elderly subjects. 26 subjects (69.1 years ± 7.7 years) received bi-frontal anodal stimulation (max. current density: 0.331 mA/cm(2)) during early NREM sleep in a double-blind placebo-controlled randomized crossover study. Stimulation effects on offline consolidation were tested by using a declarative and a procedural memory task. Furthermore, sleep stages were scored, EEG power was analyzed and spindle densities were assessed. Independently from stimulation condition, performance in both memory tasks significantly decreased overnight. Stimulation revealed no significant effect on sleep-dependent memory consolidation. Verum tDCS was accompanied by significantly more time awake and significantly less NREM stage 3 sleep during five 1-min stimulation free intervals. The results of the present study are in line with other studies showing that offline consolidation during sleep varies with age and is less pronounced in the elderly than in young or middle-aged subjects. Contrary to an almost identical positive study in young adults, slow oscillatory tDCS applied to the elderly failed to show a beneficial effect on memory consolidation in the present study. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Fracture Mechanics Analyses of Subsurface Defects in Reinforced Carbon-Carbon Joggles Subjected to Thermo-Mechanical Loads

    Science.gov (United States)

    Knight, Norman F., Jr.; Raju, Ivatury S.; Song, Kyongchan

    2011-01-01

    Coating spallation events have been observed along the slip-side joggle region of the Space Shuttle Orbiter wing-leading-edge panels. One potential contributor to the spallation event is a pressure build up within subsurface voids or defects due to volatiles or water vapor entrapped during fabrication, refurbishment, or normal operational use. The influence of entrapped pressure on the thermo-mechanical fracture-mechanics response of reinforced carbon-carbon with subsurface defects is studied. Plane-strain simulations with embedded subsurface defects are performed to characterize the fracture mechanics response for a given defect length when subjected to combined elevated-temperature and subsurface-defect pressure loadings to simulate the unvented defect condition. Various subsurface defect locations of a fixed-length substrate defect are examined for elevated temperature conditions. Fracture mechanics results suggest that entrapped pressure combined with local elevated temperatures have the potential to cause subsurface defect growth and possibly contribute to further material separation or even spallation. For this anomaly to occur, several unusual circumstances would be required making such an outcome unlikely but plausible.

  17. Mechanism of stimulated Hawking radiation in a laboratory Bose-Einstein condensate

    Science.gov (United States)

    Wang, Yi-Hsieh; Jacobson, Ted; Edwards, Mark; Clark, Charles W.

    2017-08-01

    We model a sonic black-hole analog in a quasi-one-dimensional Bose-Einstein condensate, using a Gross-Pitaevskii equation matching the configuration of a recent experiment by Steinhauer [Nat. Phys. 10, 864 (2014), 10.1038/nphys3104]. The model agrees well with important features of the experimental observations, demonstrating their hydrodynamic nature. We find that a zero-frequency bow wave is generated at the inner (white-hole) horizon, which grows in proportion to the square of the background condensate density. The relative motion of the black- and white-hole horizons produces a Doppler shift of the bow wave at the black hole, where it stimulates the emission of monochromatic Hawking radiation. The mechanism is confirmed using temporal and spatial windowed Fourier spectra of the condensate. Mean field behavior similar to that in the experiment can thus be fully explained without the presence of self-amplifying Hawking radiation.

  18. The mechanisms of action of deep brain stimulation and ideas for the future development.

    Science.gov (United States)

    Udupa, Kaviraja; Chen, Robert

    2015-10-01

    Deep brain stimulation (DBS) has been used as a treatment of movement disorders such as Parkinson's disease, dystonia, and essential tremor for over twenty years, and is a promising treatment for depression and epilepsy. However, the exact mechanisms of action of DBS are still uncertain, although different theories have emerged. This review summarizes the current understanding in this field. Different modalities used to investigate DBS such as electrophysiological, imaging and biochemical studies have revealed different mechanisms of DBS. The mechanisms may also be different depending on the structure targeted, the disease condition or the animal model employed. DBS may inhibit the target neuronal networks but activate the efferent axons. It may suppress pathological rhythms or impose new rhythms associated with beneficial effects, and involves neuronal networks with widespread connections. Different neurotransmitter systems such as dopamine and GABA upregulation are involved in the effects of DBS. There are also technical advances to prolong the battery life and specific targeting based on new electrode designs with multiple contacts which have the ability to steer the current toward a specific direction. There is ongoing work in closed loop or adaptive DBS using neural oscillations to provide the feedback signals. These oscillations need to be better characterized in a wide variety of clinical settings in future studies. Individualization of DBS parameters based on neural oscillations may optimize the clinical benefits of DBS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Mechanisms and kinetic profiles of superoxide-stimulated nitrosative processes in cells using a diaminofluorescein probe.

    Science.gov (United States)

    Damasceno, Fernando Cruvinel; Facci, Rômulo Rodrigues; da Silva, Thalita Marques; Toledo, José Carlos

    2014-12-01

    In this study, we examined the mechanisms and kinetic profiles of intracellular nitrosative processes using diaminofluorescein (DAF-2) as a target in RAW 264.7 cells. The intracellular formation of the fluorescent, nitrosated product diaminofluorescein triazol (DAFT) from both endogenous and exogenous nitric oxide (NO) was prevented by deoxygenation and by cell membrane-permeable superoxide (O2(-)) scavengers but not by extracellular bovine Cu,Zn-SOD. In addition, the DAFT formation rate decreased in the presence of cell membrane-permeable Mn porphyrins that are known to scavenge peroxynitrite (ONOO(-)) but was enhanced by HCO3(-)/CO2. Together, these results indicate that nitrosative processes in RAW 264.7 cells depend on endogenous intracellular O2(-) and are stimulated by ONOO(-)/CO2-derived radical oxidants. The N2O3 scavenger sodium azide (NaN3) only partially attenuated the DAFT formation rate and only with high NO (>120 nM), suggesting that DAFT formation occurs by nitrosation (azide-susceptible DAFT formation) and predominantly by oxidative nitrosylation (azide-resistant DAFT formation). Interestingly, the DAFT formation rate increased linearly with NO concentrations of up to 120-140 nM but thereafter underwent a sharp transition and became insensitive to NO. This behavior indicates the sudden exhaustion of an endogenous cell substrate that reacts rapidly with NO and induces nitrosative processes, consistent with the involvement of intracellular O2(-). On the other hand, intracellular DAFT formation stimulated by a fixed flux of xanthine oxidase-derived extracellular O2(-) that also occurs by nitrosation and oxidative nitrosylation increased, peaked, and then decreased with increasing NO, as previously observed. Thus, our findings complementarily show that intra- and extracellular O2(-)-dependent nitrosative processes occurring by the same chemical mechanisms do not necessarily depend on NO concentration and exhibit different unusual kinetic profiles with

  20. Spatio-temporal PLC activation in parallel with intracellular Ca2+ wave propagation in mechanically stimulated single MDCK cells.

    Science.gov (United States)

    Tsukamoto, Akira; Hayashida, Yasunori; Furukawa, Katsuko S; Ushida, Takashi

    2010-03-01

    Intracellular Ca2+ transients are evoked either by the opening of Ca2+ channels on the plasma membrane or by phospholipase C (PLC) activation resulting in IP3 production. Ca2+ wave propagation is known to occur in mechanically stimulated cells; however, it remains uncertain whether and how PLC activation is involved in intracellular Ca2+ wave propagation in mechanically stimulated cells. To answer these questions, it is indispensable to clarify the spatio-temporal relations between intracellular Ca2+ wave propagation and PLC activation. Thus, we visualized both cytosolic Ca2+ and PLC activation using a real-time dual-imaging system in individual Mardin-Darby Canine Kidney (MDCK) cells. This system allowed us to simultaneously observe intracellular Ca2+ wave propagation and PLC activation in a spatio-temporal manner in a single mechanically stimulated MDCK cell. The results showed that PLC was activated not only in the mechanically stimulated region but also in other subcellular regions in parallel with intracellular Ca2+ wave propagation. These results support a model in which PLC is involved in Ca2+ signaling amplification in mechanically stimulated cells. 2009 Elsevier Ltd. All rights reserved.

  1. Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent posttranscriptional mechanism.

    Directory of Open Access Journals (Sweden)

    Holly A Cyphert

    Full Text Available Previous studies have shown that whole body deletion of the glucagon receptor suppresses the ability of starvation to increase hepatic fibroblast growth factor 21 (FGF21 expression and plasma FGF21 concentration. Here, we investigate the mechanism by which glucagon receptor activation increases hepatic FGF21 production. Incubating primary rat hepatocyte cultures with glucagon, dibutyryl cAMP or forskolin stimulated a 3-4-fold increase in FGF21 secretion. The effect of these agents on FGF21 secretion was not associated with an increase in FGF21 mRNA abundance. Glucagon induction of FGF21 secretion was additive with the stimulatory effect of a PPARα activator (GW7647 on FGF21 secretion. Inhibition of protein kinase A (PKA and downstream components of the PKA pathway [i.e. AMP-activated protein kinase and p38 MAPK] suppressed glucagon activation of FGF21 secretion. Incubating hepatocytes with an exchange protein directly activated by cAMP (EPAC-selective cAMP analog [i.e. 8-(4-chlorophenylthio-2'-O-methyladenosine-3', 5'-cyclic monophosphate (cpTOME], stimulated a 3.9-fold increase FGF21 secretion, whereas inhibition of the EPAC effector, Rap1, suppressed glucagon activation of FGF21 secretion. Treatment of hepatocytes with insulin also increased FGF21 secretion. In contrast to glucagon, insulin activation of FGF21 secretion was associated with an increase in FGF21 mRNA abundance. Glucagon synergistically interacted with insulin to stimulate a further increase in FGF21 secretion and FGF21 mRNA abundance. These results demonstrate that glucagon increases hepatic FGF21 secretion via a posttranscriptional mechanism and provide evidence that both the PKA branch and EPAC branch of the cAMP pathway play a role in mediating this effect. These results also identify a novel synergistic interaction between glucagon and insulin in the regulation of FGF21 secretion and FGF21 mRNA abundance. We propose that this insulin/glucagon synergism plays a role in

  2. Single-subject analysis reveals variation in knee mechanics during step landing.

    Science.gov (United States)

    Scholes, Corey J; McDonald, Michael D; Parker, Anthony W

    2012-08-09

    Evidence concerning the alteration of knee function during landing suffers from a lack of consensus. This uncertainty can be attributed to methodological flaws, particularly in relation to the statistical analysis of variable human movement data. The aim of this study was to compare single-subject and group analyses in detecting changes in knee stiffness and coordination during step landing that occur independent of an experimental intervention. A group of healthy men (N=12) stepped-down from a knee-high platform for 60 consecutive trials, each trial separated by a 1-minute rest. The magnitude and within-participant variability of sagittal stiffness and coordination of the landing knee were evaluated with both group and single-subject analyses. The group analysis detected significant changes in knee coordination. However, the single-subject analyses detected changes in all dependent variables, which included increases in variability with task repetition. Between-individual variation was also present in the timing, size and direction of alterations. The results have important implications for the interpretation of existing information regarding the adaptation of knee mechanics to interventions such as fatigue, footwear or landing height. It is proposed that a participant's natural variation in knee mechanics should be analysed prior to an intervention in future experiments. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Mechanisms of body weight gain in patients with Parkinson's disease after subthalamic stimulation.

    Science.gov (United States)

    Montaurier, C; Morio, B; Bannier, S; Derost, P; Arnaud, P; Brandolini-Bunlon, M; Giraudet, C; Boirie, Y; Durif, F

    2007-07-01

    Chronic bilateral subthalamic stimulation leads to a spectacular clinical improvement in patients with motor complications. However, the post-operative body weight gain involved may limit the benefits of surgery and induce critical metabolic disorders. Twenty-four Parkinsonians (61.1 +/- 1.4 years) were examined 1 month before (M - 1) and 3 months after (M + 3) surgery. Body composition and energy expenditure (EE) were measured (1) over 36 h in calorimetric chambers (CC) with rigorous control of food intakes and activities [sleep metabolic rate, resting activities, meals, 3 or 4 sessions of 20 min on a training bicycle at 13 km/h and daily EE] and (2) in resting conditions (basal metabolic rate) during an acute L-dopa challenge (M - 1) or according to acute 'off' and 'on' stimulation (M + 3). Before surgery, EE was compared between the Parkinsonian patients and healthy subjects matched for height and body composition (metabolic rate during sleep, daily EE) or matched to predicted values (basal metabolic rate). Before surgery, in Parkinsonian men but not women, (1) daily EE was higher while sleep metabolic rate was lower compared to healthy matched men (+9.2 +/- 3.9 and -8.2 +/- 2.3%, respectively, P weight increase together with fat mass (P weight increase together with fat mass (P weight gain. Parkinson's disease is associated with profound alterations in the central control of energy metabolism. Normalization of energy metabolism after DBS-STN implantation may favour body weight gain, of which quality was gender specific. As men gained primarily fat-free mass, a reasonable weight gain may be tolerated, in contrast with women who gained only fat. Other factors such as changes in free-living physical activity may help to limit body weight gain in some patients.

  4. Transcranial direct current stimulation over the medial prefrontal cortex and left primary motor cortex (mPFC-lPMC affects subjective beauty but not ugliness

    Directory of Open Access Journals (Sweden)

    Koyo eNakamura

    2015-12-01

    Full Text Available Neuroaesthetics has been searching for the neural bases of the subjective experience of beauty. It has been demonstrated that neural activities in the medial prefrontal cortex (mPFC and the left primary motor cortex (lPMC correlate with the subjective experience of beauty. Although beauty and ugliness seem to be semantically and conceptually opposite, it is still unknown whether these two evaluations represent extreme opposites in unitary or bivariate dimensions. In this study, we applied transcranial direct current stimulation (tDCS to examine whether noninvasive brain stimulation modulates two types of aesthetic evaluation; evaluating beauty and ugliness. Participants rated the subjective beauty and ugliness of abstract paintings before and after the application of tDCS. Application of cathodal tDCS over the mPFC with anode electrode over the lPMC, which induced temporal inhibition of neural excitability of the mPFC, led to a decrease in beauty ratings but not ugliness ratings. There were no changes in ratings of both beauty and ugliness when applying anodal tDCS or sham stimulation over the mPFC. Results from our experiment indicate that the mPFC and the lPMC have a causal role in generating the subjective experience of beauty, with beauty and ugliness evaluations constituting two distinct dimensions.

  5. Separate and combined impact of acute naltrexone and alprazolam on subjective and physiological effects of oral d-amphetamine in stimulant users

    Science.gov (United States)

    Marks, Katherine R.; Lile, Joshua A.; Stoops, William W.

    2014-01-01

    Rationale Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric-acidA (GABAA) receptors (e.g., alprazolam) modestly attenuate the abuse-related effects of stimulants like amphetamine. The use of higher doses to achieve greater efficacy is precluded by side effects. Combining naltrexone and alprazolam might safely maximize efficacy while avoiding the untoward effects of the constituent compounds. Objectives The present pilot study tested the hypothesis that acute pretreatment with the combination of naltrexone and alprazolam would not produce clinically problematic physiological effects or negative subjective effects and would reduce the positive subjective effects of d-amphetamine to a greater extent than the constituent drugs alone. Methods Eight nontreatment-seeking, stimulant-using individuals completed an outpatient experiment in which oral d-amphetamine (0, 15, and 30 mg) was administered following acute pretreatment with naltrexone (0 and 50 mg) and alprazolam (0 and 0.5 mg). Subjective effects, psychomotor task performance, and physiological measures were collected. Results Oral d-amphetamine produced prototypical physiological and stimulant-like positive subjective effects (e.g., VAS ratings of Active/Alert/Energetic, Good Effect, and High). Pretreatment with naltrexone, alprazolam, and their combination did not produce clinically problematic acute physiological effects or negative subjective effects. Naltrexone and alprazolam each significantly attenuated some of the subjective effects of d-amphetamine. The combination attenuated a greater number of subjective effects than the constituent drugs alone. Conclusions The present results support the continued evaluation of an opioid receptor antagonist combined with a GABAA-positive modulator using more clinically relevant experimental conditions like examining the effect of chronic dosing with these drugs on methamphetamine self-administration. PMID:24464531

  6. Mechanical properties of two-way different configurations of prestressed concrete members subjected to axial loading

    Directory of Open Access Journals (Sweden)

    Chaobi Zhang

    2015-08-01

    Full Text Available In order to analyze the mechanical properties of two-way different configurations of prestressed concrete members subjected to axial loading, a finite element model based on the nuclear power plant containments is demonstrated. This model takes into account the influences of different principal stress directions, the uniaxial or biaxial loading, and biaxial loading ratio. The displacement-controlled load is applied to obtain the stress–strain response. The simulated results indicate that the differences of principal stress axes have great effects on the stress–strain response under uniaxial loading. When the specimens are subjected to biaxial loading, the change trend of stress with the increase of loading ratio is obviously different along different layout directions. In addition, correlation experiments and finite element analyses were conducted to verify the validity and reliability of the analysis in this study.

  7. Symptomatic response to blocked and unblocked pentagastrin stimulation in functional dyspepsia - Comparison of responders and non-responders to omeprazole identified in a single-subject trial model

    DEFF Research Database (Denmark)

    Madsen, L.G.; Bytzer, P.

    2008-01-01

    Background: The role of acid in functional dyspepsia is controversial and drug treatment trials indicate that only a subset of patients has acid-related symptoms. A novel single-subject trial design, the Random Starting Day trial (RSD trial), was developed to identify acid-related symptoms. We...... was expected not to be influenced by gastric acid stimulation or type of treatment. Methods: Nineteen patients were evaluated. Symptomatic response to pentagastrin (6 mu g/kg) was assessed twice in each patient following placebo and omeprazole (40 mg bid) treatment in a randomized, double-blind, cross......-over design. Epigastric pain was assessed every 15 for 90 min after stimulation using a 5-graded Likert scale and a VAS scale. A positive acid provocation test was defined as an increase of the Likert score of epigastric pain by at least one grade after pentagastrin stimulation during placebo treatment...

  8. Molecular Mechanisms of Glucose-Stimulated GLP-1 Secretion From Perfused Rat Small Intestine

    DEFF Research Database (Denmark)

    Kuhre, Rune E.; Frost, Charlotte R.; Svendsen, Berit

    2015-01-01

    not stimulate a response. Luminal glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (phloretin), but in contrast to SGLT1 inhibition, phloretin did not eliminate the response, and luminal glucose (20%) stimulated larger GLP-1 responses than luminal α-MGP in matched concentrations...

  9. Analgesic effect of cathodal transcranial current stimulation over right dorsolateral prefrontal cortex in subjects with muscular temporomandibular disorders: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Brandão Filho, Rivail Almeida; Baptista, Abrahão Fontes; Brandão, Renata de Assis Fonseca Santos; Meneses, Francisco Monteiro; Okeson, Jeffrey; de Sena, Eduardo Pondé

    2015-09-17

    Temporomandibular disorders are a group of orofacial pain conditions that are commonly identified in the general population. Like many other chronic pain conditions, they can be associated with anxiety/depression, which can be related to changes in the activity of the dorsolateral prefrontal cortex. Some studies have demonstrated clinical improvement in subjects with chronic pain who are given therapeutic neuromodulation. Transcranial direct current stimulation is a noninvasive brain stimulation technique that allows the modulation of neuronal membranes. This therapy can enhance or inhibit action potential generation in cortical neurons. In some instances, medications acting in the central nervous system may be helpful despite their adverse side effects. It is important to determine if cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex, an area that modulates emotion and motor cortex excitability, has an analgesic effect on chronic temporomandibular disorders pain. The investigators will run a randomized, controlled crossover double blind study with 15 chronic muscular temporomandibular disorder subjects. Each subject will undergo active (1 mA and 2 mA) and sham transcranial direct current stimulation. Inclusion criteria will be determined by the Research Diagnostic Criteria for Temporomandibular Disorders questionnaire, with subjects who have a pain visual analogic scale score of greater than 4/10 and whose pain has been present for the previous 6 months, and with a State-Trait Anxiety Inventory score of more than 42. The influence of transcranial direct current stimulation will be assessed through a visual analogic scale, quantitative sensory testing, quantitative electroencephalogram, and the State-Trait Anxiety Inventory score. Some studies have demonstrated a strong association between anxiety/depression and chronic pain, where one may be the cause of the other. This is especially true in chronic temporomandibular

  10. Multi-subject/daily-life activity EMG-based control of mechanical hands

    Directory of Open Access Journals (Sweden)

    Fiorilla Angelo

    2009-11-01

    Full Text Available Abstract Background Forearm surface electromyography (EMG has been in use since the Sixties to feed-forward control active hand prostheses in a more and more refined way. Recent research shows that it can be used to control even a dexterous polyarticulate hand prosthesis such as Touch Bionics's i-LIMB, as well as a multifingered, multi-degree-of-freedom mechanical hand such as the DLR II. In this paper we extend previous work and investigate the robustness of such fine control possibilities, in two ways: firstly, we conduct an analysis on data obtained from 10 healthy subjects, trying to assess the general applicability of the technique; secondly, we compare the baseline controlled condition (arm relaxed and still on a table with a "Daily-Life Activity" (DLA condition in which subjects walk, raise their hands and arms, sit down and stand up, etc., as an experimental proxy of what a patient is supposed to do in real life. We also propose a cross-subject model analysis, i.e., training a model on a subject and testing it on another one. The use of pre-trained models could be useful in shortening the time required by the subject/patient to become proficient in using the hand. Results A standard machine learning technique was able to achieve a real-time grip posture classification rate of about 97% in the baseline condition and 95% in the DLA condition; and an average correlation to the target of about 0.93 (0.90 while reconstructing the required force. Cross-subject analysis is encouraging although not definitive in its present state. Conclusion Performance figures obtained here are in the same order of magnitude of those obtained in previous work about healthy subjects in controlled conditions and/or amputees, which lets us claim that this technique can be used by reasonably any subject, and in DLA situations. Use of previously trained models is not fully assessed here, but more recent work indicates it is a promising way ahead.

  11. Molecular and cellular mechanisms of muscle aging and sarcopenia and effects of electrical stimulation in seniors

    Directory of Open Access Journals (Sweden)

    Laura Barberi

    2015-08-01

    Full Text Available The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers, alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors.

  12. Mechanism of stimulated Hawking radiation in a laboratory Bose-Einstein condensate

    Science.gov (United States)

    Jacobson, Ted; Wang, Yi-Hsieh; Edwards, Mark; Clark, Charles W.

    2017-01-01

    Analog black/white hole pairs have been achieved in recent experiment by J. Steinhauer, using an elongated Bose-Einstein condensate. He reported observations of self-amplifying Hawking radiation, via a lasing mechanism operating between the black and white hole horizons. Through the simulations using the 1D Gross-Pitaevskii equation, we find that the experimental observations should be attributed not to the black hole laser effect, but rather to a growing zero-frequency bow wave, generated at the white-hole horizon. The relative motion of the black and white hole horizons produces a Doppler shift of the bow wave at the black hole, where it stimulates the emission of monochromatic Hawking radiation. This mechanism is confirmed using temporal and spatial windowed Fourier spectra of the condensate. We also find that shot-to-shot atom number variations, of the type normally realized in ultracold-atom experiments, and quantum fluctuations of condensates, as computed in the Bogoliubov-De Gennes approximation, give density-density correlations consistent with those reported in the experiments. In particular, atom number variations can produce a spurious correlation signal.

  13. Mechanisms for T cell tolerance induced with granulocyte colony-stimulating factor.

    Science.gov (United States)

    Yang, Jian-Zhu; Zhang, Jin-Qiao; Sun, Li-Xia

    2016-02-01

    Granulocyte colony-stimulating factor (G-CSF) has been widely accepted as a mediator of T cell tolerance. The immune modulatory effect of G-CSF on T cells is believed to be mediated exclusively through other effector cells, such as monocytes, tolerogenic dendritic cells (DC), and myeloid-derived suppressor cells. Recent advances confirmed the direct effects of G-CSF in inducing immune tolerance of T cells through the G-CSF-G-CSF receptor pathway and related molecular mechanisms. This review aims to summarize the findings associated with the direct and indirect mechanisms for T cell tolerance induced with G-CSF. The role of G-CSF in preventing graft-versus-host disease (GVHD) and in treating autoimmune diseases (ADs) is also discussed. It is conceivable that G-CSF and immune cell compositions, such as tolerogenic DC and CD4(+)CD25(+)Foxp3(+) T cells, modulated by G-CSF could become an integral part of the immunomodulatory therapies against GVHD and ADs in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Mechanical Stimulation of the HT7 Acupuncture Point to Reduce Ethanol Self-Administration in Rats

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    Suk-Yun Kang

    2017-01-01

    Full Text Available Background. Alcoholism, which is a disabling addiction disorder, is a major public health problem worldwide. The present study was designed to determine whether the application of acupuncture at the Shenmen (HT7 point suppresses voluntary alcohol consumption in addicted rats and whether this suppressive effect is potentiated by the administration of naltrexone. Methods. Rats were initially trained to self-administer a sucrose solution by operating a lever. A mechanical acupuncture instrument (MAI for objective mechanical stimulation was used on rats whose baseline response had been determined. In addition, the effect of HT7 acupuncture on beta-endorphin concentration and ethanol intake via naltrexone were investigated in different groups. Results. We found that ethanol intake and beta-endorphin level in rats being treated with the MAI at the HT7 point reduced significantly. The treatment of naltrexone at high doses reduced the ethanol intake and low-dose injection of naltrexone in conjunction with the MAI also suppressed ethanol intake. Conclusions. The results of the current study indicate that using the MAI at the HT7 point effectively reduces ethanol consumption in rats. Furthermore, the coadministration of the MAI and a low dose of naltrexone can produce some more potent reducing effect of ethanol intake than can acupuncture alone.

  15. Structural Stability of a Stiffened Aluminum Fuselage Panel Subjected to Combined Mechanical and Internal Pressure Loads

    Science.gov (United States)

    Rouse, Marshall; Young, Richard D.; Gehrki, Ralph R.

    2003-01-01

    Results from an experimental and analytical study of a curved stiffened aluminum panel subjected to combined mechanical and internal pressure loads are presented. The panel loading conditions were simulated using a D-box test fixture. Analytical buckling load results calculated from a finite element analysis are presented and compared to experimental results. Buckling results presented indicate that the buckling load of the fuselage panel is significantly influenced by internal pressure loading. The experimental results suggest that the stress distribution is uniform in the panel prior to buckling. Nonlinear finite element analysis results correlates well with experimental results up to buckling.

  16. Characteristics and Corrosion Behavior of Pure Titanium Subjected to Surface Mechanical Attrition

    Science.gov (United States)

    Fu, Tianlin; Wang, Xiao; Liu, Jianxiong; Li, Li; Yu, Xiaohua; Zhan, Zhaolin

    2017-10-01

    A stable passive film exhibiting good corrosion resistance in a 3.5 wt.% NaCl solution was formed on the surface of pure titanium (Ti) subjected to a surface mechanical attrition treatment (SMAT). The corrosion potential (-0.21 V) of the film was significantly higher than that (-0.92 V) of the untreated sample. Moreover, the corrosion current density was an order of magnitude lower than that of the untreated sample. SMAT resulted in a decrease in the vacancy condensation in the TiO2 film, thereby inhibiting the invasion and diffusion of Cl- in the film.

  17. Mechanical property evaluation of an Al-2024 alloy subjected to HPT processing

    OpenAIRE

    Patil, Deepak C.; Venkateswarlu, K.; Kori, S.A.; Das, Goutam; Das, Mousumi; Alhajeri, Saleh N.; Langdon, Terence G.

    2014-01-01

    An aluminum-copper alloy (Al-2024) was successfully subjected to high-pressure torsion (HPT) up to five turns at room temperature under an applied pressure of 6.0 GPa. The Al-2024 alloy is used as a fuselage structural material in the aerospace sector. Mechanical properties of the HPT-processed Al-2024 alloy were evaluated using the automated ball indentation technique. This test is based on multiple cycles of loading and unloading where a spherical indenter is used. After two and five turns ...

  18. Behavior of granite-epoxy composite beams subjected to mechanical vibrations

    Directory of Open Access Journals (Sweden)

    Antonio Piratelli-Filho

    2010-12-01

    Full Text Available The capacity to damp mechanical vibrations is one of the most important properties of granite-epoxy composites, even superior to the cast iron one. For this reason, these materials have been adopted for manufacturing of tool machine foundations and precision instruments. This work presents a study concerning the behavior of particulate composite beams, based on granite powder and epoxy, subjected to mechanical vibrations. Composite samples were prepared with different combinations of processing variables, like the weight fraction of epoxy in the mixture and size distributions of granite particles. The damping behavior of the material was investigated adopting the logarithmic decrement method. Samples, in the form of prismatic beams, were excited in the middle point and the output signal was measured in a point located at the extremity. The obtained results showed that composite samples, with weight fractions of about 80% of granite and 20% of epoxy, presented damping properties approximately three times greater than gray cast iron.

  19. Loudness functions with air and bone conduction stimulation in normal-hearing subjects using a categorical loudness scaling procedure

    OpenAIRE

    Stenfelt, Stefan; Zeitooni, Mehrnaz

    2013-01-01

    In a previous study (Stenfelt and Håkansson, 2002) a loudness balance test between bone conducted (BC) sound and air conducted (AC) sound was performed at frequencies between 0.25 and 4 kHz and at levels corresponding to 30–80 dB HL. The main outcome of that study was that for maintaining equal loudness, the level increase of sound with BC stimulation was less than that of AC stimulation with a ratio between 0.8 and 0.93 dB/dB. However, because it was shown that AC and BC tone cancellation wa...

  20. Investigation into the mechanisms of vagus nerve stimulation for the treatment of intractable epilepsy, using {sup 99m}Tc-HMPAO SPET brain images

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, Anna; Chisholm, Jennifer A.; Patterson, James; Wyper, David [Department of Clinical Physics, Institute of Neurological Sciences, Southern General Hospital, 1345 Govan Road, Glasgow G51 4TF (United Kingdom); Duncan, Roderick [Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow (United Kingdom); Lindsay, Kenneth [Department of Neurosurgery, Institute of Neurological Sciences, Southern General Hospital, Glasgow (United Kingdom)

    2003-02-01

    Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies where surgical treatment is not possible. While it appears that this treatment is effective in some patients, the mechanism of action is not clearly understood. The purpose of this study was to clarify findings of other positron emission tomography and single-photon emission tomography (SPET) investigations by measuring the acute effect of VNS on patients who have normal cerebral anatomy on magnetic resonance imaging and who have not previously been exposed to VNS. We investigated six subjects (two males and four females, mean age 29.5 years, range 21-39 years) with intractable epilepsy. One patient had primary generalised epilepsy causing generalised tonic-clonic seizures; the remaining five patients had localisation-related epilepsy causing complex partial seizures. SPET imaging was performed using 250 MBq of {sup 99m}Tc-HMPAO and a four-scan paradigm - two with and two without stimulation. The stimulation began at VNS current levels of 0.25 mA and was increased according to the limit of patients' tolerance, usually defined by coughing or discomfort. The stimulating waveform was of continuous square wave pulses of 500 {mu}s duration at 30 Hz. Image analysis was by SPM99. Reduced perfusion during stimulation was observed in the ipsilateral brain stem, cingulate, amygdala and hippocampus and contralateral thalamus and cingulate. The study provides further evidence of the involvement of the limbic system in the action of vagal nerve stimulation. (orig.)

  1. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits

    Directory of Open Access Journals (Sweden)

    Sarah Kathleen Bourne

    2012-06-01

    Full Text Available Deep brain stimulation (DBS has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive-compulsive disorder (OCD, which is characterized by recurrent unwanted thoughts or ideas (obsessions and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions. Abnormal activity in cortico-striato-thalamo-cortical (CSTC circuits including the orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mediodorsal thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule, ventral capsule/ventral striatum, ventral caudate nucleus, subthalamic nucleus, nucleus accumbens, and the inferior thalamic peduncle have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.

  2. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits.

    Science.gov (United States)

    Bourne, Sarah K; Eckhardt, Christine A; Sheth, Sameer A; Eskandar, Emad N

    2012-01-01

    Deep brain stimulation (DBS) has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive compulsive disorder (OCD), which is characterized by recurrent unwanted thoughts or ideas (obsessions) and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions). Abnormal activity in cortico-striato-thalamo-cortical (CSTC) circuits including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), ventral striatum, and mediodorsal (MD) thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), ventral caudate nucleus, subthalamic nucleus (STN), and nucleus accumbens (NAc) have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.

  3. Inter-subject and Inter-session Variability of Plasticity Induction by Non-invasive Brain Stimulation

    DEFF Research Database (Denmark)

    Ziemann, Ulf; Siebner, Hartwig R

    2015-01-01

    in human cortex well beyond the time of stimulation. These aftereffects have been termed long-term potentiation (LTP)-like and long-term depression (LTD)-like plasticity because indirect evidence supported the notion that synaptic strengthening or weakening similar to LTP/D at the cellular level underlies...

  4. Testing principle working mechanisms of the health action process approach for subjective physical age groups.

    Science.gov (United States)

    Wienert, Julian; Kuhlmann, Tim; Fink, Sebastian; Hambrecht, Rainer; Lippke, Sonia

    2016-01-01

    This study investigated differences in social-cognitive predictors and self-regulatory planning, as proposed by the health action process approach (HAPA), across three different subjective physical age groups for physical activity. With a cross-sectional design, 521 participants across the chronological age span from 25 to 86 years (M = 48.79; SD = 12.66) were separated into three groups: those who feel physically younger than they are in terms of chronological age, the same perceived and chronological age, and feeling physically older compared to their chronological age. Participants were assessed regarding their perceived vulnerability, outcome expectancies, general intentions, planning, self-efficacy, and stages of physical activity (non-intenders, intenders, and actors). Data were analysed via mean comparison and multigroup structural equation modelling. Mean differences for all but one construct were eminent in all groups, generally showing that those feeling physically younger also report better social-cognitive predictors of physical activity (e.g. lower perceived vulnerability) in comparison to those who feel the same age or older. The model showed that basic working mechanisms of the HAPA can be applied to all groups. With that, the results provide for the first time evidence that principle working mechanism of the HAPA can be applied to all subjective physical age groups. These may be used to tailor health promoting interventions according to participants' needs as a more suitable proxy than chronological age.

  5. Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-infammatory mechanism

    Science.gov (United States)

    Xiang, Yao-xian; Wang, Wen-xin; Xue, Zhe; Zhu, Lei; Wang, Sheng-bao; Sun, Zheng-hui

    2015-01-01

    Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimulation (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes) 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-α and interleukin-6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor-α and interleukin-6 expression. PMID:26170817

  6. MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM--mechanism of growth hormone stimulation of skeletal muscle growth in cattle.

    Science.gov (United States)

    Jiang, H; Ge, X

    2014-01-01

    Growth hormone, also called somatotropin (ST), is a polypeptide hormone produced by the anterior pituitary. The major functions of GH include stimulating bone and skeletal muscle growth, lipolysis, milk production, and expression of the IGF-I gene in the liver. Based on these functions, recombinant bovine ST (bST) and recombinant porcine ST (pST) have been used to improve milk production in dairy cows and lean tissue growth in pigs, respectively. However, despite these applications, the mechanisms of action of GH are not fully understood. Indeed, there has been a lot of controversy over the role of liver-derived circulating IGF-I and locally produced IGF-I in mediating the growth-stimulatory effect of GH during the last 15 yr. It is in this context that we have conducted studies to further understand how GH stimulates skeletal muscle growth in cattle. Our results do not support a role of skeletal muscle-derived IGF-I in GH-stimulated skeletal muscle growth in cattle. Our results indicate that GH stimulates skeletal muscle growth in cattle, in part, by stimulating protein synthesis in muscle through a GH receptor-mediated, IGF-I-independent mechanism. In this review, besides discussing these results, we also argue that liver-derived circulating IGF-I should be still considered as the major mechanism that mediates the growth-stimulatory effect of GH on skeletal muscle in cattle and other domestic animals.

  7. Mechanical Anisotropy Development of a Two-Phase Composite Subject to Large Deformation

    Science.gov (United States)

    Dabrowski, M.; Schmid, D. W.; Yu, Podladchikov, Yu,

    2009-04-01

    Evolution of overall mechanical properties has been demonstrated in large strain deformation experiments. Strain softening is frequently employed in geodynamic simulations. In this paper, we quantify the structural and mechanical evolution of a two-phase composite rock subject to pure and simple shear. An inclusion-host type of geometry is assumed, we focus on the weak inclusion scenario and both materials obey a linear viscous behavior. Finite deformation leads to a shape preferred orientation development that results in an overall mechanical anisotropy. We derive the shape evolution model based on an analytical solution for an isolated elliptical inclusion embedded in an anisotropic host and subject to a uniform far field load. The presence of a strong anisotropy in the host leads to an enhanced inclusion stretching. A differential effective medium type of scheme predicting an overall anisotropic viscosity of a composite consisting of aligned elliptical inclusions is proposed and validated by finite element modeling. A comparison with an existing self-consistent averaging scheme is given and the new scheme is shown to provide an improved estimate of the effective normal and shear viscosity for high inclusion concentrations. The two models are combined into a final set of equations describing evolution of a two-phase rock under a shear. Hardening is predicted in pure shear. In simple shear, the hardening phase is followed by a pronounced softening after a shear strain of one, irrespective of inclusion concentration. Numerical simulations resolving evolution of inclusion-host systems under pure and simple shear demonstrate the high accuracy of our model prediction. The shape evolution model provides a sufficient approximation to the shape preferred orientation developing in an aggregate of interacting inclusions. Both in pure and simple shear, deformation localizes into conjugate trails of inclusions leading to formation of complex sigmoidal inclusion shapes.

  8. Structure and mechanical properties of a high-carbon steel subjected to severe deformation

    Science.gov (United States)

    Gorkunov, E. S.; Zadvorkin, S. M.; Goruleva, L. S.; Makarov, A. V.; Pecherkina, N. L.

    2017-10-01

    The structure and mechanical properties of a high-carbon eutectic steel subjected to the cold plastic deformation by hydrostatic extrusion in a wide range of true strain have been studied. Using scanning and transmission electron microscopy, it has been shown that the formation of cellular, fragmented, and submicrocrystalline structures occurs in the ferritic constituent of the pearlite structure of the steel upon extrusion. This is a consequence of the occurrence of dynamic recovery and continuous dynamic and post-dynamic recrystallization, which cause a decrease in the density of free dislocations at the true strain of more than 1.62. The partial dissolution of the carbide phase is also observed. It has been found that, at a true strain of up to 0.81, the strength properties of the investigated steel are determined mainly by subgrain, dislocation, and precipitation mechanisms of the strengthening; in the deformation range of 0.81-1.62, the role of the grainboundary strengthening increases. At strains above 1.62, grain-boundary strengthening is a prevailing mechanism in the formation of the level of strength properties of the extruded U8A steel. The ultimate tensile strength and yield stress over the entire strain range only uniquely correlate with the density of highangle boundaries; the dependences of the strength characteristics on other structural parameters are not monotonic.

  9. Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive-Compulsive Disorder.

    Science.gov (United States)

    van Westen, Maarten; Rietveld, Erik; Figee, Martijn; Denys, Damiaan

    Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients regain a normal quality of life (QoL) after DBS. Reviewing the literature of the last 4 years, we argue that the mechanisms of action of DBS are a combination of excitatory and inhibitory as well as local and distal effects. Evidence from DBS animal models converges with human DBS EEG and imaging findings, in that DBS may be effective for OCD by reduction of hyperconnectivity between frontal and striatal areas. This is achieved through reduction of top-down-directed synchrony and reduction of frontal low-frequency oscillations. DBS appears to counteract striatal dysfunction through an increase in striatal dopamine and through improvement of reward processing. DBS affects anxiety levels through reduction of stress hormones and improvement of fear extinction.

  10. Mechanical ventilation or phrenic nerve stimulation for treatment of spinal cord injury-induced respiratory insufficiency.

    Science.gov (United States)

    Hirschfeld, S; Exner, G; Luukkaala, T; Baer, G A

    2008-11-01

    Prospective clinical study of two treatments. To compare mechanical ventilation (MV) with phrenic nerve stimulation (PNS) for treatment of respiratory device-dependent (RDD) spinal cord-injured (SCI) patients. Department for spinal cord-injured patients of an insurance-company-run trauma hospital in Hamburg, Germany. Prospective data collection of treatment-related data over 20 years. In total, 64 SCI-RDD patients were treated during the study period. Of these, 32 of the patients with functioning phrenic nerves and diaphragm muscles were treated with PNS and 32 patients with destroyed phrenic nerves were mechanically ventilated. Incidence of respiratory infections (RIs per 100 days) prior to use of final respiratory device was equal in both groups, that is (median (interquartile range)) 1.43 (0.05-3.92) with PNS and 1.33 (0.89-2.21) with MV (P=0.888); with final device in our institution it was 0 (0-0.92) with PNS and 2.07 (1.49-4.19) with MV (Prespiratory treatment with PNS significantly reduces frequency of RI. Quality of speech is significantly better with PNS. Nine patients with PNS, but only two with MV, were employed or learned after rehabilitation (P=0.093). The primary investment in the respiratory device is higher with PNS, but it can be paid off in our setting within 1 year because of the reduced amount of single use equipment, easier nursing and fewer RIs compared to MV. PNS instead of MV for treatment of SCI-RDD reduces RIs, running costs of respiratory treatment and obviously improves patients' quality of life.

  11. Modulating phonemic fluency performance in healthy subjects with transcranial magnetic stimulation over the left or right lateral frontal cortex.

    Science.gov (United States)

    Smirni, Daniela; Turriziani, Patrizia; Mangano, Giuseppa Renata; Bracco, Martina; Oliveri, Massimiliano; Cipolotti, Lisa

    2017-07-28

    A growing body of evidence have suggested that non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can improve the performance of aphasic patients in language tasks. For example, application of inhibitory rTMS or tDCs over the right frontal lobe of dysphasic patients resulted in improved naming abilities. Several studies have also reported that in healthy controls (HC) tDCS application over the left prefrontal cortex (PFC) improve performance in naming and semantic fluency tasks. The aim of this study was to investigate in HC, for the first time, the effects of inhibitory repetitive TMS (rTMS) over left and right lateral frontal cortex (BA 47) on two phonemic fluency tasks (FAS or FPL). 44 right-handed HCs were administered rTMS or sham over the left or right lateral frontal cortex in two separate testing sessions, with a 24h interval, followed by the two phonemic fluency tasks. To account for possible practice effects, an additional 22 HCs were tested on only the phonemic fluency task across two sessions with no stimulation. We found that rTMS-inhibition over the left lateral frontal cortex significantly worsened phonemic fluency performance when compared to sham. In contrast, rTMS-inhibition over the right lateral frontal cortex significantly improved phonemic fluency performance when compared to sham. These results were not accounted for practice effects. We speculated that rTMS over the right lateral frontal cortex may induce plastic neural changes to the left lateral frontal cortex by suppressing interhemispheric inhibitory interactions. This resulted in an increased excitability (disinhibition) of the contralateral unstimulated left lateral frontal cortex, consequently enhancing phonemic fluency performance. Conversely, application of rTMS over the left lateral frontal cortex may induce a temporary, virtual lesion, with effects similar to those reported in left frontal

  12. A system for delivering mechanical stimulation and robot-assisted therapy to the rat whisker pad during facial nerve regeneration.

    Science.gov (United States)

    Heaton, James T; Knox, Christopher J; Malo, Juan S; Kobler, James B; Hadlock, Tessa A

    2013-11-01

    Functional recovery is typically poor after facial nerve transection and surgical repair. In rats, whisking amplitude remains greatly diminished after facial nerve regeneration, but can recover more completely if the whiskers are periodically mechanically stimulated during recovery. Here we present a robotic "whisk assist" system for mechanically driving whisker movement after facial nerve injury. Movement patterns were either preprogrammed to reflect natural amplitudes and frequencies, or movements of the contralateral (healthy) side of the face were detected and used to control real-time mirror-like motion on the denervated side. In a pilot study, 20 rats were divided into nine groups and administered one of eight different whisk assist driving patterns (or control) for 5-20 minutes, five days per week, across eight weeks of recovery after unilateral facial nerve cut and suture repair. All rats tolerated the mechanical stimulation well. Seven of the eight treatment groups recovered average whisking amplitudes that exceeded controls, although small group sizes precluded statistical confirmation of group differences. The potential to substantially improve facial nerve recovery through mechanical stimulation has important clinical implications, and we have developed a system to control the pattern and dose of stimulation in the rat facial nerve model.

  13. A pilot study of a new method of cognitive stimulation using abacus arithmetic in healthy and cognitively impaired elderly subjects.

    Science.gov (United States)

    Matías-Guiu, J A; Pérez-Martínez, D A; Matías-Guiu, J

    2016-06-01

    This study explores the applicability of a cognitive stimulation method based on abacus arithmetic in elderly people with and without cognitive impairment. This observational and prospective pilot study was performed in 2 hospitals. The study assessed the applicability of a programme of arithmetic training developed for use in the elderly population. The primary endpoint was an evaluation of the stimulation programme, in terms of usability, satisfaction, and participation, in healthy elderly controls and elderly patients with mild cognitive impairment or Alzheimer disease. Secondary endpoints were family satisfaction, caregiver burden, and the behaviour and cognition of patients. Usability, satisfaction, and degree of participation were high. The Mini-Mental State Examination showed significant changes (23.1±4.8 before the intervention vs 24.9±4.2 afterwards, P=.002); there were no changes on the Trail Making Test parts A and B, Yesavage Geriatric Depression scale, and Zarit caregiver burden scale. The study suggests that cognitive stimulation with abacus arithmetic may be used in elderly people with and without cognitive impairment. Further studies will be needed to evaluate the efficacy of this kind of programmes. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Mechanical stimulation promote the osteogenic differentiation of bone marrow stromal cells through epigenetic regulation of Sonic Hedgehog.

    Science.gov (United States)

    Wang, Chuandong; Shan, Shengzhou; Wang, Chenglong; Wang, Jing; Li, Jiao; Hu, Guoli; Dai, Kerong; Li, Qingfeng; Zhang, Xiaoling

    2017-03-15

    Mechanical unloading leads to bone loss and disuse osteoporosis partly due to impaired osteoblastogenesis of bone marrow stromal cells (BMSCs). However, the underlying molecular mechanisms of this phenomenon are not fully understood. In this study, we demonstrated that cyclic mechanical stretch (CMS) promotes osteoblastogenesis of BMSCs both in vivo and in vitro. Besides, we found that Hedgehog (Hh) signaling pathway was activated in this process. Inhibition of which by either knockdown of Sonic hedgehog (Shh) or treating BMSCs with Hh inhibitors attenuated the osteogenic effect of CMS on BMSCs, suggesting that Hh signaling pathway acts as an endogenous mediator of mechanical stimuli on BMSCs. Furthermore, we demonstrated that Shh expression level was regulated by DNA methylation mechanism. Chromatin Immunoprecipitation (ChIP) assay showed that DNA methyltransferase 3b (Dnmt3b) binds to Shh gene promoter, leading to DNA hypermethylation in mechanical unloading BMSCs. However, mechanical stimulation down-regulates the protein level of Dnmt3b, results in DNA demethylation and Shh expression. More importantly, we found that inhibition of Dnmt3b partly rescued bone loss in HU mice by mechanical unloading. Our results demonstrate, for the first time, that mechanical stimulation regulates osteoblastic genes expression via direct regulation of Dnmt3b, and the therapeutic inhibition of Dnmt3b may be an efficient strategy for enhancing bone formation under mechanical unloading. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Estimation of first excursion probability for mechanical appendage system subjected to nonstationary earthquake excitation

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, Shigeru; Suzuki, Kohei (Tokyo Metropolitan Univ. (Japan))

    1984-06-01

    An estimation technique whereby the first excursion probability of the mechanical appendage system subjected to the nonstationary seismic excitation can be conventionally calculated is proposed. The first excursion probability of the appendage system is estimated by using this method and the following results are obtained. (1) The probability from this technique is more convervative than that from a simulation technique taking artificial time histories compatible to the design spectrum as input excitation. (2) The first excursion probability is practically independent of the natural period of the appendage system when the tolerable barrier level is normalized by the response amplification factor given by the design spectrum. (3) The first excursion probability decreases as the damping ratio of the appendage system increases. It also decreases as the mass ratio of the appendage system to the supporting system increases. (4) For the inelastic appendage system, the first excursion probability is reduced, if an appropriate elongation is permitted.

  16. Topical negative pressure stimulates endothelial migration and proliferation: a suggested mechanism for improved integration of Integra.

    Science.gov (United States)

    Baldwin, Christopher; Potter, Matthew; Clayton, Elizabeth; Irvine, Laurie; Dye, Julian

    2009-01-01

    Topical negative pressure is an effective technique to promote wound healing and the integration of skin graft and synthetic dermal equivalents. We describe an in vitro model to investigate the effect of negative pressure on angiogenesis, a pivotal step. Dermal fibroblasts or human microvascular endothelial cells were cultured on Integra and subjected to intermittent or continuous negative pressure. At fixed intervals of over 120 hours, the Integra was fixed and assessed for cell migration (microscopy), cell viability (MTS assay), and cell proliferation (Ki67 immunostaining). Under control conditions, endothelial cells formed a monolayer and failed to ingress, whereas fibroblasts migrated throughout the Integra within 24 hours. Negative pressure switches endothelial cell to a migratory and proliferative phenotype. Ingress is greatest with intermittent rather than continuous negative pressure. It has no effect on dermal fibroblast function. This study identifies an important, potential pro-angiogenic mechanism by which topical negative pressure promotes wound healing.

  17. Electrical stimulation of the primate lateral habenula suppresses saccadic eye movement through a learning mechanism.

    Directory of Open Access Journals (Sweden)

    Masayuki Matsumoto

    Full Text Available The lateral habenula (LHb is a brain structure which represents negative motivational value. Neurons in the LHb are excited by unpleasant events such as reward omission and aversive stimuli, and transmit these signals to midbrain dopamine neurons which are involved in learning and motivation. However, it remains unclear whether these phasic changes in LHb neuronal activity actually influence animal behavior. To answer this question, we artificially activated the LHb by electrical stimulation while monkeys were performing a visually guided saccade task. In one block of trials, saccades to one fixed direction (e.g., right direction were followed by electrical stimulation of the LHb while saccades to the other direction (e.g., left direction were not. The direction-stimulation contingency was reversed in the next block. We found that the post-saccadic stimulation of the LHb increased the latencies of saccades in subsequent trials. Notably, the increase of the latency occurred gradually as the saccade was repeatedly followed by the stimulation, suggesting that the effect of the post-saccadic stimulation was accumulated across trials. LHb stimulation starting before saccades, on the other hand, had no effect on saccade latency. Together with previous studies showing LHb activation by reward omission and aversive stimuli, the present stimulation experiment suggests that LHb activity contributes to learning to suppress actions which lead to unpleasant events.

  18. Patients' expectations of deep brain stimulation, and subjective perceived outcome related to clinical measures in Parkinson's disease: a mixed-method approach.

    Science.gov (United States)

    Maier, Franziska; Lewis, Catharine J; Horstkoetter, Nina; Eggers, Carsten; Kalbe, Elke; Maarouf, Mohammad; Kuhn, Jens; Zurowski, Mateusz; Moro, Elena; Woopen, Christiane; Timmermann, Lars

    2013-11-01

    To study patients' expectations of subthalamic deep brain stimulation (STN-DBS) and their subjective perceived outcome, by using qualitative and quantitative methods in Parkinson's disease (PD). PD patients were prospectively examined before and 3 months after surgery. Semistructured interviews regarding preoperative expectations and postsurgical subjective perceived outcome were conducted. These were analysed using content analysis. For statistical analyses, patients were classified according to their subjective perceived outcome, resulting in three different subjective outcome groups (negative, mixed, positive outcome). The groups were used for multiple comparisons between and within each group regarding motor impairment, quality of life (QoL), neuropsychiatric status and cognitive functioning, using standard instruments. A logistic regression analysis was conducted to find predictors of subjective negative outcome. Receiver operating characteristic curves were used to analyse cut-off scores for predictive tests. Of the 30 PD patients participating, 8 had a subjective negative outcome, 8 a mixed and 14 a positive outcome. All groups significantly improved in motor functioning. Patients with subjective negative outcome were characterised by preoperative unrealistic expectations, no postsurgical improvement in QoL, and significantly higher presurgical and postsurgical apathy and depression scores. Higher preoperative apathy and depression scores were significant predictors of negative subjective outcome. Cut-off scores for apathy and depression were identified. The mixed-method approach proved useful in examining a patient's subjective perception of STN-DBS outcome. Our results show that significant motor improvement does not necessarily lead to a positive subjective outcome. Moreover, PD patients should be screened carefully before surgery regarding apathy and depression. (DRKS-ID: DRKS00003221).

  19. Shear Induced Reaction Localizations and Mechanisms of Energy Dissipation in PBX Subjected to Strong Shock

    Science.gov (United States)

    Plaksin, Igor

    2007-06-01

    Paper addresses two emerging topics: how reaction initiation arises when PBX is subjected to shock and how detonation wave becomes oscillating. We apply the 96-channel optical analyzer for simultaneous measurements of radiation from the reaction spots surface and stress field caused by shock or detonation reaction zone in multi-layer optical monitor. This metrology allows meso-scale probing of the 3-D structure of shock- or detonation- reaction-zone as well as revealing mechanisms of its formation at different initiation scenarios. The dominant role of the shear driven plastic deformation in initiation scenario is disclosed in all tested PBX-s (including simulants of PBXN-110, PBAN-128, PBXN-109, 111, 121 and B-2208), in wide range of PBX sample sizes: from 1 mm^3 (single crystal within the binder) up to few cm^3. This research is complementing a separate, longer running, theoretical effort by Dr. Steve Coffey that examines the solid state--quantum physics responsible for initiation of explosive crystals subjected to shock or impact. Finally, this represents a novel research effort to relate plastic deformation, energy dissipation and localization in crystals to shear and shear deformation. The accompanying experimental results strongly support Coffey's theoretical prediction that initiation is due to shear driven plastic deformation and is not due solely to uniform shock pressure. Finally, we will present and discuss the recently revealed phenomenon of the thermal precursor origination caused by the reaction front radiation. The role of this earlier unknown energy localization mechanism, at Shock-to-Detonation transition in PBX, will be shown as a function of HMX particle sizes and the PBX porosity.

  20. Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism.

    Science.gov (United States)

    Catherino, W. H.; Jeng, M. H.; Jordan, V. C.

    1993-01-01

    There is great concern over the long-term influence of oral contraceptives on the development of breast cancer in women. Oestrogens are known to stimulate the growth of human breast cancer cells, and this laboratory has previously reported (Jeng & Jordan, 1991) that the 19-norprogestin norethindrone could stimulate the proliferation of MCF-7 human breast cancer cells. We studied the influence of the 19-norprogestins norgestrel and gestodene compared to a 'non' 19-norprogestin medroxyprogesterone acetate (MPA) on MCF-7 cell proliferation. The 19-norprogestins stimulated proliferation at a concentration of 10(-8) M, while MPA could not stimulate proliferation at concentrations as great as 3 x 10(-6) M. The stimulatory activity of the 19-norprogestins could be blocked by the antioestrogen ICI 164,384, but not by the antiprogestin RU486. Transfection studies with the reporter plasmids containing an oestrogen response element or progesterone response element (vitERE-CAT, pS2ERE-CAT, and PRE15-CAT) were performed to determine the intracellular action of norgestrel and gestodene. The 19-norprogestins stimulated the vitERE-CAT activity maximally at 10(-6) M, and this stimulation was inhibited by the addition of ICI 164,384. MPA did not stimulate vitERE-CAT activity. A single base pair alteration in the palindromic sequence of vitERE (resulting in the pS2ERE) led to a dramatic decrease in CAT expression by the 19-norprogestins, suggesting that the progestin activity required specific response element base sequencing. PRE15-CAT activity was stimulated by norgestrel, gestodene and MPA at concentrations well below growth stimulatory activity. This stimulation could be blocked by RU486. These studies suggest that the 19-norprogestins norgestrel and gestodene stimulate MCF-7 breast cancer cell growth by activating the oestrogen receptor. PMID:8494728

  1. Comparing maximum rate and sustainability of pacing by mechanical vs. electrical stimulation in the Langendorff-perfused rabbit heart.

    Science.gov (United States)

    Quinn, T Alexander; Kohl, Peter

    2016-12-01

    Mechanical stimulation (MS) represents a readily available, non-invasive means of pacing the asystolic or bradycardic heart in patients, but benefits of MS at higher heart rates are unclear. Our aim was to assess the maximum rate and sustainability of excitation by MS vs. electrical stimulation (ES) in the isolated heart under normal physiological conditions. Trains of local MS or ES at rates exceeding intrinsic sinus rhythm (overdrive pacing; lowest pacing rates 2.5±0.5 Hz) were applied to the same mid-left ventricular free-wall site on the epicardium of Langendorff-perfused rabbit hearts. Stimulation rates were progressively increased, with a recovery period of normal sinus rhythm between each stimulation period. Trains of MS caused repeated focal ventricular excitation from the site of stimulation. The maximum rate at which MS achieved 1:1 capture was lower than during ES (4.2±0.2 vs. 5.9±0.2 Hz, respectively). At all overdrive pacing rates for which repetitive MS was possible, 1:1 capture was reversibly lost after a finite number of cycles, even though same-site capture by ES remained possible. The number of MS cycles until loss of capture decreased with rising stimulation rate. If interspersed with ES, the number of MS to failure of capture was lower than for MS only. In this study, we demonstrate that the maximum pacing rate at which MS can be sustained is lower than that for same-site ES in isolated heart, and that, in contrast to ES, the sustainability of successful 1:1 capture by MS is limited. The mechanism(s) of differences in MS vs. ES pacing ability, potentially important for emergency heart rhythm management, are currently unknown, thus warranting further investigation. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  2. Cutaneous nociceptors lack sensitisation, but reveal μ-opioid receptor-mediated reduction in excitability to mechanical stimulation in neuropathy

    Directory of Open Access Journals (Sweden)

    Schmidt Yvonne

    2012-11-01

    Full Text Available Abstract Background Peripheral nerve injuries often trigger a hypersensitivity to tactile stimulation. Behavioural studies demonstrated efficient and side effect-free analgesia mediated by opioid receptors on peripheral sensory neurons. However, mechanistic approaches addressing such opioid properties in painful neuropathies are lacking. Here we investigated whether opioids can directly inhibit primary afferent neuron transmission of mechanical stimuli in neuropathy. We analysed the mechanical thresholds, the firing rates and response latencies of sensory fibres to mechanical stimulation of their cutaneous receptive fields. Results Two weeks following a chronic constriction injury of the saphenous nerve, mice developed a profound mechanical hypersensitivity in the paw innervated by the damaged nerve. Using an in vitro skin-nerve preparation we found no changes in the mechanical thresholds and latencies of sensory fibres from injured nerves. The firing rates to mechanical stimulation were unchanged or reduced following injury. Importantly, μ-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5]-ol-enkephalin (DAMGO significantly elevated the mechanical thresholds of nociceptive Aδ and C fibres. Furthermore, DAMGO substantially diminished the mechanically evoked discharges of C nociceptors in injured nerves. These effects were blocked by DAMGO washout and pre-treatment with the selective μ-opioid receptor antagonist Cys2-Tyr3-Orn5-Pen7-amide. DAMGO did not alter the responses of sensory fibres in uninjured nerves. Conclusions Our findings suggest that behaviourally manifested neuropathy-induced mechanosensitivity does not require a sensitised state of cutaneous nociceptors in damaged nerves. Yet, nerve injury renders nociceptors sensitive to opioids. Prevention of action potential generation or propagation in nociceptors might represent a cellular mechanism underlying peripheral opioid-mediated alleviation of mechanical hypersensitivity in neuropathy.

  3. Blunted Peripheral and Central Responses to Gastric Mechanical and Electrical Stimulations in Diet-induced Obese Rats.

    Science.gov (United States)

    Zhang, Jing; Sha, Weihong; Zhu, Hongbing; Chen, Jiande D Z

    2013-10-01

    The increase in the prevalence of obesity is attributed to increased food intake and decreased physical activity in addition to genetic factors. Altered gut functions have been reported in obese subjects, whereas, little is known on the possible alterations in brain-gut interactions in obesity. The aim of the study was to explore possible alterations in gastric myoelectrical activity, gastric emptying, autonomic functions and central neuronal responses to gastric stimulations in diet-induced obese rats. Gastric myoelectrical activity, gastric emptying and heart rate variability were recorded in lean and obese rats; extracellular neuronal activity in the ventromedial hypothalamus and its responses to gastric stimulations were also assessed. (1) Gastric emptying was significantly accelerated but gastric myoelectrical activity was not altered in obese rats; (2) the normal autonomic responses to feeding were absent in obese rats, suggesting an impairment of postprandial modulation of autonomic functions; and (3) central neuronal responses to gastric stimulations (both balloon distention and electrical stimulation) were blunted in obese rats, suggesting impairment in the brain-gut interaction. In diet-induced obese rats, gastric emptying is accelerated, postprandial modulations of autonomic functions is altered and central neuronal responses to gastric stimulations are attenuated. These alterations in peripheral, autonomic and brain-gut interactions may help better understand pathogenesis of obesity and develop novel therapeutic approaches for obesity.

  4. Mobility power flow analysis of coupled plate structure subjected to mechanical and acoustic excitation

    Science.gov (United States)

    Cuschieri, J. M.

    1992-01-01

    The mobility power flow approach that was previously applied in the derivation of expressions for the vibrational power flow between coupled plate substructures forming an L configuration and subjected to mechanical loading is generalized. Using the generalized expressions, both point and distributed mechanical loads on one or both of the plates can be considered. The generalized approach is extended to deal with acoustic excitation of one of the plate substructures. In this case, the forces (acoustic pressures) acting on the structure are dependent on the response of the structure because of the scattered pressure component. The interaction between the plate structure and the acoustic fluid leads to the derivation of a corrected mode shape for the plates' normal surface velocity and also for the structure mobility functions. The determination of the scattered pressure components in the expressions for the power flow represents an additional component in the power flow balance for the source plate and the receiver plate. This component represents the radiated acoustical power from the plate structure. For a number of coupled plate substrates, the acoustic pressure generated by one substructure will interact with the motion of another substructure. That is, in the case of the L-shaped plate, acoustic interaction exists between the two plate substructures due to the generation of the acoustic waves by each of the substructures. An approach to deal with this phenomena is described.

  5. Soil properties and perceived disturbance of grasslands subjected to mechanized military training: Evaluation of an index

    Science.gov (United States)

    Althoff, Donald P.; Althoff, P.S.; Lambrecht, N.D.; Gipson, P.S.; Pontius, J.S.; Woodford, P.B.

    2007-01-01

    Mechanized maneuver training impacts the landscape by creating depressions, compacting soils, producing bare ground areas, transporting seeds of invasive plants, and crushing vegetation. We measured 3 physical, 13 chemical, and 2 biological soil properties and used a disturbance index (DI) based on perceptions of soil conditions on a military installation to assess the condition of 100 ?? 100 m plots (1 ha): 10 in 2002 and 10 in 2004. Potential DI scores range from 0 (no appreciable evidence of disturbance) to 1 (>95 per cent of the plot disturbed). Bulk density, porosity (%), and water content (%) - all at 5-1-10-0cm depth, and nematode family richness (NFR) were significantly, negatively correlated (Spearman coefficients, rs) with the DI of both years. The strong negative correlation (rs., = -0.69 in 2002, -0.79 in 2004) of NFR with the DI appears to reflect the status of nematode diversity and, therefore, may serve as a useful, inexpensive approach to rapidly assessing grasslands subjected to mechanized military training. Copyright ?? 2007 John Wiley & Sons, Ltd.

  6. Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study.

    Science.gov (United States)

    Kumagai, Yuji; Fujita, Tomoe; Ozaki, Machiko; Sahashi, Kunihiko; Ohkura, Masayuki; Ohtsu, Tomoko; Arai, Yoshihiro; Sonehara, Yusuke; Nichol, Janet L

    2007-12-01

    AMG 531 is a novel thrombopoiesis-stimulating peptibody being investigated for the treatment of chronic immune thrombocytopenic purpura. This double-blind, phase I study evaluated the safety, pharmacodynamics, and pharmacokinetics of AMG 531 in healthy Japanese men. Thirty subjects were randomly assigned 4:1 (AMG 531/placebo) to receive 1 dose of AMG 531 (0.3, 1, or 2 microg/kg) or placebo by subcutaneous injection; subjects were evaluated for 6 weeks. AMG 531 was generally well tolerated, with adverse events similar to placebo. Treatment-related adverse events (headache, "feeling hot," malaise) were reported for 5 of 24 AMG 531-treated subjects. Platelets generated after exposure to AMG 531 functioned normally. Four of 8 subjects receiving 1 microg/kg and 7 of 8 receiving 2 microg/kg had platelet count increases > or =1.5-fold over baseline, an effect similar to that seen in non-Japanese subjects. Serum AMG 531 concentrations were below the lower limit of quantification in all but 2 subjects receiving 2 microg/kg.

  7. Localized and non-contact mechanical stimulation of dorsal root ganglion sensory neurons using scanning ion conductance microscopy.

    Science.gov (United States)

    Sánchez, Daniel; Anand, Uma; Gorelik, Julia; Benham, Christopher D; Bountra, Chas; Lab, Max; Klenerman, David; Birch, Rolfe; Anand, Praveen; Korchev, Yuri

    2007-01-15

    Mechanosensitive ion channels convert external mechanical force into electrical and chemical signals in cells, but their physiological function in different tissues is not clearly understood. One reason for this is that there is as yet no satisfactory physiological method to stimulate these channels in living cells. Using the nanopipette-probe of the Scanning Ion Conductance Microscope (SICM), we have developed a new technique to apply local mechanical stimulus to living cells to an area of about 0.385 microm2, determined by the pipette diameter. Our method prevents any physical contact and damage to the cell membrane by use of a pressure jet applied via the nanopipette. The study used whole-cell patch-clamp recordings and measurements of intracellular Ca2+ concentration to validate the application of the mechanical stimulation protocols in human and rat dorsal root ganglia (DRG) sensory neurons. We were able, for the first time, to produce a non-contact, controlled mechanical stimulation on living neurites of human DRG neurons. Our methods will enable the identification and characterisation of compounds being developed for the treatment of clinical mechanical hypersensitivity states.

  8. Quantitative computed tomography determined regional lung mechanics in normal nonsmokers, normal smokers and metastatic sarcoma subjects.

    Directory of Open Access Journals (Sweden)

    Jiwoong Choi

    Full Text Available Extra-thoracic tumors send out pilot cells that attach to the pulmonary endothelium. We hypothesized that this could alter regional lung mechanics (tissue stiffening or accumulation of fluid and inflammatory cells through interactions with host cells. We explored this with serial inspiratory computed tomography (CT and image matching to assess regional changes in lung expansion.We retrospectively assessed 44 pairs of two serial CT scans on 21 sarcoma patients: 12 without lung metastases and 9 with lung metastases. For each subject, two or more serial inspiratory clinically-derived CT scans were retrospectively collected. Two research-derived control groups were included: 7 normal nonsmokers and 12 asymptomatic smokers with two inspiratory scans taken the same day or one year apart respectively. We performed image registration for local-to-local matching scans to baseline, and derived local expansion and density changes at an acinar scale. Welch two sample t test was used for comparison between groups. Statistical significance was determined with a p value < 0.05.Lung regions of metastatic sarcoma patients (but not the normal control group demonstrated an increased proportion of normalized lung expansion between the first and second CT. These hyper-expanded regions were associated with, but not limited to, visible metastatic lung lesions. Compared with the normal control group, the percent of increased normalized hyper-expanded lung in sarcoma subjects was significantly increased (p < 0.05. There was also evidence of increased lung "tissue" volume (non-air components in the hyper-expanded regions of the cancer subjects relative to non-hyper-expanded regions. "Tissue" volume increase was present in the hyper-expanded regions of metastatic and non-metastatic sarcoma subjects. This putatively could represent regional inflammation related to the presence of tumor pilot cell-host related interactions.This new quantitative CT (QCT method for linking

  9. Incorporating Refractory Period in Mechanical Stimulation Mitigates Obesity-Induced Adipose Tissue Dysfunction in Adult Mice.

    Science.gov (United States)

    Patel, Vihitaben S; Chan, M Ete; Pagnotti, Gabriel M; Frechette, Danielle M; Rubin, Janet; Rubin, Clinton T

    2017-10-01

    The aim of this study was to determine whether inclusion of a refractory period between bouts of low-magnitude mechanical stimulation (LMMS) can curb obesity-induced adipose tissue dysfunction and sequelae in adult mice. A diet-induced obesity model that included a diet with 45% of kilocalories from fat was employed with intention to treat. C57BL/6J mice were weight matched into four groups: low-fat diet (LFD, n = 8), high-fat diet (HFD, n = 8), HFD with one bout of 30-minute LMMS (HFDv, n = 9), and HFD with two bouts of 15-minute LMMS with a 5-hour separation (refractory period, RHFDv, n = 9). Two weeks of diet was followed by 6 weeks of diet plus LMMS. HFD and HFDv mice continued gaining body weight and visceral adiposity throughout the experiment, which was mitigated in RHFDv mice. Compared with LFD mice, HFD and HFDv mice had increased rates of adipocyte hypertrophy, increased immune cell infiltration (B cells, T cells, and macrophages) into adipose tissue, increased adipose tissue inflammation (tumor necrosis factor alpha gene expression), and a decreased proportion of mesenchymal stem cells in adipose tissue, all of which were rescued in RHFDv mice. Glucose intolerance and insulin resistance were elevated in HFD and HFDv mice, but not in RHFDv mice, as compared with LFD mice. Incorporating a 5-hour refractory period between bouts of LMMS attenuates obesity-induced adipose tissue dysfunction and improves glucose metabolism. © 2017 The Obesity Society.

  10. Electro-Mechanical Stimulation of the Cochlea by Vibrating Cochlear Implant Electrodes.

    Science.gov (United States)

    Mueller, Mathias; Salcher, Rolf; Majdani, Omid; Lenarz, Thomas; Maier, Hannes

    2015-12-01

    Electro-acoustic stimulation (EAS) of the cochlea uses the preserved residual low-frequency hearing for acoustic stimulation in combination with electrical stimulation. The acoustic low-frequency component is amplified and high-frequency hearing is enhanced by a cochlear implant (CI). In this work, the feasibility of EAS by the floating mass transducers (FMTs) firmly attached to the implanted electrode was investigated and the achieved stapes displacement was compared with sound stimulation. Experiments were performed in eight fresh human temporal bones compliant to the ASTM standard (F2504-5). Four EAS custom-made prototypes (EAS-CMP) were tested, consisting of standard MED-EL CI electrodes with Vibrant Soundbridge (VSB) FMTs or a Bonebridge (BB) FMT tightly molded to the electrode in different orientations. The stapes footplate (SFP) response to EAS-CMP stimulation and sound stimulation was measured using a Laser Doppler Vibrometer (LDV). The SFP displacement amplitudes achieved by EAS-CMP stimulation were calculated to 1 VRMS FMT input and were pair-wise statistically compared between prototypes yielding no significant differences at frequencies ≤1 kHz. At frequencies ≤1 kHz stimulation by the BB FMT resulted in a flat and potentially highest SFP displacement amplitude of approximately -40 dB re μm at 1 VRMS input voltage. Estimated equivalent sound pressure levels achieved by the BB FMT prototype were approximately 83-90 eq. dB SPL at frequencies ≤1 kHz. The feasibility of cochlear stimulation by vibrating electrodes was shown although the achieved output level at frequencies ≤1 kHz was too low for EAS applications.

  11. Impact of cyclic mechanical stimulation on the expression of extracellular matrix proteins in human primary rotator cuff fibroblasts.

    Science.gov (United States)

    Lohberger, Birgit; Kaltenegger, Heike; Stuendl, Nicole; Rinner, Beate; Leithner, Andreas; Sadoghi, Patrick

    2016-12-01

    Mechanical stimulation plays an important role in the development and remodelling of tendons. The aim of the study was to evaluate the effects of mechanical stimulation on the expression of extracellular matrix proteins in human primary rotator cuff (RC) fibroblasts. RC fibroblasts were isolated from patients with degenerative RC tears and characterized using flow cytometry and immunohistochemistry. Cells were stimulated using the Flexcell FX5K™ Tension System. The stimulation regime was a uniaxial sinusoidal waveform with 10 % elongation and a frequency of 0.5 Hz, whereby each cycle consists of 10-s strain and 30-s relaxation. Data were normalized to mechanically unstimulated control groups for every experimental condition. RT-qPCR was performed to determine relative mRNA levels, and collagen production was measured by a colorimetric assay. The positive expression of CD91 and CD10, and negativity for CD45 and CD4 confirmed the fibroblast phenotype of RC primary cells. RT-qPCR revealed that 10 % continuous cyclic strain for 7 and 14 days induced a significant increase in the mRNA expression both on the matrix metalloproteinases MMP1, MMP3, MMP13, and MMP14 and on the extracellular matrix proteins decorin, tenascin-C, and scleraxis. Furthermore, mechanically stimulated groups produced significantly higher amounts of total collagen. These results may contribute to a better understanding of strain-induced tendon remodelling and will form the basis for the correct choice of applied force in rehabilitation after orthopaedic surgery. These findings underline the fact that early passive motion of the joint in order to induce remodelling of the tendon should be included within a rehabilitation protocol for rotator cuff repair.

  12. Mechanical stimulation of skeletal muscle cells mitigates glucocorticoid-induced decreases in prostaglandin production and prostaglandin synthase activity

    Science.gov (United States)

    Chromiak, J. A.; Vandenburgh, H. H.

    1994-01-01

    The glucocorticoid dexamethasone (Dex) induces a decline in protein synthesis and protein content in tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch. Since the prostaglandin synthesis inhibitor indomethacin mitigated this stretch attenuation of muscle atrophy, the effects of Dex and mechanical stretch on prostaglandin production and prostaglandin H synthase (PGHS) activity were examined. In static cultures, 10(-8) M Dex reduced PGF2 alpha production 55-65% and PGE2 production 84-90% after 24-72 h of incubation. Repetitive 10% stretch-relaxations of non-Dex-treated cultures increased PGF2 alpha efflux 41% at 24 h and 276% at 72 h, and increased PGE2 production 51% at 24 h and 236% at 72 h. Mechanical stimulation of Dex-treated cultures increased PGF2 alpha production 162% after 24 h, returning PGF2 alpha efflux to the level of non-Dex-treated cultures. At 72 h, stretch increased PGF2 alpha efflux 65% in Dex-treated cultures. Mechanical stimulation of Dex-treated cultures also increased PGE2 production at 24 h, but not at 72 h. Dex reduced PGHS activity in the muscle cultures by 70% after 8-24 h of incubation, and mechanical stimulation of the Dex-treated cultures increased PGHS activity by 98% after 24 h. Repetitive mechanical stimulation attenuates the catabolic effects of Dex on cultured skeletal muscle cells in part by mitigating the Dex-induced declines in PGHS activity and prostaglandin production.

  13. Neuroplasticity-dependent and -independent mechanisms of chronic deep brain stimulation in stressed rats

    National Research Council Canada - National Science Library

    Bambico, F R; Bregman, T; Diwan, M; Li, J; Darvish-Ghane, S; Li, Z; Laver, B; Amorim, B O; Covolan, L; Nobrega, J N; Hamani, C

    2015-01-01

    ...) and elevated plus maze were countered by chronic vmPFC DBS. In addition, stressed rats receiving stimulation had significant increases in hippocampal neurogenesis, PFC and hippocampal brain-derived neurotrophic factor levels...

  14. Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism.

    OpenAIRE

    Catherino, W. H.; Jeng, M. H.; Jordan, V. C.

    1993-01-01

    There is great concern over the long-term influence of oral contraceptives on the development of breast cancer in women. Oestrogens are known to stimulate the growth of human breast cancer cells, and this laboratory has previously reported (Jeng & Jordan, 1991) that the 19-norprogestin norethindrone could stimulate the proliferation of MCF-7 human breast cancer cells. We studied the influence of the 19-norprogestins norgestrel and gestodene compared to a 'non' 19-norprogestin medroxyprogester...

  15. NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions.

    Science.gov (United States)

    Tantiwong, Puntip; Shanmugasundaram, Karthigayan; Monroy, Adriana; Ghosh, Sangeeta; Li, Mengyao; DeFronzo, Ralph A; Cersosimo, Eugenio; Sriwijitkamol, Apiradee; Mohan, Sumathy; Musi, Nicolas

    2010-11-01

    NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise.

  16. Stimulators of mineralization limit the invasive phenotype of human osteosarcoma cells by a mechanism involving impaired invadopodia formation.

    Directory of Open Access Journals (Sweden)

    Anna Cmoch

    Full Text Available BACKGROUND: Osteosarcoma (OS is a highly aggressive bone cancer affecting children and young adults. Growing evidence connects the invasive potential of OS cells with their ability to form invadopodia (structures specialized in extracellular matrix proteolysis. RESULTS: In this study, we tested the hypothesis that commonly used in vitro stimulators of mineralization limit the invadopodia formation in OS cells. Here we examined the invasive potential of human osteoblast-like cells (Saos-2 and osteolytic-like (143B OS cells treated with the stimulators of mineralization (ascorbic acid and B-glycerophosphate and observed a significant difference in response of the tested cells to the treatment. In contrast to 143B cells, osteoblast-like cells developed a mineralization phenotype that was accompanied by a decreased proliferation rate, prolongation of the cell cycle progression and apoptosis. On the other hand, stimulators of mineralization limited osteolytic-like OS cell invasiveness into collagen matrix. We are the first to evidence the ability of 143B cells to degrade extracellular matrix to be driven by invadopodia. Herein, we show that this ability of osteolytic-like cells in vitro is limited by stimulators of mineralization. CONCLUSIONS: Our study demonstrates that mineralization competency determines the invasive potential of cancer cells. A better understanding of the molecular mechanisms by which stimulators of mineralization regulate and execute invadopodia formation would reveal novel clinical targets for treating osteosarcoma.

  17. [Results of an artificial airway management protocol in critical patients subjected to mechanical ventilation].

    Science.gov (United States)

    Prieto-González, M; López-Messa, J B; Moradillo-González, S; Franzón-Laz, Z M; Ortega-Sáez, M; Poncela-Blanco, M; Alonso-Castañeira, I; Andrés-de Llano, J

    2013-01-01

    To determine the results of the implementation of a protocol in an intensive care unit (ICU) referred to critically ill patients requiring a prolonged artificial airway. A prospective, observational cohort study was carried out. Management strategies were established on the airway by endotracheal intubation (ETI) or tracheostomy, and guidelines were developed for action in the decannulation process. A polyvalent ICU. We studied 169 patients subjected to mechanical ventilation (MV), 67 with ETI ≥ 10 days of MV and 102 with percutaneous (PT) or surgical tracheostomy (TQ). ICU and hospital stays, days of ETI and MV, mortality, tracheostomy, anatomical risk factors, surgical complications, and postoperative decannulation period. ETI versus tracheotomy involved fewer days of MV (17 vs. 30 days, p<0.001), a shorter ICU stay (20 vs. 35 days, p<0.001), and a shorter hospital stay (34 vs. 51 days, p<0.001).There were more TQ procedures in patients with risk factors (47% TP vs. 89% TQ, p<0.001). Intraoperative minor bleeding was the most common complication, being associated with TQ (31% vs. 11%, p = 0.03). TP was associated with a shorter cannulationperiod (25 days vs. 34 days, p<0.04). The protocol variants showed no differences in terms of complications and mortality, when orienting application to patients with similar characteristics. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  18. STUDY ON THE DAMAGE MECHANISM OF PORE STRUCTURE IN CONCRETE SUBJECTED TO FREEZE-THAW CYCLES

    Directory of Open Access Journals (Sweden)

    Ben Li

    2015-07-01

    Full Text Available It is well know that freeze-thaw cycles play the most significant role in the durability evolution in concrete structures, freeze-thaw cycles have been accounted as one of the major factors on the damage and demolition of concrete. Microscopic parameters have been used for describing the characterizations of damage in concrete under freeze-thaw actions by researchers. However, their models could not provide specific damage factors or parameters. In this paper, a new damage model and equation based on variations of pore structure in concrete is established. This new pore damage model is used for analysing freeze-thaw damage of concrete and validated by experiments. The results show that the measurement of pore structure becomes larger, the diameters of most probably pore structure, critical pore structure, and the variations of porosity increase with the process of freeze-thaw cycles. The pore damage factor or parameter is suitable for describing the mechanism of freeze-thaw damage. Furthermore, the damage results calculated by this new freeze-thaw damage equation, based on variations of pore structure in concrete gives an excellent correlation with experimental results. This pore damage equation was proved to be effective for evaluating the degradation of concrete which is subjected to freezing and thawing cycles in low or sub-zero regions.

  19. Design and validation of a bi-axial loading bioreactor for mechanical stimulation of engineered cartilage.

    Science.gov (United States)

    Yusoff, Norwahida; Abu Osman, Noor Azuan; Pingguan-Murphy, Belinda

    2011-07-01

    A mechanical-conditioning bioreactor has been developed to provide bi-axial loading to three-dimensional (3D) tissue constructs within a highly controlled environment. The computer-controlled bioreactor is capable of applying axial compressive and shear deformations, individually or simultaneously at various regimes of strain and frequency. The reliability and reproducibility of the system were verified through validation of the spatial and temporal accuracy of platen movement, which was maintained over the operating length of the system. In the presence of actual specimens, the system was verified to be able to deliver precise bi-axial load to the specimens, in which the deformation of every specimen was observed to be relatively homogeneous. The primary use of the bioreactor is in the culture of chondrocytes seeded within an agarose hydrogel while subjected to physiological compressive and shear deformation. The system has been designed specifically to permit the repeatable quantification and characterisation of the biosynthetic activity of cells in response to a wide range of short and long term multi-dimensional loading regimes. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

  20. Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

    LENUS (Irish Health Repository)

    McCarron, Mark

    2012-02-01

    In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate\\'s natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.

  1. Functional brain networks in healthy subjects under acupuncture stimulation: An EEG study based on nonlinear synchronization likelihood analysis

    Science.gov (United States)

    Yu, Haitao; Liu, Jing; Cai, Lihui; Wang, Jiang; Cao, Yibin; Hao, Chongqing

    2017-02-01

    Electroencephalogram (EEG) signal evoked by acupuncture stimulation at "Zusanli" acupoint is analyzed to investigate the modulatory effect of manual acupuncture on the functional brain activity. Power spectral density of EEG signal is first calculated based on the autoregressive Burg method. It is shown that the EEG power is significantly increased during and after acupuncture in delta and theta bands, but decreased in alpha band. Furthermore, synchronization likelihood is used to estimate the nonlinear correlation between each pairwise EEG signals. By applying a threshold to resulting synchronization matrices, functional networks for each band are reconstructed and further quantitatively analyzed to study the impact of acupuncture on network structure. Graph theoretical analysis demonstrates that the functional connectivity of the brain undergoes obvious change under different conditions: pre-acupuncture, acupuncture, and post-acupuncture. The minimum path length is largely decreased and the clustering coefficient keeps increasing during and after acupuncture in delta and theta bands. It is indicated that acupuncture can significantly modulate the functional activity of the brain, and facilitate the information transmission within different brain areas. The obtained results may facilitate our understanding of the long-lasting effect of acupuncture on the brain function.

  2. Mechanical-tactile stimulation (MTS) during neonatal stress prevents hyperinsulinemia despite stress-induced adiposity in weanling rat pups

    OpenAIRE

    Moyer-Mileur, Laurie J.; Haley, Shannon; Gulliver, Kristina; Thomson, Anne; Slater, Hillarie; Barrett, Brett; Joss-Moore, Lisa A; Callaway, Christopher; McKnight, Robert A.; Moore, Barry; Lane, Robert H.

    2011-01-01

    Stress in early life negatively influences growth quality through perturbations in body composition including increased fat mass. At term (40 weeks) preterm infants have greater fat mass and abdominal visceral adipose tissue than term-born infants. Mechanical-tactile stimulation (MTS) attenuates the stress response in preterm infants and rodents. We tested the hypothesis that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent a...

  3. Mechanical stimulation (pulsed electromagnetic fields "PEMF" and extracorporeal shock wave therapy "ESWT" and tendon regeneration: a possible alternative.

    Directory of Open Access Journals (Sweden)

    Federica eRosso

    2015-11-01

    Full Text Available The pathogenesis of tendon degeneration and tendinopathy is still partially unclear. However, an active role of metalloproteinases (MMP, growth factors, such as vascular endothelial growth factor (VEGF and a crucial role of inflammatory elements and cytokines was demonstrated. Mechanical stimulation may play a role in regulation of inflammation. In vitro studies demonstrated that both pulsed electromagnetic fields (PEMF and extracorporeal shock wave therapy (ESWT increased the expression of pro-inflammatory cytokine such as interleukin (IL-6 and IL-10. Moreover ESWT increases the expression of growth factors, such as transforming growth factor beta (TGF-beta, Vascular Endothelial Growth Factor (VEGF, and insulin-like growth factor 1 (IGF1, as well as the synthesis of collagen I fibers. These pre-clinical results, in association with several clinical studies, suggest a potential effectiveness of ESWT for tendinopathy treatment. Recently PEMF gained popularity as adjuvant for fracture healing and bone regeneration. Similarly to ESWT, the mechanical stimulation obtained using PEMFs may play a role for treatment of tendinopathy and for tendon regeneration, increasing in-vitro TGF-beta production, as well as scleraxis and collagen I gene expression. In this manuscript the rational of mechanical stimulations and the clinical studies on the efficacy of extracorporeal shock wave (ESW and PEMF will be discussed. However, no clear evidence of a clinical value of ESW and PEMF has been found in literature with regards to the treatment of tendinopathy in human, so further clinical trials are needed to confirm the promising hypotheses concerning the effectiveness of ESWT and PEMF mechanical stimulation.

  4. Normative Values for Intertrial Variability of Motor Responses to Nerve Root and Transcranial Stimulation: A Condition for Follow-Up Studies in Individual Subjects.

    Directory of Open Access Journals (Sweden)

    Walter Troni

    Full Text Available Intertrial variability (ITV of motor responses to peripheral (CMAP and transcranial (MEP stimulation prevents their use in follow-up studies. Our purpose was to develop strategies to reduce and measure CMAP and MEP ITV to guide long-term monitoring of conduction slowing and conduction failure of peripheral and central motor pathway in the individual patient.Maximal compound muscle action potentials to High Voltage Electrical Stimulation (HVES of lumbo-sacral nerve roots (r-CMAP and activated, averaged motor evoked potentials (MEPs to Transcranial Magnetic Stimulation (TMS using double cone coil were recorded from 10 proximal and distal muscle districts of lower limbs. The procedure was repeated twice, 1-2 days apart, in 30 subjects, including healthy volunteers and clinically stable multiple sclerosis patients, using constant stimulating and recording sites and adopting a standardized procedure of voluntary activation. ITV for latency and area indexes and for the ratio between MEP and r-CMAP areas (a-Ratio was expressed as Relative Intertrial Variation (RIV, 5th-95th percentile. As an inverse correlation between the size of area and ITV was found, raw ITV values were normalized as a function of area to make them comparable with one another.All RIV values for latencies were significantly below the optimum threshold of ± 10%, with the exception of r-CMAP latencies recorded from Vastus Lateralis muscle. RIVs for a-Ratio, the most important index of central conduction failure, ranged from a maximum of -25.3% to +32.2% (Vastus Medialis to a minimum of -15.0% to + 17.4% (Flexor Hallucis Brevis.The described procedure represents an effort to lower as much as possible variability of motor responses in serial recording; the reported ITV normative values are the necessary premise to detect significant changes of motor conduction slowing and failure in the individual patient in follow-up studies.

  5. Normative Values for Intertrial Variability of Motor Responses to Nerve Root and Transcranial Stimulation: A Condition for Follow-Up Studies in Individual Subjects

    Science.gov (United States)

    Malucchi, Simona; Capobianco, Marco; Sperli, Francesca

    2016-01-01

    Objective Intertrial variability (ITV) of motor responses to peripheral (CMAP) and transcranial (MEP) stimulation prevents their use in follow-up studies. Our purpose was to develop strategies to reduce and measure CMAP and MEP ITV to guide long-term monitoring of conduction slowing and conduction failure of peripheral and central motor pathway in the individual patient. Methods Maximal compound muscle action potentials to High Voltage Electrical Stimulation (HVES) of lumbo-sacral nerve roots (r-CMAP) and activated, averaged motor evoked potentials (MEPs) to Transcranial Magnetic Stimulation (TMS) using double cone coil were recorded from 10 proximal and distal muscle districts of lower limbs. The procedure was repeated twice, 1–2 days apart, in 30 subjects, including healthy volunteers and clinically stable multiple sclerosis patients, using constant stimulating and recording sites and adopting a standardized procedure of voluntary activation. ITV for latency and area indexes and for the ratio between MEP and r-CMAP areas (a-Ratio) was expressed as Relative Intertrial Variation (RIV, 5th-95th percentile). As an inverse correlation between the size of area and ITV was found, raw ITV values were normalized as a function of area to make them comparable with one another. Results All RIV values for latencies were significantly below the optimum threshold of ± 10%, with the exception of r-CMAP latencies recorded from Vastus Lateralis muscle. RIVs for a-Ratio, the most important index of central conduction failure, ranged from a maximum of -25.3% to +32.2% (Vastus Medialis) to a minimum of -15.0% to + 17.4% (Flexor Hallucis Brevis). Conclusions The described procedure represents an effort to lower as much as possible variability of motor responses in serial recording; the reported ITV normative values are the necessary premise to detect significant changes of motor conduction slowing and failure in the individual patient in follow-up studies. PMID:27182973

  6. Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta 2-adrenergic stimulation with terbutaline in healthy subjects

    DEFF Research Database (Denmark)

    Tveskov, C; Djurhuus, M S; Klitgaard, N A

    1994-01-01

    .001). The urinary excretion of potassium decreased from 0.077 mmol/min (0.052 to 0.102) to 0.038 mmol/min (0.025 to 0.051) (p sodium potassium pumps from 1,104.1 nmol/kg dry weight (1,030.6 to 1,177.5) to 1,273.3 nmol/kg dry weight (1,193.5 to 1,353.2) (p ... of sodium-potassium pumps. Furthermore, terbutaline induced changes in ECG with a highly significant lengthening of the QTc interval but with an unchanged number of ventricular ectopic beats in healthy subjects....... or terbutaline (bolus, 0.25 mg; maintenance dose, 5 micrograms/min). SETTING: University Department of Clinical Chemistry. PARTICIPANTS: Ten healthy male volunteers. Mean age was 24.1 (range, 20 to 31) years. MAIN OUTCOME MEASURES: Serum potassium and magnesium muscle potassium and magnesium, and muscle sodium...

  7. Bloom syndrome helicase stimulates RAD51 DNA strand exchange activity through a novel mechanism.

    Science.gov (United States)

    Bugreev, Dmitry V; Mazina, Olga M; Mazin, Alexander V

    2009-09-25

    Loss or inactivation of BLM, a helicase of the RecQ family, causes Bloom syndrome, a genetic disorder with a strong predisposition to cancer. Although the precise function of BLM remains unknown, genetic data has implicated BLM in the process of genetic recombination and DNA repair. Previously, we demonstrated that BLM can disrupt the RAD51-single-stranded DNA filament that promotes the initial steps of homologous recombination. However, this disruption occurs only if RAD51 is present in an inactive ADP-bound form. Here, we investigate interactions of BLM with the active ATP-bound form of the RAD51-single-stranded DNA filament. Surprisingly, we found that BLM stimulates DNA strand exchange activity of RAD51. In contrast to the helicase activity of BLM, this stimulation does not require ATP hydrolysis. These data suggest a novel BLM function that is stimulation of the RAD51 DNA pairing. Our results demonstrate the important role of the RAD51 nucleoprotein filament conformation in stimulation of DNA pairing by BLM.

  8. Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive-Compulsive Disorder

    NARCIS (Netherlands)

    van Westen, Maarten; Rietveld, Erik; Figee, Martijn; Denys, D.

    2015-01-01

    Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients

  9. Vascular Growth in Ischemic Limbs: A Review of Mechanisms and Possible Therapeutic Stimulation

    NARCIS (Netherlands)

    Weel, V. van; Tongeren, R.B. van; Hinsbergh, V.W.M. van; Bockel, J.H. van; Quax, P.H.A.

    2008-01-01

    Stimulation of vascular growth to treat limb ischemia is promising, and early results obtained from uncontrolled clinical trials using angiogenic agents, e.g., vascular endothelial growth factor, led to high expectations. However, negative results from recent placebo-controlled trials warrant

  10. [Basic mechanisms of QRS voltage changes on ECG of healthy subjects during the exercise test].

    Science.gov (United States)

    Saltykova, M M

    2015-01-01

    Electrocardiography is the most commonly used technique for detection stress-induced myocardial ischemia. However, the sensitivity of ECG-criteria is not high. One of the major problem is the difficulty in differentiating ECG changes caused by various factors. The aim of this study was to evaluate the dependence of the QRS voltage changes during exercise on parameters of central hemodynamics, gender particularities and to reveal mechanisms causing these changes. To eliminate the effect of changes in cardiomyocytes transmembrane potentials under the influence of the neurotransmitters of the autonomic nervous system during stepwise increasing exercises and/or due to a lack of ATP results from inadequate myocardial blood flow only healthy subjects not older than 35 years were included in the study (7 men and 7 women) and only periods of ventricular depolarization (QRS complex on the ECG) were included in the analysis. We compared the changes of QRS waves during exercise sessions with two upper and one lower limbs in both men and women. The exercise load was twice bigger in exercise with one leg relative to exercise with two arms. Responses of heart rate and systolic arterial pressure were similar. Amplitude of S-wave in left chest leads significantly increased in both sessions without significant difference between augmentations in the sessions and in groups of men and women. Significant relationship between the S wave augmentation and the peak systolic arterial pressure were revealed. Furthermore, the QRS changes during the exercise with vertical and a horizontal torso position were compared to assess the impact of diastolic arterial pressure and displacement of the diaphragm and heart rotation due to increase of abdominal pressure during the last steps of exercise. The obtained results allow us to exclude the impact of the heart position and size changes, as well as the exercise load on S-wave changes and make a conclusion about the dependence of this parameter on

  11. Assessment of Mechanical Pain Thresholds in the Orofacial Region: A Comparison Between Pinprick Stimulators and Electronic Von Frey Device.

    Science.gov (United States)

    Suzuki, Kayo; Baad-Hansen, Lene; Pigg, Maria; Svensson, Peter

    2016-01-01

    To compare mechanical pain thresholds (MPTs) in the orofacial region assessed with two different approaches: with an electronic von Frey (EvF) device and with custom-made weighted pinprick stimulators. The test-retest reliability, variability of MPTs, and time duration of each test were also compared, as well as the ability of each test to create stimulus-response (S-R) curves. A total of 16 healthy volunteers participated. The MPT and S-R curve measurements were done with the two different techniques at three sites: on the skin of the right cheek (face), on the buccal gingival mucosa of the right upper premolar region (gingiva), and on the tip of the tongue (tongue). The same protocol was repeated 1 to 2 weeks later to determine test-retest reliability. The MPT measurements with the EvF device were significantly faster (74.4 ± 20.8 seconds) than those with the pinprick stimulators (196.1 ± 33.0 seconds; P orofacial region with the EvF device were significantly higher than MPTs tested with the pinprick stimulators. However, the EvF device can be used with higher reliability and less time consumption for assessment of MPTs in the orofacial region than the pinprick stimulator technique, and also allows comparable construction of S-R curves.

  12. Mechanisms of Neural Reorganization in Chronic Stroke Subjects after Virtual Reality Training

    OpenAIRE

    Saleh, S.; Bagce, H; Qiu, Q; Fluet, G; Merians, A; Adamovich, S; Tunik, E

    2011-01-01

    This study investigates patterns of brain reorganization in chronic stroke subjects after two weeks of robot-assisted arm and hand training in virtual reality (VR). Four subjects were studied with event-related fMRI while doing simple paretic hand finger movements before (double baseline) and after training. Bilateral hand movements were recorded and used to provide real-time feedback to subjects during scanning to eliminate performance confounds on fMRI results. The kinematic parameters of e...

  13. Mechanical Stress Conditioning and Electrical Stimulation Promote Contractility and Force Maturation of Induced Pluripotent Stem Cell-Derived Human Cardiac Tissue.

    Science.gov (United States)

    Ruan, Jia-Ling; Tulloch, Nathaniel L; Razumova, Maria V; Saiget, Mark; Muskheli, Veronica; Pabon, Lil; Reinecke, Hans; Regnier, Michael; Murry, Charles E

    2016-11-15

    Tissue engineering enables the generation of functional human cardiac tissue with cells derived in vitro in combination with biocompatible materials. Human-induced pluripotent stem cell-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electric pacing on the maturation of human-induced pluripotent stem cell-derived cardiac tissues. Cardiomyocytes derived from human-induced pluripotent stem cells were used to generate collagen-based bioengineered human cardiac tissue. Engineered tissue constructs were subjected to different mechanical stress and electric pacing conditions. The engineered human myocardium exhibits Frank-Starling-type force-length relationships. After 2 weeks of static stress conditioning, the engineered myocardium demonstrated increases in contractility (0.63±0.10 mN/mm(2) vs 0.055±0.009 mN/mm(2) for no stress), tensile stiffness, construct alignment, and cell size. Stress conditioning also increased SERCA2 (Sarco/Endoplasmic Reticulum Calcium ATPase 2) expression, which correlated with a less negative force-frequency relationship. When electric pacing was combined with static stress conditioning, the tissues showed an additional increase in force production (1.34±0.19 mN/mm(2)), with no change in construct alignment or cell size, suggesting maturation of excitation-contraction coupling. Supporting this notion, we found expression of RYR2 (Ryanodine Receptor 2) and SERCA2 further increased by combined static stress and electric stimulation. These studies demonstrate that electric pacing and mechanical stimulation promote maturation of the structural, mechanical, and force generation properties of human-induced pluripotent stem cell-derived cardiac tissues. © 2016 American Heart Association, Inc.

  14. Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism

    Science.gov (United States)

    Boo, Yong Chool; Hwang, Jinah; Sykes, Michelle; Michell, Belinda J.; Kemp, Bruce E.; Lum, Hazel; Jo, Hanjoong

    2002-01-01

    Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser(1179) in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser(116), Thr(497), and Ser(635). Here, we studied these potential phosphorylation sites in response to shear, vascular endothelial growth factor (VEGF), and 8-bromocAMP (8-BRcAMP) in bovine aortic endothelial cells (BAEC). All three stimuli induced phosphorylation of eNOS at Ser(635), which was consistently slower than that at Ser(1179). Thr(497) was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser(116). Whereas shear-stimulated Ser(635) phosphorylation was not affected by phosphoinositide-3-kinase inhibitors wortmannin and LY-294002, it was blocked by either treating the cells with a PKA inhibitor H89 or infecting them with a recombinant adenovirus-expressing PKA inhibitor. These results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) PKA-dependent but PI3K-independent pathways. Phosphorylation of Ser(635) may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli.

  15. Growth differentiation factor 11 improves neurobehavioral recovery and stimulates angiogenesis in rats subjected to cerebral ischemia/reperfusion.

    Science.gov (United States)

    Ma, Jingxi; Zhang, Lina; Niu, Tengfei; Ai, Chibo; Jia, Gongwei; Jin, Xinhao; Wen, Lan; Zhang, Keming; Zhang, Qinbin; Li, Changqing

    2018-02-09

    The recent suggestion that growth differentiation factor 11 (GDF11) acts as a rejuvenation factor has remained controversial. However, in addition to its role in aging, the relationship between GDF11 and cerebral ischemia is still an important area that needs more investigation. Here we examined effects of GDF11 on angiogenesis and recovery of neurological function in a rat model of stroke. Exogenous recombinant GDF11 (rGDF11) at different doses were directly injected into the tail vein in rats subjected to cerebral ischemia/reperfusion (I/R). Neurobehavioral tests were performed, the proliferation of endothelial cells (ECs) and GDF11 downstream signal activin-like kinase 5 (ALK5) were assessed, and functional microvessels were measured. Results showed that rGDF11 at a dosage of 0.1 mg/kg/day could effectively activate cerebral angiogenesis in vivo. In addition, rGDF11 improved the modified neurological severity scores and the adhesive removal somatosensory test, promoted proliferation of ECs, induced ALK5 and increased vascular surface area and the number of vascular branch points in the peri-infarct cerebral cortex after cerebral I/R. These effects were suppressed by blocking ALK5. Our novel findings shed new light on the role of GDF11. Our results strongly suggest that GDF11 improves neurofunctional recovery from cerebral I/R injury and that this effect is mediated partly through its proangiogenic effect in the peri-infarct cerebral cortex, which is associated with ALK5. Thus, GDF11/ALK5 may represent new therapeutic targets for aiding recovery from stroke. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects

    DEFF Research Database (Denmark)

    Kjems, Lise L; Holst, Jens J; Vølund, Aage

    2003-01-01

    , 4, 6, 8, and 12 mg x kg(-1) x min(-1) over 150 min on four occasions with infusion of saline or GLP-1 at 0.5, 1.0, and 2.0 pmol x kg(-1) x min(-1). GLP-1 enhanced ISR in a dose-dependent manner during the graded glucose infusion from 332 +/- 51 to 975 +/- 198 pmol/kg in the patients with type 2....... However, the dose-response relationship between GLP-1 and basal and glucose-stimulated prehepatic insulin secretion rate (ISR) is currently not known. Seven patients with type 2 diabetes and seven matched nondiabetic control subjects were studied. ISR was determined during a graded glucose infusion of 2...... that of the control subjects without GLP-1. Our results show that GLP-1 increases insulin secretion in patients with type 2 diabetes and control subjects in a dose-dependent manner and that the beta-cell responsiveness to glucose may be increased to normal levels with a low dose of GLP-1 infusion. Nevertheless...

  17. A new device combining mechanical stimulation of plantar sole and Achilles' tendon to alleviate the consequences of muscle deconditioning.

    Science.gov (United States)

    Canu, Marie-Hélène; Fryziel, Fabrice; Noel, Jean-Pierre; Tiffreau, Vincent; Digumber, Marc; Bastide, Bruno

    2016-05-01

    Limb immobilization or confinement to bed results in a severe atrophy and weakness of lower leg muscles. Full recovery of muscle strength and physical function is rare and may impact the patient's outcome. Studies performed on rodents have demonstrated that the deleterious structural and functional adaptations which occur during muscle deconditioning can be counteracted through adequate physiological stimuli. Thus, based on this fundamental work, we developed a device that combines mechanical stimulation of proprioceptors located in the plantar sole and Achilles' tendon. The device is adapted to patients immobilized and confined to bed. Stimulations can be applied on muscle in passive state. The protocol is non-invasive and is well accepted by patients. This paper presents the technical features of the device, as well as preliminary results of the first clinical study. This device might allow considering new therapeutic strategies for prevention of atrophy in many pathologies.

  18. Fed-state clamp stimulates cellular mechanisms of muscle protein anabolism and modulates glucose disposal in normal men.

    Science.gov (United States)

    Adegoke, Olasunkanmi A J; Chevalier, Stéphanie; Morais, José A; Gougeon, Réjeanne; Kimball, Scot R; Jefferson, Leonard S; Wing, Simon S; Marliss, Errol B

    2009-01-01

    Since maximum anabolism occurs postprandially, we developed a simulated fed state with clamped hyperinsulinemia, physiological hyperglycemia, and hyperaminoacidemia (Hyper-3) and explored muscle cellular mechanisms. Whole body [1-(13)C]leucine and [3-(3)H]glucose kinetics in healthy men were compared between hyperinsulinemic, euglycemic, isoaminoacidemic (Hyper-1, n = 10) and Hyper-3 (n = 9) clamps. In Hyper-3 vs. Hyper-1, nonoxidative leucine R(d) [rate of disappearance (synthesis)] was stimulated more (45 +/- 4 vs. 24 +/- 4 micromol/min, P anabolism, and muscle protein translation initiation pathways and decreases protein ubiquitination. The main contribution of hyperaminoacidemia is stimulation of synthesis rather than inhibition of proteolysis, and it attenuates the expected increment of glucose disposal.

  19. New numerical model for thermal quenching mechanism in quartz based on two-stage thermal stimulation of thermoluminescence model

    Directory of Open Access Journals (Sweden)

    Ahmed Kadari

    2015-11-01

    Full Text Available The effect of thermal quenching plays an important role in the thermoluminescence (TL of quartz on which many applications of TL are based. The studies of the stability and kinetics of the 325 °C thermoluminescence peak in quartz are described by Wintle (1975, which show the occurrence of thermal quenching, the decrease in luminescence efficiency with rise in temperature. The thermal quenching of thermoluminescence in quartz was studied experimentally by several authors. The simulations work presented in the literature is based on the single-stage thermal stimulation model of thermoluminescence, in spite of that the mechanisms of this effect remain incomplete. This paper presents a new numerical model for thermal quenching in quartz, using the previously published two-stage thermal stimulation of thermoluminescence model.

  20. Stability of Neural Firing in the Trigeminal Nuclei under Mechanical Whisker Stimulation

    Directory of Open Access Journals (Sweden)

    Valeri A. Makarov

    2010-01-01

    Full Text Available Sensory information handling is an essentially nonstationary process even under a periodic stimulation. We show how the time evolution of ridges in the wavelet spectrum of spike trains can be used for quantification of the dynamical stability of the neuronal responses to a stimulus. We employ this method to study neuronal responses in trigeminal nuclei of the rat provoked by tactile whisker stimulation. Neurons from principalis (Pr5 and interpolaris (Sp5i show the maximal stability at the intermediate (50 ms stimulus duration, whereas Sp5o cells “prefer” shorter (10 ms stimulation. We also show that neurons in all three nuclei can perform as stimulus frequency filters. The response stability of about 33% of cells exhibits low-pass frequency dynamics. About 57% of cells have band-pass dynamics with the optimal frequency at 5 Hz for Pr5 and Sp5i, and 4 Hz for Sp5o, and the remaining 10% show no prominent dependence on the stimulus frequency. This suggests that the neural coding scheme in trigeminal nuclei is not fixed, but instead it adapts to the stimulus characteristics.

  1. Mechanism of surface texture evolution in pure copper strips subjected to double rolling

    Directory of Open Access Journals (Sweden)

    Xiyong Wang

    2014-02-01

    Full Text Available Developing ultra-thin copper foils with different surface roughness and microstructure has important significance for improving the service performance and reducing the production cost of high-end circuit boards. In this paper, pure copper strips with initial cube texture were subjected to a double rolling process (deformation amount ranges from 50% to 95%, and the surface textures evolution law and mechanism of double-rolled strips were studied by an X-ray diffraction technique. The results show that when a deformation amount increased from 50% to 70%, the grains of two surfaces rotate away from the cube orientation, and the formed textures of two surfaces mainly consisted of C, S and B orientation components. The orientation density values for these three components on bright surface only had slight difference; the orientation density values for C and S components were much larger than that for B components on a matt surface. When the deformation amount increased to 90%, the increase extents of orientation density values for C and S components were obviously larger than that for B components on a bright surface; the increase extents of orientation density values for these three components were almost the same on the matt surface. It has been found that when deformation amount reaches 95%, the grains orientation of bright surface were relatively concentrated, and the orientation density value for C texture obviously increased to 11.68 and that for B texture was only 3.15; the grains orientation of matt surface were relatively dispersed, and the orientation density value for C texture increased to 9.26 and that for B texture obviously increased to 6.35, and the density values of these two textures had less difference. For the condition of strong compressive and shear stress on the bright surface, grains were mainly rotating to C texture orientation; compared with the bright surface, “semi-free” deformation condition on the matt surface is

  2. Evaluation of Mechanical Properties of Glass Fiber Posts Subjected to Laser Surface Treatments.

    Science.gov (United States)

    Barbosa Siqueira, Carolina; Spadini de Faria, Natália; Raucci-Neto, Walter; Colucci, Vivian; Alves Gomes, Erica

    2016-10-01

    The aim of this study was to evaluate the influence of laser irradiation on flexural strength, elastic modulus, and surface roughness and morphology of glass fiber posts (GFPs). Laser treatment of GFPs has been introduced to improve its adhesion properties. A total of 40 GFPs were divided into 4 groups according to the irradiation protocol: GC-no irradiation, GYAG-irradiation with erbium:yttrium-aluminum-garnet [Er:YAG], GCR-irradiation with erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG), and GDI-irradiation with diode laser. The GFP roughness and morphology were evaluated through laser confocal microscopy before and after surface treatment. Three-point bending flexural test measured flexural strength and elastic modulus. Data about elastic modulus and flexural strength were subjected to one-way ANOVA and Bonferroni test (p < 0.05). The effect of roughness was evaluated using the linear mixed effects model and Bonferroni test (p < 0.05). Laser treatment changed surface roughness in the groups GCR (p = 0.000) and GDI (p = 0.007). The mean flexural strength in GYAG (995.22 MPa) was similar to that in GC (980.48 MPa) (p = 1.000) but different from that in GCR (746.83 MPa) and that in GDI (691.34 MPa) (p = 0.000). No difference was found between the groups GCR and GDI (p = 0.86). For elastic modulus: GYAG (24.47 GPa) was similar to GC (25.92 GPa) (p = 1.000) but different from GCR (19.88 GPa) (p = 0.002) and GDI (17.20 GPa) (p = 0.000). The different types of lasers, especially Er,Cr:YSGG and 980 ηm diode, influenced the mechanical properties of GFPs.

  3. Mechanisms of neural reorganization in chronic stroke subjects after virtual reality training.

    Science.gov (United States)

    Saleh, S; Bagce, H; Qiu, Q; Fluet, G; Merians, A; Adamovich, S; Tunik, E

    2011-01-01

    This study investigates patterns of brain reorganization in chronic stroke subjects after two weeks of robot-assisted arm and hand training in virtual reality (VR). Four subjects were studied with event-related fMRI while doing simple paretic hand finger movements before (double baseline) and after training. Bilateral hand movements were recorded and used to provide real-time feedback to subjects during scanning to eliminate performance confounds on fMRI results. The kinematic parameters of each movement were also used in the general linear model with the BOLD signal to investigate training-induced changes in neuromotor coupling. Univariate analysis showed an increase in BOLD signal in the ipsilesional hemisphere in two subjects and a decrease in activity in the other two subjects. Seed voxel based functional connectivity analysis revealed an increase in connectivity between ipsilesional motor cortex and bilateral sensorimotor cortex during finger movements in all four subjects. Hemispheric laterality index values showed a tendency to decrease reflecting a reduction in the over-dominance of the contralesional hemisphere. The study is novel in terms of 1) tracking finger movement during a motor task in the scanner, 2) monitoring motor performance during the experiment and 3) giving online visual feedback of subjects' movement. This pilot study introduces a novel approach to study neural plasticity by combining measures of regional intensity, interregional interactions (using functional connectivity analysis and hemispheric laterality index), and modulation in the strength of neuromotor coupling.

  4. Declines in stimulated striatal dopamine release over the first 32 h following microdialysis probe insertion: generalization across releasing mechanisms.

    Science.gov (United States)

    Holson, R R; Gazzara, R A; Gough, B

    1998-10-19

    In a recent paper [R.R. Holson, J.F. Bowyer, P. Clausing, B. Gough, Methamphetamine-stimulated striatal dopamine release declines rapidly over time following microdialysis probe insertion, Brain Res. 739 (1996) 301-307] we reported that methamphetamine-stimulated striatal dopamine release declined rapidly over the first eight hours following microdialysis probe insertion. This decline was strictly a function of time post-probe implantation, and not due to tolerance or desensitization. To further examine this phenomenon, we subjected rats to three brief pulses of several DA-releasing compounds at 2, 4 and 6 h post-probe insertion, and compared these results to those caused by a single pulse 6 h post-insertion, or in some cases to pulses given more than 24 h post-insertion. We found that when buproprion, a dopamine reuptake blocker, was infused briefly into the striatum via the microdialysis probe, there was a pronounced drop in the amount of dopamine released at 6 h vs. 2 h post-insertion; this drop was not due to repeated exposure, since dopamine release at 6 h post-insertion was the same for a single pulse, or when preceded by two earlier pulses. Twenty-four hours later, buproprion-stimulated dopamine release was still lower, but did not appear to drop further thereafter. Potassium-stimulated dopamine release, on the other hand, dropped rapidly over the first 8 h post-insertion, and this decline continued throughout the 24-32 h interval post-insertion. Similarly, a single i.p. injection of 0.5 mg/kg haloperidol released three times as much dopamine when given two compared to six hours post-implantation. Both bupropion- and potassium-stimulated dopamine release were accompanied by declines in extracellular DOPAC concentrations, and these declines were the same 2 or 26 h post-insertion. In contrast, haloperidol exposure increased extracellular DOPAC, and this haloperidol-stimulated DOPAC increase was also greatly attenuated at 6 compared to 2 h post-insertion. We

  5. Improving chondrogenesis: potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering.

    Science.gov (United States)

    Kupcsik, Laszlo; Stoddart, Martin J; Li, Zhen; Benneker, Lorin M; Alini, Mauro

    2010-06-01

    Articular cartilage injuries and degeneration affect a large proportion of the population in developed countries world wide. Stem cells can be differentiated into chondrocytes by adding transforming growth factor-beta1 and dexamethasone to a pellet culture, which are unfeasible for tissue engineering purposes. We attempted to achieve stable chondrogenesis without any requirement for exogenous growth factors. Human mesenchymal stem cells were transduced with an adenoviral vector containing the SRY-related HMG-box gene 9 (SOX9), and were cultured in a three-dimensional (3D) hydrogel scaffold composite. As an additional treatment, mechanical stimulation was applied in a custom-made bioreactor. SOX9 increased the expression level of its known target genes, as well as its cofactors: the long form of SOX5 and SOX6. However, it was unable to increase the synthesis of sulfated glycosaminoglycans (GAGs). Mechanical stimulation slightly enhanced collagen type X and increased lubricin expression. The combination of SOX9 and mechanical load boosted GAG synthesis as shown by (35)S incorporation. GAG production rate corresponded well with the amount of (endogenous) transforming growth factor-beta1. Finally, cartilage oligomeric matrix protein expression was increased by both treatments. These findings provide insight into the mechanotransduction of mesenchymal stem cells and demonstrate the potential of a transcription factor in stem cell therapy.

  6. Mechanical stimulated reaction of metal/polymer mixed powders; Kinzoku/kobunshi kongo funmatsu no kikaiteki reiki hanno

    Energy Technology Data Exchange (ETDEWEB)

    Tobita, M.; Sakakibara, A.; Takemoto, Y. [Okayama University, Okayama (Japan). Faculty of Engineering; Iwabu, H. [Kurare Co. Ltd., Osaka (Japan)

    1999-12-15

    Mechanical grinding (MG) with mechanically stimulated reaction was performed on metal/polymer mixed powders. The starting materials used in this study were the metals of Mg, Ti and Mg{sub 2}Ni powders, arid polymer of PTFE, PVC and PE powders. The MG process was investigated using XRD, IR, SEM and TEM. According to XRD results, magnesium fluoride (MgF{sub 2}, TiF{sub 2}) and chloride (MgCl{sub 2}) were detected from MG products of the Mg/PTFE, Ti/PTFE and Mg/PVC blending systems, respectively. Explosive reaction was found during MG of both Mg/PTFE and Ti/PTFE. It was also confirmed by XRD results that the production of MgF{sub 2} had already been formed just before the explosive reaction in Mg/PTFE system. It was found from IR analysis that C-C single bond in the polymers, not only both in PTFE and PVC but also in PE, changed to double bond C=C. Hydrogen produced due to decomposition of PE on blending Mg{sub 2}Ni/PE was absorbed into C-Mg{sub 2}Ni-H as amorphous solutes. These mechanically stimulated reaction was powerful method for decomposition of engineering plastics. (author)

  7. Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion.

    Directory of Open Access Journals (Sweden)

    Wagner Shin Nishitani

    Full Text Available A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs in terms of calcium signaling. The intracellular calcium ion concentration was measured by the genetically encoded Cameleon biosensor, with the Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7 expression inhibited. As TRPM7 expression also regulates adhesion, a relatively simple method for measuring adhesion of cells was also developed, tested and used to study the effect of adhesion alone. Three adhesion conditions of HUVECs on polyacrylamide gel dishes were compared. In the first condition, the substrate is fully treated with Sulfo-SANPAH crosslinking and fibronectin. The other two conditions had increasingly reduced adhesion: partially treated (only coated with fibronectin, with no use of Sulfo-SANPAH, at 5% of the normal amount and non-treated polyacrylamide gels. The cells showed adhesion and calcium response to the mechanical stimulation correlated to the degree of gel treatment: highest for fully treated gels and lowest for non-treated ones. TRPM7 inhibition by siRNA on HUVECs caused an increase in adhesion relative to control (no siRNA treatment and non-targeting siRNA, but a decrease to 80% of calcium response relative to non-targeting siRNA which confirms the important role of TRPM7 in mechanotransduction despite the increase in adhesion.

  8. Mechanism of dorsal column stimulation to treat neuropathic but not nociceptive pain: analysis with a computational model.

    Science.gov (United States)

    Arle, Jeffrey E; Carlson, Kristen W; Mei, Longzhi; Iftimia, Nicolae; Shils, Jay L

    2014-10-01

    Stimulation of axons within the dorsal columns of the human spinal cord has become a widely used therapy to treat refractory neuropathic pain. The mechanisms have yet to be fully elucidated and may even be contrary to standard "gate control theory." Our hypothesis is that a computational model provides a plausible description of the mechanism by which dorsal column stimulation (DCS) inhibits wide dynamic range (WDR) cell output in a neuropathic model but not in a nociceptive pain model. We created a computational model of the human spinal cord involving approximately 360,000 individual neurons and dendritic processing of some 60 million synapses--the most elaborate dynamic computational model of the human spinal cord to date. Neuropathic and nociceptive "pain" signals were created by activating topographically isolated regions of excitatory interneurons and high-threshold nociceptive fiber inputs, driving analogous regions of WDR neurons. Dorsal column fiber activity was then added at clinically relevant levels (e.g., Aβ firing rate between 0 and 110 Hz by using a 210-μsec pulse width, 50-150 Hz frequency, at 1-3 V amplitude). Analysis of the nociceptive pain, neuropathic pain, and modulated circuits shows that, in contradiction to gate control theory, 1) nociceptive and neuropathic pain signaling must be distinct, and 2) DCS neuromodulation predominantly affects the neuropathic signal only, inhibiting centrally sensitized pathological neuron groups and ultimately the WDR pain transmission cells. We offer a different set of necessary premises than gate control theory to explain neuropathic pain inhibition and the relative lack of nociceptive pain inhibition by using retrograde DCS. Hypotheses regarding not only the pain relief mechanisms of DCS were made but also regarding the circuitry of pain itself, both nociceptive and neuropathic. These hypotheses and further use of the model may lead to novel stimulation paradigms. © 2014 International Neuromodulation

  9. Mechanism of stimulated Hawking radiation in a laboratory Bose-Einstein condensate

    CERN Document Server

    Wang, Yi-Hsieh; Edwards, Mark; Clark, Charles W

    2016-01-01

    We model a sonic black hole analog in a quasi one-dimensional Bose-Einstein condensate, using a Gross-Pitaevskii equation matching the configuration of a recent experiment by Steinhauer. The model agrees well with the experimental observations, with no adjustable parameters, demonstrating their hydrodynamic nature. With enhanced but experimentally feasible parameters we establish by spectral analysis that a growing bow wave is generated at the inner (white hole) horizon, stimulating the emission of Hawking radiation. The black hole laser effect plays no role.

  10. Neural mechanisms underlying contextual dependency of subjective values: converging evidence from monkeys and humans.

    Science.gov (United States)

    Abitbol, Raphaëlle; Lebreton, Maël; Hollard, Guillaume; Richmond, Barry J; Bouret, Sébastien; Pessiglione, Mathias

    2015-02-04

    A major challenge for decision theory is to account for the instability of expressed preferences across time and context. Such variability could arise from specific properties of the brain system used to assign subjective values. Growing evidence has identified the ventromedial prefrontal cortex (VMPFC) as a key node of the human brain valuation system. Here, we first replicate this observation with an fMRI study in humans showing that subjective values of painting pictures, as expressed in explicit pleasantness ratings, are specifically encoded in the VMPFC. We then establish a bridge with monkey electrophysiology, by comparing single-unit activity evoked by visual cues between the VMPFC and the orbitofrontal cortex. At the neural population level, expected reward magnitude was only encoded in the VMPFC, which also reflected subjective cue values, as expressed in Pavlovian appetitive responses. In addition, we demonstrate in both species that the additive effect of prestimulus activity on evoked activity has a significant impact on subjective values. In monkeys, the factor dominating prestimulus VMPFC activity was trial number, which likely indexed variations in internal dispositions related to fatigue or satiety. In humans, prestimulus VMPFC activity was externally manipulated through changes in the musical context, which induced a systematic bias in subjective values. Thus, the apparent stochasticity of preferences might relate to the VMPFC automatically aggregating the values of contextual features, which would bias subsequent valuation because of temporal autocorrelation in neural activity. Copyright © 2015 the authors 0270-6474/15/352308-13$15.00/0.

  11. Hypothalamic-pituitary axis and peripheral tissue responses to TRH stimulation and liothyronine suppression tests in normal subjects evaluated by current methods.

    Science.gov (United States)

    Dare, Gustavo Leopoldo Rodrigues; de Castro, Margaret; Maciel, Lea Maria Zanini

    2008-04-01

    To reevaluate the responses of thyrotropin-releasing hormone (TRH) stimulation test in baseline condition as well as after the administration of graded supraphysiological doses of liothyronine (L-T(3)) in normal subjects. To assess various parameters related to the hypothalamic-pituitary axis and peripheral tissue responses to L-T(3) in 22 normal individuals (median age: 30.5 years). Subjects were submitted to an intravenous TRH test at baseline condition and also to the oral administration of sequential and graded doses of L-T(3) (50, 100, and 200 microg/day), each given over 3 days, at an outpatient clinic. Blood samples were obtained for thyrotropin (TSH) and prolactin (PRL) at basal and then 15, 30, and 60 minutes after the TRH injection. Effects of L-T(3) administration on cholesterol, creatine kinase, retinol, ferritin, and sex hormone-binding globulin (SHBG) were also measured at basal and after the oral administration of L-T(3). TRH administration resulted in an increase of 4- to 14-fold rise in serum TSH (8.3 +/- 2.5-fold), and in a slight rise in serum PRL concentrations (3.8 +/- 1.5-fold). Administration of graded doses of triiodothyronine (T(3)) resulted in a dose-dependent suppression of TSH and PRL. Basal thyroxine-binding globulin (TBG) and cholesterol levels decreased, and ferritin and SHBG increased after L-T(3) administration, while creatine kinase and retinol did not change throughout the study. There was a positive correlation between basal TSH and TSH peak response to TRH at basal condition and after each sequential L-T(3) doses. On the other hand, TSH peak response to the TRH test did not predict cholesterol, TBG, ferritin, or SHBG values. Using the current methods on hormone and biochemical analysis, we standardized the response of many parameters to TRH stimulation test after sequential and graded T(3) suppression test in normal subjects. Our data suggest that the evaluation of the responses of the hypothalamus-pituitary axis to TRH test as

  12. Effective electric fields along realistic DTI-based neural trajectories for modelling the stimulation mechanisms of TMS.

    Science.gov (United States)

    De Geeter, N; Crevecoeur, G; Leemans, A; Dupré, L

    2015-01-21

    In transcranial magnetic stimulation (TMS), an applied alternating magnetic field induces an electric field in the brain that can interact with the neural system. It is generally assumed that this induced electric field is the crucial effect exciting a certain region of the brain. More specifically, it is the component of this field parallel to the neuron's local orientation, the so-called effective electric field, that can initiate neuronal stimulation. Deeper insights on the stimulation mechanisms can be acquired through extensive TMS modelling. Most models study simple representations of neurons with assumed geometries, whereas we embed realistic neural trajectories computed using tractography based on diffusion tensor images. This way of modelling ensures a more accurate spatial distribution of the effective electric field that is in addition patient and case specific. The case study of this paper focuses on the single pulse stimulation of the left primary motor cortex with a standard figure-of-eight coil. Including realistic neural geometry in the model demonstrates the strong and localized variations of the effective electric field between the tracts themselves and along them due to the interplay of factors such as the tract's position and orientation in relation to the TMS coil, the neural trajectory and its course along the white and grey matter interface. Furthermore, the influence of changes in the coil orientation is studied. Investigating the impact of tissue anisotropy confirms that its contribution is not negligible. Moreover, assuming isotropic tissues lead to errors of the same size as rotating or tilting the coil with 10 degrees. In contrast, the model proves to be less sensitive towards the not well-known tissue conductivity values.

  13. A subject-specific musculoskeletal modeling framework to predict in vivo mechanics of total knee arthroplasty

    NARCIS (Netherlands)

    Marra, M.A.; Vanheule, V.; Fluit, R.; Koopman, B.H.; Rasmussen, J.; Verdonschot, N.J.; Andersen, M.S.

    2015-01-01

    Musculoskeletal (MS) models should be able to integrate patient-specific MS architecture and undergo thorough validation prior to their introduction into clinical practice. We present a methodology to develop subject-specific models able to simultaneously predict muscle, ligament, and knee joint

  14. A coupled hygro-thermo-mechanical model for concrete subjected to variable environmental conditions

    National Research Council Canada - National Science Library

    Gasch, Tobias; Malm, Richard; Ansell, Anders

    2016-01-01

    .... Variations of these fields must therefore be included implicitly in an analysis. This paper presents a coupled hygro-thermo-mechanical model for hardened concrete based on the framework of the Microprestress-Solidification theory...

  15. An Exploratory Study in Healthy Male Subjects of the Mechanism of Mirabegron-Induced Cardiovascular Effects.

    Science.gov (United States)

    van Gelderen, Marcel; Stölzel, Matthias; Meijer, John; Kerbusch, Virginie; Collins, Christiane; Korstanje, Cees

    2017-12-01

    To explore the role of β1 -adrenoceptors (ARs) in the heart rate response to the selective β3 -adrenoceptor agonist mirabegron, 12 young male volunteers received single oral doses of the nonselective β1/2 -AR antagonist propranolol (160 mg), the selective β1 -AR antagonist bisoprolol (10 mg), or placebo on days 1 and 5 of each period in a 3-period crossover study. On day 5, dosing was followed by a supratherapeutic dose of mirabegron (200 mg). Vital signs, impedance cardiography, and plasma renin activity were collected. Mirabegron increased heart rate and systolic blood pressure and reduced stroke volume, whereas cardiac output and diastolic blood pressure were unaffected. Mirabegron-induced changes were attenuated by propranolol and bisoprolol. The data indicate that mirabegron has a positive chronotropic effect at supratherapeutic concentrations, which is at least partly mediated by stimulation of β1 -AR. © 2017, The American College of Clinical Pharmacology.

  16. Stimulation of microbial nitrogen cycling in aquatic ecosystems by benthic macrofauna: mechanisms and environmental implications

    DEFF Research Database (Denmark)

    Stief, P.

    2013-01-01

    -microbe interactions, which potentially affect the trophic status of aquatic ecosystems. This review contrasts three types of animal-microbe interactions in the benthos of aquatic ecosystems: (i) ecosystem engineering, (ii) grazing, and (iii) symbiosis. Their specific contributions to the turnover of fixed nitrogen...... (mainly nitrate and ammonium) and the emission of the greenhouse gas nitrous oxide are evaluated. Published data indicate that ecosystem engineering by sediment-burrowing macrofauna stimulates benthic nitrification and denitrification, which together allows fixed nitrogen removal. However, the release...... of ammonium from sediments is enhanced more strongly than the sedimentary uptake of nitrate. Ecosystem engineering by reef-building macrofauna increases nitrogen retention and ammonium concentrations in shallow aquatic ecosystems, but allows organic nitrogen removal through harvesting. Grazing by macrofauna...

  17. Tetanus toxin potently stimulates tissue transglutaminase. A possible mechanism of neurotoxicity.

    Science.gov (United States)

    Facchiano, F; Luini, A

    1992-07-05

    The observation that tetanus toxin (TT) contains two sequences that show homology to known transglutaminase (TGase) substrate sites suggested that the toxin and TGase might interact. This prediction was confirmed by two pieces of evidence. First, TT potently stimulated the enzymatic activity of TGase. The effect was maximal at physiological (micromolar) concentrations of the endogenous TGase regulators calcium and GTP. Second, TT and TGase displayed marked variations of their intrinsic fluorescence properties when they were coincubated, indicating the occurrence of binding between them. TT-TGase binding and TGase activation occurred at similar concentrations of TT and are probably causally related. The activation of TGase, an enzyme present in nerve endings that, when activated, can irreversibly cross-link cellular proteins, might mediate the neurotoxic action of TT.

  18. Recombinant acylation stimulating protein administration to C3-/- mice increases insulin resistance via adipocyte inflammatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Mercedes Nancy Munkonda

    Full Text Available BACKGROUND: Complement 3 (C3, a key component of the innate immune system, is involved in early inflammatory responses. Acylation stimulating protein (ASP; aka C3adesArg, a C3 cleavage product, is produced in adipose tissue and stimulates lipid storage. We hypothesized that, depending on the diet, chronic ASP administration in C3(-/- mice would affect lipid metabolism and insulin sensitivity via an adaptive adipose tissue inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: C3(-/- mice on normal low fat diet (ND or high fat diet (HFD were chronically administered recombinant ASP (rASP for 25 days via an osmotic mini-pump. While there was no effect on food intake, there was a decrease in activity, with a relative increase in adipose tissue weight on ND, and a shift in adipocyte size distribution. While rASP administration to C3(-/- mice on a ND increased insulin sensitivity, on a HFD, rASP administration had the opposite effect. Specifically, rASP administration in C3(-/- HFD mice resulted in decreased gene expression of IRS1, GLUT4, SREBF1 and NFκB in muscle, and decreased C5L2 but increased JNK, CD36, CD11c, CCR2 and NFκB gene expression in adipose tissue as well as increased secretion of proinflammatory cytokines (Rantes, KC, MCP-1, IL-6 and G-CSF. In adipose tissue, although IRS1 and GLUT4 mRNA were unchanged, insulin response was reduced. CONCLUSION: The effects of chronic rASP administration are tissue and diet specific, rASP administration enhances the HFD induced inflammatory response leading to an insulin-resistant state. These results suggest that, in humans, the increased plasma ASP associated with obesity and cardiovascular disease could be an additional factor directly contributing to development of metabolic syndrome, insulin resistance and diabetes.

  19. Some growth factors stimulate cultured adult rabbit ventricular myocyte hypertrophy in the absence of mechanical loading

    Science.gov (United States)

    Decker, R. S.; Cook, M. G.; Behnke-Barclay, M.; Decker, M. L.

    1995-01-01

    Cultured adult rabbit cardiac myocytes treated with recombinant growth factors display enhanced rates of protein accumulation (ie, growth) in response to insulin and insulin-like growth factors (IGFs), but epidermal growth factor, acidic or basic fibroblast growth factor, and platelet-derived growth factor failed to increase contractile protein synthesis or growth of the heart cells. Insulin and IGF-1 increased growth rates by stimulating anabolic while simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein accumulation. A monoclonal antibody directed against the IGF-1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF-1 but not IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1 increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta-MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However, the other growth factors were able to modestly stimulate the rate of DNA synthesis in this preparation. Bromodeoxyuridine labeling revealed that these growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the heart cells displayed neither karyokinesis or cytokinesis. In contrast, cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture medium failed to enhance the rate of cardiac MHC synthesis or its accumulation, implying that quiescent heart cells do not respond to "conditioning" by cardiac nonmyocytes. These findings demonstrated that insulin and the IGFs promote passively loaded cultured adult rabbit heart cells to hypertrophy but suggest that other growth factors tested may be limited in this regard.

  20. Theoretical Analysis of the Mechanism of Fracture Network Propagation with Stimulated Reservoir Volume (SRV Fracturing in Tight Oil Reservoirs.

    Directory of Open Access Journals (Sweden)

    Yuliang Su

    Full Text Available Stimulated reservoir volume (SRV fracturing in tight oil reservoirs often induces complex fracture-network growth, which has a fundamentally different formation mechanism from traditional planar bi-winged fracturing. To reveal the mechanism of fracture network propagation, this paper employs a modified displacement discontinuity method (DDM, mechanical mechanism analysis and initiation and propagation criteria for the theoretical model of fracture network propagation and its derivation. A reasonable solution of the theoretical model for a tight oil reservoir is obtained and verified by a numerical discrete method. Through theoretical calculation and computer programming, the variation rules of formation stress fields, hydraulic fracture propagation patterns (FPP and branch fracture propagation angles and pressures are analyzed. The results show that during the process of fracture propagation, the initial orientation of the principal stress deflects, and the stress fields at the fracture tips change dramatically in the region surrounding the fracture. Whether the ideal fracture network can be produced depends on the geological conditions and on the engineering treatments. This study has both theoretical significance and practical application value by contributing to a better understanding of fracture network propagation mechanisms in unconventional oil/gas reservoirs and to the improvement of the science and design efficiency of reservoir fracturing.

  1. Source mechanism characterization and integrated interpretation of microseismic data monitoring two hydraulic stimulations in pouce coupe field, Alberta

    Science.gov (United States)

    Lindholm, Garrison J.

    The study of the Pouce Coupe Field is a joint effort between the Reservoir Characterization Project (RCP) and Talisman Energy Inc. My study focuses on the hydraulic stimulation of two horizontal wells within the Montney Formation located in north-western Alberta. The Montney is an example of a modern-day tight, engineering-driven play in which recent advances in drilling of horizontal wells and hydraulic fracturing have made shale gas exploitation economical. The wells were completed in December 2008 and were part of a science driven project in which a multitude of data were collected including multicomponent seismic, microseismic, and production logs. Since this time, a number of studies have been performed by students at Colorado School of Mines to better understand the effects the completions have had on the reservoir. This thesis utilizes the microseismic data that were recorded during the stimulation of the two horizontal wells in order to understand the origin of the microseismic events themselves. The data are then used to understand and correlate to the well production. To gain insight into the source of the microseismic events, amplitude ratios of recorded seismic modes (P, Sh and Sv) for the microseismic events are studied. By fitting trends of simple end member source mechanisms (strike-slip, dip-slip, and tensile) to groups of amplitude ratio data, the events are found to be of strike-slip nature. By comparing the focal mechanisms to other independent natural fracture determination techniques (shear-wave splitting analysis, FMI log), it is shown that the source of recorded microseismic events is likely to be a portion of the shear slip along existing weak planes (fractures) within a reservoir. The technique described in this work is one that is occasionally but increasingly used but offers the opportunity to draw further information from microseismic data using results that are already part of a typical processing workflow. The microseismic events are

  2. Pre-strain stimulation of electro-mechanical sensitivity of carbon nanotube network/polyurethane composites

    Czech Academy of Sciences Publication Activity Database

    Slobodian, P.; Říha, Pavel; Olejník, R.; Matyáš, J.; Machovský, M.

    2016-01-01

    Roč. 16, č. 15 (2016), s. 5898-5903 ISSN 1530-437X Grant - others:Ministerstvo školství, mládeže a tělovýchovy (MŠMT)(CZ) LO1504 Institutional research plan: CEZ:AV0Z20600510 Institutional support: RVO:67985874 Keywords : carbon nanotubes * deformation sensing polymer composite * polymer composite Subject RIV: BK - Fluid Dynamics Impact factor: 2.512, year: 2016

  3. Mechanisms underlying center of pressure displacements in obese subjects during quiet stance

    Directory of Open Access Journals (Sweden)

    Priano Lorenzo

    2011-04-01

    Full Text Available Abstract Objective the aim of this study was to assess whether reduced balance capacity in obese subjects is secondary to altered sensory information. Design cross sectional study. Subjects 44 obese (BMI = 40.6 ± 4.6 kg/m2 , age = 34.2 ± 10.8 years, body weight: 114,0 ± 16,0 Kg, body height 167,5 ± 9,8 cm and 20 healthy controls (10 females, 10 males, BMI: 21.6 ± 2.2 kg/m2, age: 30.5 ± 5.5 years, body weight: 62,9 ± 9,3 Kg, body height 170,1 ± 5,8 cm were enrolled. Measurements center of pressure (CoP displacements were evaluated during quiet stance on a force platform with eyes open (EO and closed (EC. The Romberg quotient (EC/EO was computed and compared between groups. Results we found statistically significant differences between obese and controls in CoP displacements (p 0.08. Conclusion the increased CoP displacements in obese subjects do not need an hypothesis about altered sensory information. The integration of different sensory inputs appears similar in controls and obese. In the latter, the increased mass, ankle torque and muscle activity may probably account for the higher CoP displacements.

  4. Mechanical behavior of fast reactor fuel pin cladding subjected to simulated overpower transients

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, G.D.; Hunter, C.W.

    1978-06-01

    Cladding mechanical property data for analysis and prediction of fuel pin transient behavior were obtained under experimental conditions in which the temperature ramps of reactor transients were simulated. All cladding specimens were 20% CW Type 316 stainless steel and were cut from EBR-II irradiated fuel pins. It was determined that irradiation degraded the cladding ductility and failure strength. Specimens that had been adjacent to the fuel exhibited the poorest properties. Correlations were developed to describe the effect of neutron fluence on the mechanical behavior of the cladding. Metallographic examinations were conducted to characterize the failure mode and to establish the nature of internal and external surface corrosion. Various mechanisms for the fuel adjacency effect were examined and results for helium concentration profiles were presented. Results from the simulated transient tests were compared with TREAT test results.

  5. Model-based respiratory mechanics to titrate PEEP and monitor disease state for experimental ARDS subjects.

    Science.gov (United States)

    van Drunen, Erwin J; Chiew, Yeong Shiong; Chase, J Geoffrey; Lambermont, Bernard; Janssen, Nathalie; Desaive, Thomas

    2013-01-01

    Modelling the respiratory mechanics of mechanically ventilated (MV) patients can provide useful information to guide MV therapy. Two model-based methods were evaluated based on data from three experimental acute respiratory distress syndrome (ARDS) induced piglets and validated against values available from ventilators. A single compartment lung model with integral-based parameter identification was found to be effective in capturing fundamental respiratory mechanics during inspiration. The trends matched clinical expectation and provided better resolution than clinically derived linear model metrics. An expiration time constant model also captured the same trend in respiratory elastance. However, the assumption of constant resistance and a slightly higher fitting error results in less insight than the single compartment model. Further research is required to confirm its application in titrating to optimal MV settings.

  6. Decision dynamics in complex networks subject to mass media and social contact transmission mechanisms

    CERN Document Server

    Lucatero, Carlos Rodríguez; Jaquez, Roberto Bernal; Schaum, Alexander

    2012-01-01

    The dynamics of decisions in complex networks is studied within a Markov process framework using numerical simulations combined with mathematical insight into the process mechanisms. A mathematical discrete-time model is derived based on a set of basic assumptions on the convincing mechanisms associated to two opinions. The model is analyzed with respect to multiplicity of critical points, illustrating in this way the main behavior to be expected in the network. Particular interest is focussed on the effect of social network and exogenous mass media-based influences on the decision behavior. A set of numerical simulation results is provided illustrating how these mechanisms impact the final decision results. The analysis reveals (i) the presence of fixed-point multiplicity (with a maximum of four different fixed points), multistability, and sensitivity with respect to process parameters, and (ii) that mass media have a strong impact on the decision behavior.

  7. Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation.

    Directory of Open Access Journals (Sweden)

    Jun-Il Kang

    Full Text Available Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1 induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR, M1 and M2 muscarinic (mAChR or GABAergic A (GABAAR receptors was performed during the training session and visual evoked potentials (VEPs were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABAAR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD, suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by n

  8. Neurophysiological mechanisms of formation of non-chemical dependence through self-stimulation of positive emotiogenic areas of rats’ brains

    Directory of Open Access Journals (Sweden)

    O. G. Berchenko

    2016-05-01

    Full Text Available The aim of our research was to study the limbic-neocortical mechanisms of addictive behaviour in rats formed throughthe arousal of intense emotions on the model of self-stimulation reaction of the brain. We carried out investigations by conducting a chronic experiment on 15 nonlinear laboratory male rats weighing 250 to 320 grams, at the ages of 5 to 6 months. As a model of receiving positive emotions we used the behaviour of animals held in a Skinner box which was formed through self stimulation of the positive emotional zones of the posterior ventrolateral hypothalamus. We registered the frequency of self-stimulation reactions of the ventrolateral hypothalamus daily for 4 days and on the 7th day after its ccessation (state of deprivation. We performed visual and spectral analysis of the electrical activity of the brain using "Neuron-spektr.net" software. We assessed the absolute spectral density of the power of rhythm signals of the following frequency bands: delta (0.5–4.0 Hz, theta (4.0–7.0 Hz, alpha (8.0–12.0 Hz and low frequency beta (14.0–20.0 Hz. The formation of behaviour dependent on receiving intense emotions as a result of self-stimulation of the positive zones of the ventrolateral hypothalamus is caused by the initial high level of need for positive emotional reinforcement and further growth in the implementation of desire and is associated with activation of emotional memory mechanisms, changes in electrogenesis in the hippocampus and the reticular formation in the form of decrease in the spectral power of rhythms of alpha and beta bands and increased spectral power of biopotentials of the delta range in the hippocampus and theta range in the reticular formation with severe manifestations of seizure and paroxysmal activity components and increased activity of the sympatho-adrenal system. The syndrome of withdrawal fromthe receiving of positive emotions in some rats with implementation of a programme of a phobic character

  9. Subject-specific left ventricular dysfunction modeling using composite material mechanics approach

    Science.gov (United States)

    Haddad, Seyed Mohammad Hassan; Karami, Elham; Samani, Abbas

    2017-03-01

    Diverse cardiac conditions such as myocardial infarction and hypertension can lead to diastolic dysfunction as a prevalent cardiac condition. Diastolic dysfunctions can be diagnosed through different adverse mechanisms such as abnormal left ventricle (LV) relaxation, filling, and diastolic stiffness. This paper is geared towards evaluating diastolic stiffness and measuring the LV blood pressure non-invasively. Diastolic stiffness is an important parameter which can be exploited for more accurate diagnosis of diastolic dysfunction. For this purpose, a finite element (FE) LV mechanical model, which works based on a novel composite material model of the cardiac tissue, was utilized. Here, this model was tested for inversion-based applications where it was applied for estimating the cardiac tissue passive stiffness mechanical properties as well as diastolic LV blood pressure. To this end, the model was applied to simulate diastolic inflation of the human LV. The start-diastolic LV geometry was obtained from MR image data segmentation of a healthy human volunteer. The obtained LV geometry was discretized into a FE mesh before FE simulation was conducted. The LV tissue stiffness and diastolic LV blood pressure were adjusted through optimization to achieve the best match between the calculated LV geometry and the one obtained from imaging data. The performance of the LV mechanical simulations using the optimal values of tissue stiffness and blood pressure was validated by comparing the geometrical parameters of the dilated LV model as well as the stress and strain distributions through the LV model with available measurements reported on the LV dilation.

  10. Mechanisms of napelline action stimulating the regeneration of hemopoietic tissue in cytostatic myelosuppression.

    Science.gov (United States)

    Zyuz'kov, G N; Zhdanov, V V; Udut, E V; Miroshnichenko, L A; Losev, E A; Simanina, E V; Chaikovskiy, A V; Suslov, N I; Povet'eva, T N; Krapivin, A V; Nesterova, Yu V; Agafonov, V I; Minakova, M Yu; Stavrova, L A; Danilets, M G; Ligacheva, A A; Trofimova, E S; Ivanova, A N; Goldberg, V E; Reikchart, D V; Dygai, A M

    2013-08-01

    Pronounced regenerative effects of alkaloid napelline extracted from Aconitum baicalense on granulocytic hemopoiesis were revealed in the model of cytostatic myelosuppression. Activation of functions of hemopoietic progenitor cells along with increased feeder capacity of the stromal elements in the hemopoiesis inducing microenvironment with decreased levels mesenchymal progenitor cells in the bone marrow are the mechanisms underlying the hemostimulating action of this substance.

  11. A Novel Pulsatile Bioreactor for Mechanical Stimulation of Tissue Engineered Cardiac Constructs

    Directory of Open Access Journals (Sweden)

    Günther Eissner

    2011-07-01

    Full Text Available After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro.

  12. Microtrauma stimulates rat Achilles tendon healing via an early gene expression pattern similar to mechanical loading

    DEFF Research Database (Denmark)

    Hammerman, Malin; Aspenberg, Per; Eliasson, Pernilla

    2014-01-01

    rats received Botox into the calf muscle to reduce loading, and the Achilles tendon was transected. Ten rats were randomized to needling days 2-5. Mechanical testing on day 8 showed increased strength by 45% in the needling group. Next, another 24 rats were similarly unloaded, and 16 randomized...

  13. FAILURE MECHANISM OF THE SCABBING OF CONCRETE PLATES SUBJECTED TO HIGH VELOCITY IMPACT AND EFFECTS OF FIBER SHEET REINFORCEMENT

    Science.gov (United States)

    Beppu, Masuhiro; Miwa, Koji; Takahashi, Jun

    This paper presents failure mechanism of the scabbing of concrete plates subjected to high velocity impact and effects of fiber sheet reinforcement. Prior to impact tests, strain measurement method using acrylic bar with strain gauges is validated by conducting impact test to concrete bar specimen. Then, impact tests are carried out to examine the failure mechanism of scabbing of concrete plates. In the tests, the strain measurement method is applied and strain behavior inside the concrete plate is discussed. After that, impact tests of fiber sheet reinforced concrete plates are conducted. Based on failure mode and strain behavior, effects of fiber sheet reinforcement on the failure of concrete plates are examined.

  14. A CHROMATIN MODIFYING ENZYME, SDG8, IS REQUIRED FOR MORPHOLOGICAL, GENE EXPRESSION, AND EPIGENETIC RESPONSES TO MECHANICAL STIMULATION

    Directory of Open Access Journals (Sweden)

    Christopher Ian Cazzonelli

    2014-10-01

    Full Text Available Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzyme, SDG8/ASHH2, which can regulate the expression of many touch responsive genes identified in Arabidopsis. SDG8 is required for the permissive expression of touch induced genes; and the loss of function of sdg8 perturbs the maximum levels of induction on selected touch gene targets. SDG8 is required to maintain permissive H3K4 trimethylation marks surrounding the Arabidopsis touch-inducible gene TOUCH 3 (TCH3, which encodes a calmodulin-like protein (CML12. The gene neighbouring was also slightly down regulated, revealing a new target for SDG8 mediated chromatin modification. Finally, sdg8 mutants show perturbed morphological response to wind-agitated mechanical stimuli, implicating an epigenetic memory-forming process in the acclimation response of thigmomorphogenesis.

  15. Deformation and failure mechanism of excavation in clay subjected to hydraulic uplift

    CERN Document Server

    Hong, Yi

    2016-01-01

    This book presents the latest experimental and numerical analysis work in the field of ground deformation and base instability of deep excavations in soft clay subjected to hydraulic uplift. The authors’ latest research findings, based on dimensional analyses, well-instrumented full-scale field tests, systematic coupled-consolidation finite element analyses and centrifuge tests are reported. This book shows how to systematically approach a complex geotechnical problem, from identifying existing problems, reviewing literature, to dimensional and numerical analyses, validation through full-scale testing and centrifuge model testing. The methodologies are also introduced as major tools adopted in geotechnical research.

  16. Robust adaptive control modeling of human arm movements subject to altered gravity and mechanical loads

    Science.gov (United States)

    Tryfonidis, Michail

    It has been observed that during orbital spaceflight the absence of gravitation related sensory inputs causes incongruence between the expected and the actual sensory feedback resulting from voluntary movements. This incongruence results in a reinterpretation or neglect of gravity-induced sensory input signals. Over time, new internal models develop, gradually compensating for the loss of spatial reference. The study of adaptation of goal-directed movements is the main focus of this thesis. The hypothesis is that during the adaptive learning process the neural connections behave in ways that can be described by an adaptive control method. The investigation presented in this thesis includes two different sets of experiments. A series of dart throwing experiments took place onboard the space station Mir. Experiments also took place at the Biomechanics lab at MIT, where the subjects performed a series of continuous trajectory tracking movements while a planar robotic manipulandum exerted external torques on the subjects' moving arms. The experimental hypothesis for both experiments is that during the first few trials the subjects will perform poorly trying to follow a prescribed trajectory, or trying to hit a target. A theoretical framework is developed that is a modification of the sliding control method used in robotics. The new control framework is an attempt to explain the adaptive behavior of the subjects. Numerical simulations of the proposed framework are compared with experimental results and predictions from competitive models. The proposed control methodology extends the results of the sliding mode theory to human motor control. The resulting adaptive control model of the motor system is robust to external dynamics, even those of negative gain, uses only position and velocity feedback, and achieves bounded steady-state error without explicit knowledge of the system's nonlinearities. In addition, the experimental and modeling results demonstrate that

  17. Residual stress redistribution in shot peened samples subject to mechanical loading

    Energy Technology Data Exchange (ETDEWEB)

    Buchanan, Dennis J., E-mail: dennis.buchanan@udri.udayton.edu [University of Dayton Research Institute, 300 College Park, Dayton, OH 45469-0020 (United States); John, Reji [Materials and Manufacturing Directorate, Air Force Research Laboratory (AFRL/RXCM), Wright-Patterson Air Force Base, OH 45433-7817 (United States)

    2014-10-06

    Shot peening is a well-established surface treatment process that imparts large compressive residual stresses onto the surface and at shallow depths to retard initiation and growth of fatigue cracks. The plastic deformation developed during the surface treatment sets up a constraint that retains compressive stresses on the surface balanced by tensile residual stresses in the interior. However, component service histories that produce subsequent plastic deformation may redistribute these residual stresses. In most engineering components, this additional plastic deformation is localized to stress concentration sites such as holes, notches, and fillets. In the case of gross plastic deformation where the entire cross section experiences material yielding the residual stress profile may redistribute, resulting in tensile stresses on the outside surface balanced by compression in the interior. This paper describes a series of experiments combined with models to explain the redistribution in residual stress depth profiles subject to applied stresses producing gross plastic strains in shot peened laboratory specimens. The initial room temperature residual stress and plastic strain profiles provide initial conditions for predictions. Model predictions correlate well with experimental results on shot peened dogbone specimens subject to single cycle and fatigue loading conditions at elevated temperature. Experiments on shot peened notched specimens do not exhibit the same stress redistribution even for larger applied stresses.

  18. Dissipative structure of mechanically stimulated reaction; Kikaiteki reiki hanno ni okeru san`itsu kozo

    Energy Technology Data Exchange (ETDEWEB)

    Hida, M. [Okayama Univ., Okayama (Japan). Faculty of Engineering

    1994-12-20

    Recently various studies have been conducted concerning the state changes of materials obtained through mechanical alloying (MA) or mechano-chemical (MC) processing. What is noticeable is the quasi-steady state of almost all the materials obtained through various processes including MA and MC, and that the super cooling, supersaturating and high residue distortion realized under unbalanced conditions have not been clarified. In other words, the tracing capability to the external binding conditions is low. In this report, the appearance of the high temperature phase and high pressure phase obtained through MA or MC processing, the forming of amorphous, the mesomerism of the amorphous materials, the interesting phenomena generated by combination between the mechanical disturbance and chemical reactions were discussed with concrete examples, and a steady dissipative organization theory was approached from the viewpoint of dissipative structure development which is equal to the forming process of the quasi-steady phase. 34 refs., 2 figs.

  19. Modeling and Analysis Tools for Linear and Nonlinear Mechanical Systems Subjected to Extreme Impulsive Loading

    Science.gov (United States)

    2015-03-23

    and seismic motion analysis [3]. In many military and civil applications, nonlinear mechanical wave prop- agation occurs through structural...ture are prepared and performed by using MATLAB . The proposed force iden- tification method is also implemented and studied by using MATLAB and...methods is listed in Table. 3. A Dell desktop with a Intel Core Quad CPU is used for all simulations. The parallel computing toolbox in MATLAB is used to

  20. Mechanical and time-dependent behavior of wood-plastic composites subjected to bending

    Science.gov (United States)

    S. E. Hamel; John Hermanson; S. M. Cramer

    2015-01-01

    The most popular use of wood–plastic composite (WPC) members in the United States has been as outdoor decking material in residential construction. If the use of these products expands into more structural applications, such as beams and joists, it is imperative that the material’s mechanical behavior be understood. Since most of the potential structural uses of this...

  1. Curcumin Stimulates Biochemical Mechanisms of Apis Mellifera Resistance and Extends the Apian Life-Span

    Directory of Open Access Journals (Sweden)

    Strachecka Aneta J.

    2015-06-01

    Full Text Available We examined the influence of curcumin-supplemented feeding on worker lifespan, Nosema resistance, key enzyme activities, metabolic compound concentrations and percentage of the global DNA methylation. Two worker groups (Apis mellifera were set up: 1 control group; workers were fed ad libitum with sucrose syrup; 2 workers were fed with the syrup with the addition of curcumin. Dead workers were removed every two days and the Nosema spp. infection levels were assessed. Hemolymph was taken from living workers for biochemical analyses. The global DNA methylation level was analysed using DNA from worker heads and thoraces. The bees that consumed curcumin lived longer and were less infested with Nosema spp. The curcumin-treated workers had higher concentrations of proteins, non-enzymatic biomarkers (triglycerides, glucose, cholesterol, Mg2+ and Ca2+, uric acid and creatinine, as well as elevated activities of antioxidant enzymes (SOD , GPx, CAT , GST , neutral proteases, protease inhibitors, enzymatic biomarkers (AST , ALT , ALP . The concentrations of albumin and urea, and the activities of acidic and alkaline proteases were higher in the control group. Curcumin decreased global DNA methylation levels especially in older bees in which the natural, age-related level increase was observed. Most of the parameters increased over the apian youth and adulthood, and decreased in older bees. The decrease was markedly delayed in the bees fed with curcumin. Curcumin appeared to be an unexpectedly effective natural bio-stimulator, improving apian health and vitality. This multifactorial effect is caused by the activation of many biochemical processes involved in the formation of apian resistance.

  2. A single-subject study to evaluate the inhibitory repetitive transcranial magnetic stimulation combined with traditional dysphagia therapy in patients with post-stroke dysphagia.

    Science.gov (United States)

    Ghelichi, Leila; Joghataei, Mohammad Taghi; Jalaie, Shohreh; Nakhostin-Ansari, Noureddin; Forogh, Bijan; Mehrpour, Masoud

    2016-07-06

    Post-stroke dysphagia is common and is associated with the development of pneumonia. To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) combined with traditional dysphagia therapy (TDT) on swallowing function in patients with post-stroke dysphagia. In this single-subject study, four patients with dysphagia post-stroke included. The patients received the rTMS applied to the intact cerebral hemisphere at 1 Hz with train of 1200 for 5 consecutive days combined with TDT 3 days per week for 6 weeks. The main outcome measure was the Mann Assessment of Swallowing Ability (MASA). Measurements were taken before, after the end of 5(th), 10(th), 15(th) treatment sessions, and after the end of the treatment (18(th) session). The MASA scores improved in all patients following treatment. The maximum and minimum change in level between the baseline phase and treatment phase was +84 and +36. The greatest percentage improvement was observed after 5(th) treatment sessions ranging between 11 and 35%. The treatment trend was upward shown by the directions of the slopes indicated by positive values (+9.1-+20.7). The dysphagia was resolved after 10(th) treatment session in all participants. The aspiration resolved in two participants after the 5(th) treatment session and resolved in another 2 participants after the 10(th) treatment session. The combination therapy of rTMS plus TDT improved swallowing function in patients with post-stroke dysphagia. Further research with a larger sample size is recommended.

  3. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects

    DEFF Research Database (Denmark)

    Kjems, Lise L; Holst, Jens J; Vølund, Aage

    2003-01-01

    The intestinally derived hormone glucagon-like peptide 1 (GLP-1) (7-36 amide) has potent effects on glucose-mediated insulin secretion, insulin gene expression, and beta-cell growth and differentiation. It is, therefore, considered a potential therapeutic agent for the treatment of type 2 diabetes....... However, the dose-response relationship between GLP-1 and basal and glucose-stimulated prehepatic insulin secretion rate (ISR) is currently not known. Seven patients with type 2 diabetes and seven matched nondiabetic control subjects were studied. ISR was determined during a graded glucose infusion of 2......, 4, 6, 8, and 12 mg x kg(-1) x min(-1) over 150 min on four occasions with infusion of saline or GLP-1 at 0.5, 1.0, and 2.0 pmol x kg(-1) x min(-1). GLP-1 enhanced ISR in a dose-dependent manner during the graded glucose infusion from 332 +/- 51 to 975 +/- 198 pmol/kg in the patients with type 2...

  4. Lycra garments designed for patients with upper limb spasticity: mechanical effects in normal subjects.

    Science.gov (United States)

    Gracies, J M; Fitzpatrick, R; Wilson, L; Burke, D; Gandevia, S C

    1997-10-01

    To assess the stretch of pronator muscles produced by a specifically designed upper-limb Lycra garment that could have a better acceptability than rigid splints in treating upper-limb spasticity. Double-blind comparison among three garments. They were designed to produce a supinating, a pronating, and no torsional force, and were individually manufactured and tested in 10 healthy volunteers. Angular position and passive rotational stiffness of the forearm were measured with and without each of the garments immediately after the garment was fitted and every hour for 6 hours. When put on by a trained person, the supinator garment supinated the forearm in all subjects (mean, 17 degrees; p spasticity. The garments, however, must be put on by a trained person and their position adjusted when necessary.

  5. Immunomodulation and signaling mechanism of Lactobacillus rhamnosus GG and its components on porcine intestinal epithelial cells stimulated by lipopolysaccharide.

    Science.gov (United States)

    Gao, Kan; Wang, Chong; Liu, Li; Dou, Xiaoxiao; Liu, Jianxin; Yuan, Lijuan; Zhang, Wenming; Wang, Haifeng

    2017-10-01

    This study aimed to evaluate the immunomodulatory effects and signaling mechanisms of Lactobacillus rhamnosus GG (LGG) and its components [surface-layer protein (SLP), DNA, exopolysaccharides, and CpG oligodeoxynucleotides] on lipopolysaccharide (LPS)-stimulated porcine intestinal epithelial cell (IEC) IPEC-J2. The mRNA expressions of inflammatory cytokines and Toll-like receptors (TLRs) were measured by quantitative real-time polymerase chain reaction. Activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling was detected by western blot and immunofluorescence. Pretreatment of IPEC-J2 cells with LGG, SLP, or exopolysaccharides significantly alleviated LPS-induced inflammatory cytokines and TLR activation at mRNA level. LGG, SLP, and exopolysaccharides also attenuated LPS-induced MAPK and NF-κB signaling activations. CpG oligodeoxynucleotides significantly increased the interleukin 12, tumor necrosis factor α, and TLR9 mRNA levels and enhanced NF-κB signaling activation in LPS-stimulated cells. LGG had immunomodulatory effects on LPS-induced porcine IECs by modulating TLR expressions and inhibiting MAPK and NF-κB signaling to decrease inflammatory cytokine expressions. Components of LGG exerted immunomodulatory effects on porcine IECs, especially immunostimulatory CpG oligodeoxynucleotides. Copyright © 2015. Published by Elsevier B.V.

  6. Variability of respiratory mechanics during sleep in overweight and obese subjects with and without asthma.

    Science.gov (United States)

    Campana, L M; Owens, R L; Butler, J P; Suki, B; Malhotra, A

    2013-05-01

    Variability of respiration may provide information regarding disease states. We sought to characterize variability of ventilation and resistance in healthy and asthma, to determine how respiratory control may be altered in sleep and with bi-level positive airway pressure (BPAP). Overweight and obese subjects with and without asthma were studied during sleep at baseline and with BPAP, while measuring respiratory system resistance (Rrs) continuously. Stable periods (>20min) of wake, NREM, and REM sleep were identified and correlation metrics of respiratory parameters were calculated, including coefficient of variation (CV). Variability of Rrs was also characterized over short time scales (20 breaths) during sleep and defined as either "leading to arousal" or "not leading to arousal". Data from 10 control and 10 subjects with asthma were analyzed. CV of Rrs was decreased in asthma at baseline (p<0.001) and decreased on BPAP as compared to baseline (p<0.001). Long time scale correlations were found in respiratory parameters, but the degree of correlations was decreased from wake to sleep (p<0.05). The variance and CV of Rrs was increased preceding an arousal from sleep at baseline; however, during BPAP, the CV was decreased and was not increased preceding arousals. At baseline, resistance was greater in those with asthma, but variability was smaller. BPAP reduced both resistance and overall variability. We conclude that the BPAP-induced decrease in variability may indicate that those with asthma are more likely to remain in a low resistance state, and that low resistance variability may reduce arousals from sleep. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Mechanical behavior of fiber/matrix interfaces in CFRP sheets subjected to plastic deformation

    Directory of Open Access Journals (Sweden)

    Kamiya Ryuta

    2016-01-01

    Full Text Available The use of Carbon Fiber Reinforced Plastic (CFRP is increasing markedly, partially in the aviation industry, but it has been considered that CFRP sheets cannot be formed by press-forming techniques owing to the low ductility of CFRP. Since the mechanical characteristics of CFRP are dominated by the microscale structure, it is possible to improve its formability by optimizing the material structure. Therefore, to improve the formability, the interaction between the carbon fibers and the matrix must be clarified. In this study, microscale analyses were conducted by a finite-element model with cohesive zone elements.

  8. Assessment of Mechanical Properties and Damage of High Performance Concrete Subjected to Magnesium Sulfate Environment

    Directory of Open Access Journals (Sweden)

    Sheng Cang

    2017-01-01

    Full Text Available Sulfate attack is one of the most important problems affecting concrete structures, especially magnesium sulfate attack. This paper presents an investigation on the mechanical properties and damage evolution of high performance concrete (HPC with different contents of fly ash exposure to magnesium sulfate environment. The microstructure, porosity, mass loss, dimensional variation, compressive strength, and splitting tensile strength of HPC were investigated at various erosion times up to 392 days. The ultrasonic pulse velocity (UPV propagation in HPC at different erosion time was determined by using ultrasonic testing technique. A relationship between damage and UPV of HPC was derived according to damage mechanics, and a correlation between the damage of HPC and erosion time was obtained eventually. The results indicated that (1 the average increasing amplitude of porosity for HPCs was 34.01% before and after exposure to magnesium sulfate solution; (2 the damage evolution of HPCs under sulfate attack could be described by an exponential fitting; (3 HPC containing 20% fly ash had the strongest resistance to magnesium sulfate attack.

  9. Destruction Mechanism of ZnAl4 as Cast Alloy Subjected to Cavitational Erosion Using Different Laboratory Stands

    Directory of Open Access Journals (Sweden)

    Jasionowski R.

    2016-03-01

    Full Text Available The main reason of a cavitational destruction is the mechanical action of cavitation pulses onto the material’s surface. The course of cavitation destruction process is very complex and depends on the physicochemical and structural features of a material. A resistance to cavitation destruction of the material increases with the increase of its mechanical strength, fatigue resistance as well as hardness. Nevertheless, the effect of structural features on the material’s cavitational resistance has been not fully clarified. In the present paper, the cavitation destruction of ZnAl4 as cast alloy was investigated on three laboratory stands: vibration, jet-impact and flow stands. The destruction mechanism of ZnAl4 as cast alloy subjected to cavitational erosion using various laboratory stands is shown in the present paper.

  10. The Shear Mechanisms of Natural Fractures during the Hydraulic Stimulation of Shale Gas Reservoirs.

    Science.gov (United States)

    Zhang, Zhaobin; Li, Xiao

    2016-08-23

    The shearing of natural fractures is important in the permeability enhancement of shale gas reservoirs during hydraulic fracturing treatment. In this work, the shearing mechanisms of natural fractures are analyzed using a newly proposed numerical model based on the displacement discontinuities method. The fluid-rock coupling system of the model is carefully designed to calculate the shearing of fractures. Both a single fracture and a complex fracture network are used to investigate the shear mechanisms. The investigation based on a single fracture shows that the non-ignorable shearing length of a natural fracture could be formed before the natural fracture is filled by pressurized fluid. Therefore, for the hydraulic fracturing treatment of the naturally fractured shale gas reservoirs, the shear strength of shale is generally more important than the tensile strength. The fluid-rock coupling propagation processes of a complex fracture network are simulated under different crustal stress conditions and the results agree well with those of the single fracture. The propagation processes of complex fracture network show that a smaller crustal stress difference is unfavorable to the shearing of natural fractures, but is favorable to the formation of complex fracture network.

  11. The Shear Mechanisms of Natural Fractures during the Hydraulic Stimulation of Shale Gas Reservoirs

    Directory of Open Access Journals (Sweden)

    Zhaobin Zhang

    2016-08-01

    Full Text Available The shearing of natural fractures is important in the permeability enhancement of shale gas reservoirs during hydraulic fracturing treatment. In this work, the shearing mechanisms of natural fractures are analyzed using a newly proposed numerical model based on the displacement discontinuities method. The fluid-rock coupling system of the model is carefully designed to calculate the shearing of fractures. Both a single fracture and a complex fracture network are used to investigate the shear mechanisms. The investigation based on a single fracture shows that the non-ignorable shearing length of a natural fracture could be formed before the natural fracture is filled by pressurized fluid. Therefore, for the hydraulic fracturing treatment of the naturally fractured shale gas reservoirs, the shear strength of shale is generally more important than the tensile strength. The fluid-rock coupling propagation processes of a complex fracture network are simulated under different crustal stress conditions and the results agree well with those of the single fracture. The propagation processes of complex fracture network show that a smaller crustal stress difference is unfavorable to the shearing of natural fractures, but is favorable to the formation of complex fracture network.

  12. Enhancement of motor learning by focal intermittent theta burst stimulation (iTBS) of either the primary motor (M1) or somatosensory area (S1) in healthy human subjects.

    Science.gov (United States)

    Platz, Thomas; Adler-Wiebe, Marija; Roschka, Sybille; Lotze, Martin

    2018-01-01

    Motor rehabilitation after brain damage relies on motor re-learning as induced by specific training. Non-invasive brain stimulation (NIBS) can alter cortical excitability and thereby has a potential to enhance subsequent training-induced learning. Knowledge about any priming effects of NIBS on motor learning in healthy subjects can help to design targeted therapeutic applications in brain-damaged subjects. To examine whether complex motor learning in healthy subjects can be enhanced by intermittent theta burst stimulation (iTBS) to primary motor or sensory cortical areas. Eighteen young healthy subjects trained eight different arm motor tasks (arm ability training, AAT) once a day for 5 days using their left non-dominant arm. Except for day 1 (baseline), training was performed after applying an excitatory form of repetitive transcranial magnetic stimulation (iTBS) to either (I) right M1 or (II) S1, or (III) sham stimulation to the right M1. Subjects were randomly assigned to conditions I, II, or III. A principal component analysis of the motor behaviour data suggested eight independent motor abilities corresponding to the 8 trained tasks. AAT induced substantial motor learning across abilities with generalisation to a non-trained test of finger dexterity (Nine-Hole-Peg-Test, NHPT). Participants receiving iTBS (to either M1 or S1) showed better performance with the AAT tasks over the period of training compared to sham stimulation as well as a bigger improvement with the generalisation task (NHPT) for the trained left hand after training completion. Priming with an excitatory repetitive transcranial magnetic stimulation as iTBS of either M1 or S1 can enhance motor learning across different sensorimotor abilities.

  13. Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

    Science.gov (United States)

    2015-01-01

    Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24–48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

  14. On dynamic analysis of variable thickness disks and complex rotors subjected to thermal and mechanical prestresses

    Science.gov (United States)

    Entezari, A.; Filippi, M.; Carrera, E.

    2017-09-01

    This paper is focused on the analysis of complex rotating structures subjected to plausible operating conditions. Effects of the temperature gradient and the centrifugal stiffening contribution have been evaluated. In particular, the analyses have been performed considering disks with constant and variable thicknesses, which have been assumed either clamped at the bore or supported by a deformable shaft. The prestress contributions have been obtained through the integration of the three-dimensional stress state, which is generated by centrifugal and thermal loads, multiplied by the non-linear terms of the strain field. The weak form of the governing equations has been solved using the Finite Element method. High-fidelity one-dimensional elements have been developed according to the Carrera Unified Formulation. The comparisons between the current results and those obtained from solid finite element solutions have demonstrated that the proposed methodology can represent a valuable alternative to the three-dimensional modelling technique by ensuring a comparable accuracy with a lower computational effort.

  15. Left atrial mechanics strongly predict functional capacity assessed by cardiopulmonary exercise testing in subjects without structural heart disease.

    Science.gov (United States)

    Leite, Luís; Mendes, Sofia Lázaro; Baptista, Rui; Teixeira, Rogério; Oliveira-Santos, Manuel; Ribeiro, Nelson; Coutinho, Rosa; Monteiro, Victor; Martins, Rui; Castro, Graça; Ferreira, Maria João; Pego, Mariano

    2017-05-01

    Left atrium function is essential for cardiovascular performance and is evaluable by two-dimensional speckle-tracking echocardiography (2D-STE). Our aim was to determine how echocardiographic parameters interrelate with exercise capacity and ventilatory efficiency in subjects with no structural heart disease. Asymptomatic volunteers, in sinus rhythm and with normal biventricular size and function, were recruited from a community-based population. Individuals with moderate-to-severe valvular disease, pulmonary hypertension, and history of cardiac disease were excluded. We performed a transthoracic echocardiogram and assessed left atrial (LA) and left ventricular (LV) mechanics via 2D-STE. Cardiopulmonary exercise testing by treadmill took place immediately thereafter. Peak oxygen uptake (VO2) served as measure of functional capacity and ventilation/carbon dioxide output (VE/VCO2) slope as surrogate of ventilation/perfusion mismatch. 20 subjects were included (age 51 ± 14 years, male gender 65%). Peak VO2 strongly correlated with age (r = -0.83; P mechanics, particularly with LA conduit strain rate (SR) (r = -0.82; P mechanics. A similar pattern of associations was identified for VE/VCO2 slope. In multivariate analysis, LA conduit SR (β = -0.69; P = 0.02) emerged as sole independent correlate of peak VO2, adjusted for age and for E/e' ratio (adjusted r 2  = 0.76; P mechanics displayed strong associations with peak VO2 and VE/VCO2 slope. LA conduit-phase SR seems best suited as echocardiographic marker of functional capacity in subjects with no structural heart disease.

  16. Nanocrystallization mechanism of beta phase in Ti-6Al-4V subjected to severe plastic deformation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yingang; Li, Miaoquan, E-mail: honeymli@nwpu.edu.cn

    2016-07-04

    Nanocrystallization mechanism of beta phase in the bulk coarse-grained Ti-6Al-4V by high energy shot peening was investigated via high-resolution transmission electron microscopy. The results suggested that dislocation gliding was first initiated in beta phase at and around the intersections of the phase boundary with the high-density dislocation structures in alpha phase followed by the formation of dislocation tangles and dislocation walls. As the short axis sizes of alpha phase approached that of beta phase, the dislocation tangles and dislocation walls gradually evolved into the high-angle grain boundaries and subdivided the original grains into the equiaxed ultrafine grains. Under the ultrahigh strain and strain rate, the equiaxed ultrafine grains were eventually refined to randomly oriented nanograins via dynamic recrystallization. In addition, the nanograins would be further refined via dislocation motion upon further straining.

  17. Fracture mechanics analysis for a mooring system subjected to tension and out-of-plane bending

    Science.gov (United States)

    Xue, X.; Chen, N.-Z.

    2017-12-01

    A fracture mechanics analysis for the mooring system of a semi-submersible accounting for out-of-plane bending (OPB) is presented in this paper. Stress ranges acting on the mooring chain links are calculated based on tension and OPB of mooring chain links induced by motions of wave frequency (WF) and low frequency (LF). The narrow-banded method is used for predicting the combined mooring loading process. Initial cracks are assumed to propagate from surfaces of chain links and stress intensity factors are then calculated in terms of stress ranges determined by a finite element analysis. The influence of the OPB on the remaining service life of mooring chain links is investigated and the results show that the remaining service life of mooring chain links connecting to fairleads is significantly reduced due to the OPB effects.

  18. β-adrenergic receptor activation in immortalized human urothelial cells stimulates inflammatory responses by PKA-independent mechanisms

    Directory of Open Access Journals (Sweden)

    Porter James E

    2005-08-01

    Full Text Available Abstract Background Interstitial cystitis (IC is a debilitating disease characterized by chronic inflammation of the urinary bladder, yet specific cellular mechanisms of inflammation in IC are largely unknown. Multiple lines of evidence suggest that β-adrenergic receptor (AR signaling is increased in the inflamed urothelium, however the precise effects of these urothelial cell signals have not been studied. In order to better elucidate the AR signaling mechanisms of inflammation associated with IC, we have examined the effects of β-AR stimulation in an immortalized human urothelial cell line (UROtsa. For these studies, UROtsa cells were treated with effective concentrations of the selective β-AR agonist isoproterenol, in the absence or presence of selective inhibitors of protein kinase A (PKA. Cell lysates were analyzed by radioimmunoassay for generation of cAMP or by Western blotting for induction of protein products associated with inflammatory responses. Results Radioligand binding demonstrated the presence of β-ARs on human urothelial UROtsa cell membranes. Stimulating UROtsa cells with isoproterenol led to concentration-dependent increases of cAMP production that could be inhibited by pretreatment with a blocking concentration of the selective β-AR antagonist propranolol. In addition, isoproterenol activation of these same cells led to significant increases in the amount of phosphorylated extracellular signal-regulated kinase (pERK, inducible nitric oxide synthase (iNOS and the induced form of cyclooxygenase (COX-2 when compared to control. Moreover, preincubation of UROtsa cells with the selective PKA inhibitors H-89 or Rp-cAMPs did not diminish this isoproterenol mediated phosphorylation of ERK or production of iNOS and COX-2. Conclusion Functional β-ARs expressed on human urothelial UROtsa cell membranes increase the generation of cAMP and production of protein products associated with inflammation when activated by the selective

  19. Clinical and microbiological effects of a combined mechanic-antibiotic therapy in subjects with Actinobacillus actinomycetemcomitans-associated periodontitis.

    Science.gov (United States)

    Dannewitz, Bettina; Pohl, Sabine; Eickholz, Peter; Kim, Ti-Sun

    2007-06-01

    To evaluate the clinical and microbiological effects of a combined mechanic-antibiotic periodontal therapy in subjects that were tested positive for subgingival Actinobacillus actinomycetemcomitans (A.a.). The postoperative follow-up ranged from 12-115 months (average 39.2 months). This follow-up study analyzed the data of 53 subjects (37 females) aged from 16-59 years, who underwent systemic periodontal therapy with adjunctive systemic antibiotics between 1992-2001 and had their last re-examination including microbiological analysis done in 2003. The antibiotic regime was either amoxicillin/metronidazole or ciprofloxacine/metronidazole. During this study, A.a. was detected with two gene probe tests (IAI PadoTest 4.5 and DMDx/PathoTek) and cultivation on TSBV agar plates. The clinical situation was characterized with the help of pocket probing depths and subsequent categorization into three different groups ( or = 7 mm). After therapy, A.a. was detected with IAI PadoTest 4.5 in a magnitude between 3.0 x 10(3) up to 2.06 x 10(5) counts per specimen in 9 out of 53 subjects. Only two subjects tested positive for A.a. with the DMDx/PathoTek-assays and the agar cultivation. The clinical situation improved significantly in all subjects after systemic periodontal therapy. The treatment results remained stable during the course of the postoperative follow-up. Concerning the clinical data, no differences were found between the subjects that were tested positive and negative for A.a in the postoperative period.

  20. Experimental approach and modelling of the mechanical behaviour of graphite fuel elements subjected to compression pulses

    Directory of Open Access Journals (Sweden)

    Forquin P.

    2010-06-01

    Full Text Available Among the activities led by the Generation IV International Forum (GIF relative to the future nuclear systems, the improvement of recycling of fuel elements and their components is a major issue. One of the studied systems by the GIF is the graphite-moderated high-temperature gas cooled reactor (HTGR. The fuel elements are composed of fuel roads half-inch in diameter named compacts. The compacts contain spherical particles made of actinide kernels about 500 m in diameter coated with three layers of carbon and silicon carbide, each about 50 m thick, dispersed in a graphite matrix. Recycling of compacts requires first a separation of triso-particles from the graphite matrix and secondly, the separation of the triso-coating from the kernels. This aim may be achieved by using pulsed currents: the compacts are placed within a cell filled by water and exposed to high voltage between 200 – 500 kV and discharge currents from 10 to 20 kA during short laps of time (about 2 µs [1-2]. This repeated treatment leads to a progressive fragmentation of the graphite matrix and a disassembly of the compacts. In order to improve understanding of the fragmentation properties of compacts a series of quasi-static and dynamic experiments have been conducted with similar cylindrical samples containing 10% (volume fraction of SiC particles coated in a graphite matrix. First, quasi-static compression tests have been performed to identify the mechanical behaviour of the material at low strain-rates (Fig.1. The experiments reveal a complex elasto-visco-plastic behaviour before a brittle failure. The mechanical response is characterised by a low yield stress (about 1 MPa, a strong strain-hardening in the loading phase and marked hysteresis-loops during unloading-reloading stages. Brittle failure is observed for axial stress about 13 MPa. In parallel, a series of flexural tests have been performed with the aim to characterise the quasi-static tensile strength of the

  1. Application of CCG Sensors to a High-Temperature Structure Subjected to Thermo-Mechanical Load

    Science.gov (United States)

    Xie, Weihua; Meng, Songhe; Jin, Hua; Du, Chong; Wang, Libin; Peng, Tao; Scarpa, Fabrizio; Xu, Chenghai

    2016-01-01

    This paper presents a simple methodology to perform a high temperature coupled thermo-mechanical test using ultra-high temperature ceramic material specimens (UHTCs), which are equipped with chemical composition gratings sensors (CCGs). The methodology also considers the presence of coupled loading within the response provided by the CCG sensors. The theoretical strain of the UHTCs specimens calculated with this technique shows a maximum relative error of 2.15% between the analytical and experimental data. To further verify the validity of the results from the tests, a Finite Element (FE) model has been developed to simulate the temperature, stress and strain fields within the UHTC structure equipped with the CCG. The results show that the compressive stress exceeds the material strength at the bonding area, and this originates a failure by fracture of the supporting structure in the hot environment. The results related to the strain fields show that the relative error with the experimental data decrease with an increase of temperature. The relative error is less than 15% when the temperature is higher than 200 °C, and only 6.71% at 695 °C. PMID:27754356

  2. Application of CCG Sensors to a High-Temperature Structure Subjected to Thermo-Mechanical Load

    Directory of Open Access Journals (Sweden)

    Weihua Xie

    2016-10-01

    Full Text Available This paper presents a simple methodology to perform a high temperature coupled thermo-mechanical test using ultra-high temperature ceramic material specimens (UHTCs, which are equipped with chemical composition gratings sensors (CCGs. The methodology also considers the presence of coupled loading within the response provided by the CCG sensors. The theoretical strain of the UHTCs specimens calculated with this technique shows a maximum relative error of 2.15% between the analytical and experimental data. To further verify the validity of the results from the tests, a Finite Element (FE model has been developed to simulate the temperature, stress and strain fields within the UHTC structure equipped with the CCG. The results show that the compressive stress exceeds the material strength at the bonding area, and this originates a failure by fracture of the supporting structure in the hot environment. The results related to the strain fields show that the relative error with the experimental data decrease with an increase of temperature. The relative error is less than 15% when the temperature is higher than 200 °C, and only 6.71% at 695 °C.

  3. Mechanical strength of bone allografts subjected to chemical sterilization and other terminal processing methods.

    Science.gov (United States)

    Mikhael, Mark M; Huddleston, Paul M; Zobitz, Mark E; Chen, Quingshan; Zhao, Kristin D; An, Kai-Nan

    2008-09-18

    Infectious disease transmission through the use of human donor allografts can be a catastrophic complication in an otherwise straightforward surgical procedure. The use of bone allograft in reconstructive orthopedic surgeries is increasing, yet severe complications, including death, can result if the transplanted tissues transmit a communicable disease to the tissue recipient. The BioCleanse tissue sterilization process is a fully automated, low-temperature chemical sterilization process that renders allograft tissue sterile. The purpose of this study was to evaluate the effect of a chemical tissue sterilization process on the mechanical strength of cortical bone allografts prior to implantation. Cylindrical cortical bone specimens were harvested from seven human cadaver donors and treated either by: chemical sterilization alone; chemical sterilization and terminal sterilization by gamma irradiation; chemical sterilization, lyophilization, terminal sterilization by STERRAD and rehydration; or untreated. The specimens were tested to failure in axial compression, diametral compression, shear, or bending. There were no significant differences in ultimate stress, strain, or fracture energy between the chemically sterilized and control groups in any of the testing modes.

  4. A dynamic pattern of mechanical stimulation promotes ossification in avian embryonic long bones.

    Science.gov (United States)

    Nowlan, Niamh C; Murphy, Paula; Prendergast, Patrick J

    2008-01-01

    We have performed a set of finite element analyses of embryonic chick hindlimb skeletal rudiments at several time points during development, around the time of initial bone formation. Using optical projection tomography, we created anatomically accurate rudiment and muscle morphologies for each stage. The changes in pattern and magnitude of biophysical stimuli (such as stress, strain, hydrostatic pressure and fluid flow) were computed, and were found to transform as bone formation proceeded in the rudiment. For each biophysical stimulus, a single concentration of the stimulus was predicted at the mid-diaphysis some time before initial bone formation begins. Then, several hours before ossification, two concentrations of the stimuli were predicted distal and proximal to the prospective bone collar. Once bone formation had begun, high concentrations of the stimuli were maintained proximal and distal to the bone collar. We propose the hypothesis that patterns of biophysical stimuli resulting from mechanical loading due to muscle contractions initiate and propagate ossification in avian embryonic long bones, whereby a region of the perichondrium experiences a period of time under high cyclic stimulus levels, promoting chondrocyte hypertrophy at the core and prompting bone collar formation some hours later.

  5. Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory

    National Research Council Canada - National Science Library

    Censor, Nitzan; Cohen, Leonardo G

    2011-01-01

    .... Repetitive transcranial magnetic stimulation (rTMS), a safe non‐invasive brain stimulation technique, enables the study of the functional role of specific cortical areas by evaluating the behavioural consequences of selective modulation of activity...

  6. Elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation.

    Science.gov (United States)

    Li, Yan; Deng, Jianxin; Zhou, Jun; Li, Xueen

    2016-11-01

    Corresponding to pre-puncture and post-puncture insertion, elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation are investigated, respectively. Elastic mechanical properties in pre-puncture are investigated through pre-puncture needle insertion experiments using whole porcine brains. A linear polynomial and a second order polynomial are fitted to the average insertion force in pre-puncture. The Young's modulus in pre-puncture is calculated from the slope of the two fittings. Viscoelastic mechanical properties of brain tissues in post-puncture insertion are investigated through indentation stress relaxation tests for six interested regions along a planned trajectory. A linear viscoelastic model with a Prony series approximation is fitted to the average load trace of each region using Boltzmann hereditary integral. Shear relaxation moduli of each region are calculated using the parameters of the Prony series approximation. The results show that, in pre-puncture insertion, needle force almost increases linearly with needle displacement. Both fitting lines can perfectly fit the average insertion force. The Young's moduli calculated from the slope of the two fittings are worthy of trust to model linearly or nonlinearly instantaneous elastic responses of brain tissues, respectively. In post-puncture insertion, both region and time significantly affect the viscoelastic behaviors. Six tested regions can be classified into three categories in stiffness. Shear relaxation moduli decay dramatically in short time scales but equilibrium is never truly achieved. The regional and temporal viscoelastic mechanical properties in post-puncture insertion are valuable for guiding probe insertion into each region on the implanting trajectory.

  7. The effects of endocrine and mechanical stimulation on stage I lactogenesis in bovine mammary epithelial cells.

    Science.gov (United States)

    Stiening, C M; Hoying, J B; Abdallah, M B; Hoying, A M; Pandey, R; Greer, K; Collier, R J

    2008-03-01

    The study objective was to evaluate the effect of endocrine and mechanical (gel release) signaling on bovine mammary epithelial cell ultrastructure and gene expression. Cultures receiving only one stimulus demonstrated partially differentiated ultrastructure, which included abundant polysomes, limited rough endoplasmic reticulum, and absence of secretory products, whereas the 2 stimuli together induced a more complete lactogenic phenotype that included increased rough endoplasmic reticulum, abundant lipid droplets, and secretory vesicles containing casein micelles. The structural data indicated that although synthesis of milk components was initiated, the copious synthesis and secretion associated with stage II lactogenesis was not evident. Microarray analysis revealed that both prolactin and gel release independently regulated several genes linked to a wide array of cellular activities. In combination, they regulated fewer genes targeted to lactogenesis. Genes regulated by the combination treatment included claudin 7, multiple caseins, xanthine oxidoreductase, and several protein synthesis, packaging, and transport genes. Genes related to structural activity including keratin 15 (morphogenesis), alpha-spectrin (cell shape via actin cytoskeleton), and chitinase-like protein 1 (tissue remodeling) were up-regulated by the combination treatment as was the transcription factor Kruppel-like factor 2 (KLF-2). However, Snail 2, which down-regulates and inhibits tight junction components, was repressed in response to the combination treatment. These results suggest coordination between endocrine and physical signals at the genomic level that produces a more specific and targeted transcriptional response associated with stage I lactogenesis. A molecular pathway analysis of the differentially expressed genes revealed that genes regulating cell signaling were linked to those regulating cell structure and adhesion.

  8. THE STIMULATING MECHANISMS OF REGIONAL ECONOMIC ACTIVITY IN SPAIN: LESSOUS FOR RUSSIA

    Directory of Open Access Journals (Sweden)

    K. S. Seredinskaya

    2017-01-01

    Full Text Available Spain is a country that traditionally suffers a lot from high level of regional disparities. From the end of XX century Spanish government has taken different measures to smooth them. For example, the state of autonomies was established, statutes were approved for every region, more powers were transferred to regional authorities. There are several institutions in Spain that increase the efficiency of cooperation between different levels of authorities and between autonomies, such as conference of the presidents, sectoral conferences, agreements on cooperation and bilateral commissions. Activity of these mechanisms is of a great interest for the author. The author tries to find the ways to modernize Russian regional policy using Spanish experience, considering its pros and cons. Undoubtedly it is impossible to copy other countries practice as Russia and Spain differ a lot, for example, in size, population, the level of socialeconomic development and the supply of mineral resources. Still there is something in common, like high level of regional disparities and amount of authorities the territories obtain. Even though Spain is a unitary state, its autonomies are quite independent. Territorial status of the country is a hybrid between unitary and federative state. Its institutional structure of regional policy is pretty diversified. So both these aspects are worth considering. Regional policy is one the most important directions of the state activity in Russia, because of its extensive territories. Today Russia has to face a number of regional challenges and regional policy cannot cope with them. The growing territorial polarization slow down the development of the whole country. It is useful to analyze foreign institutions, which solve regional problems in the other states, to adapt their practice to the Russian realities. 

  9. Impact of short-term high-fat feeding and insulin-stimulated FGF21 levels in subjects with low birth weight and controls.

    Science.gov (United States)

    Vienberg, Sara G; Brøns, Charlotte; Nilsson, Emma; Astrup, Arne; Vaag, Allan; Andersen, Birgitte

    2012-07-01

    Fibroblast growth factor 21 (FGF21) is a metabolic factor involved in glucose and lipid metabolism. However, little is known about the physiological role of FGF21 during a dietary challenge in humans. Twenty healthy low birth weight (LBW) with known risk of type 2 diabetes and 26 control (normal birth weight (NBW)) young men were subjected to 5 days of high-fat (HF) overfeeding (+50%). Basal and clamp insulin-stimulated serum FGF21 levels were examined before and after the diet, and FGF21 mRNA expression was measured in muscle and fat biopsies respectively. Five days of HF overfeeding diet significantly (Pincreased fasting serum FGF21 levels in both the groups (Pinsulin infusion additionally increased serum FGF21 levels to a similar extent in both the groups. Basal mRNA expression of FGF21 in muscle was near the detection limit and not present in fat in both the groups before and after the dietary challenge. However, insulin significantly (Pincreased FGF21 mRNA in both muscle and fat in both the groups during both diets. Short-term HF overfeeding markedly increased serum FGF21 levels in healthy young men with and without LBW but failed to increase muscle or fat FGF21 mRNA levels. This suggests that the liver may be responsible for the rise of serum FGF21 levels during overfeeding. In contrast, the increase in serum FGF21 levels during insulin infusion may arise from increased transcription in muscle and fat. We speculate that increased serum FGF21 levels during HF overfeeding may be a compensatory response to increase fatty acid oxidation and energy expenditure.

  10. Role of the insula and vestibular system in patients with chronic subjective dizziness: An fMRI study using sound-evoked vestibular stimulation

    Directory of Open Access Journals (Sweden)

    Iole eIndovina

    2015-12-01

    Full Text Available Chronic subjective dizziness (CSD is a common vestibular disorder characterized by persistent non-vertiginous dizziness, unsteadiness, and heightened sensitivity to motion stimuli that may last for months to years after events that cause acute vestibular symptoms or disrupt balance. CSD is not associated with abnormalities of basic vestibular or oculomotor reflexes. Rather, it is thought to arise from persistent use of high-threat postural control strategies and greater reliance on visual cues for spatial orientation (i.e., visual dependence, long after triggering events resolve. Anxiety-related personality traits confer vulnerability to CSD. Anomalous interactions between the central vestibular system and neural structures related to anxiety may sustain it. Vestibular- and anxiety-related processes overlap in the brain, particularly in the insula and hippocampus. Alterations in activity and connectivity in these brain regions in response to vestibular stimuli may be the neural basis of CSD.We examined this hypothesis by comparing brain activity from 18 patients with CSD and 18 healthy controls measured by functional magnetic resonance imaging during loud short tone bursts, which are auditory stimuli that evoke robust vestibular responses. Relative to controls, patients with CSD showed reduced activations to sound-evoked vestibular stimulation in the parieto-insular vestibular cortex (PIVC including the posterior insula, and in the anterior insula, inferior frontal gyrus, hippocampus, and anterior cingulate cortex. Patients with CSD also showed altered connectivity between the anterior insula and PIVC, anterior insula and middle occipital cortex, hippocampus and PIVC, and anterior cingulate cortex and PIVC.We conclude that reduced activation in PIVC, hippocampus, anterior insula, inferior frontal gyrus, and anterior cingulate cortex, as well as connectivity changes among these regions, may be linked to long-term vestibular symptoms in patients

  11. Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: a placebo-controlled, double-blind 8-week intervention in obese subjects.

    Science.gov (United States)

    Belza, A; Frandsen, E; Kondrup, J

    2007-01-01

    A combination of tyrosine, capsaicin, catechines and caffeine may stimulate the sympathetic nervous system and promote satiety, lipolysis and thermogenesis. In addition, dietary calcium may increase fecal fat excretion. To investigate the acute and subchronic effect of a supplement containing the above mentioned agents or placebo taken t.i.d on thermogenesis, body fat loss and fecal fat excretion. In total, 80 overweight-obese subjects ((body mass index) 31.2+/-2.5 kg/m(2), mean+/-s.d.) underwent an initial 4-week hypocaloric diet (3.4 MJ/day). Those who lost>4% body weight were instructed to consume a hypocaloric diet (-1.3 MJ/day) and were randomized to receive either placebo (n=23) or bioactive supplement (n=57) in a double-blind, 8-week intervention. The thermogenic effect of the compound was tested at the first and last day of intervention, and blood pressure, heart rate, body weight and composition were assessed. Weight loss during the induction phase was 6.8+/-1.9 kg. At the first exposure the thermogenic effect of the bioactive supplement exceeded that of placebo by 87.3 kJ/4 h (95%CI: 50.9;123.7, P=0.005) and after 8 weeks this effect was sustained (85.5 kJ/4 h (47.6;123.4), P=0.03). Body fat mass decreased more in the supplement group by 0.9 kg (0.5; 1.3) compared with placebo (P<0.05). The bioactive supplement had no effect on fecal fat excretion, blood pressure or heart rate. The bioactive supplement increased 4-h thermogenesis by 90 kJ more than placebo, and the effect was maintained after 8 weeks and accompanied by a slight reduction in fat mass. These bioactive components may support weight maintenance after a hypocaloric diet.

  12. Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering.

    Science.gov (United States)

    Parvizi, Mojtaba; Bolhuis-Versteeg, Lydia A M; Poot, André A; Harmsen, Martin C

    2016-07-01

    Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-β1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-β1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well-aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre-differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-β1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3-D constructs for cartilage tissue engineering.

    Science.gov (United States)

    Hilz, Florian M; Ahrens, Philipp; Grad, Sibylle; Stoddart, Martin J; Dahmani, Chiheb; Wilken, Frauke L; Sauerschnig, Martin; Niemeyer, Philipp; Zwingmann, Jörn; Burgkart, Rainer; von Eisenhart-Rothe, Rüdiger; Südkamp, Norbert P; Weyh, Thomas; Imhoff, Andreas B; Alini, Mauro; Salzmann, Gian M

    2014-02-01

    Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production. © 2013 Wiley Periodicals, Inc.

  14. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    Science.gov (United States)

    Soman, N. R.; Marsh, J. N.; Lanza, G. M.; Wickline, S. A.

    2008-05-01

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

  15. The effect of mechanical stimulation on the maturation of TDSCs-poly(L-lactide-co-e-caprolactone)/collagen scaffold constructs for tendon tissue engineering.

    Science.gov (United States)

    Xu, Yuan; Dong, Shiwu; Zhou, Qiang; Mo, Xiumei; Song, Lei; Hou, Tianyong; Wu, Jinglei; Li, Songtao; Li, Yudong; Li, Pei; Gan, Yibo; Xu, Jianzhong

    2014-03-01

    Mechanical stimulation plays an important role in the development and remodeling of tendons. Tendon-derived stem cells (TDSCs) are an attractive cell source for tendon injury and tendon tissue engineering. However, these cells have not yet been fully explored for tendon tissue engineering application, and there is also lack of understanding to the effect of mechanical stimulation on the maturation of TDSCs-scaffold construct for tendon tissue engineering. In this study, we assessed the efficacy of TDSCs in a poly(L-lactide-co-ε-caprolactone)/collagen (P(LLA-CL)/Col) scaffold under mechanical stimulation for tendon tissue engineering both in vitro and in vivo, and evaluated the utility of the transplanted TDSCs-scaffold construct to promote rabbit patellar tendon defect regeneration. TDSCs displayed good proliferation and positive expressed tendon-related extracellular matrix (ECM) genes and proteins under mechanical stimulation in vitro. After implanting into the nude mice, the fluorescence imaging indicated that TDSCs had long-term survival, and the macroscopic evaluation, histology and immunohistochemistry examinations showed high-quality neo-tendon formation under mechanical stimulation in vivo. Furthermore, the histology, immunohistochemistry, collagen content assay and biomechanical testing data indicated that dynamically cultured TDSCs-scaffold construct could significantly contributed to tendon regeneration in a rabbit patellar tendon window defect model. TDSCs have significant potential to be used as seeded cells in the development of tissue-engineered tendons, which can be successfully fabricated through seeding of TDSCs in a P(LLA-CL)/Col scaffold followed by mechanical stimulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat.

    Science.gov (United States)

    Bechara, Ranya G; Lyne, Ronan; Kelly, Áine M

    2014-12-15

    Exercise-induced improvements in learning are associated with neurotrophic and neurogenic changes in the dentate gyrus, but the intracellular signalling mechanisms that may mediate these improvements remain unknown. In the current study we investigate the effects of one week of forced exercise on spatial memory and analyse in parallel BDNF-stimulated signalling pathways in cells of the dentate gyrus. Additionally, we test whether a single intracerebroventricular (i.c.v.) injection of BDNF can mimic the observed cognitive and signalling changes. Male Wistar rats were assigned to exercised and sedentary groups and tested in a spatial task post-exercise. Tissue from the dentate gyrus was assessed for expression and release of BDNF, and for changes in expression and activation of TrkB, ERK and synapsin-1. In a separate set of experiments, male Wistar rats received a single i.c.v. injection of BDNF and were then tested in the same spatial learning task. Exercised and BDNF-treated (but not control) rats could successfully complete an object displacement task that tests spatial learning. Exercised rats and BDNF-treated rats displayed increases BDNF expression and ERK1 activation, while exercised rats showed increases in cell division, stimulated BDNF release, TrkB activation, and synapsin-1 expression in the dentate gyrus. We conclude that exercise-induced increases in BDNF in the dentate gyrus are sufficient to cause improvements in spatial memory by activating signalling cascades that enhance synaptic transmission in the hippocampus. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Mechanisms involved in abdominal nociception induced by either TRPV1 or TRPA1 stimulation of rat peritoneum.

    Science.gov (United States)

    Trevisan, Gabriela; Rossato, Mateus F; Hoffmeister, Carin; Oliveira, Sara M; Silva, Cássia R; Matheus, Filipe C; Mello, Gláucia C; Antunes, Edson; Prediger, Rui D S; Ferreira, Juliano

    2013-08-15

    Abdominal pain is a frequent symptom of peritoneal cavity irritation, but little is known about the role of the receptors for irritant substances, transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), in this painful condition. Thus, we investigated the abdominal nociception caused by peritoneal stimulation with TRPV1 (capsaicin) and TRPA1 (allyl isothiocyanate, AITC) agonists and their mechanisms in rats. The intraperitoneal (i.p.) injection of either capsaicin or AITC (0.03-10 mg/kg) induced short-term (up to 20 min) and dose-dependent abdominal nociception, and also produced c-fos expression in spinal afferents of the dorsal horn. TRPV1 antagonism prevented (94 ± 4% inhibition) nociception induced by capsaicin but not by AITC. In contrast, the TRPA1 antagonism almost abolished AITC-induced nociception (95 ± 2% inhibition) without altering the capsaicin response. Moreover, nociception induced by either capsaicin or AITC was reduced by the desensitisation of TRPV1-positive sensory fibres with resiniferatoxin (73 ± 18 and 76 ± 15% inhibitions, respectively) and by the NK1 receptor antagonist aprepitant (56 ± 5 and 53 ± 8% inhibitions, respectively). Likewise, the i.p. injections of capsaicin or AITC increased the content of substance P in the peritoneal fluid. Nevertheless, neither the mast cell membrane stabiliser cromoglycate, nor the H1 antagonist promethazine, nor depletion of peritoneal macrophages affected abdominal nociception induced either by capsaicin or AITC. Accordingly, neither capsaicin nor AITC increased the histamine content in the peritoneal fluid or provoked peritoneal mast cell degranulation in vitro. Collectively, our findings suggest that TRPV1 and TRPA1 stimulation in the peritoneum produces abdominal nociception that is mediated by sensory fibres activation. © 2013 Elsevier B.V. All rights reserved.

  18. Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

    Science.gov (United States)

    Zhang, Yong; Li, Fenxia; Liu, Fu-Qiang; Chu, Chao; Wang, Yang; Wang, Dan; Guo, Tong-Shuai; Wang, Jun-Kui; Guan, Gong-Chang; Ren, Ke-Yu; Mu, Jian-Jun

    2016-05-26

    Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years) were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl), then a high-salt diet for seven days (18 g/day). The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA). High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL) than during the low-salt diet (172.9 ± 8.9 pg/mL). The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

  19. MECHANISM FOR DESIGNING COMPETENCE-ORIENTED TASKS IN VARIOUS ACADEMIC SUBJECTS AND REQUIREMENTS FOR ITS IMPLEMENTATION IN HIGHER EDUCATIONAL ESTABLISHMENTS

    Directory of Open Access Journals (Sweden)

    Natalya M. Zhukova

    2015-01-01

    Full Text Available The research objective is to develop a mechanism for designing competence-oriented tasks in various academic subjects and requirements for its implementation in higher educational establishments. Methods. The authors conducted a theoretical analysis of philosophical, psychological and pedagogical literature sources on the research issues to implement the objectives of the study; Russian and foreign educational experience on the use of study tasks in the study process is studied and summarized; educational and syllabus documentation and training materials are analyzed (syllabi, textbooks, manuals, task and exercise books, etc.; normative documents are studied (State Educational Standards, Federal State Educational Standards, Main Syllabi, curricula, instructional acts, etc.. Empirical research methods involve observation, testing, questioning, modeling, peer review, pedagogical experiment and statistical interpretation of the study results. The study was carried out from 2007 to 2012 in the Engineering-Pedagogical Faculty of Moscow State Agroengineering Goryachkin University. 240 students were engaged in the pedagogical experiment. The following Moscow colleges provided facilities for the peer review of the list and solution frequency of vocational education tasks by secondary vocational school teachers: Colleges of Civil Engineering No 1 and No 12, Small Business College No 48, Polytechnic College No 13, Printing and Publishing College No 56, and Electromechanical College No 55. Results. The research findings demonstrate that the competence-oriented tasks are shown as an integrative didactic unit of professional competence development. Its functions, classification, and structural components are given. The mechanism of designing competence-oriented tasks in various academic subjects is developed and tested. The proposed mechanism is an invariant for academic and teaching staff of educational establishments at all levels of professional

  20. Facilitation of corticospinal excitability by virtual reality exercise following anodal transcranial direct current stimulation in healthy volunteers and subacute stroke subjects

    OpenAIRE

    Kim, Yeun Joon; Ku, Jeonghun; Cho, Sangwoo; Kim, Hyun Jung; Cho, Yun Kyung; Lim, Teo; Kang, Youn Joo

    2014-01-01

    Background There is growing evidence that the combination of non-invasive brain stimulation and motor skill training is an effective new treatment option in neurorehabilitation. We investigated the beneficial effects of the application of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) motor training. Methods In total, 15 healthy, right-handed volunteers and 15 patients with stroke in the subacute stage participated. Four different conditions (A: active wrist...

  1. Cerebellar Fastigial Nucleus Electrical Stimulation Alleviates Depressive-Like Behaviors in Post-Stroke Depression Rat Model and Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2017-03-01

    Full Text Available Objective: To identify the molecular mechanism of post-stroke depression (PSD, and observe the therapeutic effects of cerebellar fastigial nucleus electrical stimulation (FNS on the behaviors and regional cerebral blood flow (rCBF in a PSD rat model. Methods: Healthy SD rats were randomly divided into four groups (sham, stroke, post-stroke depress and FNS group. Sham group (n = 6 underwent sham operation. The other three groups (n = 6*3 underwent MCAO. Rats were examined twice a week in open filed test. Moreover, neuroprotective effect on cerebellar Purkinje cells and expression of cytokines in hippocampal tissue were examined. Results: The PSD group showed a significant weight loss, decreased consumption of sucrose water, reduced rearing and locomotor activities. The FNS significantly alleviates the body weight loss and sucrose preference, locomotor and rearing activities. The bilateral rCBF was also restored after FNS treatment. Moreover, FNS improved the neuroprotection via suppressing apoptosis of cerebellar Purkinje cells. And the inflammatory cytokines mRNA level in hippocampus was significantly decreased. Conclusion: FNS treatment alleviates depressive-like behaviors and rCBF in PSD rats model, which could be attributed to its ability to protect cerebellar Purkinje cells and decrease the mRNA level of inflammatory cytokines.

  2. Mechanical bone growth stimulation by magnetic fibre networks obtained through a competent finite element technique.

    Science.gov (United States)

    Bosbach, Wolfram A

    2017-09-11

    Fibre networks combined with a matrix material in their void phase make the design of novel and smart composite materials possible. Their application is of great interest in the field of advanced paper or as bioactive tissue engineering scaffolds. In the present study, we analyse the mechanical interaction between metallic fibre networks under magnetic actuation and a matrix material. Experimentally validated FE models are combined for that purpose in one joint simulation. High performance computing facilities are used. The resulting strain in the composite's matrix is not uniform across the sample volume. Instead we show that boundary conditions and proximity to the fibre structure strongly influence the local strain magnitude. An analytical model of local strain magnitude is derived. The strain magnitude of 0.001 which is of particular interest for bone growth stimulation is achievable by this assembly. In light of these findings, the investigated composite structure is suitable for creating and for regulating contactless a stress field which is to be imposed on the matrix material. Topics for future research will be the advanced modelling of the biological components and the potential medical utilisation.

  3. Paired associative stimulation of left and right human motor cortex shapes interhemispheric motor inhibition based on a Hebbian mechanism.

    Science.gov (United States)

    Rizzo, V; Siebner, H S; Morgante, F; Mastroeni, C; Girlanda, P; Quartarone, A

    2009-04-01

    This study was designed to examine whether corticocortical paired associative stimulation (cc-PAS) can modulate interhemispheric inhibition (IHI) in the human brain. Twelve healthy right-handed volunteers received 90 paired transcranial stimuli to the right and left primary motor hand area (M1(HAND)) at an interstimulus interval (ISI) of 8 ms. Left-to-right cc-PAS (first pulse given to left M1(HAND)) attenuated left-to-right IHI for one hour after cc-PAS. Left-to-right cc-PAS also increased corticospinal excitability in the conditioned right M1(HAND). These effects were not seen in an asymptomatic individual with callosal agenesis. Additional experiments showed no changes in left-to-right IHI or corticospinal excitability when left-to-right cc-PAS was given at an ISI of 1 ms or at multiple ISIs in random order. At the behavioral level, left-to-right cc-PAS speeded responses with the left but not right index finger during a simple reaction time task. Right-to-left cc-PAS (first pulse given to right M1(HAND)) reduced right-to-left IHI without increasing corticospinal excitability in left M1(HAND). These results provide a proof of principle that cc-PAS can induce associative plasticity in connections between the targeted cortical areas. The efficacy of cc-PAS to induce lasting changes in excitability depends on the exact timing of the stimulus pairs suggesting an underlying Hebbian mechanism.

  4. Mechanical-tactile stimulation (MTS) intervention in a neonatal stress model improves long-term outcomes on bone.

    Science.gov (United States)

    Haley, S; O'Grady, S; Gulliver, K; Bowman, B; Baldassarre, R; Miller, S; Lane, R H; Moyer-Mileur, L J

    2011-09-01

    Neonatal stress impairs postnatal bone mineralization. Evidence suggests that mechanical tactile stimulation (MTS) in early life decreases stress hormones and improves bone mineralization. Insulin-like growth factor (IGF1) is impacted by stress and essential to bone development. We hypothesized that MTS administered during neonatal stress would improve bone phenotype in later life. We also predicted an increase in bone specific mRNA expression of IGF1 related pathways. Neonatal stress (STRESS) and MTS (STRESS+10 min of MTS) were given from D6 to D10 of rat life and tissue was harvested on D60 of life. Dual energy x-ray absorptiometry (DXA), bone morphometry, serum osteocalcin, type I procollagen N-terminal propeptide (PINP), tartrate-resistant acid phosphatase (TRAP), and bone and liver mRNA levels of IGF1, IGF1 receptor (IGF1R), and growth hormone receptor (GHR) were measured. Stress resulted in reduced bone area and bone mineral content (BMC) compared to naive control (CTL). MTS intervention increased BMC and tibial growth plate width compared to STRESS. MTS also resulted in higher osteocalcin, and, in males, lower TRAP (pMTS resulted in three-fold, two-fold, and six-fold higher bone specific IGF1, IGF1R, and GHR, respectively (p ≤ 0.001) compared to STRESS. MTS in early postnatal life improves long-term bone mineralization. IGF1 and related pathways may explain improved BMC.

  5. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

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    Hui Zhou

    2015-07-01

    Full Text Available Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

  6. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation.

    Science.gov (United States)

    Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

    2015-07-16

    Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

  7. Effects of mechanical stimulating treatment on self-organization phenomena of materials; Kikaiteki reiki shori. Zairyo no jiko soshikia gensho ni oyobosu sono koka

    Energy Technology Data Exchange (ETDEWEB)

    Hida, M. [Okayama University, Okayama (Japan). Faculty of Mechanical Engineering

    1999-03-31

    The atoms and atom clusters around dislocation cores in crystals or surface layer deformed by mechanical energy are locally excited so as to give rise some chemical reactions and to self-organize their products into a kind of Spatial-Temporal Pattern Formation as a dissipative structure. A famous coupling phenomenon between mechanical and chemical process in solid materials must have been mechanical alloing. This report explains that various mechano-chemical treatments are powerfull method for entraining the solid system into non-equilibrium states and interesting phenomena stimulated by the mechanical self-catalysis reaction causing self-organization. (author)

  8. Electrical stimulation of the substantia nigra reticulata : Detection of neuronal extracellular GABA in the ventromedial thalamus and its regulatory mechanism using microdialysis in awake rats

    NARCIS (Netherlands)

    Timmerman, W; Westerink, B.H.C.

    A combination of electrical stimulation and microdialysis was used to study the nigrothalamic gamma aminobutyric acid (GABA)ergic system and its regulatory mechanisms in awake rats. Extracellular GABA levels in the ventromedial nucleus of the thalamus were detected in S-min fractions collected

  9. Anti-inflammatory mechanism of galangin in lipopolysaccharide-stimulated microglia: Critical role of PPAR-γ signaling pathway.

    Science.gov (United States)

    Choi, Min-Ji; Lee, Eun-Jung; Park, Jin-Sun; Kim, Su-Nam; Park, Eun-Mi; Kim, Hee-Sun

    2017-11-15

    Since microglia-associated neuroinflammation plays a pivotal role in the progression of neurodegenerative diseases, controlling microglial activation has been suggested as a potential therapeutic strategy. Here, we investigated the anti-inflammatory effects of galangin (3,5,7-trihydroxyflavone) in microglia and analyzed the underlying molecular mechanisms. Galangin inhibited the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines and enhanced the expression of anti-inflammatory interleukin (IL)-10 in lipopolysaccharide (LPS)-stimulated BV2 microglia. Galangin also suppressed microglial activation and the expression of pro-inflammatory markers in LPS-injected mouse brains. The results of mechanistic studies have shown that galangin inhibited LPS-induced phosphorylation of p38 mitogen activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor (NF)-κB activity. On the contrary, galangin increased the activity of transcription factors, such as nuclear factor-E2-related factor 2 (Nrf2), cAMP response element-binding protein (CREB), and peroxisome proliferator-activated receptor (PPAR)-γ, known to play an anti-inflammatory role. In addition, galangin showed antioxidant effects by suppressing the expression of NADPH oxidase subunits p47phox and gp91phox, and by enhancing hemeoxygenase-1. We then investigated whether PPAR-γ was involved in the anti-inflammatory function of galangin. Pretreatment with a PPAR-γ antagonist or siRNA significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-α, nitric oxide (NO), and IL-6 in LPS-stimulated microglia. Moreover, the PPAR-γ antagonist reversed the effects of galangin on NF-κB, Nrf2, and CREB. Altogether, our data suggest that PPAR-γ plays a key role in mediating the anti-inflammatory effects of galangin by modulating the NF-κB and Nrf2/CREB signaling pathways

  10. Forecast of reliability for mechanical components subjected to wearing; Pronostico de la fiabilidad de componentes mecanicos sometidos a desgaste

    Energy Technology Data Exchange (ETDEWEB)

    Angulo-Zevallos, J.; Castellote-Varona, C.; Alanbari, M.

    2010-07-01

    Generally, improving quality and price of products, obtaining a complete customer satisfaction and achieving excellence in all the processes are some of the challenges currently set up by every company. To do this, knowing frequently the reliability of some component is necessary. To achieve this goal, a research, that contributes with clear ideas and offers a methodology for the assessment of the parameters involved in the reliability calculation, becomes necessary. A parameter closely related to this concept is the probability of product failure depending on the operating time. It is known that mechanical components fail by: creep, fatigue, wear, corrosion, etc. This article proposes a methodology for finding the reliability of a component subject to wear, such as brake pads, grinding wheels, brake linings of clutch discs, etc. (Author)

  11. Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2016-05-01

    Full Text Available Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl, then a high-salt diet for seven days (18 g/day. The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA. High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL than during the low-salt diet (172.9 ± 8.9 pg/mL. The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01. A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

  12. Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation.

    Science.gov (United States)

    Wu, Shaohua; Wang, Ying; Streubel, Philipp N; Duan, Bin

    2017-10-15

    synergize the multiple cell interaction and mechanical stimulation for promoting tendon regeneration. Tendon grafts are essential for the treatment of various tendon-related conditions due to the inherently poor healing capacity of native tendon tissues. In this study, we combined electrospun nanofiber yarns with textile manufacturing strategies to fabricate nanofibrous woven biotextiles with hierarchical features, aligned fibrous topography, and sufficient mechanical properties as tendon tissue engineered scaffolds. Comparing to traditional electrospun random or aligned meshes, our novel nanofibrous woven fabrics possess strong tensile and suture-retention strengths and larger pore size. We also demonstrated that the incorporation of tendon cells and vascular cells promoted the tenogenic differentiation of the engineered tendon constructs, especially under dynamic stretch. This study not only presents a novel tissue engineered tendon scaffold fabrication technique but also provides a useful strategy to promote tendon differentiation and regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. FRACTURE MECHANICS UNCERTAINTY ANALYSIS IN THE RELIABILITY ASSESSMENT OF THE REACTOR PRESSURE VESSEL: (2D SUBJECTED TO INTERNAL PRESSURE

    Directory of Open Access Journals (Sweden)

    Entin Hartini

    2016-06-01

    Full Text Available ABSTRACT FRACTURE MECHANICS UNCERTAINTY ANALYSIS IN THE RELIABILITY ASSESSMENT OF THE REACTOR PRESSURE VESSEL: (2D SUBJECTED TO INTERNAL PRESSURE. The reactor pressure vessel (RPV is a pressure boundary in the PWR type reactor which serves to confine radioactive material during chain reaction process. The integrity of the RPV must be guaranteed either  in a normal operation or accident conditions. In analyzing the integrity of RPV, especially related to the crack behavior which can introduce break to the reactor pressure vessel, a fracture mechanic approach should be taken for this assessment. The uncertainty of input used in the assessment, such as mechanical properties and physical environment, becomes a reason that the assessment is not sufficient if it is perfomed only by deterministic approach. Therefore, the uncertainty approach should be applied. The aim of this study is to analize the uncertainty of fracture mechanics calculations in evaluating the reliability of PWR`s reactor pressure vessel. Random character of input quantity was generated using probabilistic principles and theories. Fracture mechanics analysis is solved by Finite Element Method (FEM with  MSC MARC software, while uncertainty input analysis is done based on probability density function with Latin Hypercube Sampling (LHS using python script. The output of MSC MARC is a J-integral value, which is converted into stress intensity factor for evaluating the reliability of RPV’s 2D. From the result of the calculation, it can be concluded that the SIF from  probabilistic method, reached the limit value of  fracture toughness earlier than SIF from  deterministic method.  The SIF generated by the probabilistic method is 105.240 MPa m0.5. Meanwhile, the SIF generated by deterministic method is 100.876 MPa m0.5. Keywords: Uncertainty analysis, fracture mechanics, LHS, FEM, reactor pressure vessels   ABSTRAK ANALISIS KETIDAKPASTIAN FRACTURE MECHANIC PADA EVALUASI KEANDALAN

  14. Peripheral noxious stimulation reduces withdrawal threshold to mechanical stimuli after spinal cord injury: Role of tumor necrosis factor alpha and apoptosis

    Science.gov (United States)

    Woller, Sarah A.; Huie, J. Russell; Hartman, John J.; Hook, Michelle A.; Miranda, Rajesh C.; Huang, Yung-Jen; Ferguson, Adam R.; Grau, James W.

    2014-01-01

    We previously showed that peripheral noxious input after spinal cord injury (SCI) inhibits beneficial spinal plasticity and impairs recovery of locomotor and bladder functions. These observations suggest that noxious input may similarly affect the development and maintenance of chronic neuropathic pain, an important consequence of SCI. In adult rats with a moderate contusion SCI, we investigated the effect of noxious tail stimulation, administered one day after SCI, on mechanical withdrawal responses to von Frey stimuli from 1 to 28 days, post-treatment. In addition, because the pro-inflammatory cytokine tumor necrosis factor α (TNFα) is implicated in numerous injury-induced processes including pain hypersensitivity, we assessed the temporal and spatial expression of TNFα, TNF receptors, and several downstream signaling targets after stimulation. Our results showed that unlike sham surgery or SCI only, nociceptive stimulation following SCI induced mechanical sensitivity by 24 hours. These behavioral changes were accompanied by increased expression of TNFα. Cellular assessments of downstream targets of TNFα revealed that nociceptive stimulation increased the expression of caspase 8 and the active subunit (12 kDa) of caspase 3 at a time point consistent with the onset of mechanical allodynia, indicative of active apoptosis. In addition, immunohistochemical analysis revealed distinct morphological signs of apoptosis in neurons and microglia at 24 hours post-stimulation. Interestingly, expression of the inflammatory mediator NFκB was unaltered by nociceptive stimulation. These results suggest that noxious input caudal to the level of SCI can increase the onset and expression of behavioral responses indicative of pain, potentially involving TNFα signaling. PMID:25180012

  15. Psychopathological symptoms, defense mechanisms and time perspectives among subjects with alcohol dependence (AD) presenting different patterns of coping with stress.

    Science.gov (United States)

    Iwanicka, Katarzyna; Gerhant, Aneta; Olajossy, Marcin

    2017-01-01

    The problem of coping with stress is an important one in the context of development and persistence of alcohol dependence. In the literature to date very little attention has been paid to coping patterns construed as a configuration of specific coping styles, particularly as regards the functioning of addicted individuals. The aim of the study was to verify whether individuals with alcohol dependence characterized by different coping patterns differ with respect to the severity of psychopathological symptoms, defense mechanisms and time perspectives. Participants were given a battery of psychological tests-Coping Inventory for Stresfull Situations (CISS), Defense Style Questionnaire (DSQ 40), Syndrom Checklist (SCL-90) and Short Zimbardo Time Perspective Inventory (SZPTI-PL). The sample comprised 112 individuals with alcohol dependence, aged 20 to 63 years old, the average age was 37.86; 78 percent were men. There were identified three sub-groups of individuals characterized by a distinctive patterns of coping with stress -"emotional-avoidant", "task oriented" and a "mixed one". Individuals with the predominant emotional-avoidant coping pattern are characterized by significantly higher severity of psychopathological symptoms, less mature defense mechanisms and past time perspectives. Subjects reliant on task-oriented coping pattern were characterized by the highest level of adaptation and the most constructive way of functioning in the face of difficulties. It is worth regarding the examination of patterns of coping as an indispensable element of collecting medical history from alcohol dependent individuals.

  16. Protein characterization of a candidate mechanism SNP for Crohn's disease: the macrophage stimulating protein R689C substitution.

    Directory of Open Access Journals (Sweden)

    Natalia Gorlatova

    Full Text Available High throughput genome wide associations studies (GWAS are now identifying a large number of genome loci related to risk of common human disease. Each such locus presents a challenge in identifying the relevant underlying mechanism. Here we report the experimental characterization of a proposed causal single nucleotide polymorphism (SNP in a locus related to risk of Crohn's disease and ulcerative colitis. The SNP lies in the MST1 gene encoding Macrophage Stimulating Protein (MSP, and results in an R689C amino acid substitution within the β-chain of MSP (MSPβ. MSP binding to the RON receptor tyrosine kinase activates signaling pathways involved in the inflammatory response. We have purified wild-type and mutant MSPβ proteins and compared biochemical and biophysical properties that might impact the MSP/RON signaling pathway. Surface plasmon resonance (SPR binding studies showed that MSPβ R689C affinity to RON is approximately 10-fold lower than that of the wild-type MSPβ and differential scanning fluorimetry (DSF showed that the thermal stability of the mutant MSPβ was slightly lower than that of wild-type MSPβ, by 1.6 K. The substitution was found not to impair the specific Arg483-Val484 peptide bond cleavage by matriptase-1, required for MSP activation, and mass spectrometry of tryptic fragments of the mutated protein showed that the free thiol introduced by the R689C mutation did not form an aberrant disulfide bond. Together, the studies indicate that the missense SNP impairs MSP function by reducing its affinity to RON and perhaps through a secondary effect on in vivo concentration arising from reduced thermodynamic stability, resulting in down-regulation of the MSP/RON signaling pathway.

  17. Integrin - dependent mechanotransduction in mechanically stimulated human annulus fibrosus cells: evidence for an alternative mechanotransduction pathway operating with degeneration.

    Science.gov (United States)

    Gilbert, Hamish T J; Nagra, Navraj S; Freemont, Anthony J; Millward-Sadler, Sarah J; Hoyland, Judith A

    2013-01-01

    Intervertebral disc (IVD) cells derived from degenerate tissue respond aberrantly to mechanical stimuli, potentially due to altered mechanotransduction pathways. Elucidation of the altered, or alternative, mechanotransduction pathways operating with degeneration could yield novel targets for the treatment of IVD disease. Our aim here was to investigate the involvement of RGD-recognising integrins and associated signalling molecules in the response to cyclic tensile strain (CTS) of human annulus fibrosus (AF) cells derived from non-degenerate and degenerate IVDs. AF cells from non-degenerate and degenerate human IVDs were cyclically strained with and without function blocking RGD - peptides with 10% strain, 1.0 Hz for 20 minutes using a Flexercell® strain device. QRT-PCR and Western blotting were performed to analyse gene expression of type I collagen and ADAMTS -4, and phosphorylation of focal adhesion kinase (FAK), respectively. The response to 1.0 Hz CTS differed between the two groups of AF cells, with decreased ADAMTS -4 gene expression and decreased type I collagen gene expression post load in AF cells derived from non-degenerate and degenerate IVDs, respectively. Pre-treatment of non-degenerate AF cells with RGD peptides prevented the CTS-induced decrease in ADAMTS -4 gene expression, but caused an increase in expression at 24 hours, a response not observed in degenerate AF cells where RGD pre-treatment failed to inhibit the mechano-response. In addition, FAK phosphorylation increased in CTS stimulated AF cells derived from non-degenerate, but not degenerate IVDs, with RGD pre-treatment inhibiting the CTS - dependent increase in phosphorylated FAK. Our findings suggest that RGD -integrins are involved in the 1.0 Hz CTS - induced mechano-response observed in AF cells derived from non-degenerate, but not degenerate IVDs. This data supports our previous work, suggesting an alternative mechanotransduction pathway may be operating in degenerate AF cells.

  18. Integrin - dependent mechanotransduction in mechanically stimulated human annulus fibrosus cells: evidence for an alternative mechanotransduction pathway operating with degeneration.

    Directory of Open Access Journals (Sweden)

    Hamish T J Gilbert

    Full Text Available Intervertebral disc (IVD cells derived from degenerate tissue respond aberrantly to mechanical stimuli, potentially due to altered mechanotransduction pathways. Elucidation of the altered, or alternative, mechanotransduction pathways operating with degeneration could yield novel targets for the treatment of IVD disease. Our aim here was to investigate the involvement of RGD-recognising integrins and associated signalling molecules in the response to cyclic tensile strain (CTS of human annulus fibrosus (AF cells derived from non-degenerate and degenerate IVDs. AF cells from non-degenerate and degenerate human IVDs were cyclically strained with and without function blocking RGD - peptides with 10% strain, 1.0 Hz for 20 minutes using a Flexercell® strain device. QRT-PCR and Western blotting were performed to analyse gene expression of type I collagen and ADAMTS -4, and phosphorylation of focal adhesion kinase (FAK, respectively. The response to 1.0 Hz CTS differed between the two groups of AF cells, with decreased ADAMTS -4 gene expression and decreased type I collagen gene expression post load in AF cells derived from non-degenerate and degenerate IVDs, respectively. Pre-treatment of non-degenerate AF cells with RGD peptides prevented the CTS-induced decrease in ADAMTS -4 gene expression, but caused an increase in expression at 24 hours, a response not observed in degenerate AF cells where RGD pre-treatment failed to inhibit the mechano-response. In addition, FAK phosphorylation increased in CTS stimulated AF cells derived from non-degenerate, but not degenerate IVDs, with RGD pre-treatment inhibiting the CTS - dependent increase in phosphorylated FAK. Our findings suggest that RGD -integrins are involved in the 1.0 Hz CTS - induced mechano-response observed in AF cells derived from non-degenerate, but not degenerate IVDs. This data supports our previous work, suggesting an alternative mechanotransduction pathway may be operating in degenerate AF

  19. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

    Science.gov (United States)

    Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

    2016-01-01

    The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

  20. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion.

    Directory of Open Access Journals (Sweden)

    Nicolás M Kouyoumdzian

    Full Text Available The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP on organic cation transporters (OCTs expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T, ANP, dopamine (DA, D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects.

  1. Mechanical-tactile stimulation (MTS) during neonatal stress prevents hyperinsulinemia despite stress-induced adiposity in weanling rat pups.

    Science.gov (United States)

    Moyer-Mileur, Laurie J; Haley, Shannon; Gulliver, Kristina; Thomson, Anne; Slater, Hillarie; Barrett, Brett; Joss-Moore, Lisa A; Callaway, Christopher; McKnight, Robert A; Moore, Barry; Lane, Robert H

    2011-03-01

    Stress in early life negatively influences growth quality through perturbations in body composition including increased fat mass. At term (40 weeks) preterm infants have greater fat mass and abdominal visceral adipose tissue than term-born infants. Mechanical-tactile stimulation (MTS) attenuates the stress response in preterm infants and rodents. We tested the hypothesis that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent associated metabolic imbalances in rat pups. Pups received one of three treatments from postnatal days 5 to P9: Neonatal Stress (Stress; n=20) = painful stimulus and hypoxic/hyperoxic challenge during 60 min of maternal separation; MTS (n=20) = neonatal stress+10 min of MTS; or Control (n=20). Body weight, DXA whole body fat mass (g), MRI subcutaneous and visceral adipose tissue, and fasting adiponectin, leptin, glucose, insulin, and corticosterone were measured at weaning (P21). Stress and MTS weight gain (g/d) were accelerated following neonatal stress with greater fat mass, abdominal subcutaneous adipose tissue, serum adiponectin, leptin, and fasting glucose at weaning (P21). Male Stress and MTS pups had greater visceral adipose tissue depot. Male and female Stress pups were hyperinsulinemic. In summary, neonatal stress compromised body composition by increasing fat mass and abdominal subcutaneous adipose tissue depot, and in males, visceral adipose tissue depot. Importantly, MTS prevented hyperinsulinemia despite of stress-induced adiposity. We conclude that MTS during neonatal stress has the potential to minimize metabolic consequences associated with stress-driven perturbations in fat mass and abdominal adipose depots. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  2. Benefits of Repetitive Transcranial Magnetic Stimulation (rTMS for Spastic Subjects: Clinical, Functional, and Biomechanical Parameters for Lower Limb and Walking in Five Hemiparetic Patients

    Directory of Open Access Journals (Sweden)

    Luc Terreaux

    2014-01-01

    Full Text Available Introduction. Spasticity is a disabling symptom resulting from reorganization of spinal reflexes no longer inhibited by supraspinal control. Several studies have demonstrated interest in repetitive transcranial magnetic stimulation in spastic patients. We conducted a prospective, randomized, double-blind crossover study on five spastic hemiparetic patients to determine whether this type of stimulation of the premotor cortex can provide a clinical benefit. Material and Methods. Two stimulation frequencies (1 Hz and 10 Hz were tested versus placebo. Patients were assessed clinically, by quantitative analysis of walking and measurement of neuromechanical parameters (H and T reflexes, musculoarticular stiffness of the ankle. Results. No change was observed after placebo and 10 Hz protocols. Clinical parameters were not significantly modified after 1 Hz stimulation, apart from a tendency towards improved recruitment of antagonist muscles on the Fügl-Meyer scale. Only cadence and recurvatum were significantly modified on quantitative analysis of walking. Neuromechanical parameters were modified with significant decreases in Hmax⁡ /Mmax⁡ and T/Mmax⁡ ratios and stiffness indices 9 days or 31 days after initiation of TMS. Conclusion. This preliminary study supports the efficacy of low-frequency TMS to reduce reflex excitability and stiffness of ankle plantar flexors, while clinical signs of spasticity were not significantly modified.

  3. Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Karl Nowak

    2011-01-01

    instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1 elucidating the electrochemical processes at the electrode/tissue interface, (2 analyzing the molecular, cellular and behavioral stimulation effects, (3 testing new target regions for DBS, (4 screening for potential neuroprotective DBS effects, and (5 improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation.

  4. Salivary Glucose Concentration and Excretion in Normal and Diabetic Subjects

    OpenAIRE

    Jurysta, Cedric; Bulur, Nurdan; Oguzhan, Berrin; Satman, Ilhan; Yilmaz, Temel M.; Malaisse, Willy J.; Sener, Abdullah

    2009-01-01

    The present report aims mainly at a reevaluation of salivary glucose concentration and excretion in unstimulated and mechanically stimulated saliva in both normal and diabetic subjects. In normal subjects, a decrease in saliva glucose concentration, an increase in salivary flow, but an unchanged glucose excretion rate were recorded when comparing stimulated saliva to unstimulated saliva. In diabetic patients, an increase in salivary flow with unchanged salivary glucose concentration and gluco...

  5. Angiotensin II inhibits insulin-stimulated GLUT4 translocation and Akt activation through tyrosine nitration-dependent mechanisms.

    Directory of Open Access Journals (Sweden)

    Alfredo Csibi

    Full Text Available Angiotensin II (Ang II plays a major role in the pathogenesis of insulin resistance and diabetes by inhibiting insulin's metabolic and potentiating its trophic effects. Whereas the precise mechanisms involved remain ill-defined, they appear to be associated with and dependent upon increased oxidative stress. We found Ang II to block insulin-dependent GLUT4 translocation in L6 myotubes in an NO- and O(2(*--dependent fashion suggesting the involvement of peroxynitrite. This hypothesis was confirmed by the ability of Ang II to induce tyrosine nitration of the MAP kinases ERK1/2 and of protein kinase B/Akt (Akt. Tyrosine nitration of ERK1/2 was required for their phosphorylation on Thr and Tyr and their subsequent activation, whereas it completely inhibited Akt phosphorylation on Ser(473 and Thr(308 as well as its activity. The inhibitory effect of nitration on Akt activity was confirmed by the ability of SIN-1 to completely block GSK3alpha phosphorylation in vitro. Inhibition of nitric oxide synthase and NAD(PHoxidase and scavenging of free radicals with myricetin restored insulin-stimulated Akt phosphorylation and GLUT4 translocation in the presence of Ang II. Similar restoration was obtained by inhibiting the ERK activating kinase MEK, indicating that these kinases regulate Akt activation. We found a conserved nitration site of ERK1/2 to be located in their kinase domain on Tyr(156/139, close to their active site Asp(166/149, in agreement with a permissive function of nitration for their activation. Taken together, our data show that Ang II inhibits insulin-mediated GLUT4 translocation in this skeletal muscle model through at least two pathways: first through the transient activation of ERK1/2 which inhibit IRS-1/2 and second through a direct inhibitory nitration of Akt. These observations indicate that not only oxidative but also nitrative stress play a key role in the pathogenesis of insulin resistance. They underline the role of protein

  6. Overexpression of transcription factor AP-2 stimulates the PA promoter of the human uracil-DNA glycosylase (UNG) gene through a mechanism involving derepression

    DEFF Research Database (Denmark)

    Aas, Per Arne; Pena Diaz, Javier; Liabakk, Nina Beate

    2009-01-01

    RNA. Chromatin immunoprecipitation with AP-2 antibody demonstrated that endogenous AP-2 binds to the PA promoter in vivo. Overexpression of AP-2alpha, -beta or -gamma all stimulated expression from a PA-luciferase reporter gene construct approximately 3- to 4-fold. Interestingly, an N-terminally truncated AP-2...... within the region of DNA marked by PA. Footprinting analysis and electrophoretic mobility shift assays of PA and putative AP-2 binding regions with HeLa cell nuclear extract and recombinant AP-2alpha protein indicate that AP-2 transcription factors are central in the regulated expression of UNG2 m......alpha, lacking the activation domain but retaining the DNA binding and dimerization domains, stimulated PA to a level approaching that of full-length AP-2, suggesting that AP-2 overexpression stimulates PA activity by a mechanism involving derepression rather than activation, possibly by neutralizing...

  7. Mechanical stimulation of C2C12 cells increases m-calpain expression, focal adhesion plaque protein degradation and cell differentiation

    DEFF Research Database (Denmark)

    Grossi, Alberto; Lawson, Moira Ann

    have shown that m-calpain is necessary for myoblast fusion leading to the formation of muscle fibers and that inhibition of this enzyme restricts myotube formation. Whether there is a link between stretchor load induced signaling and m-calpain expression and activation is not known. Using a magnetic...... documented and has been shown to affect transcription of specific gene sequences, protein synthesis, the immune system and increase in Ca2+ influx. The past 10 years has seen a dramatic increase in the understanding of how proteolytic enzymes such as calpains can affect the growth of muscle. In vivo studies...... bead stimulation assay and a C2C12 mouse myoblast cell population, we have found that mechanical stimulation via laminin receptors leads to an increase in m-calpain expression, an enzyme found to be required for muscle cell fusion. After a short period of stimulation, m-calpain relocates into focal...

  8. Cellular mechanisms by which oxytocin stimulates uterine PGF2 alpha synthesis in bovine endometrium: roles of phospholipases C and A2.

    Science.gov (United States)

    Burns, P D; Graf, G A; Hayes, S H; Silvia, W J

    1997-05-01

    The objective of these experiments was to identify the cellular mechanisms by which oxytocin stimulates prostaglandin (PG) F2 alpha synthesis in bovine endometrial tissue. Uteri were collected on the day after spontaneous luteal regression. Caruncular endometrial explants were dissected and incubated in vitro to assess PGF2 alpha release or phospholipase (PL) C activity. Oxytocin (10(-6) M) stimulated PGF2 alpha release and PLC activity within 30 min of incubation (P PGF2 alpha release was not detected until 10(-8) M (P PGF2 alpha release at 10(-6) M and higher doses (P PGF2 alpha release at 10(-5) M and higher doses (P PGF2 alpha release induced by A1F4-, a nonspecific stimulator of G protein (10(-5) M) and melittin (10(-4) M; P 0.10). By comparing the time course of stimulation and dose-response relationships between PGF2 alpha and PLC activity, it appears that oxytocin may stimulate PGF2 alpha secretion by activating PLC. The effects of melittin and aristolochic acid indicate that PLA2 may play a role in mediating the stimulatory effect of oxytocin on PGF2 alpha secretion, as well.

  9. [Selective stimulations and lesions of the rat brain nuclei as the models for research of the human sleep pathology mechanisms].

    Science.gov (United States)

    Šaponjić, Jasna

    2011-01-01

    Many complex behavioral phenomena such as sleep can not be explained without multidisciplinary experimental approach, and complementay approaches in the animal models "in vivo" and human studies. Electrophysiological, pharmacological, anatomical and immunohistochemical techniques, and particularly stereotaxically guided local nanovolume microinjection technique, enable us to selectively stimulate and lesion the brain nuclei or their specific neuronal subpopulation, and to reslove the mechanisms of certain brain structure regulatory role, and its afferent-efferent connectivity within the brain. Local stereotaxically guided nanovolume microinjection technique enable us to investigate in animals the brain nulcei functional topography with a resolution of sleep neuronal substrates is based on animal studies primarly in cat and rat. Selective pharmacological stimulation of the pedunculopontine tegmentum (PPT) in freely moving rat, using glutamate microinjection, proved that excitation of its cholinergic part is necessary for induction of wakefulness or REM (Datta S, 2001). Local nanovolume glutamate microinjection into PPT of anesthetized rats (Saponjić et al, 2003a) additionally evidenced P-wave and respiratory regulating neuronal subpopulation within the cholinergic compartment of PPT (apneogenic neuronal zone). Local microinjection of serotonin and noradrenaline into cholinergic PPT apneogenic zone evidenced their opposed impact through PPT on breathing, in contrast to their convergent regulatory role in behavioral state control (Saponjić et al., 2005a). Also, selective pharmacological stimulation by microinjection of DL-homocysteic acid defined four neuronal micro-circuitry approximately 500 microm in lenght of breathing-related neurons within the ventral respiratory group of medulla oblongata, which when stimulated produce different effects on respiratory rate, rhythm and amplitude, and on blood pressure. This study was the first high resolution study in order to

  10. Facilitation of corticospinal excitability by virtual reality exercise following anodal transcranial direct current stimulation in healthy volunteers and subacute stroke subjects.

    Science.gov (United States)

    Kim, Yeun Joon; Ku, Jeonghun; Cho, Sangwoo; Kim, Hyun Jung; Cho, Yun Kyung; Lim, Teo; Kang, Youn Joo

    2014-08-18

    There is growing evidence that the combination of non-invasive brain stimulation and motor skill training is an effective new treatment option in neurorehabilitation. We investigated the beneficial effects of the application of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) motor training. In total, 15 healthy, right-handed volunteers and 15 patients with stroke in the subacute stage participated. Four different conditions (A: active wrist exercise, B: VR wrist exercise, C: VR wrist exercise following anodal tDCS (1 mV, 20 min) on the left (healthy volunteer) or affected (stroke patient) primary motor cortex, and D: anodal tDCS without exercise) were provided in random order on separate days. We compared during and post-exercise corticospinal excitability under different conditions in healthy volunteers (A, B, C, D) and stroke patients (B, C, D) by measuring the changes in amplitudes of motor evoked potentials in the extensor carpi radialis muscle, elicited with single-pulse transcranial magnetic stimulation. For statistical analyses, a linear mixed model for a repeated-measures covariance pattern model with unstructured covariance within groups (healthy or stroke groups) was used. The VR wrist exercise (B) facilitated post-exercise corticospinal excitability more than the active wrist exercise (A) or anodal tDCS without exercise (D) in healthy volunteers. Moreover, the post-exercise corticospinal facilitation after tDCS and VR exercise (C) was greater and was sustained for 20 min after exercise versus the other conditions in healthy volunteers (A, B, D) and in subacute stroke patients (B, D). The combined effect of VR motor training following tDCS was synergistic and short-term corticospinal facilitation was superior to the application of VR training, active motor training, or tDCS without exercise condition. These results support the concept of combining brain stimulation with VR motor training to promote recovery after a stroke.

  11. Sex differences in subjective and objective responses to a stimulant medication (methylphenidate): Comparisons between overweight/obese adults with and without binge-eating disorder.

    Science.gov (United States)

    Davis, Caroline; Levitan, Robert D; Kaplan, Allan S; Carter-Major, Jacqueline C; Kennedy, James L

    2016-05-01

    The purpose of this study was to examine sex differences in response to a single dose of a psychomotor-stimulant medication (methylphenidate: MP) and to assess whether expected differences were moderated by binge-eating disorder (BED) status. It is anticipated that findings will shed light on factors that contribute to response variation in the use of stimulant pharmacotherapy to treat BED. The study employed a double-blind, drug-placebo, cross-over design in overweight/obese adults with BED (n = 90) and without BED (n = 108). Emotional/mood ratings were assessed every 15 minutes after oral administration of the drug/placebo, and appetite, cravings, and consumption were assessed during a laboratory-based snack-food challenge. Women reported earlier and more sustained "overall" effects of the drug-including "feeling high"-than the men. There was also a significantly greater suppression in appetite ratings, food cravings, and food consumption from the placebo to the drug condition among the women. Indeed, among men there were no significant differences between the two conditions on any of the food-related variables. BED status also did not moderate any of the drug-placebo differences. These findings are relevant to the use of stimulant pharmacotherapy for BED, and raise the possibility that overweight/obese men may be relatively less responsive to this form of treatment. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:473-481). © 2015 Wiley Periodicals, Inc.

  12. [Efficiency and safety of the intravenous application of esomeprazole (nexium - Astra Zeneca) in high risk patients subjected to mechanic ventilation].

    Science.gov (United States)

    Stefanov, Ch; Batashki, I; Dimitrov, D; Dimov, G; Dobrev, K; Kirina, V; Petrov, A; Karakolev, Zh

    2007-01-01

    The aim of the research was to determine the effectivity and the safety of the intravenous application of Esomeprazole (Nexium - Astra Zeneca) like prevention of the development of stress-ulcers of the gastric mucous with high risk patients at ICU with mechanic ventilation. 47 patients subjected to mechanic ventilation over 48 hours with availability of just one more risk factor for development of stress-ulcers of gastric musous were included in the study. Samples of gastric juice for determination of the acidity and presence of fresh erythrocytes and microbiological cultures from gastric contents, wash away of the mouth cavity and tracheal aspiration were tested on the 1st, the 3rd and the 5th day from the start of the treatment. At the end of the therapy there has been determinated the outcome - survivor or died and total quantity of the haemotransfusions. The acidity of the gastric juice changed in the range over pH 5 during the 24 hours by the application of esomeprazole. Fibrogastroscopic examinations were performed of patients who were found to have fresh erythrocytes in the gastric contents. No one was registered with bleeding of the gastric mucous. The isolated microorganisms of the gastric juice and wash away of mouth cavity were identical with those of tracheobronchial aspiration in about 13 %. In our study the application of esomeprazole i.v. was effective and safe approach for profilaxy of the stress-ulcers and the bleeding of the gastric mucous. Comparative studies with H2-blockers and sucralfat are necessary for clarifying and objectifying the significance of the microbiologic isolates of the gastric contents and wash away from mouth cavity and their relation to the development of nosocomial pneumonia.

  13. Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome.

    Directory of Open Access Journals (Sweden)

    Maria Clara Bonaglia

    2011-07-01

    Full Text Available In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome, as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%, ring chromosomes (14%, and unbalanced translocations (7%. We also discovered interstitial deletions between 17-74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS.

  14. Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2

    Directory of Open Access Journals (Sweden)

    Côté Claude H

    2011-10-01

    Full Text Available Abstract Background Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2. The possibility that a tryptase/PAR-2 signaling pathway exists in skeletal muscle cell has never been investigated. The aim of this study was to evaluate whether tryptase can stimulate myoblast proliferation and determine the downstream cascade. Methods Proliferation of L6 rat skeletal myoblasts stimulated with PAR-2 agonists (tryptase, trypsin and SLIGKV was assessed. The specificity of the tryptase effect was evaluated with a specific inhibitor, APC-366. Western blot analyses were used to evaluate the expression and functionality of PAR-2 receptor and to assess the expression of COX-2. COX-2 activity was evaluated with a commercial activity assay kit and by measurement of PGF2α production. Proliferation assays were also performed in presence of different prostaglandins (PGs. Results Tryptase increased L6 myoblast proliferation by 35% above control group and this effect was completely inhibited by APC-366. We confirmed the expression of PAR-2 receptor in vivo in skeletal muscle cells and in satellite cells and in vitro in L6 cells, where PAR-2 was found to be functional. Trypsin and SLIGKV increased L6 cells proliferation by 76% and 26% above control, respectively. COX-2 activity was increased following stimulation with PAR-2 agonist but its expression remained unchanged. Inhibition of COX-2 activity by NS-398 abolished the stimulation of cell proliferation induced by tryptase and trypsin. Finally, 15-deoxy-Δ-12,14-prostaglandin J2 (15Δ-PGJ2, a product of COX-2-derived prostaglandin D2, stimulated myoblast proliferation, but not PGE2 and PGF2α. Conclusions Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream

  15. Modular Organization of the NusA- and NusG-Stimulated RNA Polymerase Pause Signal That Participates in the Bacillus subtilis trp Operon Attenuation Mechanism.

    Science.gov (United States)

    Mondal, Smarajit; Yakhnin, Alexander V; Babitzke, Paul

    2017-07-15

    The Bacillus subtilis trpEDCFBA operon is regulated by a transcription attenuation mechanism in which tryptophan-activated TRAP binds to the nascent transcript and blocks the formation of an antiterminator structure such that the formation of an overlapping intrinsic terminator causes termination in the 5' untranslated region (5' UTR). In the absence of bound TRAP, the antiterminator forms and transcription continues into the trp genes. RNA polymerase pauses at positions U107 and U144 in the 5' UTR. The general transcription elongation factors NusA and NusG stimulate pausing at both positions. NusG-stimulated pausing at U144 requires sequence-specific contacts with a T tract in the nontemplate DNA (ntDNA) strand within the paused transcription bubble. Pausing at U144 participates in a trpE translation repression mechanism. Since U107 just precedes the critical overlap between the antiterminator and terminator structures, pausing at this position is thought to participate in attenuation. Here we carried out in vitro pausing and termination experiments to identify components of the U107 pause signal and to determine whether pausing affects the termination efficiency in the 5' UTR. We determined that the U107 and U144 pause signals are organized in a modular fashion containing distinct RNA hairpin, U-tract, and T-tract components. NusA-stimulated pausing was affected by hairpin strength and the U-tract sequence, whereas NusG-stimulated pausing was affected by hairpin strength and the T-tract sequence. We also determined that pausing at U107 results in increased TRAP-dependent termination in the 5' UTR, implying that NusA- and NusG-stimulated pausing participates in the trp operon attenuation mechanism by providing additional time for TRAP binding.IMPORTANCE The expression of several bacterial operons is controlled by regulated termination in the 5' untranslated region (5' UTR). Transcription attenuation is defined as situations in which the binding of a regulatory

  16. Mechanical stretch stimulates protein kinase B/Akt phosphorylation in epidermal cells via angiotensin II type 1 receptor and epidermal growth factor receptor.

    Science.gov (United States)

    Kippenberger, Stefan; Loitsch, Stefan; Guschel, Maike; Müller, Jutta; Knies, Yvonne; Kaufmann, Roland; Bernd, August

    2005-01-28

    Mechanical stress is known to modulate fundamental events such as cell life and death. Mechanical stretch in particular has been identified as a positive regulator of proliferation in skin keratinocytes and other cell systems. In the present study it was investigated whether antiapoptotic signaling is also stimulated by mechanical stretch. It was demonstrated that mechanical stretch rapidly induced the phosphorylation of the proto-oncogene protein kinase B (PKB)/Akt at both phosphorylation sites (serine 473/threonine 308) in different epithelial cells (HaCaT, A-431, and human embryonic kidney-293). Blocking of phosphoinositide 3-OH kinase by selective inhibitors (LY-294002 and wortmannin) abrogated the stretch-induced PKB/Akt phosphorylation. Furthermore mechanical stretch stimulated phosphorylation of epidermal growth factor receptor (EGFR) and the formation of EGFR membrane clusters. Functional blocking of EGFR phosphorylation by either selective inhibitors (AG1478 and PD168393) or dominant-negative expression suppressed stretch-induced PKB/Akt phosphorylation. Finally, the angiotensin II type 1 receptor (AT1-R) was shown to induce positive transactivation of EGFR in response to cell stretch. These findings define a novel signaling pathway of mechanical stretch, namely the activation of PKB/Akt by transactivation of EGFR via angiotensin II type 1 receptor. Evidence is provided that stretch-induced activation of PKB/Akt protects cells against induced apoptosis.

  17. Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca2+ release

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Sylow, Lykke; Rose, Adam John

    2014-01-01

    signals through proteins such as AMPK. Here, we demonstrate in incubated mouse muscle that Ca(2+) release is neither sufficient nor strictly necessary to increase glucose transport. Rather, the glucose transport response is associated with metabolic feedback signals through AMPK, and mechanical stress......-activated signals. Furthermore, artificial stimulation of AMPK combined with passive stretch of muscle is additive and sufficient to elicit the full contraction glucose transport response. These results suggest that ATP-turnover and mechanical stress feedback are sufficient to fully increase glucose transport...

  18. BRAIN PLASTICITY INVESTIGATED WITH TRANSCRANIAL MAGNETIC STIMULATION IN HEALTHY HUMANS AND IN PATIENTS WITH MOVEMENT DISORDERS

    OpenAIRE

    Suppa, Antonio

    2011-01-01

    Investigating mechanisms of short-term and long-term synaptic plasticity in primary motor cortex with the transcranial magnetic stimulation (TMS) technique in healthy subjects and in patients with different types of movement disorders.

  19. Emotional maltreatment is associated with atypical responding to stimulation of endogenous oxytocin release through mechanically delivered massage in males

    NARCIS (Netherlands)

    Hendricx-Riem, M.M.E.; De Carli, P.; van IJzendoorn, M.H.; Linting, M.; Grewen, K.M.; Bakermans-Kranenburg, M. J.

    2017-01-01

    The neuropeptide oxytocin plays an important role in social behavior, parenting, and affectionate touch and there is some evidence that oxytocin release can be stimulated by massage or affectionate touch. We examined the effects of massage applied by a massage seat cover on salivary oxytocin levels

  20. Short-term adaptations in spinal cord circuits evoked by repetitive transcranial magnetic stimulation: possible underlying mechanisms

    DEFF Research Database (Denmark)

    Perez, Monica A.; Lungholt, Bjarke K.S.; Nielsen, Jens Bo

    2005-01-01

    Repetitive transcranial magnetic stimulation (rTMS) has been shown to induce adaptations in cortical neuronal circuitries. In the present study we investigated whether rTMS, through its effect on corticospinal pathways, also produces adaptations at the spinal level, and what the neuronal mechanis...

  1. Effective electric fields along realistic DTI-based neural trajectories for modelling the stimulation mechanisms of TMS

    NARCIS (Netherlands)

    De Geeter, N.; Crevecoeur, G.; Leemans, A.; Dupré, L.

    2015-01-01

    In transcranial magnetic stimulation (TMS), an applied alternating magnetic field induces an electric field in the brain that can interact with the neural system. It is generally assumed that this induced electric field is the crucial effect exciting a certain region of the brain. More specifically,

  2. The development and use of a drug-induced immunosuppressed rat-model to screen Phela for mechanism of immune stimulation.

    Science.gov (United States)

    Lekhooa, Makhotso Rose; Walubo, Andrew; du Plessis, Jan B; Matsabisa, Motlalepula Gilbert

    2017-07-12

    Phela, is code name for a medicinal product made from four South African traditional medicinal plants (Clerodendrum glabrum E. Mey, Polianthes tuberosa (Linn.), Rotheca myricoides (Hochst.) Steane & Mabb. and Senna occidentalis (L.) Link). All these plants have established traditional use in a wide spectrum of diseases. Phela is under development for use as an immune booster in immunocompromised patients, which includes patients with the human immunodeficiency virus (HIV). Already several studies, both pre-clinical and clinical, have shown that Phela is a safe and effective immune booster. Despite some studies on the action of Phela, the mechanism of action by Phela is still not known. Understanding the mechanism of action will enable safer and effective use of the drug for the right indications. Unfortunately, there is no well characterized test-system for screening products for immune stimulant activity. Therefore, the objective of this study was to use Phela as the test article, to develop and validate a rat-model (test system) by which to screen medicines for immune stimulant activity. First, the batch of Phela used was authenticated by high performance liquid chromatography (HPLC) techniques; analytical methods for the immunosuppressant drugs, cyclosporine A (CsA), cyclophosphamide (CP) and dexamethasone (Dex) were developed and validated; and a slide-A-Lyzer dialysis was used to test for potential interactions in rat plasma of Phela with CsA, CP and Dex. Thereafter, using Sprague Dawley (SD) rats and in separate experiments, the effective dose of Phela in the study animals was determined in a dose ranging study with levamisole, a known immune stimulant as the positive control; the appropriate doses for immunosuppression by CsA, CP and Dex were determined; the time to reach 'established immunosuppression' with each drug was determined (it was also the time for intervention with Phela); and eventually, the effect of Phela on the immune system was tested

  3. Different mechanisms for the short-term effects of real versus sham transcutaneous electrical nerve stimulation (TENS) in patients with chronic pain: a pilot study.

    Science.gov (United States)

    Oosterhof, Jan; Wilder-Smith, Oliver H; Oostendorp, Rob A; Crul, Ben J

    2012-01-01

    Transcutaneous electrical nerve stimulation (TENS) has existed since the early 1970s. However, randomized placebo controlled studies show inconclusive results in the treatment of chronic pain. These results could be explained by assuming that TENS elicits a placebo response. However, in animal research TENS has been found to decrease hyperalgesia, which contradicts this assumption. The aim of this study is to use quantitative sensory testing to explore changes in pain processing during sham versus real TENS in patients with chronic pain. Patients with chronic pain (N = 20) were randomly allocated to real TENS or sham TENS application. Electrical pain thresholds (EPTs) were determined inside and outside the segment stimulated, before and after the first 20 minutes of the intervention, and after a period of 10 days of daily real/sham TENS application. Pain relief did not differ significantly for real versus sham TENS. However, by comparing time courses of EPTs, it was found that EPT values outside the segment of stimulation increased for sham TENS, whereas for real TENS these values decreased. There were, however, no differences for EPT measurements inside the segment stimulated. These results illustrate the importance of including mechanism-reflecting parameters in addition to symptoms when conducting pain research.

  4. [Effects of prolonged endocardial stimulation on left ventricular mechanical synchrony. A pilot study applying gated-SPECT phase analysis. Endocardial stimulation and dyssynchrony].

    Science.gov (United States)

    Ferrando-Castagnetto, Federico; Ricca-Mallada, Roberto; Vidal, Alejandro; Ferrando, Rodolfo

    To evaluate left ventricular mechanical dyssynchrony (LVMD) associated with prolonged right ventricular pacing through an innovative imaging technique as a pilot study in Uruguay. A 99mTc-MIBI gated-SPECT and phase analysis was performed in 12 patients with pace-makers implanted at least one year before scintigraphy, due to advanced atrioventricular block. Clinical data, QRS duration, rate, mode and site of pacing in right ventricle, chamber diameters, presence and extension of myocardial scar and ischaemia, as well as LVEF at rest, were recorded. Using V-Sync of Emory Cardiac Toolbox, a standard deviation (PSD) and bandwidth (PBW) from rest phase histogram was obtained and these indexes were compared with controls in the subgroups of patients with LVEF≥50% and <50%. Patients with prolonged RV endocardial pacing exhibited marked LVMD. More severe dyssynchrony was found in patients with impaired LVEF than in patients with preserved LVEF (PSD: 46.67(o) vs. 26.81(o), P<.05; PBW: 144.33(o) vs. 77.41(o), P<.05). Higher left ventricle diameters, extensive infarct, or significant ischaemia were found in patients with impaired LVEF. Chronic right ventricular pacing was invariably associated with LVMD, even when systolic function was preserved. Phase analysis could be a potentially useful technique to evaluate LMVD associated with myocardial scar in patients with pacemakers, and to decide promptly the upgrading to biventricular pacing. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Do subjects with whiplash-associated disorders respond differently in the short-term to manual therapy and exercise than those with mechanical neck pain?

    DEFF Research Database (Denmark)

    Castaldo, Matteo; Catena, Antonella; Chiarotto, Alessandro

    2017-01-01

    OBJECTIVE : To compare the short-term effects of manual therapy and exercise on pain, related disability, range of motion, and pressure pain thresholds between subjects with mechanical neck pain and whiplash-associated disorders. METHODS : Twenty-two subjects with mechanical neck pain and 28...... with whiplash-associated disorders participated. Clinical and physical outcomes including neck pain intensity, neck-related disability, and pain area, as well as cervical range of motion and pressure pain thresholds over the upper trapezius and tibialis anterior muscles, were obtained at baseline and after...... the intervention by a blinded assessor. Each subject received six sessions of manual therapy and specific neck exercises. Mixed-model repeated measures analyses of covariance (ANCOVAs) were used for the analyses. RESULTS : Subjects with whiplash-associated disorders exhibited higher neck-related disability (P = 0...

  6. Gluten stimulation induces an in vitro expansion of peripheral blood T gamma delta cells from HLA-DQ2-positive subjects of families of patients with celiac disease.

    Science.gov (United States)

    Lio, D; Bonanno, C T; D'Anna, C; De Luca, S; Gervasi, F; Cavataio, F; Iacono, F; Salerno, A

    1998-01-01

    The intestinal gluten sensitivity formally known as celiac disease (CD) is characterized by an evident involvement of local immune response and it is associated with the expression of HLA-DQ2 allele. The major role in the disease seems to be played by the T lymphocyte population bearing gamma delta T cell receptor (T gamma delta cells) which are increased both in peripheral blood and intestinal mucosae of celiac patients. In this paper data on the effects of in vitro gluten stimulation on lymphocytes expressing the T gamma delta phenotype are reported. Gluten seems to be able to induce the expansion of the T gamma delta cell population both in CD patients and their HLA-DQ2-positive asymptomatic relatives, in spite of the absence of clinical evidence of the disease. In addition, the evaluation of gluten-induced cytokine production shows that interleukin-4 could be implied in the early phases of pathogenesis of CD.

  7. Study of thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in subjects with dental fluorosis.

    Science.gov (United States)

    Hosur, Mahadevi B; Puranik, R S; Vanaki, Shrinivas; Puranik, Surekha R

    2012-04-01

    Apart from its well-known deleterious dental and skeletal effects, fluoride excess can have toxic effects on many other tissues. Fluoride, when in excess, is known to interfere with thyroid gland function. Fluoride-induced thyroid disturbances similar to those observed in iodine deficiency state in spite of adequate iodine intake have been documented. Similar thyroid disturbances in individuals with dental fluorosis have not been well studied in populations with endemic fluorosis. This work was undertaken to study the effects of fluoride-induced thyroid disturbances in individuals with dental fluorosis. The study group included 65 subjects with dental fluorosis from endemic fluorosis populations. An additional control group was comprised of 10 subjects without dental fluorosis. The drinking water fluoride levels of the study populations were analyzed. Serum free FT3, FT4, and TSH levels of both groups were assessed. All subjects with dental fluorosis had serum levels of thyroid hormones (FT3, FT4, and TSH) within the normal range, with the exception of 1 individual, who had elevated levels of TSH. Statistical significance was found when FT3 and TSH values were compared with different Dean's index groups by a 1-way ANOVA test: FT3 (F = 3.4572; P=.0377) and TSH (F = 3.2649 and P=.0449). Findings of this study did not show any significant alterations in the levels of the thyroid hormones FT3, FT4, and TSH in subjects with dental fluorosis. Our observations suggest that thyroid hormone levels were not altered in subjects with dental fluorosis. Hence, future studies of this kind, along with more detailed investigations are needed.

  8. Differential mechanisms of action understanding in left and right handed subjects: the role of perspective and handedness

    Directory of Open Access Journals (Sweden)

    Rachel Louise Kelly

    2013-12-01

    Full Text Available The ability to comprehend outcomes of skilled action is important for understanding the world around us. Prior studies have evaluated the perspective an action is performed in, but few have evaluated how handedness of the actor and the observer interact with action perspective. Understanding handedness affords the opportunity to identify the role of mirroring and matched limb action encoding, which may display unique strategies of action understanding. Right and left-handed subjects were presented with images of tools from egocentric or allocentric perspectives performing movements by either a left or right hand. Subjects had to judge the outcome of the task, and accuracy and latency were evaluated. Our hypothesis was that both left and right-handed subjects would predict action best from an egocentric perspective. In allocentric perspectives, identification of action outcomes would occur best in the mirror matched dominant limb for all subjects. Results showed there was a significant effect on accuracy and latency with respect to perspective for both right and left-handed subjects. The highest accuracies and fastest latencies were found in the egocentric perspective. Handedness of subject also showed an effect on accuracy, where right-handed subjects were significantly more accurate in the task than left-handed subjects. An interaction effect revealed that left-handed subjects were less accurate at judging images from an allocentric viewpoint compared to all other conditions. These findings suggest that action outcomes are best facilitated in an internal perspective, regardless of the hand being used. The decreased accuracy for left-handed subjects on allocentric images could be due to asymmetrical lateralization of encoding action and motoric dominance, which may interfere with translating allocentric limb action outcomes. Further neurophysiological studies will help us understand the specific processes of how left and right-handed subjects

  9. Palmitate stimulates glucose transport in rat adipocytes by a mechanism involving translocation of the insulin sensitive glucose transporter (GLUT4)

    Science.gov (United States)

    Hardy, R. W.; Ladenson, J. H.; Henriksen, E. J.; Holloszy, J. O.; McDonald, J. M.

    1991-01-01

    In rat adipocytes, palmitate: a) increases basal 2-deoxyglucose transport 129 +/- 27% (p less than 0.02), b) decreases the insulin sensitive glucose transporter (GLUT4) in low density microsomes and increases GLUT4 in plasma membranes and c) increases the activity of the insulin receptor tyrosine kinase. Palmitate-stimulated glucose transport is not additive with the effect of insulin and is not inhibited by the protein kinase C inhibitors staurosporine and sphingosine. In rat muscle, palmitate: a) does not affect basal glucose transport in either the soleus or epitrochlearis and b) inhibits insulin-stimulated glucose transport by 28% (p less than 0.005) in soleus but not in epitrochlearis muscle. These studies demonstrate a potentially important differential role for fatty acids in the regulation of glucose transport in different insulin target tissues.

  10. Mechanisms underlying enhancements in muscle force and power output during maximal cycle ergometer exercise induced by chronic β2-adrenergic stimulation in men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Onslev, Johan

    2015-01-01

    The study was a randomized placebo-controlled trial investigating mechanisms by which chronic β2-adrenergic stimulation enhances muscle force and power output during maximal cycle ergometer exercise in young men. Eighteen trained men were assigned to an experimental group (oral terbutaline 5 mg∙30...... output during 30-s of maximal cycling increased (P≤0.01) by 32±8 and 25±9 W, respectively, with the intervention in TER compared to PLA. Maximal oxygen consumption (V̇o2 max) and time to fatigue during incremental cycling did not change with the intervention. Lean body mass increased by 1.95±0.8 kg (P≤0...... and peak power during maximal cycling induced by chronic β2-adrenergic stimulation in humans....

  11. The mechanism of 5-lipoxygenase in the impairment of learning and memory in rats subjected to chronic unpredictable mild stress.

    Science.gov (United States)

    Luo, Ying; Kuang, Shengnan; Xue, Lai; Yang, Junqing

    2016-12-01

    To examine the mechanism of 5-lipoxygenase (5-LO) in the learning and memory dysfunction in rats subjected to chronic unpredictable mild stress (CUMS). Eighty rats were divided into eight groups: the 0.5% sodium carboxymethyl cellulose solution (NaCMC)-treated group, empty vector (LV-Mock)-treated group, CUMS+NaCMC-treated group, CUMS+sertraline-treated group, CUMS+caffeic acid (10mg/kg)-treated group, CUMS+caffeic acid (30mg/kg)-treated group, CUMS+LV-Mock-treated group, and CUMS+5-LO-silencers lentiviral vectors (LV-si-5-LO)-treated group, n=10. Sucrose preference tests were performed to assess depression-like behavior. The Morris water maze and step-down tests were used to evaluate learning and memory performance. The levels of inflammatory cytokines, malondialdehyde, and the activity of superoxide dismutase (SOD) were detected to estimate inflammation and oxidative stress. Changes in 5-LO mRNA and protein were detected using reverse transcription polymerase chain reaction and Western blotting. The expression of synaptophysin, postsynaptic density-95 (PSD-95), and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured using immunohistochemical staining. Treatment with caffeic acid or LV-si-5-LO increased sucrose consumption, decreased escape latency and increased the number of platform crosses in the Morris water maze test, and decreased the number of errors and prolonged the latency in the step-down test. We observed a decreased expression of 5-LO, and levels of malondialdehyde, leukotriene-B4, tumor necrosis factor-α, and interleukin-6, while the protein levels of synaptophysin, PSD-95, BDNF, and the activity of SOD were increased in the hippocampus of the CUMS-treated rats. CUMS-induced impairment in learning and memory could be triggered by an inflammatory response in the rat hippocampus, which results in oxidative stress injury and impacts the synaptic plasticity of hippocampal neurons. Inhibition of the activity or expression of 5-LO

  12. Monoassociation with Lactobacillus acidophilus UFV-H2b20 stimulates the immune defense mechanisms of germfree mice

    Directory of Open Access Journals (Sweden)

    Neumann E.

    1998-01-01

    Full Text Available Probiotics are formulations containing live microorganisms or microbial stimulants that have some beneficial influence on the maintenance of a balanced intestinal microbiota and on the resistance to infections. The search for probiotics to be used in prevention or treatment of enteric infections, as an alternative to antibiotic therapy, has gained significant impulse in the last few years. Several studies have demonstrated the beneficial effects of lactic acid bacteria in controlling infection by intestinal pathogens and in boosting the host's nonspecific immune response. Here, we studied the use of Lactobacillus acidophilus UFV-H2b20, a lactic acid bacterium isolated from a human newborn from Viçosa, Minas Gerais, Brazil, as a probiotic. A suspension containing 108 cells of Lactobacillus acidophilus UFV-H2b20 was inoculated into groups of at least five conventional and germfree Swiss mice to determine its capacity to stimulate the host mononuclear phagocytic activity. We demonstrate that this strain can survive the stressing conditions of the intestinal tract in vivo. Moreover, the monoassociation of germfree mice with this strain for seven days improved the host's macrophage phagocytic capacity, as demonstrated by the clearance of a Gram-negative bacterium inoculated intravenously. Monoassociated mice showed an undetectable number of circulating E. coli, while 0.1% of the original inoculum was still present in germfree animals. Mice treated with viable or heat-killed Lactobacillus acidophilus UFV-H2b20 presented similarly improved clearance capacity when compared with germfree controls. In addition, monoassociated mice had twice the amount of Kupffer cells, which are responsible for the clearance of circulating bacteria, compared to germfree controls. These results suggest that the L. acidophilus strain used here stimulates a nonspecific immune response and is a strong candidate to be used as a probiotic.

  13. Novel methods of applying direct chemical and mechanical stimulation to the oral mucosa for traditional behavioral pain assays in conscious rats.

    Science.gov (United States)

    Hitomi, Suzuro; Ono, Kentaro; Miyano, Kanako; Ota, Yojiro; Uezono, Yasuhito; Matoba, Motohiro; Kuramitsu, Sachiko; Yamaguchi, Kiichiro; Matsuo, Kou; Seta, Yuji; Harano, Nozomu; Inenaga, Kiyotoshi

    2015-01-15

    Stomatitis induces severe and painful hypersensitivity to pungency and physical contact during meals. Many studies have used anesthetized animals to examine evoked nociception in the oral mucosa, but no reports have used traditional behavioral assays to evaluate nociception in conscious animals. We developed two new methods of applying chemical or mechanical stimulation directly to the oral mucosa of the mandibular vestibule of conscious rats. Nociceptive evaluations were performed by measuring facial grooming time and the head withdrawal threshold to von Frey stimulations. (1) For the intraoral dropping method, rat mucosa was transiently exposed by hand, and a drop of a pungent solution was applied. (2) For the stable intraoral opening method, rat mucosa was long-term exposed following piercing surgery of the mental skin after habitual training for 2-3 weeks. In the intraoral dropping method, the application of 100 μM capsaicin or 100 mM allyl isothiocyanate prolonged mouth-rubbing time. Capsaicin-induced mouth-rubbing time was further enhanced following the development of an acetic acid-induced ulcer. The stable intraoral opening method enabled stable measurements of the mechanical withdrawal threshold in the oral mucosa of conscious rats. Ulcer development decreased the mechanical threshold, whereas topical lidocaine treatment increased the threshold. These new methods enable the evaluations of motivational nocifensive behaviors in response to intraoral stimulations without any anesthetic effects. The intraoral dropping and stable intraoral opening methods can be used in combination with traditional behavioral assays to evaluate nociception in the oral mucosa of conscious rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Human Articular Cartilage Progenitor Cells Are Responsive to Mechanical Stimulation and Adenoviral-Mediated Overexpression of Bone-Morphogenetic Protein 2.

    Directory of Open Access Journals (Sweden)

    Alexander J Neumann

    Full Text Available Articular cartilage progenitor cells (ACPCs represent a new and potentially powerful alternative cell source to commonly used cell sources for cartilage repair, such as chondrocytes and bone-marrow derived mesenchymal stem cells (MSCs. This is particularly due to the apparent resistance of ACPCs to hypertrophy. The current study opted to investigate whether human ACPCs (hACPCs are responsive towards mechanical stimulation and/or adenoviral-mediated overexpression of bone morphogenetic protein 2 (BMP-2. hACPCs were cultured in fibrin-polyurethane composite scaffolds. Cells were cultured in a defined chondro-permissive medium, lacking exogenous growth factors. Constructs were cultured, for 7 or 28 days, under free-swelling conditions or with the application of complex mechanical stimulation, using a custom built bioreactor that is able to generate joint-like movements. Outcome parameters were quantification of BMP-2 and transforming growth factor beta 1 (TGF-β1 concentration within the cell culture medium, biochemical and gene expression analyses, histology and immunohistochemistry. The application of mechanical stimulation alone resulted in the initiation of chondrogenesis, demonstrating the cells are mechanoresponsive. This was evidenced by increased GAG production, lack of expression of hypertrophic markers and a promising gene expression profile (significant up-regulation of cartilaginous marker genes, specifically collagen type II, accompanied by no increase in the hypertrophic marker collagen type X or the osteogenic marker alkaline phosphatase. To further investigate the resistance of ACPCs to hypertrophy, overexpression of a factor associated with hypertrophic differentiation, BMP-2, was investigated. A novel, three-dimensional, transduction protocol was used to transduce cells with an adenovirus coding for BMP-2. Over-expression of BMP-2, independent of load, led to an increase in markers associated with hypertropy. Taken together ACPCs

  15. Role of 5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects

    NARCIS (Netherlands)

    Gentilcore, Diana; Little, Tanya J.; Feinle-Bisset, Christine; Samsom, Melvin; Smout, Andre J. P. M.; Horowitz, Michael; Jones, Karen L.

    2007-01-01

    5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects. Am J Physiol Gastrointest Liver Physiol 293: G692-G698, 2007. First published August 9, 2007; doi:10.1152/ajpgi.00199.2007.-Postprandial

  16. Stimulants and narcotic drugs.

    Science.gov (United States)

    King, P; Coleman, J H

    1987-04-01

    This article focuses on the use of stimulant and narcotic drugs, as well as lookalike preparations that are subject to abuse. There is a brief discussion of the pharmacology of these agents, demographic use patterns, and treatment modalities.

  17. Mechanical Stimulation of C2C12 Cells Increases m-Calpain Expression and Activity, Focal Adhesion Plaque Degradation and Cell Fusion

    DEFF Research Database (Denmark)

    Grossi, Alberto; Lawson, Moira Ann; Karlsson, Anders H

    to stretch- or load-induced signaling is now beginning to be understood as a factor which affects gene sequences, protein synthesis and an increase in Ca2+ infux in myocytes. Evidence of the involvement of Ca2+ dependent activity in myoblast fusion, cell membrane and cytoskeleton component reorganization due......Abstract Mechanical Stimulation of C2C12 Cells Increases m-calpain Expression and Activity, Focal Adhesion Plaque Degradation and Cell Fusion A. Grossi, A. H. Karlsson, M. A. Lawson; Department of Dairy and Food Science, Royal Veterinary and Agricultural University, Frederiksberg C, Denmark...

  18. Regulation on RhoA in vascular smooth muscle cells under inflammatory stimulation proposes a novel mechanism mediating the multiple-beneficial action of acetylsalicylic acid.

    Science.gov (United States)

    Li, Dong-Bo; Yang, Guo-Jie; Xu, Hong-Wei; Fu, Zhi-Xuan; Wang, Shan-Wei; Hu, Shen-Jiang

    2013-12-01

    Recent studies have revealed the additional beneficial effects of acetylsalicylic acid (aspirin) in the medication of cardiovascular diseases. The small GTPase RhoA as an important signaling factor is implicated in a wide range of cell functions. This study aimed to investigate the regulatory effect of acetylsalicylic acid on RhoA in vascular smooth muscle cells (VSMCs). We found that aspirin at 300 μM suppressed VSMCs proliferation stimulated by LPS, and this inhibitory effect was partially mediated by inhibiting the iNOS/NO pathway. RhoA overexpression was downregulated by aspirin (both 30 and 300 μM) because of enhanced degradation of RhoA protein. The effect of LPS on increasing active RhoA level was significantly attenuated by aspirin (300 μM), which exerted no effect on RhoA translocation. The promoted RhoA phosphorylation under LPS stimulation, coupled with RhoA protein expression, was greatly decreased by aspirin treatment. No effect of aspirin was found on the expression, activation, and phosphorylation of RhoA in VSMCs devoid of inflammatory stimulation. Our investigation indicates that the regulation of RhoA by aspirin in VSMCs under inflammatory stimulus could be a novel mechanism via which aspirin, apart from the COX-dependent action, exerted the multiple beneficial effects.

  19. Expression of TRPV4 in the stimulated rat oral mucous membrane--nociceptive mechanisms of lingual conical papillae.

    Science.gov (United States)

    Nakatsuka, Michiko; Iwai, Yasutomo

    2009-08-01

    The study was supported by 2006-2007 Aid Program for Overseas Training of the Promotion and Mutual Aid Corporation for Private School of Japan and International Exchange Grant, Osaka Dental University. We studied the function of TRPV4 expression and its neuronal activation in response to noxious stimulation of oral mucosa. The intermolar region of dorsal lingual eminence (IDLE) of rats was stimulated with 10 microl of either normal saline or 5% formalin. Immunohistological studies of the TRPV4, pERK and serotonin (5HT) expression in designated regions of tongues and brainstems were performed for studying the descending pain modulatory system in response to nociception. Specimens of the experimental IDLE demonstrated a significant increase of TRPV4 activity in particular in stratum basale of conical papillae (p mucosa is nociceptor of peripheral hyperalgesia, and pERK expression in the Sp5C is closely related with central hyperalgesia of the nociception. Furthermore, pERK-IR cells of the central 5HT nervous system are activated to accelerate 5HT release for neuronal modulation of the descending pain modulatory system in response to nociception.

  20. Kinetics of left ventricular strains and torsion during incremental exercise in healthy subjects: the key role of torsional mechanics for systolic-diastolic coupling.

    Science.gov (United States)

    Doucende, Grégory; Schuster, Iris; Rupp, Thomas; Startun, Aliona; Dauzat, Michel; Obert, Philippe; Nottin, Stéphane

    2010-09-01

    The dynamics of systolic and diastolic strains and torsional mechanics of the left ventricle (LV) and their relation to diastolic filling never have been evaluated at various exercise intensities. Speckle tracking echocardiography was performed in 20 healthy sedentary subjects at rest and during a progressive submaximal exercise test at 20%, 30%, and 40% of maximal aerobic power. LV twist increased progressively with exercise intensity (10.5 ± 3.2 to 15.8 ± 4.5°; Pmechanical events were unchanged during effort. Untwisting was driven mainly by apical rotation and determined mitral opening and isovolumic relaxation time (R=0.47 and 0.61, respectively; Pmechanics during incremental exercise in healthy subjects, underlining the key role of torsional mechanics. It might be useful to better understand the mechanisms of diastolic dysfunction and exercise intolerance in various pathological conditions.

  1. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...

  2. A bovine whey protein extract stimulates human neutrophils to generate bioactive IL-1Ra through a NF-kappaB- and MAPK-dependent mechanism.

    Science.gov (United States)

    Rusu, Daniel; Drouin, Réjean; Pouliot, Yves; Gauthier, Sylvie; Poubelle, Patrice E

    2010-02-01

    Innate immunity depends on the efficiency of neutrophils to be activated rapidly to restore homeostasis. It can benefit from priming agents that enhance neutrophil capacity to respond more efficiently to a subsequent stimulation. Among natural products, a bovine whey protein extract (WPE) has been shown to prime normal human blood neutrophils by enhancing their chemotaxis, phagocytosis, oxidative burst, and degranulation. These leukocytes are also an important source of cytokines, some of which have antiinflammatory functions. We investigated the role of WPE, as well as its mechanisms of action, on the production of interleukin (IL)-1 receptor antagonist (IL-1Ra) by neutrophils in vitro. WPE dose-dependently stimulated de novo synthesis and release of IL-1Ra by normal human blood neutrophils. Among the major proteins present in WPE, beta-lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA) were the only active components. They had additive effects that exactly reproduced those of WPE. Similarly to WPE, they also stimulated the accumulation of IL-1beta, IL-8, IL-6, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and tumor necrosis factor-alpha. However, neutrophils incubated with WPE, beta-LG, and alpha-LA produced IL-1Ra in excess of IL-1beta and the ratio IL-1Ra:IL-1beta increased linearly. The amounts of IL-1Ra stimulated by WPE or beta-LG + alpha-LA significantly reduced the IL-1 activity in EL4 cells. Inhibitors of p38 and extracellular signal-regulated kinases (ERK)1/2 mitogen-activated protein kinase, and nuclear factor-kappaB cascades reduced neutrophil production of IL-1Ra. Our data suggest that WPE, through beta-LG + alpha-LA, has immunomodulatory properties and the potential to increase host defenses.

  3. Potential macro-detritivore range expansion into the subarctic stimulates litter decomposition: a new positive feedback mechanism to climate change?

    Science.gov (United States)

    van Geffen, Koert G; Berg, Matty P; Aerts, Rien

    2011-12-01

    As a result of low decomposition rates, high-latitude ecosystems store large amounts of carbon. Litter decomposition in these ecosystems is constrained by harsh abiotic conditions, but also by the absence of macro-detritivores. We have studied the potential effects of their climate change-driven northward range expansion on the decomposition of two contrasting subarctic litter types. Litter of Alnus incana and Betula pubescens was incubated in microcosms together with monocultures and all possible combinations of three functionally different macro-detritivores (the earthworm Lumbricus rubellus, isopod Oniscus asellus, and millipede Julus scandinavius). Our results show that these macro-detritivores stimulated decomposition, especially of the high-quality A. incana litter and that the macro-detritivores tested differed in their decomposition-stimulating effects, with earthworms having the largest influence. Decomposition processes increased with increasing number of macro-detritivore species, and positive net diveristy effects occurred in several macro-detritivore treatments. However, after correction for macro-detritivore biomass, all interspecific differences in macro-detritivore effects, as well as the positive effects of species number on subarctic litter decomposition disappeared. The net diversity effects also appeared to be driven by variation in biomass, with a possible exception of net diversity effects in mass loss. Based on these results, we conclude that the expected climate change-induced range expansion of macro-detritivores into subarctic regions is likely to result in accelerated decomposition rates. Our results also indicate that the magnitude of macro-detritivore effects on subarctic decomposition will mainly depend on macro-detritivore biomass, rather than on macro-detritivore species number or identity.

  4. Reflecting on mirror mechanisms: motor resonance effects during action observation only present with low-intensity transcranial magnetic stimulation.

    Directory of Open Access Journals (Sweden)

    Michela Loporto

    Full Text Available Transcranial magnetic stimulation (TMS studies indicate that the observation of other people's actions influences the excitability of the observer's motor system. Motor evoked potential (MEP amplitudes typically increase in muscles which would be active during the execution of the observed action. This 'motor resonance' effect is thought to result from activity in mirror neuron regions, which enhance the excitability of the primary motor cortex (M1 via cortico-cortical pathways. The importance of TMS intensity has not yet been recognised in this area of research. Low-intensity TMS predominately activates corticospinal neurons indirectly, whereas high-intensity TMS can directly activate corticospinal axons. This indicates that motor resonance effects should be more prominent when using low-intensity TMS. A related issue is that TMS is typically applied over a single optimal scalp position (OSP to simultaneously elicit MEPs from several muscles. Whether this confounds results, due to differences in the manner that TMS activates spatially separate cortical representations, has not yet been explored. In the current study, MEP amplitudes, resulting from single-pulse TMS applied over M1, were recorded from the first dorsal interosseous (FDI and abductor digiti minimi (ADM muscles during the observation of simple finger abductions. We tested if the TMS intensity (110% vs. 130% resting motor threshold or stimulating position (FDI-OSP vs. ADM-OSP influenced the magnitude of the motor resonance effects. Results showed that the MEP facilitation recorded in the FDI muscle during the observation of index-finger abductions was only detected using low-intensity TMS. In contrast, changes in the OSP had a negligible effect on the presence of motor resonance effects in either the FDI or ADM muscles. These findings support the hypothesis that MN activity enhances M1 excitability via cortico-cortical pathways and highlight a methodological framework by which the

  5. Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca2+ release

    Directory of Open Access Journals (Sweden)

    Thomas E. Jensen

    2014-10-01

    Full Text Available Understanding how muscle contraction orchestrates insulin-independent muscle glucose transport may enable development of hyperglycemia-treating drugs. The prevailing concept implicates Ca2+ as a key feed forward regulator of glucose transport with secondary fine-tuning by metabolic feedback signals through proteins such as AMPK. Here, we demonstrate in incubated mouse muscle that Ca2+ release is neither sufficient nor strictly necessary to increase glucose transport. Rather, the glucose transport response is associated with metabolic feedback signals through AMPK, and mechanical stress-activated signals. Furthermore, artificial stimulation of AMPK combined with passive stretch of muscle is additive and sufficient to elicit the full contraction glucose transport response. These results suggest that ATP-turnover and mechanical stress feedback are sufficient to fully increase glucose transport during muscle contraction, and call for a major reconsideration of the established Ca2+ centric paradigm.

  6. SUBJECT-SPECIFIC MODELS REVEAL THE EXISTANCE OF A RELATIONSHIP BETWEEN MORPHOLOGY OF THE ANKLE JOINT COMPLEX AND ITS PASSIVE MECHANICAL PROPERTIES

    Science.gov (United States)

    Imhauser, Carl W.; Siegler, Sorin; Udupa, Jayaram K.; Toy, Jason

    2008-01-01

    The morphology of the bones, articular surfaces and ligaments and the passive mechanical characteristics of the ankle complex were reported to vary greatly among individuals. The goal of this study was to test the hypothesis that the variations observed in the passive mechanical properties of the healthy ankle complex are strongly influenced by morphological variations. To evaluate this hypothesis six numerical models of the ankle joint complex were developed from morphological data obtained from MRI of six cadaver lower limbs, and from average reported data on the mechanical properties of ligaments and articular cartilage. The passive mechanical behavior of each model, under a variety of loading conditions, was found to closely match the experimental data obtained from each corresponding specimen. Since all models used identical material properties and were subjected to identical loads and boundary conditions, it was concluded that the observed variations in passive mechanical characteristics were due to variations in morphology, thus confirming the hypothesis. In addition, the average and large variations in passive mechanical behavior observed between the models were similar to those observed experimentally between cadaver specimens. The results suggest that individualized subject-specific treatment procedures for ankle complex disorders are potentially superior to one-size-fits-all approach. PMID:18316088

  7. Pulmonary venous hypertension and mechanical strain stimulate monocyte chemoattractant protein-1 release and structural remodelling of the lung in human and rodent chronic heart failure models.

    Science.gov (United States)

    Park, John E S; Lyon, Alexander R; Shao, Dongmin; Hector, Lauren R; Xu, Hua; O'Gara, Peter; Pinhu, Liao; Chambers, Rachel C; Wort, S John; Griffiths, Mark J D

    2014-12-01

    The burden of chronic heart failure (HF) is rising owing to an increased survivorship after myocardial infarction (MI). Pulmonary structural remodelling in patients with HF may protect against oedema while causing dyspnoea, the predominant symptom associated with HF. The cellular and molecular mechanisms underlying these processes in HF are poorly understood. We hypothesised that pulmonary venous hypertension (PVH) following MI provides a mechanical stimulus for structural remodelling of the lung via monocyte chemoattractant protein-1 (MCP-1). Human lung microvascular endothelial cells (HLMVEC) and Ea.Hy 926 cells exposed to cyclic mechanical strain (CMS) in vitro were analysed for MCP-1 expression and activation of signalling intermediates. HF was induced in Sprague-Dawley rats 16 weeks after MI; a cohort was rescued with AAV9.SERCA2a gene therapy to reduce PVH. HLMVEC and Ea.Hy 926 cells exposed to CMS upregulated MCP-1 gene expression and protein release in an extracellular-signal-regulated kinase (ERK) 1/2 dependent manner. Supernatants from these experiments stimulated fibroblast (human fetal lung fibroblast -1) and pulmonary artery smooth muscle cell proliferation and differentiation. Total lung collagen, a marker of structural remodelling, and MCP-1 gene expression were increased in the lungs of rats with post-MI HF. SERCA2a gene therapy that attenuated PVH after MI was associated with lower levels of lung collagen and MCP-1 gene expression in the lung. Mechanical strain associated with PVH may stimulate pulmonary structural remodelling through ERK 1/2 dependent induction of MCP-1. These findings provide insights into the pathophysiology of lung remodelling in HF and highlight novel, potential therapeutic targets. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a study of 20 years of cognitive decline.

    Science.gov (United States)

    Amieva, Hélène; Mokri, Hind; Le Goff, Mélanie; Meillon, Céline; Jacqmin-Gadda, Hélène; Foubert-Samier, Alexandra; Orgogozo, Jean-Marc; Stern, Yaakov; Dartigues, Jean-François

    2014-04-01

    A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimer's dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimer's disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimer's dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up. The sample comprises 442 participants with incident Alzheimer's disease (27.2% were male)--171 with low education (mean age=86.2 years; standard deviation=5.3 years) and 271 with higher education (mean age=86.5; standard deviation=5.4)--and 442 control subjects matched according to age, sex and education. At each visit and up to the 20-year follow-up visit, several cognitive and clinical measures were collected and incident cases of Alzheimer's disease clinically diagnosed. The evolution of clinical measures in pre-demented subjects and matched controls was analysed with a semi-parametric extension of the mixed effects linear model. The results show that the first signs of cognitive decline occurred 15 to 16 years before achieving dementia threshold in higher-educated subjects whereas signs occurred at 7 years before dementia in low-educated subjects. There seemed to be two successive periods of decline in higher-educated subjects. Decline started ∼15 to 16 years before dementia with subtle impairment restricted to some cognitive tests and with no impact during the first 7 to 8 years on global cognition, cognitive complaints, or activities of daily living scales. Then, ∼7 years before dementia, global cognitive abilities begin to deteriorate, along with difficulties dealing with complex activities of daily living, the increase in self-perceived difficulties and depressive symptoms. By contrast, lower-educated subjects presented a single period of decline lasting ∼7 years, characterized by

  9. An attempt for a unified description of mechanical testing on Zircaloy-4 cladding subjected to simulated LOCA transient

    Directory of Open Access Journals (Sweden)

    Desquines Jean

    2016-01-01

    Full Text Available During a Loss Of Coolant Accident (LOCA, an important safety requirement is that the reflooding of the core by the emergency core cooling system should not lead to a complete rupture of the fuel rods. Several types of mechanical tests are usually performed in the industry to determine the degree of cladding embrittlement, such as ring compression tests or four-point bending of rodlets. Many other tests can be found in the open literature. However, there is presently no real intrinsic understanding of the failure conditions in these tests which would allow translation of the results from one kind of mechanical testing to another. The present study is an attempt to provide a unified description of the failure not directly depending on the tested geometry. This effort aims at providing a better understanding of the link between several existing safety criteria relying on very different mechanical testing. To achieve this objective, the failure mechanisms of pre-oxidized and pre-hydrided cladding samples are characterized by comparing the behavior of two different mechanical tests: Axial Tensile (AT test and “C”-shaped Ring Compression Test (CCT. The failure of samples in both cases can be described by usual linear elastic fracture mechanics theory. Using interrupted mechanical tests, metallographic examinations have evidenced that a set of parallel cracks are nucleated at the inner and outer surface of the samples just before failure, crossing both the oxide layer and the oxygen rich alpha layer. The stress intensity factors for multiple crack geometry are determined for both AT and CCT samples using finite element calculations. After each mechanical test performed on high temperature steam oxidized samples, metallography is then used to individually determine the crack depth and crack spacing. Using these two important parameters and considering the applied load at fracture, the stress intensity factor at failure is derived for each tested

  10. Cross-Reactivity, Epitope Spreading, and De Novo Immune Stimulation Are Possible Mechanisms of Cross-Protection of Nonvaccine Human Papillomavirus (HPV) Types in Recipients of HPV Therapeutic Vaccines

    Science.gov (United States)

    Greenfield, William; Moerman-Herzog, Andrea; Coleman, Hannah N.

    2015-01-01

    Numerous versions of human papillomavirus (HPV) therapeutic vaccines designed to treat individuals with established HPV infection, including those with cervical intraepithelial neoplasia (CIN), are in development because approved prophylactic vaccines are not effective once HPV infection is established. As human papillomavirus 16 (HPV-16) is the most commonly detected type worldwide, all versions of HPV therapeutic vaccines contain HPV-16, and some also contain HPV-18. While these two HPV types are responsible for approximately 70% of cervical cancer cases, there are other high-risk HPV types known to cause malignancy. Therefore, it would be of interest to assess whether these HPV therapeutic vaccines may confer cross-protection against other high-risk HPV types. Data available from a few clinical trials that enrolled subjects with CINs regardless of the HPV type(s) present demonstrated clinical responses, as measured by CIN regression, in subjects with both vaccine-matched and nonvaccine HPV types. The currently available evidence demonstrating cross-reactivity, epitope spreading, and de novo immune stimulation as possible mechanisms of cross-protection conferred by investigational HPV therapeutic vaccines is discussed. PMID:25947147

  11. Preventing Facial Nerve Stimulation by Triphasic Pulse Stimulation in Cochlear Implant Users: Intraoperative Recordings.

    Science.gov (United States)

    Bahmer, Andreas; Adel, Youssef; Baumann, Uwe

    2017-12-01

    Triphasic pulse stimulation of the auditory nerve can prevent unintended facial nerve stimulation (FNS) due to a different electromyographic (EMG) input-output function compared with biphasic pulses. FNS is sometimes observed in cochlear implant (CI) users as an unpleasant side effect of electrical stimulation using biphasic pulse patterns (BPP). Clinical remedies to alleviate FNS are 1) to extend stimulus phase duration or 2) to completely deactivate the electrode. In some cases, these options do not provide sufficient FNS reduction or are detrimental to subject performance. Stimulation using triphasic pulse patterns (TPP) has been shown to prevent FNS more effectively, yet the underlying mechanism remains unclear. EMG potentials of muscles innervated by the facial nerve (orbicularis oculi and oris muscles) were recorded to quantitatively compare the effect of BPP and TPP stimulation on FNS. Recordings were conducted in five subjects during CI surgery. In two exemplary cases, different leading phase polarities in alternating and non-alternating order were tested. Compared with our previous study in awake patients using surface electrodes (Bahmer and Baumann, 2016), intraoperative recordings using subdermal electrodes showed lower noise content and allowed higher sampling resolution. While inter-subject variation remained high, intra-subject results for different electrode positions were comparable: FNS was strongly reduced for cathodic-first TPP stimulation. In contrast, exemplary cases showed little reduction for anodic-first TPP as well as for alternating stimulation. FNS in CI users can be reduced using TPP stimulation, but the ameliorative effect appears to be dependent on the leading stimulus polarity.

  12. Almen intensity effect on microstructure and mechanical properties of low carbon steel subjected to severe shot peening

    Energy Technology Data Exchange (ETDEWEB)

    Unal, Okan, E-mail: ounal@bartin.edu.tr [Department of Mechanical Engineering, Bartin University, 74100, Bartin (Turkey); Varol, Remzi, E-mail: remzivarol@sdu.edu.tr [Department of Mechanical Engineering, Suleyman Demirel University, 32260 Isparta (Turkey)

    2014-01-30

    This paper discusses alteration of microstructure and mechanical properties of low carbon steel after severe shot peening process. An ultra fine grained surface layer was formed on AISI 1017 mild steel by means of severe shot peening process. Surface characteristics were affirmed using optical microscopy, scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HRTEM). Nano hardness measurements were taken along the depth from shot peened surface using nanoindentation methods. The results showed that severe (unconventional) air blast shot peening process is an effective way to obtain ultra fine grained surface layer and to obtain superior mechanical properties.

  13. Shear stress stimulates phosphorylation of endothelial nitric-oxide synthase at Ser1179 by Akt-independent mechanisms: role of protein kinase A

    Science.gov (United States)

    Boo, Yong Chool; Sorescu, George; Boyd, Nolan; Shiojima, Ichiro; Walsh, Kenneth; Du, Jie; Jo, Hanjoong

    2002-01-01

    Recently, we have shown that shear stress stimulates NO(*) production by the protein kinase B/Akt (Akt)-dependent mechanisms in bovine aortic endothelial cells (BAEC) (Go, Y. M., Boo, Y. C., Park, H., Maland, M. C., Patel, R., Pritchard, K. A., Jr., Fujio, Y., Walsh, K., Darley-Usmar, V., and Jo, H. (2001) J. Appl. Physiol. 91, 1574-1581). Akt has been believed to regulate shear-dependent production of NO(*) by directly phosphorylating endothelial nitric-oxide synthase (eNOS) at the Ser(1179) residue (eNOS-S(1179)), but a critical evaluation using specific inhibitors or dominant negative mutants (Akt(AA) or Akt(AAA)) has not been reported. In addition, other kinases, including protein kinase A (PKA) and AMP kinase have also shown to phosphorylate eNOS-S(1179). Here, we show that shear-dependent phosphorylation of eNOS-S(1179) is mediated by an Akt-independent, but a PKA-dependent, mechanism. Expression of Akt(AA) or Akt(AAA) in BAEC by using recombinant adenoviral constructs inhibited phosphorylation of eNOS-S(1179) if cells were stimulated by vascular endothelial growth factor (VEGF), but not by shear stress. As shown before, expression of Akt(AA) inhibited shear-dependent NO(*) production, suggesting that Akt is still an important regulator in NO production. Further studies showed that a selective inhibitor of PKA, H89, inhibited shear-dependent phosphorylation of eNOS-S(1179) and NO(*) production. In contrast, H89 did not inhibit phosphorylation of eNOS-S(1179) induced by expressing a constitutively active Akt mutant (Akt(Myr)) in BAEC, showing that the inhibitor did not affect the Akt pathway. 8-Bromo-cAMP alone phosphorylated eNOS-S(1179) within 5 min without activating Akt, in an H89-sensitive manner. Collectively, these results demonstrate that shear stimulates phosphorylation of eNOS-S(1179) in a PKA-dependent, but Aktindependent manner, whereas the NO(*) production is regulated by the mechanisms dependent on both PKA and Akt. A coordinated interaction

  14. Exosomes bind to autotaxin and act as a physiological delivery mechanism to stimulate LPA receptor signalling in cells

    Science.gov (United States)

    Jethwa, Susanna A.; Leah, Emma J.; Zhang, Qifeng; Bright, Nicholas A.; Oxley, David; Bootman, Martin D.; Rudge, Simon A.

    2016-01-01

    ABSTRACT Autotaxin (ATX; also known as ENPP2), the lysophospholipase responsible for generating the lipid receptor agonist lysophosphatidic acid (LPA), is a secreted enzyme. Here we show that, once secreted, ATX can bind to the surface of cell-secreted exosomes. Exosome-bound ATX is catalytically active and carries generated LPA. Once bound to a cell, through specific integrin interactions, ATX releases the LPA to activate cell surface G-protein-coupled receptors of LPA; inhibition of signalling by the receptor antagonist Ki1642 suggests that these receptors are LPAR1 and LPAR3. The binding stimulates downstream signalling, including phosphorylation of AKT and mitogen-activated protein kinases, the release of intracellular stored Ca2+ and cell migration. We propose that exosomal binding of LPA-loaded ATX provides a means of efficiently delivering the lipid agonist to cell surface receptors to promote signalling. We further propose that this is a means by which ATX–LPA signalling operates physiologically. PMID:27557622

  15. Mechanism of Werner DNA helicase: POT1 and RPA stimulates WRN to unwind beyond gaps in the translocating strand.

    Directory of Open Access Journals (Sweden)

    Byungchan Ahn

    Full Text Available WRN belongs to the RecQ family of DNA helicases and it plays a role in recombination, replication, telomere maintenance and long-patch base excision repair. Here, we demonstrate that WRN efficiently unwinds DNA substrates containing a 1-nucleotide gap in the translocating DNA strand, but when the gap size is increased to 3-nucleotides unwinding activity significantly declines. In contrast, E. coli UvrD (3'-->5' helicase, which recognizes nicks in DNA to initiate unwinding, does not unwind past a 1-nucleotide gap. This unique ability of WRN to bypass gaps supports its involvement in DNA replication and LP-BER where such gaps can be produced by glycosylases and the apurinic/apyrimidinic endonuclease 1 (APE1. Furthermore, we tested telomere repeat binding factor 2 (TRF2, both variants 1 and 2 of protector of telomeres 1 (POT1v1 and POT1v2 and RPA on telomeric DNA substrates containing much bigger gaps than 3-nucleotides in order to determine whether unwinding could be facilitated through WRN-protein interaction. Interestingly, POT1v1 and RPA are capable of stimulating WRN helicase on gapped DNA and 5'-overhang substrates, respectively.

  16. Mechanical unfolding kinetics of the SRV-1 gag-pro mRNA pseudoknot: possible implications for -1 ribosomal frameshifting stimulation

    Science.gov (United States)

    Zhong, Zhensheng; Yang, Lixia; Zhang, Haiping; Shi, Jiahao; Vandana, J. Jeya; Lam, Do Thuy Uyen Ha; Olsthoorn, René C. L.; Lu, Lanyuan; Chen, Gang

    2016-12-01

    Minus-one ribosomal frameshifting is a translational recoding mechanism widely utilized by many RNA viruses to generate accurate ratios of structural and catalytic proteins. An RNA pseudoknot structure located in the overlapping region of the gag and pro genes of Simian Retrovirus type 1 (SRV-1) stimulates frameshifting. However, the experimental characterization of SRV-1 pseudoknot (un)folding dynamics and the effect of the base triple formation is lacking. Here, we report the results of our single-molecule nanomanipulation using optical tweezers and theoretical simulation by steered molecular dynamics. Our results directly reveal that the energetic coupling between loop 2 and stem 1 via minor-groove base triple formation enhances the mechanical stability. The terminal base pair in stem 1 (directly in contact with a translating ribosome at the slippery site) also affects the mechanical stability of the pseudoknot. The -1 frameshifting efficiency is positively correlated with the cooperative one-step unfolding force and inversely correlated with the one-step mechanical unfolding rate at zero force. A significantly improved correlation was observed between -1 frameshifting efficiency and unfolding rate at forces of 15-35 pN, consistent with the fact that the ribosome is a force-generating molecular motor with helicase activity. No correlation was observed between thermal stability and -1 frameshifting efficiency.

  17. Brain Stimulation in Addiction.

    Science.gov (United States)

    Salling, Michael C; Martinez, Diana

    2016-11-01

    Localized stimulation of the human brain to treat neuropsychiatric disorders has been in place for over 20 years. Although these methods have been used to a greater extent for mood and movement disorders, recent work has explored brain stimulation methods as potential treatments for addiction. The rationale behind stimulation therapy in addiction involves reestablishing normal brain function in target regions in an effort to dampen addictive behaviors. In this review, we present the rationale and studies investigating brain stimulation in addiction, including transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Overall, these studies indicate that brain stimulation has an acute effect on craving for drugs and alcohol, but few studies have investigated the effect of brain stimulation on actual drug and alcohol use or relapse. Stimulation therapies may achieve their effect through direct or indirect modulation of brain regions involved in addiction, either acutely or through plastic changes in neuronal transmission. Although these mechanisms are not well understood, further identification of the underlying neurobiology of addiction and rigorous evaluation of brain stimulation methods has the potential for unlocking an effective, long-term treatment of addiction.

  18. Enhanced Soft Tissue Attachment and Fixation Using a Mechanically-Stimulated Cytoselective Tissue-Specific ECM Coating

    Science.gov (United States)

    2012-08-01

    The original Page 18 of 38 design used Weld -On 4 as a welding /bonding agent to create a watertight seal between the walls and base of the chamber...Two main design changes occurred. The first change involved removing the Weld -On and using clear 100% silicone as a weld /caulk and 316L stainless...to understanding the effects of culture and mechanical strains on the scaffolding construct prior to implantation . Task 6 is completed

  19. Molecular mechanism of ethylene stimulation of latex yield in rubber tree (Hevea brasiliensis) revealed by de novo sequencing and transcriptome analysis.

    Science.gov (United States)

    Liu, Jin-Ping; Zhuang, Yu-Fen; Guo, Xiu-Li; Li, Yi-Jian

    2016-03-24

    Rubber tree (Hevea brasiliensis) is an important industrial crop cultivated in tropical areas for natural rubber production. Treatment of the bark of rubber trees with ehephon (an ethylene releaser) has been a routine measure to increase latex yield, but the molecular mechanism behind the stimulation of rubber production by ethylene still remains a puzzle. Deciphering the enigma is of great importance for improvement of rubber tree for high yield. De novo sequencing and assembly of the bark transciptomes of Hevea brasiliensis induced with ethephon for 8 h (E8) and 24 h (E24) were performed. 51,965,770, 52,303,714 and 53,177,976 high-quality clean reads from E8, E24 and C (control) samples were assembled into 81,335, 80,048 and 80,800 unigenes respectively, with a total of 84,425 unigenes and an average length of 1,101 bp generated. 10,216 and 9,374 differentially expressed genes (DEGs) in E8 and E24 compared with C were respectively detected. The expression of several enzymes in crucial points of regulation in glycolysis were up-regulated and DEGs were not significantly enriched in isopentenyl diphosphate (IPP) biosynthesis pathway. In addition, up-regulated genes of great regulatory importance in carbon fixation (Calvin cycle) were identified. The rapid acceleration of glycolytic pathway supplying precursors for the biosynthesis of IPP and natural rubber, instead of rubber biosynthesis per se, may be responsible for ethylene stimulation of latex yield in rubber tree. The elevated rate of flux throughout the Calvin cycle may account for some durability of ethylene-induced stimulation. Our finding lays the foundations for molecular diagnostic and genetic engineering for high-yielding improvement of rubber tree.

  20. Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A2-dependent mechanism

    Science.gov (United States)

    Itagaki, Kiyoshi; Menconi, Michael; Antoniu, Bozena; Zhang, Qin; Gonnella, Patricia; Soybel, David; Hauser, Carl

    2010-01-01

    Muscle wasting in various catabolic conditions is at least in part regulated by glucocorticoids. Increased calcium levels have been reported in atrophying muscle. Mechanisms regulating calcium homeostasis in muscle wasting, in particular the role of glucocorticoids, are poorly understood. Here we tested the hypothesis that glucocorticoids increase intracellular calcium concentrations in skeletal muscle and stimulate store-operated calcium entry (SOCE) and that these effects of glucocorticoids may at least in part be responsible for glucocorticoid-induced protein degradation. Treatment of cultured myotubes with dexamethasone, a frequently used in vitro model of muscle wasting, resulted in increased intracellular calcium concentrations determined by fura-2 AM fluorescence measurements. When SOCE was measured by using calcium “add-back” to muscle cells after depletion of intracellular calcium stores, results showed that SOCE was increased 15–25% by dexamethasone and that this response to dexamethasone was inhibited by the store-operated calcium channel blocker BTP2. Dexamethasone treatment stimulated the activity of calcium-independent phospholipase A2 (iPLA2), and dexamethasone-induced increase in SOCE was reduced by the iPLA2 inhibitor bromoenol lactone (BEL). In additional experiments, treatment of myotubes with the store-operated calcium channel inhibitor gadolinium ion or BEL reduced dexamethasone-induced increase in protein degradation. Taken together, the results suggest that glucocorticoids increase calcium concentrations in myocytes and stimulate iPLA2-dependent SOCE and that glucocorticoid-induced muscle protein degradation may at least in part be regulated by increased iPLA2 activity, SOCE, and cellular calcium levels. PMID:20107037

  1. A two dimensional fibre reinforced micropolar thermoelastic problem for a half-space subjected to mechanical force

    Directory of Open Access Journals (Sweden)

    Ailawalia Praveen

    2015-01-01

    Full Text Available The purpose of this paper is to study the two dimensional deformation of fibre reinforced micropolar thermoelastic medium in the context of Green-Lindsay theory of thermoelasticity. A mechanical force is applied along the interface of fluid half space and fibre reinforced micropolar thermoelastic half space. The normal mode analysis has been applied to obtain the exact expressions for displacement component, force stress, temperature distribution and tangential couple stress. The effect of anisotropy and micropolarity on the displacement component, force stress, temperature distribution and tangential couple stress has been depicted graphically.

  2. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver

    NARCIS (Netherlands)

    Beuers, U.; Bilzer, M.; Chittattu, A.; Kullak-Ublick, G. A.; Keppler, D.; Paumgartner, G.; Dombrowski, F.

    2001-01-01

    Ursodeoxycholic acid (UDCA) exerts anticholestatic effects by undefined mechanisms. Previous work suggested that UDCA stimulates biliary exocytosis via Ca(++)- and protein kinase C (PKC)-dependent mechanisms. Therefore, the effect of taurine-conjugated UDCA (TUDCA) was studied in the experimental

  3. Synergistic activation of vascular TRPC6 channel by receptor and mechanical stimulation via phospholipase C/diacylglycerol and phospholipase A2/¿-hydroxylase/20-HETE pathways

    DEFF Research Database (Denmark)

    Inoue, Ryuji; Jensen, Lars Jørn; Jian, Zhong

    2009-01-01

    interactions of receptor and mechanical stimulations in activating this channel using the patch clamp technique. In HEK293 cells expressing TRPC6, application of mechanical stimuli (hypotonicity, shear, 2,4,6-trinitrophenol) caused, albeit not effective by themselves, a prominent potentiation of cationic...

  4. Noninvasive Spinal Cord Stimulation: Technical Aspects and Therapeutic Applications.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Taylor, Alexandra; Thomschewski, Aljoscha; Orioli, Andrea; Frey, Vanessa; Trinka, Eugen; Brigo, Francesco

    2015-10-01

    Electrical and magnetic trans-spinal stimulation can be used to increase the motor output of multiple spinal segments and modulate cortico-spinal excitability. The application of direct current through the scalp as well as repetitive transcranial magnetic stimulation are known to influence brain excitability, and hence can also modulate other central nervous system structures, including spinal cord. This study aimed to evaluate the effects and the therapeutic usefulness of these noninvasive neuromodulatory techniques in healthy subjects and in the neurorehabilitation of patients with spinal cord disorders, as well as to discuss the possible mechanisms of action. A comprehensive review that summarizes previous studies using noninvasive spinal cord stimulation is lacking. PubMed (MEDLINE) and EMBASE were systematically searched to identify the most relevant published studies. We performed here an extensive review in this field. By decreasing the spinal reflex excitability, electrical and magnetic trans-spinal stimulation could be helpful in normalizing reflex hyperexcitability and treating hypertonia in subjects with lesions to upper motor neurons. Transcutaneous spinal direct current stimulation, based on applying direct current through the skin, influences the ascending and descending spinal pathways as well as spinal reflex excitability, and there is increasing evidence that it also can induce prolonged functional neuroplastic changes. When delivered repetitively, magnetic stimulation could also modulate spinal cord functions; however, at present only a few studies have documented spastic-reducing effects induced by repetitive spinal magnetic stimulation. Moreover, paired peripheral and transcranial stimulation can be used to target the spinal cord and may have potential for neuromodulation in spinal cord-injured subjects. Noninvasive electrical and magnetic spinal stimulation may provide reliable means to characterize important neurophysiologic and

  5. Mechanical Properties and Real-Time Damage Evaluations of Environmental Barrier Coated SiC/SiC CMCs Subjected to Tensile Loading Under Thermal Gradients

    Science.gov (United States)

    Appleby, Matthew; Zhu, Dongming; Morscher, Gregory

    2015-01-01

    SiC/SiC ceramic matrix composites (CMCs) require new state-of-the art environmental barrier coatings (EBCs) to withstand increased temperature requirements and high velocity combustion corrosive combustion gasses. The present work compares the response of coated and uncoated SiC/SiC CMC substrates subjected to simulated engine environments followed by high temperature mechanical testing to asses retained properties and damage mechanisms. Our focus is to explore the capabilities of electrical resistance (ER) measurements as an NDE technique for testing of retained properties under combined high heat-flux and mechanical loading conditions. Furthermore, Acoustic Emission (AE) measurements and Digital Image Correlation (DIC) were performed to determine material damage onset and accumulation.

  6. Polycystins and intercellular mechanotransduction: A precise dosage of polycystin 2 is necessary for alpha-actinin reinforcement of junctions upon mechanical stimulation.

    Science.gov (United States)

    Bhoonderowa, Laxsoomee; Hameurlaine, Fatima; Arbabian, Atousa; Faqir, Fahima; Amblard, François; Coscoy, Sylvie

    2016-10-15

    Polycystins 1 and 2, which are mutated in Autosomal Polycystic Kidney Disease, are involved in mechanotransduction through various mechanisms. In renal cells, polycystins not only have an important mechanotransductive role in primary cilia but are also present in intercellular contacts but their role there remains unclear. Here, we address the hypothesis that polycystins are involved in mechanotransduction via intercellular junctions, which would be expected to have consequences on tissue organization. We focused on the role of polycystin 2, which could be involved in mechanical organization at junctions either by its channel activity or by the direct recruitment of cytoskeleton components such as the F-actin cross-linker α-actinin. After mechanical stimulation of intercellular junctions in MDCK renal epithelial cells, α-actinin is rapidly recruited but this is inhibited upon overexpression of PC2 or the D509V mutant that lacks channel activity, and is also decreased upon PC2 silencing. This suggests that a precise dosage of PC2 is necessary for an adequate mechanosensitive α-actinin recruitment at junctions. At the multicellular level, a change in PC2 expression was associated with changes in velocity in confluent epithelia and during wound healing together with a loss of orientation. This study suggests that the mechanosensitive regulation of cytoskeleton by polycystins in intercellular contacts may be important in the context of ADPKD. Copyright © 2016. Published by Elsevier Inc.

  7. Mechanisms involved in the homologous down-regulation of transcription of the follicle-stimulating hormone receptor gene in Sertoli cells.

    Science.gov (United States)

    Griswold, M D; Kim, J S; Tribley, W A

    2001-02-28

    The action of follicle-stimulating hormone (FSH) in spermatogenesis is regulated at a fundamental level by controlling the number of competent receptors present at the surface of Sertoli cells. By controlling the number of receptors, the cell is able to modulate the timing and magnitude of subsequent signal transduction in response to FSH. One mechanism of control is the down-regulation of the steady state levels of the FSH receptor gene after exposure to FSH or agents that stimulate or prolong the cAMP signal transduction cascade (homologous down-regulation) in Sertoli cells. The goals of this study were to examine possible mechanisms involved in the down-regulation of mRNA levels of this gene. Analysis of transcription and processing by a PCR-based assay showed that treatment of Sertoli cells with FSH caused at least a 50% reduction of hnRNA for the FSH receptor gene. Reporter genes controlled by 5' flanking sequences of the FSH receptor gene that were transiently transfected into Sertoli cells were not down-regulated. In electrophoretic mobility shift assays (EMSA), cAMP-inducible nuclear protein complex containing c-Fos formed on the activator protein-1/cAMP responsive element-like site located at -216 to -210 in the promoter of the rat FSH receptor gene. We concluded from this study that there was no evidence for the putative role of ICER in the down-regulation of the FSH receptor promoter. In addition, the FSH-induced down-regulation of the transcription of the FSH receptor gene in Sertoli cells was prevented by the treatment of Sertoli cells with trichostatin A prior to the addition of FSH. This experiment coupled with other observations suggested that the down-regulation may be mediated by changes in chromatin structure.

  8. Mechanical-tactile stimulation (MTS) intervention in a neonatal stress model alters adult adipose tissue deposition and prevents hyperinsulinemia in male rats.

    Science.gov (United States)

    Haley, Shannon; Neff, Kimberly; Gulliver, Kristina; Gough, Grace; Slater, Hillarie; Lane, Robert H; Moyer-Mileur, Laurie J

    2013-06-01

    Preterm infants are exposed to numerous stressors during hospitalization and by term corrected gestational age they have lower body weight but a greater proportion of total body as well as abdominal visceral adipose tissue (VAT) accumulation. Greater abdominal VAT stores have a known association with metabolic syndrome. Mechanical-tactile stimulation (MTS) improves modulation of stress response in both humans and rodents. We hypothesize that MTS, administered during an established model of neonatal stress, would decrease stress-driven adiposity and prevent associated metabolic imbalances in adult rats. Neonatal stress, administered to rat pups from postnatal days 5 to P9, consisted of needle puncture and hypoxic/hyperoxic challenge during 60 min of maternal separation (STRESS; n=20). Mechanical-tactile stimulation (MTS; n=20) was administered to rat pups for 10 min during maternal separation in the stress protocol. Control animals received standard care (CTL; n=20). MRI measured adult (P120) abdominal total fat mass, subcutaneous (SAT) and visceral adipose tissue (VAT). Body weight and fasting serum adiponectin, leptin, glucose, insulin, and corticosterone were also measured. STRESS results in elevated VAT/SAT ratio compared to CTL but lower abdominal total fat mass and abdominal SAT. STRESS males experience hyperinsulinemia. Both STRESS and MTS had elevated leptin with lower adiponectin and corticosterone compared to CTL. In summary, neonatal stress promotes greater abdominal VAT accumulation and, in males, caused hyperinsulinemia and hypoadiponectinemia. Importantly, MTS normalized the VAT/SAT ratio and prevented hyperinsulinemia. We speculate that MTS ameliorates some of the negative metabolic consequences of early life perturbations due to neonatal stress exposure. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells

    Directory of Open Access Journals (Sweden)

    Murphy Fiona A

    2012-04-01

    Full Text Available Abstract Carbon nanotubes (CNT are high aspect ratio nanoparticles with diameters in the nanometre range but lengths extending up to hundreds of microns. The structural similarities between CNT and asbestos have raised concern that they may pose a similar inhalation hazard. Recently CNT have been shown to elicit a length-dependent, asbestos-like inflammatory response in the pleural cavity of mice, where long fibres caused inflammation but short fibres did not. However the cellular mechanisms governing this response have yet to be elucidated. This study examined the in vitro effects of a range of CNT for their ability to stimulate the release of the acute phase cytokines; IL-1β, TNFα, IL-6 and the chemokine, IL-8 from both Met5a mesothelial cells and THP-1 macrophages. Results showed that direct exposure to CNT resulted in significant cytokine release from the macrophages but not mesothelial cells. This pro-inflammatory response was length dependent but modest and was shown to be a result of frustrated phagocytosis. Furthermore the indirect actions of the CNT were examined by treating the mesothelial cells with conditioned media from CNT-treated macrophages. This resulted in a dramatic amplification of the cytokine release from the mesothelial cells, a response which could be attenuated by inhibition of phagocytosis during the initial macrophage CNT treatments. We therefore hypothesise that long fibres elicit an inflammatory response in the pleural cavity via frustrated phagocytosis in pleural macrophages. The activated macrophages then stimulate an amplified pro-inflammatory cytokine response from the adjacent pleural mesothelial cells. This mechanism for producing a pro-inflammatory environment in the pleural space exposed to long CNT has implications for the general understanding of fibre-related pleural disease and design of safe nanofibres.

  10. A new paradigm for aptamer therapeutic AS1411 action: uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism.

    Science.gov (United States)

    Reyes-Reyes, E Merit; Teng, Yun; Bates, Paula J

    2010-11-01

    AS1411 is a first-in-class anticancer agent, currently in phase II clinical trials. It is a quadruplex-forming oligodeoxynucleotide that binds to nucleolin as an aptamer, but its mechanism of action is not completely understood. Mechanistic insights could lead to clinically useful markers for AS1411 response and to novel targeted therapies. Previously, we proposed a model where cell surface nucleolin serves as the receptor for AS1411, leading to selective uptake in cancer cells. Here, we compare uptake of fluorophore-labeled AS1411 (FL-AS1411) in DU145 prostate cancer cells (sensitive to AS1411) and Hs27 nonmalignant skin fibroblasts (resistant to AS1411). Uptake of FL-AS1411 occurred by endocytosis in both cell types and was much more efficient than an inactive, nonquadruplex oligonucleotide. Unexpectedly, uptake of FL-AS1411 was lower in cancer cells compared with Hs27 cells. However, the mechanism of uptake was different, occurring by macropinocytosis in cancer cells, but by a nonmacropinocytic pathway in Hs27 cells. Additionally, treatment of various cancer cells with AS1411 caused hyperstimulation of macropinocytosis, provoking an increase in its own uptake, whereas no stimulation was observed for nonmalignant cells. Nucleolin was not required for initial FL-AS1411 uptake in DU145 cells but was necessary for induced macropinocytosis and FL-AS1411 uptake at later times. Our results are inconsistent with the previous mechanistic model but confirm that nucleolin plays a role in mediating AS1411 effects. The data suggest a new model for AS1411 action as well as a new role for nucleolin in stimulating macropinocytosis, a process with potential applications in drug delivery. ©2010 AACR.

  11. Mechanisms of the incretin effect in subjects with normal glucose tolerance and patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Mari, Andrea; Bagger, Jonatan I; Ferrannini, Ele

    2013-01-01

    The incretin effect on insulin secretion was investigated in 8 subjects with type 2 diabetes (T2D) and 8 with normal glucose tolerance (NGT), using 25, 75, and 125 g oral glucose tolerance tests (OGTT) and isoglycemic intravenous glucose infusions (IIGI). The ß-cell response was evaluated using...... a model embedding a dose-response (slope=glucose sensitivity), an early response (rate sensitivity), and potentiation (time-related secretion increase). The incretin effect, as OGTT/IIGI ratio, was calculated for each parameter. In NGT, the incretin effect on total secretion increased with dose (1.3 ± 0.......1, 1.7 ± 0.2, 2.2 ± 0.2 fold of IIGI, Peffect on glucose sensitivity (1.9 ± 0.4, 2.4 ± 0.4, 3.1 ± 0.4, P=0.005), and a dose-independent enhancement of the incretin effect on rate sensitivity (894 [1145], 454 [516], 783 [1259] pmol m(-2) L...

  12. Effects of Laser Shock Processing on Morphologies and Mechanical Properties of ANSI 304 Stainless Steel Weldments Subjected to Cavitation Erosion

    Science.gov (United States)

    Zhang, Lei; Lu, Jin-Zhong; Zhang, Yong-Kang; Ma, Hai-Le; Luo, Kai-Yu; Dai, Feng-Ze

    2017-01-01

    Effects of laser shock processing (LSP) on the cavitation erosion resistance of laser weldments were investigated by optical microscope (OM), scanning electron microscope (SEM) observations, roughness tester, micro hardness tester, and X-ray diffraction (XRD) technology. The morphological microstructures were characterized. Cumulative mass loss, incubation period, erosion rate, and damaged surface areas were monitored during cavitation erosion. Surface roughness, micro-hardness, and residual stress were measured in different zones. Results showed that LSP could improve the damage of morphological microstructures and mechanical properties after cavitation erosion. The compressive residual stresses were generated during the process of LSP, which was an effective guarantee for the improvement of the above mentioned properties. PMID:28772652

  13. Effects of Laser Shock Processing on Morphologies and Mechanical Properties of ANSI 304 Stainless Steel Weldments Subjected to Cavitation Erosion

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2017-03-01

    Full Text Available Effects of laser shock processing (LSP on the cavitation erosion resistance of laser weldments were investigated by optical microscope (OM, scanning electron microscope (SEM observations, roughness tester, micro hardness tester, and X-ray diffraction (XRD technology. The morphological microstructures were characterized. Cumulative mass loss, incubation period, erosion rate, and damaged surface areas were monitored during cavitation erosion. Surface roughness, micro-hardness, and residual stress were measured in different zones. Results showed that LSP could improve the damage of morphological microstructures and mechanical properties after cavitation erosion. The compressive residual stresses were generated during the process of LSP, which was an effective guarantee for the improvement of the above mentioned properties.

  14. Cough Augmentation in Subjects With Duchenne Muscular Dystrophy: Comparison of Air Stacking via a Resuscitator Bag Versus Mechanical Ventilation.

    Science.gov (United States)

    Toussaint, Michel; Pernet, Kurt; Steens, Marc; Haan, Jurn; Sheers, Nicole

    2016-01-01

    Air stacking improves cough effectiveness in people with Duchenne muscular dystrophy (DMD) and respiratory muscle weakness. However, it is not known whether air stacking is more effective via a resuscitator bag or a home ventilator. This prospective randomized study investigated the effect of air stacking via a volume-cycled home ventilator versus via a resuscitator bag in participants with DMD. Maximum insufflation capacity and peak expiratory flow during spontaneous (cough peak flow) and air stacking-assisted cough maneuvers (air stacking-assisted cough peak flow) were measured. Fifty-two adult DMD subjects receiving noninvasive ventilation were included in the study: 27 participants performed air stacking via their home ventilator (home-ventilator group; age = 25.3 ± 5.1 y; forced vital capacity (FVC) = 809 ± 555 mL), and 25 participants used a resuscitator bag (resuscitator-bag group; age = 24.7 ± 5.7 y, FVC = 807 ± 495 mL). Following a single training session, air stacking could be performed successfully by 89% (home ventilator) and 88% (resuscitator bag) of participants. There were comparable maximum insufflation capacities (1,481 mL for the home-ventilator group vs 1,344 mL for the resuscitator-bag group, P = .33) and mean air stacking-assisted cough peak flow values (199 L/min for the home-ventilator group vs 186 L/min for the resuscitator-bag group, P = .33) between techniques. Air stacking-assisted cough peak flow increased significantly compared with baseline in both groups (mean increase: +51% [home ventilator] vs +49% [resuscitator bag], P 160 L/min. Provision of an inexpensive resuscitator bag can effectively improve cough capacity, and it is simple to use, which may improve access to respiratory care in people with DMD. Copyright © 2016 by Daedalus Enterprises.

  15. Stimulant and sedative effects of alcohol.

    Science.gov (United States)

    Hendler, Reuben A; Ramchandani, Vijay A; Gilman, Jodi; Hommer, Daniel W

    2013-01-01

    Alcohol produces both stimulant and sedating effects in humans. These two seemingly opposite effects are central to the understanding of much of the literature on alcohol use and misuse. In this chapter we review studies that describe and attempt to measure various aspects of alcohol's subjective, autonomic, motor, cognitive and behavioral effects from the perspective of stimulation and sedation. Although subjective sedative and stimulatory effects can be measured, it is not entirely clear if all motor, cognitive and behavioral effects can be unambiguously assigned to either one or the other category. Increased heart rate and aggression seem strongly associated with stimulation, but motor slowing and cognitive impairment can also show a similar time course to stimulation, making their relation to sedation problematic. There is good agreement that alcohol's ability to induce striatal dopamine release is the mechanism underlying alcohol's stimulatory effects; however, the change in brain function underlying sedation is less well understood. In general, stimulatory effects are thought to be more rewarding than sedative effects, but this may not be true for anxiolytic effects which seem more closely related to sedation than stimulation. The two major theories of how response to alcohol predicts risk for alcoholism both postulate that individuals at high risk for alcohol use disorders have a reduced sedative response to alcohol compared to individuals not at high risk. In addition one theory proposes that alcoholism risk is also associated with a larger stimulatory response to alcohol.

  16. Low Stress Mechanical Properties of Plasma-Treated Cotton Fabric Subjected to Zinc Oxide-Anti-Microbial Treatment

    Directory of Open Access Journals (Sweden)

    Chi-Wai Kan

    2013-01-01

    Full Text Available Cotton fabrics are highly popular because of their excellent properties such as regeneration, bio-degradation, softness, affinity to skin and hygroscopic properties. When in contact with the human body, cotton fabrics offer an ideal environment for microbial growth due to their ability to retain oxygen, moisture and warmth, as well as nutrients from spillages and body sweat. Therefore, an anti-microbial coating formulation (Microfresh and Microban together with zinc oxide as catalyst was developed for cotton fabrics to improve treatment effectiveness. In addition, plasma technology was employed in the study which roughened the surface of the materials, improving the loading of zinc oxides on the surface. In this study, the low stress mechanical properties of plasma pre-treated and/or anti-microbial-treated cotton fabric were studied. The overall results show that the specimens had improved bending properties when zinc oxides were added in the anti-microbial coating recipe. Also, without plasma pre-treatment, anti-microbial-treatment of cotton fabric had a positive effect only on tensile resilience, shear stress at 0.5° and compressional energy, while plasma-treated specimens had better overall tensile properties even after anti-microbial treatment.

  17. Fully Hydro-Mechanically Coupled Experiments and Simulations on Rough Fractures Subjected to High-Pressure Fluid Injection

    Science.gov (United States)

    Vogler, D.; Settgast, R.; Annavarapu, C.; Madonna, C.; Bayer, P.; Amann, F.

    2016-12-01

    This work presents fully hydro-mechanically coupled experiments and simulations in heterogeneous fractures. Cylindrical specimens with an artificial fracture normal to the cylinder axis were axially loaded to evaluate: (i) fracture normal closure; (ii) fracture contact stress evolution; and (iii) fracture normal closure and fluid injection pressure response. The laboratory experiments were simulated with the GEOS framework, which captures the non-linear behavior of fracture normal closure and fluid pressure response. To apply the developed model on the field scale, a heterogeneous fracture aperture field is created from aperture data recorded under zero-stress on natural tensile fractures from the Grimsel Test Site (GTS), Switzerland. The field stresses measured in the GTS are applied on the model domain, yielding the unique aperture distribution and stress perturbations in the rock mass associated with the applied stress state. Next, fluid is injected into the fracture center and tortuous flow channeling is observed. Increasing fluid injection pressures result in localized fracture opening, which leads to an increasingly non-linear relationship between fluid injection flow rate and pressure.

  18. Mechanism of Butyrate Stimulation of Triglyceride Storage and Adipokine Expression during Adipogenic Differentiation of Porcine Stromovascular Cells

    Science.gov (United States)

    Yan, Hui; Ajuwon, Kolapo M.

    2015-01-01

    Short chain fatty acids (SCFA), products of microbial fermentation of dietary fiber, exert multiple metabolic effects in cells. Previously, we had demonstrated that soluble fiber influenced fat mass accumulation, gut microbial community structure and SCFA production in pigs. The current study was designed to identify effects of SCFA treatment during adipogenic differentiation of porcine stromovascular cells on lipid metabolism and adipokine expression. Differentiating cells were treated with varying concentrations of butyrate. Results show that butyrate treatment enhanced adipogenesis and lipid accumulation, perhaps through upregulation of glucose uptake and de novo lipogenesis and other mechanisms that include induction of SREBP-1c, C/EBPα/β, GLUT4, LPL, PPARγ, GPAT4, DGAT1 and DGAT2 expression. In addition, butyrate induced adiponectin expression, resulting in activation of downstream target genes, such as AMPK and AKT. Activation of AMPK by butyrate led to phosphorylation of ACC. Although increased ACO gene expression was seen with butyrate treatment, experiments with the peroxisomal fatty acid inhibitor, thioridazine, suggest that butyrate may have an inhibitory effect on peroxisomal fatty acid oxidation. Our studies also provide evidence that butyrate may inhibit lipolysis, perhaps in an FFAR3-dependent manner. Therefore, this study presents a novel paradigm for butyrate action in adipocytes and shows that adipocytes are capable of utilizing butyrate, leading to increased expression of adiponectin for enhanced glucose uptake and improved insulin sensitivity. PMID:26713737

  19. Mechanism of Butyrate Stimulation of Triglyceride Storage and Adipokine Expression during Adipogenic Differentiation of Porcine Stromovascular Cells.

    Directory of Open Access Journals (Sweden)

    Hui Yan

    Full Text Available Short chain fatty acids (SCFA, products of microbial fermentation of dietary fiber, exert multiple metabolic effects in cells. Previously, we had demonstrated that soluble fiber influenced fat mass accumulation, gut microbial community structure and SCFA production in pigs. The current study was designed to identify effects of SCFA treatment during adipogenic differentiation of porcine stromovascular cells on lipid metabolism and adipokine expression. Differentiating cells were treated with varying concentrations of butyrate. Results show that butyrate treatment enhanced adipogenesis and lipid accumulation, perhaps through upregulation of glucose uptake and de novo lipogenesis and other mechanisms that include induction of SREBP-1c, C/EBPα/β, GLUT4, LPL, PPARγ, GPAT4, DGAT1 and DGAT2 expression. In addition, butyrate induced adiponectin expression, resulting in activation of downstream target genes, such as AMPK and AKT. Activation of AMPK by butyrate led to phosphorylation of ACC. Although increased ACO gene expression was seen with butyrate treatment, experiments with the peroxisomal fatty acid inhibitor, thioridazine, suggest that butyrate may have an inhibitory effect on peroxisomal fatty acid oxidation. Our studies also provide evidence that butyrate may inhibit lipolysis, perhaps in an FFAR3-dependent manner. Therefore, this study presents a novel paradigm for butyrate action in adipocytes and shows that adipocytes are capable of utilizing butyrate, leading to increased expression of adiponectin for enhanced glucose uptake and improved insulin sensitivity.

  20. Estimulação transcraniana não invasiva em indivíduos com paralisia cerebral: uma revisão integrativa da literatura = Noninvasive brain stimulation in subjects with cerebral palsy: a integrative literature review

    National Research Council Canada - National Science Library

    Gomes, Aline Freitas; Martins, Juliana Saibt

    2016-01-01

    ... eletrônicas Scielo, Medline/PubMed, PEDro e Lilacs. Os descritores e operadores boleanos utilizados foram congenital hemiplegia OR cerebral palsy AND transcranial magnetic stimulation OR transcranial direct current stimulation. Foram...

  1. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses

    Directory of Open Access Journals (Sweden)

    Maria Dolores Fernandez-Garcia

    2016-02-01

    Full Text Available The live attenuated yellow fever virus (YFV vaccine 17D stands as a “gold standard” for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation.

  2. Estimulação mecânico-térmica dos pilares palatoglosso Mechanical-thermal stimulation of the palatoglossus pillars

    Directory of Open Access Journals (Sweden)

    Maria de Fátima Lago Alvite

    2007-09-01

    Full Text Available RACIONAL: Os pilares palatoglosso foram admitidos como a principal sede dos receptores responsáveis por iniciar a fase faríngea da deglutição. Essa fase reflexa iniciar-se-ia em resposta ao estímulo produzido pelo progresso do bolo e da língua em sentido posterior. Esses conceitos deram base à manobra mecânico-térmica que visa estimular os receptores desses pilares, produzindo respostas motoras capazes de potencializar a recuperação da função faríngea comprometida. O conceito de possível resposta motora ao estímulo desses pilares, embora comum, não é unanimemente aceito. OBJETIVO: Verificar as possíveis respostas motoras produzidas pelo estímulo mecânico- térmico sobre os pilares palatoglosso. MÉTODOS: Por entender que indivíduos sadios são capazes de prover respostas reflexas mais efetivas do que as que seriam obtidas em pacientes, avaliaram-se 51 voluntários adultos sadios de ambos os sexos reproduzindo o estímulo sobre os pilares, usando sonda metálica de ponta romba resfriada em água mantida a 10°C. RESULTADOS E CONSIDERAÇÕES: O estudo mostrou que o estímulo mecânico-térmico sobre os pilares não foi capaz de produzir qualquer resposta motora envolvida na dinâmica da fase faríngea da deglutição. É possível que as respostas contráteis observadas em alguns estudos devam-se ao reflexo de gag inadequadamente interpretado ou a contrações voluntárias inconscientes por esforço de manutenção da abertura da boca e externalização da língua durante a exposição dos pilares para execução da manobra de estimulação mecânico-térmica.BACKGROUND: The palatoglossus pillars were admitted as the main receptive responsible area by the pharyngeal swallowing reflex produced by food and tongue posterior progression. This concept sustain the mechanical-thermal maneuver used to recovery the committed pharyngeal function. A pharyngeal motor answer by pillar stimulation is common accepted but not unanimously

  3. Site-directed mutagenesis of the active site of diacylglycerol kinase alpha: calcium and phosphatidylserine stimulate enzyme activity via distinct mechanisms.

    Science.gov (United States)

    Abe, Takahiro; Lu, Xiaolan; Jiang, Ying; Boccone, Clark E; Qian, Shaomin; Vattem, Krishna M; Wek, Ronald C; Walsh, James P

    2003-11-01

    Diacylglycerol kinases (DAGKs) catalyse ATP-dependent phosphorylation of sn-1,2-diacylglycerol that arises during stimulated phosphatidylinositol turnover. DAGKa is activated in vitro by Ca2+ and by acidic phospholipids. The regulatory region of DAGKa includes an N-terminal RVH motif and EF hands that mediate Ca2+-dependent activation. DAGKa also contains tandem C1 protein kinase C homology domains. We utilized yeast, Saccharomyces cerevisiae, which lacks an endogenous DAGK, to express DAGKa and to determine the enzymic activities of different mutant forms of pig DAGKa in vitro. Six aspartate residues conserved in all DAGKs were individually examined by site-directed mutagenesis. Five of these aspartate residues reside in conserved blocks that correspond to sequences in the catalytic site of phosphofructokinases. Mutation of D434 (Asp434) or D650 abolished all DAGKa activity, whereas substitution of one among D465, D497, D529 and D697 decreased the activity to 6% or less of that for wild-type DAGKa. Roles of homologous residues in phosphofructokinases suggested that the N-terminal half of the DAGK catalytic domain binds Mg-ATP and the C-terminal half binds diacylglycerol. A DAGKa mutant with its entire regulatory region deleted showed a much decreased activity that was not activated by Ca2+, but still exhibited PS (phosphatidylserine)-dependent activation. Moreover, mutations of aspartate residues at the catalytic domain had differential effects on activation by Ca2+ and PS. These results indicate that Ca2+ and PS stimulate DAGKa via distinct mechanisms.

  4. Stimulation of sodium-dependent phosphate transport and signaling mechanisms induced by basic fibroblast growth factor in MC3T3-E1 osteoblast-like cells.

    Science.gov (United States)

    Suzuki, A; Palmer, G; Bonjour, J P; Caverzasio, J

    2000-01-01

    Physiological and pathological observations indicate that basic fibroblast growth factor (bFGF) is an important regulator of osteoblastic cell differentiation and in particular of cranial ossification. Experimental evidence suggests that inorganic phosphate (Pi) transport could be an important function of bone matrix calcification. In the present study, we address the influence of bFGF on Pi transport activity in MC3T3-E1 osteoblast-like cells derived from mouse calvaria. The results indicate that bFGF is a potent and selective stimulator of sodium-dependent Pi transport in these cells. The change in Pi transport activity induced by bFGF depends on transcription and translation and corresponds to a change in the maximum velocity of the Pi transport system (Vmax). These observations suggest that enhanced Pi transport activity in response to bFGF may result from insertion of newly synthesized Pi transporters into the plasma membrane. A selective inhibitor of fibroblast growth factor receptor (FGFR) tyrosine kinase, SU5402, blunted the stimulation of Pi transport induced by bFGF. It also prevented the increase in protein tyrosine phosphorylation induced by bFGF, including phosphorylation of FGFR-1, FGFR-2, phospholipase C-gamma (PLC-gamma), and Shc as well as the recruitment of the Grb2/Sos signaling complex. In addition, bFGF-induced the activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and p38, effects that were prevented by SU5402. Both the protein kinase C (PKC) inhibitor calphostin C and PKC down-regulation suppressed the stimulatory effect of bFGF on Pi transport. Selective inhibitors of ERK and p38 MAP kinases slightly reduced this cellular response with a significant effect observed with the highest concentration of the p38 MAP kinase inhibitor. In conclusion, the results of this study indicate that bFGF selectively stimulates Pi transport in calvaria-derived osteoblastic cells. The main signaling mechanism

  5. Effect of chemical disinfectant on the transverse strength of heat-polymerized acrylic resins subjected to mechanical and chemical polishing: an in vitro study.

    Science.gov (United States)

    Sharan, Smitha; Kavitha, H R; Konde, Harish; Kalahasti, Deepthi

    2012-05-01

    To evaluate the effect of chemical disinfectant on the transverse strength of heat-polymerized acrylic resins subjected to mechanical and chemical polishing. A total of 256 rectangular specimens (65 * 10 * 3 mm) 128 per resin (Lucitone-199 and Acralyn-H) were fabricated. One side of each specimen was not polished and the other was either mechanically (n = 96) or chemically (n = 96) polished and immersed for 10, 30 and 60 minutes in 2% alkaline glutaraldehyde. Mechanically polished (n = 32) and chemically polished (n = 32) control specimens were immersed only in distilled water. The transverse strength (N/mm(2)) was tested for failure in a universal testing machine, at a crosshead speed of 5 mm/min. Data were statistically analyzed using 2-way ANOVA and Student t-test. chemical polishing resulted in significantly lower transverse strength values than mechanical polishing. Lucitone- 199 resin demonstrated the highest overall transverse strength for the materials tested. Heat-polymerized acrylic resins either mechanically or chemically polished, did not demonstrate significant changes in transverse strength during immersion in the disinfecting solution tested, regardless of time of immersion. Lucitone-199 resin demonstrated the highest overall transverse strength for the materials tested and significantly stronger than Acralyn-H with either type of polishing following immersion in 2% alkaline glutaraldehyde. There is a concern that immersion in chemical solutions often used for cleansing and disinfection of prostheses may undermine the strength and structure of denture base resins. In this study it was observed that, the transverse strength of samples of Lucitone-199 was higher than that of the samples of Acralyn-H. The chances of fracture of the denture made of Lucitone-199 are less than that of dentures made of Acralyn-H. The chemically polished dentures may be more prone to fracture than mechanically polished dentures.

  6. An Evaluation of the Correlation between the Free Moments Applied on the Lower Extremity and the Knee Extensor Mechanism Force in Pronated Foot Subjects during the Stance Phase of Gait

    OpenAIRE

    Farzaneh Yazdani; Mohsen Razeghi; Samaneh Ebrahimi

    2016-01-01

    Background: Due to the rotatory nature of the excessive subtalar pronation and the possible impairment of the tibial rotation-knee flexion mechanism, changes of the free moment (FM) and changes of the extensor mechanism force are expected in hyper-pronated foot subjects. The purpose of this study was to evaluate the correlation between the FM applied on the lower extremity and the knee extensor mechanism force in subjects with flexible pronated feet. Methods: Fifteen asympto...

  7. Finite Element Analysis Examining the Effects of Cam FAI on Hip Joint Mechanical Loading Using Subject-Specific Geometries During Standing and Maximum Squat.

    Science.gov (United States)

    Ng, K C Geoffrey; Rouhi, Gholamreza; Lamontagne, Mario; Beaulé, Paul E

    2012-10-01

    Cam femoroacetabular impingement (FAI) can impose elevated mechanical loading in the hip, potentially leading to an eventual mechanical failure of the joint. Since in vivo data on the pathomechanisms of FAI are limited, it is still unclear how this deformity leads to osteoarthritis. The purpose of this study was to examine the effects of cam FAI on hip joint mechanical loading using finite element analysis, by incorporating subject-specific geometries, kinematics, and kinetics. The research objectives were to address and determine: (1) if hips with cam FAI demonstrate higher maximum shear stresses, in comparison with control hips; (2) the magnitude of the peak maximum shear stresses; and (3) the locations of the peak maximum shear stresses. Using finite element analysis, two patient models were control-matched and simulated during quasi-static positions from standing to squatting. Intersegmental hip forces, from a previous study, were applied to the subject-specific hip geometries, segmented from CT data, to evaluate the maximum shear stresses on the acetabular cartilage and underlying bone. Peak maximum shear stresses were found at the anterosuperior region of the underlying bone during squatting. The peaks at the anterosuperior acetabulum were substantially higher for the patients (15.2 ± 1.8 MPa) in comparison with the controls (4.5 ± 0.1 MPa). Peaks were not situated on the cartilage, but instead located on the underlying bone. The results correspond with the locations of initial cartilage degradation observed during surgical treatment and from MRI. These findings support the pathomechanism of cam FAI. Changes may originate from the underlying subchondral bone properties rather than direct shear stresses to the articular cartilage.

  8. Experimental Investigation of Cavitation as a Possible Damage Mechanism in Blast-Induced Traumatic Brain Injury in Post-Mortem Human Subject Heads.

    Science.gov (United States)

    Salzar, Robert S; Treichler, Derrick; Wardlaw, Andrew; Weiss, Greg; Goeller, Jacques

    2017-04-15

    The potential of blast-induced traumatic brain injury from the mechanism of localized cavitation of the cerebrospinal fluid (CSF) is investigated. While the mechanism and criteria for non-impact blast-induced traumatic brain injury is still unknown, this study demonstrates that local cavitation in the CSF layer of the cranial volume could contribute to these injuries. The cranial contents of three post-mortem human subject (PMHS) heads were replaced with both a normal saline solution and a ballistic gel mixture with a simulated CSF layer. Each were instrumented with multiple pressure transducers and placed inside identical shock tubes at two different research facilities. Sensor data indicates that cavitation may have occurred in the PMHS models at pressure levels below those for a 50% risk of blast lung injury. This study points to skull flexion, the result of the shock wave on the front of the skull leading to a negative pressure in the contrecoup, as a possible mechanism that contributes to the onset of cavitation. Based on observation of intracranial pressure transducer data from the PMHS model, cavitation onset is thought to occur from approximately a 140 kPa head-on incident blast.

  9. Liquid-solid phase transition of physical hydrogels subject to an externally applied electro-chemo-mechanical coupled field with mobile ionic species.

    Science.gov (United States)

    Wu, Tao; Li, Hua

    2017-08-09

    In this study, a model was multiphysically developed for the simulation of the phase transition of physical hydrogels between liquid solution and solid gel states, subject to an electro-chemo-mechanically coupled field, with the effect of the mobile ionic species in the solution. The present model consists of the governing equations for the equilibrium of forces and the conservation of mass, Maxwell's equations, and an evolution equation for the interface. Based on the second law of thermodynamics, the constitutive equations are formulated from the energy viewpoint, including a novel formulation of free energy with the effect of crosslink density. The present model may be reduced to Suo's non-equilibrium thermodynamic theory if the interface is ignored when only a single phase exists. It may also be reduced to Dolbow's model for gel-gel phase transition when the electric field is ignored. Therefore, the present model becomes more generalized since it is able to represent both the bulk phase and the interface behaviors, and the mechanical field is simultaneously coupled with both the electric and chemical fields. In the first case study, the system at equilibrium state was numerically investigated for analysis of the influences of the electrical and chemical potentials as well as the mechanical pressure externally imposed on the boundary of the system domain. The second case study presents a spherically symmetrical solution-gel phase transition at non-equilibrium states, with the emphasis on the evolution of both the interface and electrochemical potentials.

  10. The key role of twist pitch and mechanical pre-treatment in the transport properties of Nb{sub 3}Sn wires subject to bending strain

    Energy Technology Data Exchange (ETDEWEB)

    Corato, V. [ENEA, C.R. Frascati, Via E. Fermi 45, IT-00044, Frascati (Italy)], E-mail: corato@frascati.enea.it; Muzzi, L.; della Corte, A.; Viola, R. [ENEA, C.R. Frascati, Via E. Fermi 45, IT-00044, Frascati (Italy)

    2009-06-15

    In modelling the transport properties of multi-filamentary Nb{sub 3}Sn strands, the knowledge of the geometrical parameters of the superconducting filaments and the electrical and mechanical properties of the different materials composing the wire are required. In particular, the filament twist pitch and the transverse resistivity between filaments have a crucial role in the definition of the current transfer length and, consequently, in the simulation of the transport performances of superconducting wires subject to mechanical loads, as in cable-in-conduit conductors (CICC) for fusion magnets during operation. We have measured the critical current and the n-index of internal tin Nb{sub 3}Sn wires with different values of the filament twist pitch, having inserted the strand into a stainless steel jacket and under the application of pure bending strain. Results show that the degradation of the transport properties is affected by the twist pitch value and, in the limit case of non-twisted filaments, even an improvement is observed in presence of bending. Moreover, the reversibility of critical current after relaxing the mechanical load has also been checked and an improvement of the performances has been observed after pre-bending applications, presumably due to the strain relaxation. In addition, the differential analysis through the second derivative of the V-I curve evidenced a peaked critical current distribution for the UNTW-strands, while TW-strands under bending showed a higher degree of non-homogeneity, proven by broader distributions.

  11. Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Albino Villegas-Bastida

    2014-01-01

    Full Text Available Electrical vagus nerve (VN stimulation during sepsis attenuates tumor necrosis factor (TNF production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36 on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP. The septic rats were subsequently treated with EA-ST36 (CLP+ST36, and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P<0.05, and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms.

  12. [Effect of mild and strong manual acupuncture stimulation of "Huantiao" (GB 30) on mechanical pain thresholds and extracellular signal-regulated kinase protein expression in spinal dorsal horns in rats with neuropathic mirror-image pain].

    Science.gov (United States)

    Shen, Zui; Shao, Xiao-Mei; Fang, Fang; Sun, Jing; Fang, Jun-Fan; Fang, Jian-Qiao

    2014-04-01

    To observe the effect of different intensities of manual acupuncture (MA) stimulation on mechanical pain thresholds (PTs) and the expression of phosphorylated extracellular signal-regulated kinases (p-ERK) in lumbar spinal dorsal horn regions in rats with neuropathic mirror-image pain, so as to explore its mechanisms underlying analgesia. Forty male SD rats were equally and randomly divided into control, spinal nerve ligation (SNL) model, mild MA-stimulation, and strong MA-stimulation groups. Neuropathological pain model was established by ligature of the spinal nerve (L 5). Three days after the SNL, bilateral "Huantiao" (GB 30) were stimulated by rotating the thin (0.22 mm x 13 mm) or thick (0.3 mm x 13 mm) filiform needles at a frequencies of 60 times/min or 180 times/min and at an angle of 180 degrees or 360 degrees for 2 min for rats in the mild and strong MA-stimulation groups, respectively, followed by remaining the needle in place for 30 min. The mechanical PTs were measured before and after SNL. The expression of p-ERK protein in bilateral dorsal horn regions of the lumbar spinal cord (L4- L 6) was detected by Western blot. In comparison with the control group, the mechanical PTs were significantly decreased beginning from the 3rd day on after SNL on the affected side and from the 7th day on after SNL on the healthy hindpaw (P horn regions on both sides of the spinal cord were considerably up-regulated on the 12th day (P horn regions were obviously down-regulated in the strong MA-stimulation group (P horn regions (P > 0.05) except the PTs of the healthy hindpaw on 7th day (P effect in down-regulating the expression of p-ERK in the bilateral spinal dorsal horn regions.

  13. Taste transduction mechanism: similar effects of various modifications of gustatory receptors on neural responses to chemical and electrical stimulation in the frog

    Energy Technology Data Exchange (ETDEWEB)

    Kashiwayanagi, M.; Yoshii, K.; Kobatake, Y.; Kurihara, K.

    1981-09-01

    Responses in the frog glossopharyngeal nerve induced by electrical stimulation of the tongue were compared with those induced by chemical stimuli under various conditions. (a) Anodal stimulation induced much larger responses than cathodal stimulation, and anodal stimulation of the tongue adapted to 5 mM MgCl2 produced much larger responses than stimulation with the tongue adapted to 10 mM NaCl at equal current intensities, as chemical stimulation with MgCl2 produced much larger responses than stimulation with NaCl at equal concentration. (b) The enhansive and suppressive effects of 8-anilino-1-naphthalenesulfonate, NiCl2, and uranyl acetate on the responses to anodal current were similar to those on the responses to chemical stimulation. (c) Anodal stimulation of the tongue adapted to 50 mM CaCl2 resulted in a large response, whereas application of 1 M CaCl2 to the tongue adapted to 50 mM CaCl2 produced only a s