WorldWideScience

Sample records for neuromuscular junction examined

  1. Neuromuscular junction disorders.

    Science.gov (United States)

    Verschuuren, Jan; Strijbos, Ellen; Vincent, Angela

    2016-01-01

    Diseases of the neuromuscular junction comprise a wide range of disorders. Antibodies, genetic mutations, specific drugs or toxins interfere with the number or function of one of the essential proteins that control signaling between the presynaptic nerve ending and the postsynaptic muscle membrane. Acquired autoimmune disorders of the neuromuscular junction are the most common and are described here. In myasthenia gravis, antibodies to acetylcholine receptors or to proteins involved in receptor clustering, particularly muscle-specific kinase, cause direct loss of acetylcholine receptors or interfere with the agrin-induced acetylcholine receptor clustering necessary for efficient neurotransmission. In the Lambert-Eaton myasthenic syndrome (LEMS), loss of the presynaptic voltage-gated calcium channels results in reduced release of the acetylcholine transmitter. The conditions are generally recognizable clinically and the diagnosis confirmed by serologic testing and electromyography. Screening for thymomas in myasthenia or small cell cancer in LEMS is important. Fortunately, a wide range of symptomatic treatments, immunosuppressive drugs, or other immunomodulating therapies is available. Future research is directed to understanding the pathogenesis, discovering new antigens, and trying to develop disease-specific treatments. © 2016 Elsevier B.V. All rights reserved.

  2. Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration.

    Science.gov (United States)

    Liu, Wenxuan; Klose, Alanna; Forman, Sophie; Paris, Nicole D; Wei-LaPierre, Lan; Cortés-Lopéz, Mariela; Tan, Aidi; Flaherty, Morgan; Miura, Pedro; Dirksen, Robert T; Chakkalakal, Joe V

    2017-06-06

    Neuromuscular junction degeneration is a prominent aspect of sarcopenia, the age-associated loss of skeletal muscle integrity. Previously, we showed that muscle stem cells activate and contribute to mouse neuromuscular junction regeneration in response to denervation (Liu et al., 2015). Here, we examined gene expression profiles and neuromuscular junction integrity in aged mouse muscles, and unexpectedly found limited denervation despite a high level of degenerated neuromuscular junctions. Instead, degenerated neuromuscular junctions were associated with reduced contribution from muscle stem cells. Indeed, muscle stem cell depletion was sufficient to induce neuromuscular junction degeneration at a younger age. Conversely, prevention of muscle stem cell and derived myonuclei loss was associated with attenuation of age-related neuromuscular junction degeneration, muscle atrophy, and the promotion of aged muscle force generation. Our observations demonstrate that deficiencies in muscle stem cell fate and post-synaptic myogenesis provide a cellular basis for age-related neuromuscular junction degeneration and associated skeletal muscle decline.

  3. Electrophysiological study in neuromuscular junction disorders

    Directory of Open Access Journals (Sweden)

    Ajith Cherian

    2013-01-01

    Full Text Available This review is on ultrastructure and subcellular physiology at normal and abnormal neuromuscular junctions. The clinical and electrophysiological findings in myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS, congenital myasthenic syndromes, and botulinum intoxication are discussed. Single fiber electromyography (SFEMG helps to explain the basis of testing neuromuscular junction function by repetitive nerve stimulation (RNS. SFEMG requires skill and patience and its availability is limited to a few centers. For RNS supramaximal stimulation is essential and so is display of the whole waveform of each muscle response at maximum amplitude. The amplitudes of the negative phase of the first and fourth responses are measured from baseline to negative peak, and the percent change of the fourth response compared with the first represents the decrement or increment. A decrement greater than 10% is accepted as abnormal and smooth progression of response amplitude train and reproducibility form the crux. In suspected LEMS the effect of fast rates of stimulation should be determined after RNS response to slow rates of stimulation. Caution is required to avoid misinterpretation of potentiation and pseudofacilitation.

  4. Nonextensivity and self-affinity in the mammalian neuromuscular junction

    Science.gov (United States)

    da Silva, A. J.; Lima, R. F.; Moret, M. A.

    2011-10-01

    We study time series and the spontaneous miniature end-plate potentials (MEPPs) of mammals recorded at neuromuscular junctions using two different approaches: generalized thermostatistics and detrended fluctuation analysis (DFA). Classical concepts establish that the magnitude of these potentials is characterized by Gaussian statistics and that their intervals are randomly displayed. First we show that MEPP distributions adequately satisfy the q-Gaussian distributions that maximize the Tsallis entropy, indicating their nonextensive and nonequilibrium behavior. We then examine the intervals between the miniature potentials via DFA, where the profile of the intervals between events configures a deviation from the expected random behavior. Some possible physiological substrates for these findings are discussed.

  5. Formation of neuromuscular junctions in rat embryo cell cultures

    International Nuclear Information System (INIS)

    Koenig, Jeanine

    1978-01-01

    The morphological evidence of the primary nerve muscle contacts are described. They consist of areas of cholinesterase activity (detected histochemically) localized on the myotube membranes and of multiple clusters of ACh receptors whose 125 I-α-bungarotoxin binding sites are revealed by radioautography. After the stage of the primary nerve muscle contacts, some of which seem transient, characteristic neuromuscular junctions appear. These neuromuscular junctions which possess subneural infoldings are similar to the end-plates of the rat in vivo [fr

  6. Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

    Science.gov (United States)

    Ramsay, D A; Drachman, D B; Pestronk, A

    1988-10-11

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  7. Synaptic Homeostasis and Its Immunological Disturbance in Neuromuscular Junction Disorders

    Directory of Open Access Journals (Sweden)

    Masaharu Takamori

    2017-04-01

    Full Text Available In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca2+ channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal. Focusing on neural agrin, Wnts, muscle-specific tyrosine kinase (a mediator of agrin and Wnts signalings and regulator of trans-synaptic communication, low-density lipoprotein receptor-related protein 4 (the receptor of agrin and Wnts and participant in retrograde signaling, laminin-network (including muscle-derived agrin, extracellular matrix proteins (participating in the synaptic stabilization and presynaptic receptors (including muscarinic and adenosine receptors, we review the functional structures of the synapse by making reference to immunological pathogenecities in postsynaptic disease, myasthenia gravis. The synapse-related proteins including cortactin, coronin-6, caveolin-3, doublecortin, R-spondin 2, amyloid precursor family proteins, glia cell-derived neurotrophic factor and neurexins are also discussed in terms of their possible contribution to efficient synaptic transmission at the neuromuscular junction.

  8. Genetic and evolutionary analysis of the Drosophila larval neuromuscular junction

    Science.gov (United States)

    Campbell, Megan

    Although evolution of brains and behaviors is of fundamental biological importance, we lack comprehensive understanding of the general principles governing these processes or the specific mechanisms and molecules through which the evolutionary changes are effected. Because synapses are the basic structural and functional units of nervous systems, one way to address these problems is to dissect the genetic and molecular pathways responsible for morphological evolution of a defined synapse. I have undertaken such an analysis by examining morphology of the larval neuromuscular junction (NMJ) in wild caught D. melanogaster as well as in over 20 other species of Drosophila. Whereas variation in NMJ morphology within a species is limited, I discovered a surprisingly extensive variation among different species. Compared with evolution of other morphological traits, NMJ morphology appears to be evolving very rapidly. Moreover, my data indicate that natural selection rather than genetic drift is primarily responsible for evolution of NMJ morphology. To dissect underlying molecular mechanisms that may govern NMJ growth and evolutionary divergence, I focused on a naturally occurring variant in D. melanogaster that causes NMJ overgrowth. I discovered that the variant mapped to Mob2, a gene encoding a kinase adapter protein originally described in yeast as a member of the Mitotic Exit Network (MEN). I have subsequently examined mutations in the Drosophila orthologs of all the core components of the yeast MEN and found that all of them function as part of a common pathway that acts presynaptically to negatively regulate NMJ growth. As in the regulation of yeast cytokinesis, these components of the MEN appear to act ultimately by regulating actin dynamics during the process of bouton growth and division. These studies have thus led to the discovery of an entirely new role for the MEN---regulation of synaptic growth---that is separate from its function in cell division. This work

  9. Effect of ionizing radiation on neuromuscular junctions in mouse tongues

    International Nuclear Information System (INIS)

    Gorodetsky, R.; Amir, G.; Yarom, R.

    1992-01-01

    Radiation damage to neuromuscular junctions (NMJs) in mouse tongues was studied using local x-irradiation of the tongues with the rest of the body shielded. Transmission electron microscopy (TEM) revealed no significant morphological changes in fine structures and organelles of the NMJs given 4Gy. A dose of 8Gy produced degenerative morphological changes associated with axon terminal sprouting as early as 2 and 7 days following irradiation. Subsequently, 1-11 weeks later, severe degenerative changes were observed. The number of mitochondria was significantly decreased with increased occurrence of degenerative membranal features. The number of synaptic footplates without terminals or with multiple small terminals within one groove increased gradually with time. Most changes persisted for at least 3 months after irradiation. However, the myofibres, blood vessels and interstitial cells appeared unaffected throughout the period follow-up. (author)

  10. Cellular and Molecular Anatomy of the Human Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Ross A. Jones

    2017-11-01

    Full Text Available The neuromuscular junction (NMJ plays a fundamental role in transferring information from lower motor neuron to skeletal muscle to generate movement. It is also an experimentally accessible model synapse routinely studied in animal models to explore fundamental aspects of synaptic form and function. Here, we combined morphological techniques, super-resolution imaging, and proteomic profiling to reveal the detailed cellular and molecular architecture of the human NMJ. Human NMJs were significantly smaller, less complex, and more fragmented than mouse NMJs. In contrast to mice, human NMJs were also remarkably stable across the entire adult lifespan, showing no signs of age-related degeneration or remodeling. Super-resolution imaging and proteomic profiling revealed distinctive distribution of active zone proteins and differential expression of core synaptic proteins and molecular pathways at the human NMJ. Taken together, these findings reveal human-specific cellular and molecular features of the NMJ that distinguish them from comparable synapses in other mammalian species.

  11. Active zones of mammalian neuromuscular junctions: formation, density, and aging.

    Science.gov (United States)

    Nishimune, Hiroshi

    2012-12-01

    Presynaptic active zones are synaptic vesicle release sites that play essential roles in the function and pathology of mammalian neuromuscular junctions (NMJs). The molecular mechanisms of active zone organization use presynaptic voltage-dependent calcium channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the muscle-derived synapse organizer, laminin β2 and interact intracellularly with active zone-specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P/Q- and N-type VDCCs double-knockout mice, and they are consistent with the pathological conditions of Lambert-Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin β2 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies. © 2012 New York Academy of Sciences.

  12. Cross‐disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology

    Science.gov (United States)

    Nijssen, Jik; Frost‐Nylen, Johanna

    2015-01-01

    Neuromuscular junctions are primary pathological targets in the lethal motor neuron diseases spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Synaptic pathology and denervation of target muscle fibers has been reported prior to the appearance of clinical symptoms in mouse models of both diseases, suggesting that neuromuscular junctions are highly vulnerable from the very early stages, and are a key target for therapeutic intervention. Here we examined neuromuscular pathology longitudinally in three clinically relevant muscle groups in mouse models of ALS and SMA in order to assess their relative vulnerabilities. We show for the first time that neuromuscular junctions of the extraocular muscles (responsible for the control of eye movement) were resistant to degeneration in endstage SMA mice, as well as in late symptomatic ALS mice. Tongue muscle neuromuscular junctions were also spared in both animal models. Conversely, neuromuscular junctions of the lumbrical muscles of the hind‐paw were vulnerable in both SMA and ALS, with a loss of neuronal innervation and shrinkage of motor endplates in both diseases. Thus, the pattern of selective vulnerability was conserved across these two models of motor neuron disease. However, the first evidence of neuromuscular pathology occurred at different timepoints of disease progression, with much earlier evidence of presynaptic involvement in ALS, progressing to changes on the postsynaptic side. Conversely, in SMA changes appeared concomitantly at the neuromuscular junction, suggesting that mechanisms of neuromuscular disruption are distinct in these diseases. J. Comp. Neurol. 524:1424–1442, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26502195

  13. Degradation rate of acetylcholine receptors inserted into denervated vertebrate neuromuscular junctions

    International Nuclear Information System (INIS)

    Shyng, S.L.; Salpeter, M.M.

    1989-01-01

    Many studies exist on the effect of denervation on the degradation of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction (nmj). These studies have described the behavior of either the total population of junctional receptors at different times after denervation, or of the receptors present at the time of denervation. No experimental studies yet exist on the degradation rate of the receptors newly inserted into denervated junctions. In the previous studies, the original receptors of mouse sternomastoid muscles were found to retain the slow degradation (t 1/2) of approximately 8-10 d of innervated junctional receptors for up to 10 d after denervation before accelerating to a t 1/2 of approximately 3 d. The total junctional receptors, on the other hand, showed a progressive increase in degradation rate from a t 1/2 of 8-10 d to a t 1/2 of 1 d. To reconcile these earlier observations, the present study examines the degradation of new receptors inserted into the nmj after denervation. To avoid possible contamination of the data with postdenervation extrajunctional receptors, we used transmission electron microscope autoradiography to study only receptors located at the postjunctional fold of the nmj. We established that the new receptors inserted into denervated junctions have a t 1/2 of approximately 1 d, considerably faster than that of the original receptors and equivalent to that of postdenervation extrajunctional receptors. Both original and new receptors are interspersed at the top of the junctional folds. Thus, until all the original receptors are degraded, the postjunctional membrane contains two populations of AChRs that maintain a total steady-state site density but degrade at different rates

  14. "Warming yang and invigorating qi" acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Huang, Hai-Peng; Pan, Hong; Wang, Hong-Feng

    2016-03-01

    Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following "warming yang and invigorating qi" acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10), Zusanli (ST36), Pishu (BL20), and Shenshu (BL23) once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that "warming yang and invigorating qi" acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.

  15. "Warming yang and invigorating qi" acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis

    Directory of Open Access Journals (Sweden)

    Hai-peng Huang

    2016-01-01

    Full Text Available Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following "warming yang and invigorating qi" acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10, Zusanli (ST36, Pishu (BL20, and Shenshu (BL23 once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that "warming yang and invigorating qi" acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.

  16. Roles of neuro-exocytotic proteins at the neuromuscular junction

    NARCIS (Netherlands)

    Sons-Michel, Michèle S.

    2011-01-01

    The aim of the studies described in the thesis was to elucidate the roles of several neuro-exocytotic proteins at the motor nerve terminal in neuromuscular synaptic transmission, making use of genetic knockout (KO) mice, each missing one (or more) neuro-exocytotic proteins. In addition, it was

  17. Nerve terminal contributes to acetylcholine receptor organization at the dystrophic neuromuscular junction of mdx mice.

    Science.gov (United States)

    Marques, Maria Julia; Taniguti, Ana Paula Tiemi; Minatel, Elaine; Neto, Humberto Santo

    2007-02-01

    Changes in the distribution of acetylcholine receptors have been reported to occur at the neuromuscular junction of mdx mice and may be a consequence of muscle fiber regeneration rather than the absence of dystrophin. In the present study, we examined whether the nerve terminal determines the fate of acetylcholine receptor distribution in the dystrophic muscle fibers of mdx mice. The left sternomastoid muscle of young (1-month-old) and adult (6-month-old) mdx mice was injected with 60 microl lidocaine hydrochloride to induce muscle degeneration-regeneration. Some mice had their sternomastoid muscle denervated at the time of lidocaine injection. After 10 days of muscle denervation, nerve terminals and acetylcholine receptors were labeled with 4-Di-2-ASP and rhodamine-alpha-bungarotoxin, respectively, for confocal microscopy. In young mdx mice, 75% (n = 137 endplates) of the receptors were distributed in islands. The same was observed in 100% (n = 114 endplates) of the adult junctions. In denervated-regenerated fibers of young mice, the receptors were distributed as branches in 89% of the endplates (n = 90). In denervated-regenerated fibers of adult mice, the receptors were distributed in islands in 100% of the endplates (n = 100). These findings show that nerve-dependent mechanisms are also involved in the changes in receptor distribution in young dystrophic muscles. In older dystrophic muscles, other factors may play a role in receptor distribution.

  18. Excitatory effects of Buthus C56 toxin on Drosophila larval neuromuscular junction

    Directory of Open Access Journals (Sweden)

    S. P. Gawade

    2003-01-01

    Full Text Available Buthus C56 toxin from venom of the Indian red scorpion Mesobuthus tamulus was studied for its effects on spontaneous miniature excitatory junctional potentials (MEJP on Drosophila larval neuromuscular junctions. C56 toxin was isolated on CM-Cellulose with linear gradient of ammonium acetate buffer, pH 6.0. Toxin purity was determined on SDS slab gel electrophoresis. Effective concentration of C56 toxin was based on contraction paralysis units (CPU in Drosophila 3rd instar larvae by microinjection (0.1 CPU/ml = 2 x 10-6 g/ml. The toxin-induced excitatory junctional potentials were studied for calcium dependency (0.2 mM to 1.2 mM Ca2+ in Drosophila Ringer. Excitatory junctional potential amplitude was increased with increasing calcium concentration; maximum increase in the frequency at 0.4 mM Ca2+/4 mM Mg2+ Drosophila Ringer. It was suggested that while amplitude of excitatory junctional potentials was increased with concentration, maximum frequency increase at 0.4 mMCa2+/4 mM Mg2+ Drosophila Ringer may be due to augmented Ca2+ influx in 0.4 mM Ca2+, when NMDA receptors were maximally activated in C56 toxin-treated Drosophila larval neuromuscular junction.

  19. Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice.

    NARCIS (Netherlands)

    Klooster, R.; Plomp, J.J.; Huijbers, M.G.; Niks, E.H.; Straasheijm, K.R.; Detmers, F.J.M.; Hermans, P.W.M.; Sleijpen, K.; Verrips, A.; Losen, M.; Martinez-Martinez, P.; Baets, M.H.V. de; Maarel, S.M. van der; Verschuuren, J.J.

    2012-01-01

    Myasthenia gravis is a paralytic disorder with autoantibodies against acetylcholine receptors at the neuromuscular junction. A proportion of patients instead has antibodies against muscle-specific kinase, a protein essential for acetylcholine receptor clustering. These are generally of the

  20. Neuromuscular junction defects in mice with mutation of dynein heavy chain 1.

    Directory of Open Access Journals (Sweden)

    Stephanie L Courchesne

    2011-02-01

    Full Text Available Disruptions in axonal transport have been implicated in a wide range of neurodegenerative diseases. Cramping 1 (Cra1/+ and Legs at odd angles (Loa/+ mice, with hypomorphic mutations in the dynein heavy chain 1 gene, which encodes the ATPase of the retrograde motor protein dynein, were originally reported to exhibit late onset motor neuron disease. Subsequent, conflicting reports suggested that sensory neuron disease without motor neuron loss underlies the phenotypes of Cra1/+ and Loa/+ mice. Here, we present behavioral and anatomical analyses of Cra1/+ mice. We demonstrate that Cra1/+ mice exhibit early onset, stable behavioral deficits, including abnormal hindlimb posturing and decreased grip strength. These deficits do not progress through 24 months of age. No significant loss of primary motor neurons or dorsal root ganglia sensory neurons was observed at ages where the mice exhibited clear symptomatology. Instead, there is a decrease in complexity of neuromuscular junctions. These results indicate that disruption of dynein function in Cra1/+ mice results in abnormal morphology of neuromuscular junctions. The time course of behavioral deficits, as well as the nature of the morphological defects in neuromuscular junctions, suggests that disruption of dynein function in Cra1/+ mice causes a developmental defect in synapse assembly or stabilization.

  1. Abnormally Small Neuromuscular Junctions in the Extraocular Muscles From Subjects With Idiopathic Nystagmus and Nystagmus Associated With Albinism.

    Science.gov (United States)

    McLoon, Linda K; Willoughby, Christy L; Anderson, Jill S; Bothun, Erick D; Stager, David; Felius, Joost; Lee, Helena; Gottlob, Irene

    2016-04-01

    Infantile nystagmus syndrome (INS) is often associated with abnormalities of axonal outgrowth and connectivity. To determine if this manifests in extraocular muscle innervation, specimens from children with idiopathic INS or INS and albinism were examined and compared to normal age-matched control extraocular muscles. Extraocular muscles removed during normal surgery on children with idiopathic INS or INS and albinism were immunostained for neuromuscular junctions, myofiber type, the immature form of the acetylcholine receptor, and brain-derived neurotrophic factor (BDNF) and compared to age-matched controls. Muscles from both the idiopathic INS and INS and albinism groups had neuromuscular junctions that were 35% to 71% smaller based on myofiber area and myofiber perimeter than found in age-matched controls, and this was seen on both fast and slow myosin heavy chain isoform-expressing myofibers (all P albinism showed a 7-fold increase in neuromuscular junction numbers on fast myofibers expressing the immature gamma subunit of the acetylcholine receptor. The extraocular muscles from both INS subgroups showed a significant increase in the number and size of slow myofibers compared to age-matched controls. Brain-derived neurotrophic factor was expressed in control muscle but was virtually absent in the INS muscles. These studies suggest that, relative to the final common pathway, INS is not the same between different patient etiologies. It should be possible to modulate these final common pathway abnormalities, via exogenous application of appropriate drugs, with the hope that this type of treatment may reduce the involuntary oscillatory movements in these children.

  2. Drosophila Cbp53E Regulates Axon Growth at the Neuromuscular Junction.

    Directory of Open Access Journals (Sweden)

    Kimberly R Hagel

    Full Text Available Calcium is a primary second messenger in all cells that functions in processes ranging from cellular proliferation to synaptic transmission. Proper regulation of calcium is achieved through numerous mechanisms involving channels, sensors, and buffers notably containing one or more EF-hand calcium binding domains. The Drosophila genome encodes only a single 6 EF-hand domain containing protein, Cbp53E, which is likely the prototypic member of a small family of related mammalian proteins that act as calcium buffers and calcium sensors. Like the mammalian homologs, Cbp53E is broadly though discretely expressed throughout the nervous system. Despite the importance of calcium in neuronal function and growth, nothing is known about Cbp53E's function in neuronal development. To address this deficiency, we generated novel null alleles of Drosophila Cbp53E and examined neuronal development at the well-characterized larval neuromuscular junction. Loss of Cbp53E resulted in increases in axonal branching at both peptidergic and glutamatergic neuronal terminals. This overgrowth could be completely rescued by expression of exogenous Cbp53E. Overexpression of Cbp53E, however, only affected the growth of peptidergic neuronal processes. These findings indicate that Cbp53E plays a significant role in neuronal growth and suggest that it may function in both local synaptic and global cellular mechanisms.

  3. Increased acetylation of microtubules rescues human tau-induced microtubule defects and neuromuscular junction abnormalities in Drosophila

    Directory of Open Access Journals (Sweden)

    Chuan-Xi Mao

    2017-10-01

    Full Text Available Tau normally associates with and stabilizes microtubules (MTs, but is hyperphosphorylated and aggregated into neurofibrillary tangles in Alzheimer's disease and related neurodegenerative diseases, which are collectively known as tauopathies. MTs are regulated by different forms of post-translational modification, including acetylation; acetylated MTs represent a more stable microtubule population. In our previous study, we showed that inhibition of histone deacetylase 6 (HDAC6, which deacetylates tubulin at lysine 40, rescues defects in MTs and in neuromuscular junction growth caused by tau overexpression. However, HDAC6 also acts on other proteins that are involved in distinct biological processes unrelated to tubulins. In order to examine directly the role of increased tubulin acetylation against tau toxicity, we generated a site-directed α-tubulinK40Q mutation by CRISPR/Cas9 technology to mimic the acetylated MTs and found that acetylation-mimicking α-tubulin rescued tau-induced MT defects and neuromuscular junction developmental abnormalities. We also showed that late administration of ACY-1215 and tubastatin A, two potent and selective inhibitors of HDAC6, rescued the tau-induced MT defects after the abnormalities had already become apparent. Overall, our results indicate that increasing MT acetylation by either genetic manipulations or drugs might be used as potential strategies for intervention in tauopathies.

  4. VAChT overexpression increases acetylcholine at the synaptic cleft and accelerates aging of neuromuscular junctions.

    Science.gov (United States)

    Sugita, Satoshi; Fleming, Leland L; Wood, Caleb; Vaughan, Sydney K; Gomes, Matheus P S M; Camargo, Wallace; Naves, Ligia A; Prado, Vania F; Prado, Marco A M; Guatimosim, Cristina; Valdez, Gregorio

    2016-01-01

    Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS). Chat-ChR2-EYFP (VAChT Hyp ) mice containing multiple copies of the vesicular acetylcholine transporter (VAChT), mutant superoxide dismutase 1 (SOD1 G93A ), and Chat-IRES-Cre and tdTomato transgenic mice were used in this study. NMJs, muscle fibers, and α-motor neurons' somata and their axons were examined using a light microscope. Transcripts for select genes in muscles and spinal cords were assessed using real-time quantitative PCR. Motor function tests were carried out using an inverted wire mesh and a rotarod. Electrophysiological recordings were collected to examine miniature endplate potentials (MEPP) in muscles. We show that VAChT is elevated in the spinal cord and at NMJs of VAChT Hyp mice. We also show that the amplitude of MEPPs is significantly higher in VAChT Hyp muscles, indicating that more ACh is loaded into synaptic vesicles and released into the synaptic cleft at NMJs of VAChT Hyp mice compared to control mice. While the development of NMJs was not affected in VAChT Hyp mice, NMJs prematurely acquired age-related structural alterations in adult VAChT Hyp mice. These structural changes at NMJs were accompanied by motor deficits in VAChT Hyp mice. However, cellular features of muscle fibers and levels of molecules with critical functions at the NMJ and in muscle fibers were largely unchanged in VAChT Hyp mice. In the SOD1 G93A mouse model for ALS, increasing synaptic ACh accelerated degeneration of NMJs caused motor deficits and

  5. Metabotropic and ionotropic glutamate receptors mediate the modulation of acetylcholine release at the frog neuromuscular junction.

    Science.gov (United States)

    Tsentsevitsky, Andrei; Nurullin, Leniz; Nikolsky, Evgeny; Malomouzh, Artem

    2017-07-01

    There is some evidence that glutamate (Glu) acts as a signaling molecule at vertebrate neuromuscular junctions where acetylcholine (ACh) serves as a neurotransmitter. In this study, performed on the cutaneous pectoris muscle of the frog Rana ridibunda, Glu receptor mechanisms that modulate ACh release processes were analyzed. Electrophysiological experiments showed that Glu reduces both spontaneous and evoked quantal secretion of ACh and synchronizes its release in response to electrical stimulation. Quisqualate, an agonist of ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors and metabotropic Group I mGlu receptors, also exerted Glu-like inhibitory effects on the secretion of ACh but had no effect on the kinetics of quantal release. Quisqualate's inhibitory effect did not occur when a blocker of Group I mGlu receptors (LY 367385) or an inhibitor of phospholipase C (U73122) was present. An increase in the degree of synchrony of ACh quantal release, such as that produced by Glu, was obtained after application of N-methyl-D-aspartic acid (NMDA). The presence of Group I mGlu and NMDA receptors in the neuromuscular synapse was confirmed by immunocytochemistry. Thus, the data suggest that both metabotropic Group I mGlu receptors and ionotropic NMDA receptors are present at the neuromuscular synapse of amphibians, and that the activation of these receptors initiates different mechanisms for the regulation of ACh release from motor nerve terminals. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Elisa Duregotti

    2015-12-01

    Full Text Available Botulinum neurotoxins (BoNTs and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body.

  7. Alternative NF-κB Isoforms in the Drosophila Neuromuscular Junction and Brain.

    Directory of Open Access Journals (Sweden)

    Bo Zhou

    Full Text Available The Drosophila NF-κB protein Dorsal is expressed at the larval neuromuscular junction, where its expression appears unrelated to known Dorsal functions in embryonic patterning and innate immunity. Using confocal microscopy with domain-specific antisera, we demonstrate that larval muscle expresses only the B isoform of Dorsal, which arises by intron retention. We find that Dorsal B interacts with and stabilizes Cactus at the neuromuscular junction, but exhibits Cactus independent localization and an absence of detectable nuclear translocation. We further find that the Dorsal-related immune factor Dif encodes a B isoform, reflecting a conservation of B domains across a range of insect NF-κB proteins. Carrying out mutagenesis of the Dif locus via a site-specific recombineering approach, we demonstrate that Dif B is the major, if not sole, Dif isoform in the mushroom bodies of the larval brain. The Dorsal and Dif B isoforms thus share a specific association with nervous system tissues as well as an alternative protein structure.

  8. Elements of molecular machinery of GABAergic signaling in the vertebrate cholinergic neuromuscular junction.

    Science.gov (United States)

    Nurullin, Leniz F; Nikolsky, Evgeny E; Malomouzh, Artem I

    2018-04-01

    It is generally accepted that gamma-aminobutyric acid (GABA) is a signaling molecule abundant in central synapses. In a number of studies though, it has been shown that GABA signaling functions in the peripheral nervous system as well, in particular, in the synapses of sympathetic ganglia. However, there exists no firm evidence on the presence of GABAergic signaling cascade in the intercellular junctions of the somatic nerve system. By the use of immunohistochemistry methods, in the synaptic area of cholinergic neuromuscular contact in rat diaphragm, we have detected glutamate decarboxylase, the enzyme involved in synthesis of GABA, molecules of GABA, and also GAT-2, a protein responsible for transmembrane transport of GABA. Earlier we have also shown that metabotropic GABA B receptors have overlapping localization in the same compartment. Moreover, activation of GABA B receptors affects the intensity of acetylcholine release. These data taken together, allows us to suggest that in the mammalian cholinergic neuromuscular junction, GABA is synthesized and performs certain synaptic signaling function. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  9. Defective neuromuscular junction organization and postnatal myogenesis in mice with severe spinal muscular atrophy.

    Science.gov (United States)

    Dachs, Elisabet; Hereu, Marta; Piedrafita, Lídia; Casanovas, Anna; Calderó, Jordi; Esquerda, Josep E

    2011-06-01

    A detailed pathologic analysis was performed on Smn(-/-);SMN2 mice as a mouse model for human type I spinal muscular atrophy (SMA). We provide new data concerning changes in the spinal cord, neuromuscular junctions and muscle cells, and in the organs of the immune system. The expression of 10 synaptic proteins was analyzed in 3-dimensionally reconstructed neuromuscular junctions by confocal microscopy. In addition to defects in postsynaptic occupancy, there was a marked reduction in calcitonin gene-related peptide and Rab3A in the presynaptic motor terminals of some, but not all, of the skeletal muscles analyzed. Defects in the organization of presynaptic nerve terminals were also detected by electron microscopy. Moreover, degenerative changes in muscle cells, defective postnatal muscle growth, and prominent muscle satellite cell apoptosis were also observed. All of these changes occurred in the absence of massive loss of spinal cord motoneurons. On the other hand, astroglia, but not microglia, increased in the ventral horn of newborn SMA mice. In skeletal muscles, the density of interstitial macrophages was significantly reduced, and monocyte chemotactic protein-1 was downregulated. These findings raise questions regarding the primary contribution of a muscle cell defect to the SMA phenotype.

  10. Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction.

    Science.gov (United States)

    Duregotti, Elisa; Zanetti, Giulia; Scorzeto, Michele; Megighian, Aram; Montecucco, Cesare; Pirazzini, Marco; Rigoni, Michela

    2015-12-08

    Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body.

  11. Metabotropic GABAB receptors mediate GABA inhibition of acetylcholine release in the rat neuromuscular junction.

    Science.gov (United States)

    Malomouzh, Artem I; Petrov, Konstantin A; Nurullin, Leniz F; Nikolsky, Evgeny E

    2015-12-01

    Gamma-aminobutyric acid (GABA) is an amino acid which acts as a neurotransmitter in the central nervous system. Here, we studied the effects of GABA on non-quantal, spontaneous, and evoked quantal acetylcholine (ACh) release from motor nerve endings. We found that while the application of 10 μM of GABA had no effect on spontaneous quantal ACh release, as detected by the frequency of miniature endplate potentials, GABA reduced the non-quantal ACh release by 57%, as determined by the H-effect value. Finally, the evoked quantal ACh release, estimated by calculating the quantal content of full-sized endplate potentials (EPPs), was reduced by 34%. GABA's inhibitory effect remained unchanged after pre-incubation with picrotoxin, an ionotropic GABAA receptor blocker, but was attenuated following application of the GABAB receptor blocker CGP 55845, which itself had no effect on ACh release. An inhibitor of phospholipase C, U73122, completely prevented the GABA-induced decrease in ACh release. Immunofluorescence demonstrated the presence of both subunits of the GABAB receptor (GABAB R1 and GABAB R2) in the neuromuscular junction. These findings suggest that metabotropic GABAB receptors are expressed in the mammalian neuromuscular synapse and their activation results in a phospholipase C-mediated reduction in the intensity of non-quantal and evoked quantal ACh release. We investigated the effect of gamma-aminobutyric acid (GABA) on neuromuscular transmission. GABA reduced the non-quantal and evoked quantal release of acetylcholine. These effects are mediated by GABAB receptors and are implemented via phospholipase C (PLC) activation. Our findings suggest that in the mammalian neuromuscular synapse, metabotropic GABAB receptors are expressed and their activation results in a reduction in the intensity of acetylcholine release. © 2015 International Society for Neurochemistry.

  12. TrkB kinase activity maintains synaptic function and structural integrity at adult neuromuscular junctions

    Science.gov (United States)

    Stowe, Jessica M.; Sieck, Dylan C.; Ermilov, Leonid G.; Greising, Sarah M.; Zhang, Chao; Shokat, Kevan M.; Sieck, Gary C.

    2014-01-01

    Activation of the tropomyosin-related kinase receptor B (TrkB) by brain-derived neurotrophic factor acutely regulates synaptic transmission at adult neuromuscular junctions (NMJs). The role of TrkB kinase activity in the maintenance of NMJ function and structure at diaphragm muscle NMJs was explored using a chemical-genetic approach that permits reversible inactivation of TrkB kinase activity in TrkBF616A mice by 1NMPP1. Inhibiting TrkB kinase activity for 7 days resulted in significant, yet reversible, impairments in neuromuscular transmission at diaphragm NMJs. Neuromuscular transmission failure following 2 min of repetitive phrenic nerve stimulation increased from 42% in control to 59% in 1NMPP1-treated TrkBF616A mice (P = 0.010). Recovery of TrkB kinase activity following withdrawal of 1NMPP1 treatment improved neuromuscular transmission (P = 0.006). Electrophysiological measurements at individual diaphragm NMJs documented lack of differences in quantal content in control and 1NMPP1-treated mice (P = 0.845). Morphological changes at diaphragm NMJs were modest following inhibition and recovery of TrkB kinase activity. Three-dimensional reconstructions of diaphragm NMJs revealed no differences in volume at motor end plates (labeled by α-bungarotoxin; P = 0.982) or presynaptic terminals (labeled by synaptophysin; P = 0.515). Inhibition of TrkB kinase activity by 1NMPP1 resulted in more compact NMJs, with increased apposition of presynaptic terminals and motor end plates (P = 0.017) and reduced fragmentation of motor end plates (P = 0.005). Recovery of TrkB kinase activity following withdrawal of 1NMPP1 treatment resulted in postsynaptic remodeling likely reflecting increased gutter depth (P = 0.007), without significant presynaptic changes. These results support an essential role for TrkB kinase activity in maintaining synaptic function and structural integrity at NMJs in the adult mouse diaphragm muscle. PMID:25170066

  13. Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS

    Directory of Open Access Journals (Sweden)

    Xia Ruohan

    2012-03-01

    Full Text Available Abstract Backgound Amyotrophic lateral sclerosis (ALS is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus. However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a Drosophila model to examine the toxicity of Fus, its Drosophila orthologue Cabeza (Caz, and the ALS-related Fus mutants. Results Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the transgenic flies in a dose- and age-dependent manner. The expression of Fus, Caz, or FusR521G in motor neurons significantly impaired the locomotive ability of fly larvae and adults. The presynaptic structures in neuromuscular junctions were disrupted and motor neurons in the ventral nerve cord (VNC were disorganized and underwent apoptosis. Surprisingly, the interruption of Fus nuclear localization by either deleting its nuclear localization sequence (NLS or adding a nuclear export signal (NES blocked Fus toxicity. Moreover, we discovered that the loss of caz in Drosophila led to severe growth defects in the eyes and VNCs, caused locomotive disability and NMJ disruption, but did not induce apoptotic cell death. Conclusions These data demonstrate that the overexpression of Fus/Caz causes in vivo toxicity by disrupting neuromuscular junctions (NMJs and inducing apoptosis in motor neurons. In addition, the nuclear localization of Fus is essential for Fus to induce toxicity. Our findings also suggest that Fus overexpression and gene deletion can cause similar degenerative phenotypes but the underlying mechanisms are likely different.

  14. Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction.

    Science.gov (United States)

    Mattei, César; Marquais, Michel; Schlumberger, Sébastien; Molgó, Jordi; Vernoux, Jean-Paul; Lewis, Richard J; Benoit, Evelyne

    2010-10-01

    Caribbean ciguatoxin-1 (C-CTX-1) induced, after about 1h exposure, muscle membrane depolarisation and repetitive post-synaptic action potentials (APs) in frog neuromuscular preparations. This depolarising effect was also observed in a Ca(2+)-free medium with a strong enhancement of spontaneous quantal transmitter release, compared with control conditions. The ciguatoxin-induced increase in release could be accelerated when Ca(2+) was present in the extracellular medium. C-CTX-1 also enhanced nerve-evoked quantal acetylcholine (ACh) release. At normal neuromuscular junctions loaded with the fluorescent dye FM1-43, C-CTX-1 induced swelling of nerve terminals, an effect that was reversed by hyperosmotic d-mannitol. In myelinated axons, C-CTX-1 increased nodal membrane excitability, inducing spontaneous and repetitive APs. Also, the toxin enlarged the repolarising phase of APs in control and tetraethylammonium-treated axons. Overall, our data suggest that C-CTX-1 affects nerve excitability and neurotransmitter release at nerve terminals. We conclude that C-CTX-1-induced up-regulation of Na(+) channels and the inhibition of K(+) channels, at low nanomolar concentrations, produce a variety of functional dysfunctions that are in part responsible for the human muscle skeletal symptoms observed in ciguatera. All these dysfunctions seem to result from the subtle balance between ionic currents, intracellular Na(+) and Ca(2+) concentrations, and engaged second messengers. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Capsaicin delays regeneration of the neuromuscular junction of rat extensor digitorum longus muscle after ischemia.

    Science.gov (United States)

    Turchányi, Béla; Hamar, János; Tömböl, Teréz; Siklós, László

    2006-04-01

    Trauma or the tourniquet used in orthopedic surgery is often associated with ischemia-reperfusion (I/R) injury with a consequent decrease of muscle power. To explore whether components of the neuromuscular junction (NMJ) are involved in this muscle dysfunction, NMJs were ultrastructurally characterized in the extensor digitorum longus muscle of rats at reperfusion times of 1, 24, 72, and 168 h after a 120-min arterial occlusion. Disorganization of the presynaptic membrane and mitochondrial injury was noted at 1 h, followed by fragmentation and partial engulfment of nerve terminals by Schwann cells at 24 and 72 h. The magnitude of degenerative changes declined at 168 h, suggesting the commencement of regeneration. The postsynaptic membrane remained intact throughout the whole period. In our previous study, deafferentation with pretreatment of the sciatic nerve with capsaicin, which reduces neurogenic inflammation and has a selective effect on nociceptive fibers, improved functional recovery of the muscle after I/R. The present results document a significantly delayed structural regeneration of the motor nerve terminals after combined capsaicin and I/R treatment. Since capsaicin treatment alone had no discernible effect on the structure of NMJs, the findings point to a possibly indirect effect of capsaicin on the motor nerves, which may predispose them to increased susceptibility unmasked only by a subsequent injury. The mismatch between the enhanced functional improvement of the muscle and delayed regeneration of the nerve after capsaicin pretreatment questions the efficient use of such deafferentation to protect the integrity of neuromuscular junctions in I/R injury.

  16. Electrical stimulation enhances the acetylcholine receptors available for neuromuscular junction formation.

    Science.gov (United States)

    Lozano, Rodrigo; Gilmore, Kerry J; Thompson, Brianna C; Stewart, Elise M; Waters, Aaron M; Romero-Ortega, Mario; Wallace, Gordon G

    2016-11-01

    Neuromuscular junctions (NMJ) are specialized synapses that link motor neurons with muscle fibers. These sites are fundamental to human muscle activity, controlling swallowing and breathing amongst many other vital functions. Study of this synapse formation is an essential area in neuroscience; the understanding of how neurons interact and control their targets during development and regeneration are fundamental questions. Existing data reveals that during initial stages of development neurons target and form synapses driven by biophysical and biochemical cues, and during later stages they require electrical activity to develop their functional interactions. The aim of this study was to investigate the effect of exogenous electrical stimulation (ES) electrodes directly in contact with cells, on the number and size of acetylcholine receptor (AChR) clusters available for NMJ formation. We used a novel in vitro model that utilizes a flexible electrical stimulation system and allows the systematic testing of several stimulation parameters simultaneously as well as the use of alternative electrode materials such as conductive polymers to deliver the stimulation. Functionality of NMJs under our co-culture conditions was demonstrated by monitoring changes in the responses of primary myoblasts to chemical stimulants that specifically target neuronal signaling. Our results suggest that biphasic electrical stimulation at 250Hz, 100μs pulse width and current density of 1mA/cm 2 for 8h, applied via either gold-coated mylar or the conductive polymer PPy, significantly increased the number and size of AChRs clusters available for NMJ formation. This study supports the beneficial use of direct electrical stimulation as a strategic therapy for neuromuscular disorders. The beneficial effects of electrical stimulation (ES) on human cells in vitro and in vivo have long been known. Although the effects of stimulation are clear and the therapeutic benefits are known, no uniform

  17. Variation in Dube3a expression affects neurotransmission at the Drosophila neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Colleen Valdez

    2015-07-01

    Full Text Available Changes in UBE3A expression levels in neurons can cause neurogenetic disorders ranging from Angelman syndrome (AS (decreased levels to autism (increased levels. Here we investigated the effects on neuronal function of varying UBE3A levels using the Drosophila neuromuscular junction as a model for both of these neurogenetic disorders. Stimulations that evoked excitatory junction potentials (EJPs at 1 Hz intermittently failed to evoke EJPs at 15 Hz in a significantly higher proportion of Dube3a over-expressors using the pan neuronal GAL4 driver C155-GAL4 (C155-GAL4>UAS-Dube3a relative to controls (C155>+ alone. However, in the Dube3a over-expressing larval neurons with no failures, there was no difference in EJP amplitude at the beginning of the train, or the rate of decrease in EJP amplitude over the course of the train compared to controls. In the absence of tetrodotoxin (TTX, spontaneous EJPs were observed in significantly more C155-GAL4>UAS-Dube3a larva compared to controls. In the presence of TTX, spontaneous and evoked EJPs were completely blocked and mEJP amplitude and frequency did not differ among genotypes. These data suggest that over-expression of wild type Dube3a, but not a ubiquitination defective Dube3a-C/A protein, compromises the ability of motor neuron axons to support closely spaced trains of action potentials, while at the same time increasing excitability. EJPs evoked at 15 Hz in the absence of Dube3a (Dube3a15b homozygous mutant larvae decayed more rapidly over the course of 30 stimulations compared to w1118 controls, and Dube3a15b larval muscles had significantly more negative resting membrane potentials (RMP. However, these results could not be recapitulated using RNAi knockdown of Dube3a in muscle or neurons alone, suggesting more global developmental defects contribute to this phenotype. These data suggest that reduced UBE3A expression levels may cause global changes that affect RMP and neurotransmitter release from

  18. Opposite Synaptic Alterations at the Neuromuscular Junction in an ALS Mouse Model: When Motor Units Matter.

    Science.gov (United States)

    Tremblay, Elsa; Martineau, Éric; Robitaille, Richard

    2017-09-13

    Denervation of the neuromuscular junction (NMJ) precedes the loss of motor neurons (MNs) in amyotrophic lateral sclerosis (ALS). ALS is characterized by a motor unit (MU)-dependent vulnerability where MNs with fast-fatigable (FF) characteristics are lost first, followed by fast fatigue-resistant (FR) and slow (S) MNs. However, changes in NMJ properties as a function of MU types remain debated. We hypothesized that NMJ synaptic functions would be altered precociously in an MU-specific manner, before structural alterations of the NMJ. Synaptic transmission and morphological changes of NMJs have been explored in two nerve-muscle preparations of male SOD1 G37R mice and their wild-type (WT) littermates: the soleus (S and FR MU); and the extensor digitorum longus (FF MU). S, FR, and FF NMJs of WT mice showed distinct synaptic properties from which we build an MU synaptic profile (MUSP) that reports MU-dependent NMJ synaptic properties. At postnatal day 180 (P180), FF and S NMJs of SOD1 already showed, respectively, lower and higher quantal content compared with WT mice, before signs of MN death and before NMJ morphological alterations. Changes persisted in both muscles until preonset (P380), while denervation was frequent in the mutant mouse. MN death was evident at this stage. Additional changes occurred at clinical disease onset (P450) for S and FR MU. As a whole, our results reveal a reversed MUSP in SOD1 mutants and highlight MU-specific synaptic changes occurring in a precise temporal sequence. Importantly, changes in synaptic properties appear to be good predictors of vulnerability to neurodegeneration. SIGNIFICANCE STATEMENT The inadequate excitability of motor neurons and their output, the neuromuscular junctions (NMJs), has been considered a key factor in the detrimental outcome of the motor function in amyotrophic lateral sclerosis. However, a conundrum persists at the NMJ whereby persistent but incoherent opposite neurotransmission changes have been reported

  19. Endocannabinoids mediate muscarine-induced synaptic depression at the vertebrate neuromuscular junction

    Science.gov (United States)

    Newman, Zachary; Malik, Priya; Wu, Tse-Yu; Ochoa, Christopher; Watsa, Nayantara; Lindgren, Clark

    2007-01-01

    Endocannabinoids (eCBs) inhibit neurotransmitter release throughout the central nervous system. Using the Ceratomandibularis muscle from the lizard Anolis carolinensis we asked whether eCBs play a similar role at the vertebrate neuromuscular junction. We report here that the CB1 cannabinoid receptor is concentrated on motor terminals and that eCBs mediate the inhibition of neurotransmitter release induced by the activation of M3 muscarinic acetylcholine (ACh) receptors. N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, a CB1 antagonist, prevents muscarine from inhibiting release and arachidonylcyclopropylamide (ACPA), a CB1 receptor agonist, mimics M3 activation and occludes the effect of muscarine. As for its mechanism of action, ACPA reduces the action-potential-evoked calcium transient in the nerve terminal and this decrease is more than sufficient to account for the observed inhibition of neurotransmitter release. Similar to muscarine, the inhibition of synaptic transmission by ACPA requires nitric oxide, acting via the synthesis of cGMP and the activation of cGMP-dependent protein kinase. 2-Arachidonoylglycerol (2-AG) is responsible for the majority of the effects of eCB as inhibitors of phospholipase C and diacylglycerol lipase, two enzymes responsible for synthesis of 2-AG, significantly limit muscarine-induced inhibition of neurotransmitter release. Lastly, the injection of (5Z,8Z,11Z,14Z)-N-(4-hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide (an inhibitor of eCB transport) into the muscle prevents muscarine, but not ACPA, from inhibiting ACh release. These results collectively lead to a model of the vertebrate neuromuscular junction whereby 2-AG mediates the muscarine-induced inhibition of ACh release. To demonstrate the physiological relevance of this model we show that the CB1 antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide prevents synaptic

  20. Alterations in Spontaneous Transmitter Release by Divalent Cations after Treatment of the Neuromuscular Junction with Alpha-Bungarotoxin

    Science.gov (United States)

    1982-01-01

    to change the spontaneous release rate of quantal acetylcholine . The simplest interpretation of these results is that toxin treatment increases the...Gage. 1973; Kita et al.. 1981), Mn increases spontaneous relese . The potentiations of transmitte- release by cobalt and nickel after toxin treatment...and Van der Kkw.. W. (1976). Effects of the ionophore X-537A on acetylcholine release at the frog neuromuscular junction. J. PuIwOl. Loand. 29 177-4

  1. Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains

    Directory of Open Access Journals (Sweden)

    Bailey Nichols

    2015-07-01

    Full Text Available Dystrophin-glycoprotein complex (DGC is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin of a muscle fiber to the extracellular matrix (ECM. Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies, and limb-girdle muscular dystrophies (sarcoglycanopathies, are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS, which is localized at the muscle membrane by DGC members (dystrophin and syntrophins, plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain.

  2. Two Algorithms for High-throughput and Multi-parametric Quantification of Drosophila Neuromuscular Junction Morphology.

    Science.gov (United States)

    Castells-Nobau, Anna; Nijhof, Bonnie; Eidhof, Ilse; Wolf, Louis; Scheffer-de Gooyert, Jolanda M; Monedero, Ignacio; Torroja, Laura; van der Laak, Jeroen A W M; Schenck, Annette

    2017-05-03

    Synaptic morphology is tightly related to synaptic efficacy, and in many cases morphological synapse defects ultimately lead to synaptic malfunction. The Drosophila larval neuromuscular junction (NMJ), a well-established model for glutamatergic synapses, has been extensively studied for decades. Identification of mutations causing NMJ morphological defects revealed a repertoire of genes that regulate synapse development and function. Many of these were identified in large-scale studies that focused on qualitative approaches to detect morphological abnormalities of the Drosophila NMJ. A drawback of qualitative analyses is that many subtle players contributing to NMJ morphology likely remain unnoticed. Whereas quantitative analyses are required to detect the subtler morphological differences, such analyses are not yet commonly performed because they are laborious. This protocol describes in detail two image analysis algorithms "Drosophila NMJ Morphometrics" and "Drosophila NMJ Bouton Morphometrics", available as Fiji-compatible macros, for quantitative, accurate and objective morphometric analysis of the Drosophila NMJ. This methodology is developed to analyze NMJ terminals immunolabeled with the commonly used markers Dlg-1 and Brp. Additionally, its wider application to other markers such as Hrp, Csp and Syt is presented in this protocol. The macros are able to assess nine morphological NMJ features: NMJ area, NMJ perimeter, number of boutons, NMJ length, NMJ longest branch length, number of islands, number of branches, number of branching points and number of active zones in the NMJ terminal.

  3. Myotubular myopathy and the neuromuscular junction: a novel therapeutic approach from mouse models

    Directory of Open Access Journals (Sweden)

    James J. Dowling

    2012-11-01

    Myotubular myopathy (MTM is a severe congenital muscle disease characterized by profound weakness, early respiratory failure and premature lethality. MTM is defined by muscle biopsy findings that include centralized nuclei and disorganization of perinuclear organelles. No treatments currently exist for MTM. We hypothesized that aberrant neuromuscular junction (NMJ transmission is an important and potentially treatable aspect of the disease pathogenesis. We tested this hypothesis in two murine models of MTM. In both models we uncovered evidence of a disorder of NMJ transmission: fatigable weakness, improved strength with neostigmine, and electrodecrement with repetitive nerve stimulation. Histopathological analysis revealed abnormalities in the organization, appearance and size of individual NMJs, abnormalities that correlated with changes in acetylcholine receptor gene expression and subcellular localization. We additionally determined the ability of pyridostigmine, an acetylcholinesterase inhibitor, to ameliorate aspects of the behavioral phenotype related to NMJ dysfunction. Pyridostigmine treatment resulted in significant improvement in fatigable weakness and treadmill endurance. In all, these results describe a newly identified pathological abnormality in MTM, and uncover a potential disease-modifying therapy for this devastating disorder.

  4. Presynaptic active zones of mammalian neuromuscular junctions: Nanoarchitecture and selective impairments in aging.

    Science.gov (United States)

    Badawi, Yomna; Nishimune, Hiroshi

    2018-02-01

    Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification. Interestingly, the active zones of adult NMJs are not stable structures and thus become impaired during aging due to the selective degeneration of specific active zone proteins. This review will discuss recent progress in the understanding of active zone nanoarchitecture and the mechanisms underlying active zone organization in mammalian NMJs. Furthermore, we will summarize the age-related degeneration of active zones at NMJs, and the role of exercise in maintaining active zones. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  5. Integrated genomics and proteomics of the Torpedo californica electric organ: concordance with the mammalian neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Mate Suzanne E

    2011-05-01

    Full Text Available Abstract Background During development, the branchial mesoderm of Torpedo californica transdifferentiates into an electric organ capable of generating high voltage discharges to stun fish. The organ contains a high density of cholinergic synapses and has served as a biochemical model for the membrane specialization of myofibers, the neuromuscular junction (NMJ. We studied the genome and proteome of the electric organ to gain insight into its composition, to determine if there is concordance with skeletal muscle and the NMJ, and to identify novel synaptic proteins. Results Of 435 proteins identified, 300 mapped to Torpedo cDNA sequences with ≥2 peptides. We identified 14 uncharacterized proteins in the electric organ that are known to play a role in acetylcholine receptor clustering or signal transduction. In addition, two human open reading frames, C1orf123 and C6orf130, showed high sequence similarity to electric organ proteins. Our profile lists several proteins that are highly expressed in skeletal muscle or are muscle specific. Synaptic proteins such as acetylcholinesterase, acetylcholine receptor subunits, and rapsyn were present in the electric organ proteome but absent in the skeletal muscle proteome. Conclusions Our integrated genomic and proteomic analysis supports research describing a muscle-like profile of the organ. We show that it is a repository of NMJ proteins but we present limitations on its use as a comprehensive model of the NMJ. Finally, we identified several proteins that may become candidates for signaling proteins not previously characterized as components of the NMJ.

  6. Integrated genomics and proteomics of the Torpedo californica electric organ: concordance with the mammalian neuromuscular junction

    Science.gov (United States)

    2011-01-01

    Background During development, the branchial mesoderm of Torpedo californica transdifferentiates into an electric organ capable of generating high voltage discharges to stun fish. The organ contains a high density of cholinergic synapses and has served as a biochemical model for the membrane specialization of myofibers, the neuromuscular junction (NMJ). We studied the genome and proteome of the electric organ to gain insight into its composition, to determine if there is concordance with skeletal muscle and the NMJ, and to identify novel synaptic proteins. Results Of 435 proteins identified, 300 mapped to Torpedo cDNA sequences with ≥2 peptides. We identified 14 uncharacterized proteins in the electric organ that are known to play a role in acetylcholine receptor clustering or signal transduction. In addition, two human open reading frames, C1orf123 and C6orf130, showed high sequence similarity to electric organ proteins. Our profile lists several proteins that are highly expressed in skeletal muscle or are muscle specific. Synaptic proteins such as acetylcholinesterase, acetylcholine receptor subunits, and rapsyn were present in the electric organ proteome but absent in the skeletal muscle proteome. Conclusions Our integrated genomic and proteomic analysis supports research describing a muscle-like profile of the organ. We show that it is a repository of NMJ proteins but we present limitations on its use as a comprehensive model of the NMJ. Finally, we identified several proteins that may become candidates for signaling proteins not previously characterized as components of the NMJ. PMID:21798097

  7. Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression.

    Science.gov (United States)

    Lee, Kah Meng; Chand, Kirat K; Hammond, Luke A; Lavidis, Nickolas A; Noakes, Peter G

    2017-03-14

    Laminin-α4 is involved in the alignment of active zones to postjunctional folds at the neuromuscular junction (NMJ). Prior study has implicated laminin-α4 in NMJ maintenance, with altered NMJ morphology observed in adult laminin-α4 deficient mice ( lama 4 -/- ). The present study further investigated the role of laminin-α4 in NMJ maintenance by functional characterization of transmission properties, morphological investigation of synaptic proteins including synaptic laminin-α4, and neuromotor behavioral testing. Results showed maintained perturbed transmission properties at lama 4 -/- NMJs from adult (3 months) through to aged (18-22 months). Hind-limb grip force demonstrated similar trends as transmission properties, with maintained weaker grip force across age groups in lama 4 -/- . Interestingly, both transmission properties and hind-limb grip force in aged wild-types resembled those observed in adult lama 4 -/- . Most significantly, altered expression of laminin-α4 was noted at the wild-type NMJs prior to the observed decline in transmission properties, suggesting that altered laminin-α4 expression precedes the decline of neurotransmission in aging wild-types. These findings significantly support the role of laminin-α4 in maintenance of the NMJ during aging.

  8. β-Catenin gain of function in muscles impairs neuromuscular junction formation.

    Science.gov (United States)

    Wu, Haitao; Lu, Yisheng; Barik, Arnab; Joseph, Anish; Taketo, Makoto Mark; Xiong, Wen-Cheng; Mei, Lin

    2012-07-01

    Neuromuscular junction (NMJ) formation requires proper interaction between motoneurons and muscle cells. β-Catenin is required in muscle cells for NMJ formation. To understand underlying mechanisms, we investigated the effect of β-catenin gain of function (GOF) on NMJ development. In HSA-β-cat(flox(ex3)/+) mice, which express stable β-catenin specifically in muscles, motor nerve terminals became extensively defasciculated and arborized. Ectopic muscles were observed in the diaphragm and were innervated by ectopic phrenic nerve branches. Moreover, extensive outgrowth and branching of spinal axons were evident in the GOF mice. These results indicate that increased β-catenin in muscles alters presynaptic differentiation. Postsynaptically, AChR clusters in HSA-β-cat(flox(ex3)/+) diaphragms were distributed in a wider region, suggesting that muscle β-catenin GOF disrupted the signal that restricts AChR clustering to the middle region of muscle fibers. Expression of stable β-catenin in motoneurons, however, had no effect on NMJ formation. These observations provide additional genetic evidence that pre- and postsynaptic development of the NMJ requires an intricate balance of β-catenin activity in muscles.

  9. Glial Processes at the Drosophila Larval Neuromuscular Junction Match Synaptic Growth

    Science.gov (United States)

    Brink, Deidre L.; Gilbert, Mary; Xie, Xiaojun; Petley-Ragan, Lindsay; Auld, Vanessa J.

    2012-01-01

    Glia are integral participants in synaptic physiology, remodeling and maturation from blowflies to humans, yet how glial structure is coordinated with synaptic growth is unknown. To investigate the dynamics of glial development at the Drosophila larval neuromuscular junction (NMJ), we developed a live imaging system to establish the relationship between glia, neuronal boutons, and the muscle subsynaptic reticulum. Using this system we observed processes from two classes of peripheral glia present at the NMJ. Processes from the subperineurial glia formed a blood-nerve barrier around the axon proximal to the first bouton. Processes from the perineurial glial extended beyond the end of the blood-nerve barrier into the NMJ where they contacted synapses and extended across non-synaptic muscle. Growth of the glial processes was coordinated with NMJ growth and synaptic activity. Increasing synaptic size through elevated temperature or the highwire mutation increased the extent of glial processes at the NMJ and conversely blocking synaptic activity and size decreased the presence and size of glial processes. We found that elevated temperature was required during embryogenesis in order to increase glial expansion at the nmj. Therefore, in our live imaging system, glial processes at the NMJ are likely indirectly regulated by synaptic changes to ensure the coordinated growth of all components of the tripartite larval NMJ. PMID:22666403

  10. New perspectives on amyotrophic lateral sclerosis: the role of glial cells at the neuromuscular junction.

    Science.gov (United States)

    Arbour, Danielle; Vande Velde, Christine; Robitaille, Richard

    2017-02-01

    Amyotrophic lateral sclerosis (ALS) is a disease leading to the death of motor neurons (MNs). It is also recognized as a non-cell autonomous disease where glial cells in the CNS are involved in its pathogenesis and progression. However, although denervation of neuromuscular junctions (NMJs) represents an early and major event in ALS, the importance of glial cells at this synapse receives little attention. An interesting possibility is that altered relationships between glial cells and MNs in the spinal cord in ALS may also take place at the NMJ. Perisynaptic Schwann cells (PSCs), which are glial cells at the NMJ, show great morphological and functional adaptability to ensure NMJ stability, maintenance and repair. More specifically, PSCs change their properties according to the state of innervation. Hence, abnormal changes or lack of changes can have detrimental effects on NMJs in ALS. This review will provide an overview of known and hypothesized interactions between MN nerve terminals and PSCs at NMJs during development, aging and ALS-induced denervation. These neuron-PSC interactions may be crucial to the understanding of how degenerative changes begin and progress at NMJs in ALS, and represent a novel therapeutic target. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  11. Regulation of neuromuscular junction organization by Rab2 and its effector ICA69 in Drosophila.

    Science.gov (United States)

    Mallik, Bhagaban; Dwivedi, Manish Kumar; Mushtaq, Zeeshan; Kumari, Manisha; Verma, Praveen Kumar; Kumar, Vimlesh

    2017-06-01

    The mechanisms underlying synaptic differentiation, which involves neuronal membrane and cytoskeletal remodeling, are not completely understood. We performed a targeted RNAi-mediated screen of Drosophila BAR-domain proteins and identified islet cell autoantigen 69 kDa (ICA69) as one of the key regulators of morphological differentiation of the larval neuromuscular junction (NMJ). We show that Drosophila ICA69 colocalizes with α-Spectrin at the NMJ. The conserved N-BAR domain of ICA69 deforms liposomes in vitro Full-length ICA69 and the ICAC but not the N-BAR domain of ICA69 induce filopodia in cultured cells. Consistent with its cytoskeleton regulatory role, ICA69 mutants show reduced α-Spectrin immunoreactivity at the larval NMJ. Manipulating levels of ICA69 or its interactor PICK1 alters the synaptic level of ionotropic glutamate receptors (iGluRs). Moreover, reducing PICK1 or Rab2 levels phenocopies ICA69 mutation. Interestingly, Rab2 regulates not only synaptic iGluR but also ICA69 levels. Thus, our data suggest that: (1) ICA69 regulates NMJ organization through a pathway that involves PICK1 and Rab2, and (2) Rab2 functions genetically upstream of ICA69 and regulates NMJ organization and targeting/retention of iGluRs by regulating ICA69 levels. © 2017. Published by The Company of Biologists Ltd.

  12. Defects in neuromuscular junction remodelling in the Smn(2B/-) mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Murray, Lyndsay M; Beauvais, Ariane; Bhanot, Kunal; Kothary, Rashmi

    2013-01-01

    Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease caused by mutations and deletions within the survival motor neuron 1 (SMN1) gene. Although other tissues may be involved, motor neurons remain primary pathological targets, with loss of neuromuscular junctions (NMJs) representing an early and significant event in pathogenesis. Although defects in axonal outgrowth and pathfinding have been observed in cell culture and in lower organisms upon Smn depletion, developmental defects in mouse models have been less obvious. Here, we have employed the Smn(2B/-) mouse model to investigate NMJ remodelling during SMA pathology, induced reinnervation, and paralysis. We show that whilst NMJs are capable of remodelling during pathogenesis, there is a marked reduction in paralysis-induced remodelling and in the nerve-directed re-organisation of acetylcholine receptors. This reduction in remodelling potential could not be attributed to a decreased rate of axonal growth. Finally, we have identified a loss of terminal Schwann cells which could contribute to the defects in remodelling/maintenance observed. Our work demonstrates that there are specific defects in NMJ remodelling in an intermediate SMA mouse model, which could contribute to or underlie pathogenesis in SMA. The development of strategies that can promote the remodelling potential of NMJs may therefore be of significant benefit to SMA patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions.

    Directory of Open Access Journals (Sweden)

    Melanie A Samuel

    Full Text Available As synapses form and mature the synaptic partners produce organizing molecules that regulate each other's differentiation and ensure precise apposition of pre- and post-synaptic specializations. At the skeletal neuromuscular junction (NMJ, these molecules include agrin, a nerve-derived organizer of postsynaptic differentiation, and synaptic laminins, muscle-derived organizers of presynaptic differentiation. Both become concentrated in the synaptic cleft as the NMJ develops and are retained in adulthood. Here, we used mutant mice to ask whether these organizers are also required for synaptic maintenance. Deletion of agrin from a subset of adult motor neurons resulted in the loss of acetylcholine receptors and other components of the postsynaptic apparatus and synaptic cleft. Nerve terminals also atrophied and eventually withdrew from muscle fibers. On the other hand, mice lacking the presynaptic organizer laminin-α4 retained most of the synaptic cleft components but exhibited synaptic alterations reminiscent of those observed in aged animals. Although we detected no marked decrease in laminin or agrin levels at aged NMJs, we observed alterations in the distribution and organization of these synaptic cleft components suggesting that such changes could contribute to age-related synaptic disassembly. Together, these results demonstrate that pre- and post-synaptic organizers actively function to maintain the structure and function of adult NMJs.

  14. An examination of neuromuscular and metabolic fatigue thresholds

    International Nuclear Information System (INIS)

    Bergstrom, Haley C; Housh, Terry J; Cochrane, Kristen C; Jenkins, Nathaniel D M; Lewis, Robert W Jr; Traylor, Daniel A; Schmidt, Richard J; Johnson, Glen O; Cramer, Joel T; Zuniga, Jorge M

    2013-01-01

    This study examined the relationships among the physical working capacity at the fatigue threshold (PWC FT ), the power outputs associated with the gas exchange threshold (PGET) and the respiratory compensation point (PRCP), and critical power (CP) to identify possible physiological mechanisms underlying the onset of neuromuscular fatigue. Ten participants (mean ± SD age: 20 ± 1 years) performed a maximal incremental cycle ergometer test to determine the PWC FT , PGET, and PRCP. CP was determined from the 3 min all-out test. The PWC FT (197 ± 55 W), PRCP (212 ± 50 W), and CP (208 ± 63 W) were significantly greater than the PGET (168 ± 40 W), but there were no significant differences among the PWC FT , PRCP, and CP. All thresholds were significantly inter-4 (r = 0.794–0.958). The 17% greater estimates for the PWC FT than PGET were likely related to differences in the physiological mechanisms that underlie these fatigue thresholds, while the non-significant difference and high correlation between the PWC FT and the PRCP suggested that hyperkalemia may underlie both thresholds. Furthermore, it is possible that the 5% lower estimate of the PWC FT than CP could more accurately reflect the demarcation of the heavy from severe exercise intensity domains. (paper)

  15. Structural and Functional Abnormalities of the Neuromuscular Junction in the Trembler-J Homozygote Mouse Model of Congenital Hypomyelinating Neuropathy.

    Science.gov (United States)

    Scurry, Alexandra N; Heredia, Dante J; Feng, Cheng-Yuan; Gephart, Gregory B; Hennig, Grant W; Gould, Thomas W

    2016-04-01

    Mutations in peripheral myelin protein 22 (PMP22) result in the most common form of Charcot-Marie-Tooth (CMT) disease, CMT1A. This hereditary peripheral neuropathy is characterized by dysmyelination of peripheral nerves, reduced nerve conduction velocity, and muscle weakness. APMP22 point mutation in L16P (leucine 16 to proline) underlies a form of human CMT1A as well as the Trembler-J mouse model of CMT1A. Homozygote Trembler-J mice (Tr(J)) die early postnatally, fail to make peripheral myelin, and, therefore, are more similar to patients with congenital hypomyelinating neuropathy than those with CMT1A. Because recent studies of inherited neuropathies in humans and mice have demonstrated that dysfunction and degeneration of neuromuscular synapses or junctions (NMJs) often precede impairments in axonal conduction, we examined the structure and function of NMJs in Tr(J)mice. Although synapses appeared to be normally innervated even in end-stage Tr(J)mice, the growth and maturation of the NMJs were altered. In addition, the amplitudes of nerve-evoked muscle endplate potentials were reduced and there was transmission failure during sustained nerve stimulation. These results suggest that the severe congenital hypomyelinating neuropathy that characterizes Tr(J)mice results in structural and functional deficits of the developing NMJ. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

  16. Mechanisms of hydrogen sulfide (H2S) action on synaptic transmission at the mouse neuromuscular junction.

    Science.gov (United States)

    Gerasimova, E; Lebedeva, J; Yakovlev, A; Zefirov, A; Giniatullin, R; Sitdikova, G

    2015-09-10

    Hydrogen sulfide (H2S) is a widespread gasotransmitter also known as a powerful neuroprotective agent in the central nervous system. However, the action of H2S in peripheral synapses is much less studied. In the current project we studied the modulatory effects of the H2S donor sodium hydrosulfide (NaHS) on synaptic transmission in the mouse neuromuscular junction using microelectrode technique. Using focal recordings of presynaptic response and evoked transmitter release we have shown that NaHS (300 μM) increased evoked end-plate currents (EPCs) without changes of presynaptic waveforms which indicated the absence of NaHS effects on sodium and potassium currents of motor nerve endings. Using intracellular recordings it was shown that NaHS increased the frequency of miniature end-plate potentials (MEPPs) without changing their amplitudes indicating a pure presynaptic effect. Furthermore, NaHS increased the amplitude of end-plate potentials (EPPs) without influencing the resting membrane potential of muscle fibers. L-cysteine, a substrate of H2S synthesis induced, similar to NaHS, an increase of EPC amplitudes whereas inhibitors of H2S synthesis (β-cyano-L-alanine and aminooxyacetic acid) had the opposite effect. Inhibition of adenylate cyclase using MDL 12,330A hydrochloride (MDL 12,330A) or elevation of cAMP level with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (pCPT-cAMP) completely prevented the facilitatory action of NaHS indicating involvement of the cAMP signaling cascade. The facilitatory effect of NaHS was significantly diminished when intracellular calcium (Ca(2+)) was buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) and ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM). Activation of ryanodine receptors by caffeine or ryanodine increased acetylcholine release and prevented further action of NaHS on transmitter release, likely due to

  17. Reactive oxygen species contribute to the presynaptic action of extracellular ATP at the frog neuromuscular junction

    Science.gov (United States)

    Giniatullin, AR; Grishin, SN; Sharifullina, ER; Petrov, AM; Zefirov, AL; Giniatullin, RA

    2005-01-01

    During normal cell metabolism the production of intracellular ATP is associated with the generation of reactive oxygen species (ROS), which appear to be important signalling molecules. Both ATP and ROS can be released extracellularly by skeletal muscle during intense activity. Using voltage clamp recording combined with imaging and biochemical assay of ROS, we tested the hypothesis that at the neuromuscular junction extracellular ATP generates ROS to inhibit transmitter release from motor nerve endings. We found that ATP produced the presynaptic inhibitory action on multiquantal end-plate currents. The inhibitory action of ATP (but not that of adenosine) was significantly reduced by several antioxidants or extracellular catalase, which breaks down H2O2. Consistent with these data, the depressant effect of ATP was dramatically potentiated by the pro-oxidant Fe2+. Exogenous H2O2 reproduced the depressant effects of ATP and showed similar sensitivity to anti- and pro-oxidants. While NO also inhibited synaptic transmission, inhibitors of the NO-producing cascade did not prevent the depressant action of ATP. The ferrous oxidation in xylenol orange assay showed the increase of ROS production by ATP and 2-MeSADP but not by adenosine. Suramin, a non-selective antagonist of P2 receptors, and pertussis toxin prevented the action of ATP on ROS production. Likewise, imaging with the ROS-sensitive dye carboxy-2′,7′-dichlorodihydrofluorescein revealed increased production of ROS in the muscle treated with ATP or ADP while UTP or adenosine had no effect. Thus, generation of ROS contributed to the ATP-mediated negative feedback mechanism controlling quantal secretion of ACh from the motor nerve endings. PMID:15774519

  18. Eps homology domain endosomal transport proteins differentially localize to the neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Mate Suzanne E

    2012-09-01

    Full Text Available Abstract Background Recycling of endosomes is important for trafficking and maintenance of proteins at the neuromuscular junction (NMJ. We have previously shown high expression of the endocytic recycling regulator Eps15 homology domain-containing (EHD1 proteinin the Torpedo californica electric organ, a model tissue for investigating a cholinergic synapse. In this study, we investigated the localization of EHD1 and its paralogs EHD2, EHD3, and EHD4 in mouse skeletal muscle, and assessed the morphological changes in EHD1−/− NMJs. Methods Localization of the candidate NMJ protein EHD1 was assessed by confocal microscopy analysis of whole-mount mouse skeletal muscle fibers after direct gene transfer and immunolabeling. The potential function of EHD1 was assessed by specific force measurement and α-bungarotoxin-based endplate morphology mapping in EHD1−/− mouse skeletal muscle. Results Endogenous EHD1 localized to primary synaptic clefts of murine NMJ, and this localization was confirmed by expression of recombinant green fluorescent protein labeled-EHD1 in murine skeletal muscle in vivo. EHD1−/− mouse skeletal muscle had normal histology and NMJ morphology, and normal specific force generation during muscle contraction. The EHD 1–4 proteins showed differential localization in skeletal muscle: EHD2 to muscle vasculature, EHD3 to perisynaptic regions, and EHD4 to perinuclear regions and to primary synaptic clefts, but at lower levels than EHD1. Additionally, specific antibodies raised against mammalian EHD1-4 recognized proteins of the expected mass in the T. californica electric organ. Finally, we found that EHD4 expression was more abundant in EHD1−/− mouse skeletal muscle than in wild-type skeletal muscle. Conclusion EHD1 and EHD4 localize to the primary synaptic clefts of the NMJ. Lack of obvious defects in NMJ structure and muscle function in EHD1−/− muscle may be due to functional compensation by other EHD paralogs.

  19. Depressed Synaptic Transmission and Reduced Vesicle Release Sites in Huntington's Disease Neuromuscular Junctions.

    Science.gov (United States)

    Khedraki, Ahmad; Reed, Eric J; Romer, Shannon H; Wang, Qingbo; Romine, William; Rich, Mark M; Talmadge, Robert J; Voss, Andrew A

    2017-08-23

    Huntington's disease (HD) is a progressive and fatal degenerative disorder that results in debilitating cognitive and motor dysfunction. Most HD studies have focused on degeneration of the CNS. We previously discovered that skeletal muscle from transgenic R6/2 HD mice is hyperexcitable due to decreased chloride and potassium conductances. The progressive and early onset of these defects suggest a primary myopathy in HD. In this study, we examined the relationship between neuromuscular transmission and skeletal muscle hyperexcitability. We used an ex vivo preparation of the levator auris longus muscle from male and female late-stage R6/2 mice and age-matched wild-type controls. Immunostaining of the synapses and molecular analyses revealed no evidence of denervation. Physiologically, we recorded spontaneous miniature endplate currents (mEPCs) and nerve-evoked EPCs (eEPCs) under voltage-clamp, which, unlike current-clamp records, were independent of the changes in muscle membrane properties. We found a reduction in the number of vesicles released per action potential (quantal content) in R6/2 muscle, which analysis of eEPC variance and morphology indicate is caused by a reduction in the number of vesicle release sites ( n ) rather than a change in the probability of release ( p rel ). Furthermore, analysis of high-frequency stimulation trains suggests an impairment in vesicle mobilization. The depressed neuromuscular transmission in R6/2 muscle may help compensate for the muscle hyperexcitability and contribute to motor impersistence. SIGNIFICANCE STATEMENT Recent evidence indicates that Huntington's disease (HD) is a multisystem disorder. Our examination of neuromuscular transmission in this study reveals defects in the motor nerve terminal that may compensate for the muscle hyperexcitability in HD. The technique we used eliminates the effects of the altered muscle membrane properties on synaptic currents and thus provides hitherto the most detailed analysis of

  20. Isoform-specific expression of the Coxsackie and adenovirus receptor (CAR) in neuromuscular junction and cardiac intercalated discs

    Science.gov (United States)

    Shaw, Christian A; Holland, Paul C; Sinnreich, Michael; Allen, Carol; Sollerbrant, Kerstin; Karpati, George; Nalbantoglu, Josephine

    2004-01-01

    Background The Coxsackie and adenovirus receptor (CAR) has a restricted expression pattern in the adult. In skeletal muscle, although CAR is expressed in immature fibers, its transcript levels are barely detectable in mature muscle. This is in contrast to the robust expression observed in the heart. However, both heart and skeletal muscle are susceptible to infection with the Coxsackie B virus which utilizes primarily CAR for cellular internalization. The specific point of viral entry in skeletal and heart muscle remains unknown. Results Using antibodies directed against the extracellular and the cytoplasmic domains of CAR, we show CAR in normal human and mouse skeletal muscle to be a novel component of the neuromuscular junction. In cardiac muscle, CAR immunoreactivity is observed at the level of intercalated discs. We demonstrate a single isoform of CAR to be expressed exclusively at the human neuromuscular junction whereas both predominant CAR isoforms are expressed at the intercalated discs of non-diseased human heart. Conclusion The localization of CAR to these important junctional complexes suggests that CAR may play both a structural and a regulatory role in skeletal and cardiac muscle, and that these complexes may serve as a point of entry for Coxsackie B virus. PMID:15533241

  1. Endogenous purines modulate K+ -evoked ACh secretion at the mouse neuromuscular junction.

    Science.gov (United States)

    Guarracino, Juan F; Cinalli, Alejandro R; Veggetti, Mariela I; Losavio, Adriana S

    2018-06-01

    At the mouse neuromuscular junction, adenosine triphosphate (ATP) is co-released with the neurotransmitter acetylcholine (ACh), and once in the synaptic cleft, it is hydrolyzed to adenosine. Both ATP/adenosine diphosphate (ADP) and adenosine modulate ACh secretion by activating presynaptic P2Y 13 and A 1 , A 2A , and A 3 receptors, respectively. To elucidate the action of endogenous purines on K + -dependent ACh release, we studied the effect of purinergic receptor antagonists on miniature end-plate potential (MEPP) frequency in phrenic diaphragm preparations. At 10 mM K + , the P2Y 13 antagonist N-[2-(methylthio)ethyl]-2-[3,3,3-trifluoropropyl]thio-5'-adenylic acid, monoanhydride with (dichloromethylene)bis[phosphonic acid], tetrasodium salt (AR-C69931MX) increased asynchronous ACh secretion while the A 1 , A 3 , and A 2A antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), (3-Ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(±)-dihydropyridine-3,5-, dicarboxylate (MRS-1191), and 2-(2-Furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH-58261) did not modify neurosecretion. The inhibition of equilibrative adenosine transporters by S-(p-nitrobenzyl)-6-thioinosine provoked a reduction of 10 mM K + -evoked ACh release, suggesting that the adenosine generated from ATP is being removed from the synaptic space by the transporters. At 15 and 20 mM K + , endogenous ATP/ADP and adenosine bind to inhibitory P2Y 13 and A 1 and A 3 receptors since AR-C69931MX, DPCPX, and MRS-1191 increased MEPP frequency. Similar results were obtained when the generation of adenosine was prevented by using the ecto-5'-nucleotidase inhibitor α,β-methyleneadenosine 5'-diphosphate sodium salt. SCH-58261 only reduced neurosecretion at 20 mM K + , suggesting that more adenosine is needed to activate excitatory A 2A receptors. At high K + concentration, the equilibrative transporters appear to be saturated allowing the accumulation of

  2. Effect of purines on calcium-independent acetylcholine release at the mouse neuromuscular junction.

    Science.gov (United States)

    Veggetti, M; Muchnik, S; Losavio, A

    2008-07-17

    At the mouse neuromuscular junction, activation of adenosine A(1) and P2Y receptors inhibits acetylcholine release by an effect on voltage dependent calcium channels related to spontaneous and evoked secretion. However, an effect of purines upon the neurotransmitter-releasing machinery downstream of Ca(2+) influx cannot be ruled out. An excellent tool to study neurotransmitter exocytosis in a Ca(2+)-independent step is the hypertonic response. Intracellular recordings were performed on diaphragm fibers of CF1 mice to determine the action of the specific adenosine A(1) receptor agonist 2-chloro-N(6)-cyclopentyl-adenosine (CCPA) and the P2Y(12-13) agonist 2-methylthio-adenosine 5'-diphosphate (2-MeSADP) on the hypertonic response. Both purines significantly decreased such response (peak and area under the curve), and their effect was prevented by specific antagonists of A(1) and P2Y(12-13) receptors, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and N-[2-(methylthioethyl)]-2-[3,3,3-trifluoropropyl]thio-5'-adenylic acid, monoanhydride with dichloromethylenebiphosphonic acid, tetrasodium salt (AR-C69931MX), respectively. Moreover, incubation of preparations only with the antagonists induced a higher response compared with controls, suggesting that endogenous ATP/ADP and adenosine are able to modulate the hypertonic response by activating their specific receptors. To search for the intracellular pathways involved in this effect, we studied the action of CCPA and 2-MeSADP in hypertonicity in the presence of inhibitors of several pathways. We found that the effect of CPPA was prevented by the calmodulin antagonist N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) while that of 2-MeSADP was occluded by the protein kinase C antagonist chelerythrine and W-7. On the other hand, the inhibitors of protein kinase A (N-(2[pbromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide, H-89) and phosphoinositide-3 kinase (PI3K) (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran

  3. Presynaptic inhibition of spontaneous acetylcholine release induced by adenosine at the mouse neuromuscular junction.

    Science.gov (United States)

    De Lorenzo, Silvana; Veggetti, Mariela; Muchnik, Salomón; Losavio, Adriana

    2004-05-01

    1. At the mouse neuromuscular junction, adenosine (AD) and the A(1) agonist 2-chloro-N(6)-cyclopentyl-adenosine (CCPA) induce presynaptic inhibition of spontaneous acetylcholine (ACh) release by activation of A(1) AD receptors through a mechanism that is still unknown. To evaluate whether the inhibition is mediated by modulation of the voltage-dependent calcium channels (VDCCs) associated with tonic secretion (L- and N-type VDCCs), we measured the miniature end-plate potential (mepp) frequency in mouse diaphragm muscles. 2. Blockade of VDCCs by Cd(2+) prevented the effect of the CCPA. Nitrendipine (an L-type VDCC antagonist) but not omega-conotoxin GVIA (an N-type VDCC antagonist) blocked the action of CCPA, suggesting that the decrease in spontaneous mepp frequency by CCPA is associated with an action on L-type VDCCs only. 3. As A(1) receptors are coupled to a G(i/o) protein, we investigated whether the inhibition of PKA or the activation of PKC is involved in the presynaptic inhibition mechanism. Neither N-(2[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide (H-89, a PKA inhibitor), nor 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7, a PKC antagonist), nor phorbol 12-myristate 13-acetate (PHA, a PKC activator) modified CCPA-induced presynaptic inhibition, suggesting that these second messenger pathways are not involved. 4. The effect of CCPA was eliminated by the calmodulin antagonist N-(6-aminohexil)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) and by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-acetoxymethyl ester epsilon6TDelta-BM, which suggests that the action of CCPA to modulate L-type VDCCs may involve Ca(2+)-calmodulin. 5. To investigate the action of CCPA on diverse degrees of nerve terminal depolarization, we studied its effect at different external K(+) concentrations. The effect of CCPA on ACh secretion evoked by 10 mm K(+) was prevented by the P/Q-type VDCC antagonist omega-agatoxin IVA. 6. CCPA failed to

  4. APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice

    Science.gov (United States)

    Choi, Hong Y; Liu, Yun; Tennert, Christian; Sugiura, Yoshie; Karakatsani, Andromachi; Kröger, Stephan; Johnson, Eric B; Hammer, Robert E; Lin, Weichun; Herz, Joachim

    2013-01-01

    ApoE, ApoE receptors and APP cooperate in the pathogenesis of Alzheimer’s disease. Intriguingly, the ApoE receptor LRP4 and APP are also required for normal formation and function of the neuromuscular junction (NMJ). In this study, we show that APP interacts with LRP4, an obligate co-receptor for muscle-specific tyrosine kinase (MuSK). Agrin, a ligand for LRP4, also binds to APP and co-operatively enhances the interaction of APP with LRP4. In cultured myotubes, APP synergistically increases agrin-induced acetylcholine receptor (AChR) clustering. Deletion of the transmembrane domain of LRP4 (LRP4 ECD) results in growth retardation of the NMJ, and these defects are markedly enhanced in APP−/−;LRP4ECD/ECD mice. Double mutant NMJs are significantly reduced in size and number, resulting in perinatal lethality. Our findings reveal novel roles for APP in regulating neuromuscular synapse formation through hetero-oligomeric interaction with LRP4 and agrin and thereby provide new insights into the molecular mechanisms that govern NMJ formation and maintenance. DOI: http://dx.doi.org/10.7554/eLife.00220.001 PMID:23986861

  5. INTERACTION OF VERAPAMIL AND LITHIUM AT THE NEUROMUSCULAR JUNCTION ON RAT ISOLATED MUSCLE-HEMIDIAPHRAGM

    Directory of Open Access Journals (Sweden)

    H. R. Sadeghipour

    1998-08-01

    Full Text Available It has been reported that cither lithium or verapamil can potentiate the neuromuscular blocking activity of certain neuromuscular blockers. In the present investigation, possible interaction of verapamil with lithium has been described. The dose ■ response effects of verapamil and lithium on diaphragmatic contractility were assessed in vitro. Mechanical responses of the muscle to indirect (nerve and direct (muscle electrical stimulation were recorded. Verapamil depressed rat diaphragm twitch tensions induced by nerve stimulation in a dose - dependent manner with the 50 percent depression of the original twitch tensions (ICSQ by 5.6 xlO^mmol/l."nThe IC50 of verapamil for direct stimulation of the muscle was LI x W'5 mmol II. Partial replacement of sodium chloride by lithium chloride (0.5, 1.5 and 5 mmol /1 in the medium did not change the depressant effect of verapamil on muscle twitches induced by direct (muscle or indirect (nerve electrical stimulation.

  6. Injection of a soluble fragment of neural agrin (NT-1654 considerably improves the muscle pathology caused by the disassembly of the neuromuscular junction.

    Directory of Open Access Journals (Sweden)

    Stefan Hettwer

    Full Text Available Treatment of neuromuscular diseases is still an unsolved problem. Evidence over the last years strongly indicates the involvement of malformation and dysfunction of neuromuscular junctions in the development of such medical conditions. Stabilization of NMJs thus seems to be a promising approach to attenuate the disease progression of muscle wasting diseases. An important pathway for the formation and maintenance of NMJs is the agrin/Lrp4/MuSK pathway. Here we demonstrate that the agrin biologic NT-1654 is capable of activating the agrin/Lrp4/MuSK system in vivo, leading to an almost full reversal of the sarcopenia-like phenotype in neurotrypsin-overexpressing (SARCO mice. We also show that injection of NT-1654 accelerates muscle re-innervation after nerve crush. This report demonstrates that a systemically administered agrin fragment has the potential to counteract the symptoms of neuromuscular disorders.

  7. Synaptic Deficits at Neuromuscular Junctions in Two Mouse Models of Charcot-Marie-Tooth Type 2d.

    Science.gov (United States)

    Spaulding, Emily L; Sleigh, James N; Morelli, Kathryn H; Pinter, Martin J; Burgess, Robert W; Seburn, Kevin L

    2016-03-16

    Patients with Charcot-Marie-Tooth Type 2D (CMT2D), caused by dominant mutations in Glycl tRNA synthetase (GARS), present with progressive weakness, consistently in the hands, but often in the feet also. Electromyography shows denervation, and patients often report that early symptoms include cramps brought on by cold or exertion. Based on reported clinical observations, and studies of mouse models of CMT2D, we sought to determine whether weakened synaptic transmission at the neuromuscular junction (NMJ) is an aspect of CMT2D. Quantal analysis of NMJs in two different mouse models of CMT2D (Gars(P278KY), Gars(C201R)), found synaptic deficits that correlated with disease severity and progressed with age. Results of voltage-clamp studies revealed presynaptic defects characterized by: (1) decreased frequency of spontaneous release without any change in quantal amplitude (miniature endplate current), (2) reduced amplitude of evoked release (endplate current) and quantal content, (3) age-dependent changes in the extent of depression in response to repetitive stimulation, and (4) release failures at some NMJs with high-frequency, long-duration stimulation. Drugs that modify synaptic efficacy were tested to see whether neuromuscular performance improved. The presynaptic action of 3,4 diaminopyridine was not beneficial, whereas postsynaptic-acting physostigmine did improve performance. Smaller mutant NMJs with correspondingly fewer vesicles and partial denervation that eliminates some release sites also contribute to the reduction of release at a proportion of mutant NMJs. Together, these voltage-clamp data suggest that a number of release processes, while essentially intact, likely operate suboptimally at most NMJs of CMT2D mice. We have uncovered a previously unrecognized aspect of axonal Charcot-Marie-Tooth disease in mouse models of CMT2D. Synaptic dysfunction contributes to impaired neuromuscular performance and disease progression. This suggests that drugs which

  8. Short-term and long-term control of synaptic strength by light activatable glutamate receptors at the Drosophila neuromuscular junction

    OpenAIRE

    Kauwe, Grant

    2010-01-01

    Drosophila neuromuscular junctions (NMJs) exhibit structural and physiological homeostasis during larval development in which the number of boutons and the amount of neurotransmitter released increases in coordination with larval muscle size growth. The Bone Morphogenetic Protein (BMP) signaling pathway, including Glass bottom-boat (Gbb), a BMP ligand, and Wishful thinking (Wit), its presynaptic BMP receptor, are important for regulating this homeostatic growth in larvae. Genetic analysis o...

  9. The Extracellular and Cytoplasmic Domains of Syndecan Cooperate Postsynaptically to Promote Synapse Growth at the Drosophila Neuromuscular Junction.

    Science.gov (United States)

    Nguyen, Margaret U; Kwong, Jereen; Chang, Julia; Gillet, Victoria G; Lee, Rachel M; Johnson, Karl Gregory

    2016-01-01

    The heparan sulfate proteoglycan (HSPG) Syndecan (Sdc) is a crucial regulator of synapse development and growth in both vertebrates and invertebrates. In Drosophila, Sdc binds via its extracellular heparan sulfate (HS) sidechains to the receptor protein tyrosine phosphatase LAR to promote the morphological growth of the neuromuscular junction (NMJ). To date, however, little else is known about the molecular mechanisms by which Sdc functions to promote synapse growth. Here we show that all detectable Sdc found at the NMJ is provided by the muscle, strongly suggesting a post-synaptic role for Sdc. We also show that both the cytoplasmic and extracellular domains of Sdc are required to promote synapse growth or to rescue Sdc loss of function. We report the results of a yeast two-hybrid screen using the cytoplasmic domains of Sdc as bait, and identify several novel candidate binding partners for the cytoplasmic domains of Sdc. Together, these studies provide new insight into the mechanism of Sdc function at the NMJ, and provide enticing future directions for further exploring how Sdc promotes synapse growth.

  10. The Extracellular and Cytoplasmic Domains of Syndecan Cooperate Postsynaptically to Promote Synapse Growth at the Drosophila Neuromuscular Junction.

    Directory of Open Access Journals (Sweden)

    Margaret U Nguyen

    Full Text Available The heparan sulfate proteoglycan (HSPG Syndecan (Sdc is a crucial regulator of synapse development and growth in both vertebrates and invertebrates. In Drosophila, Sdc binds via its extracellular heparan sulfate (HS sidechains to the receptor protein tyrosine phosphatase LAR to promote the morphological growth of the neuromuscular junction (NMJ. To date, however, little else is known about the molecular mechanisms by which Sdc functions to promote synapse growth. Here we show that all detectable Sdc found at the NMJ is provided by the muscle, strongly suggesting a post-synaptic role for Sdc. We also show that both the cytoplasmic and extracellular domains of Sdc are required to promote synapse growth or to rescue Sdc loss of function. We report the results of a yeast two-hybrid screen using the cytoplasmic domains of Sdc as bait, and identify several novel candidate binding partners for the cytoplasmic domains of Sdc. Together, these studies provide new insight into the mechanism of Sdc function at the NMJ, and provide enticing future directions for further exploring how Sdc promotes synapse growth.

  11. Validation of simple and inexpensive algometry using sphygmomanometer cuff and neuromuscular junction monitor with standardized laboratory algometer.

    Science.gov (United States)

    Durga, Padmaja; Wudaru, Sreedhar Reddy; Khambam, Sunil Kumar Reddy; Chandra, Shobha Jagadish; Ramachandran, Gopinath

    2016-01-01

    The availability, ergonomics and economics prohibit the routine use of algometers in clinical practice and research by the anesthesiologists. A simple bedside technique of quantitative pain measurement would enable the routine use of algometry. We proposed to validate simple pain provocation using sphygmomanometer cuff and the electric stimulation of neuromuscular junction monitor (TOF-guard, Organon Teknika) to measure pain against a standardized laboratory pressure algometer. Pain detection threshold (Pdt) and pain tolerance threshold (Ptt) were measured in forty healthy volunteers of both genders, using the above three techniques. All measurements were repeated three times. The co-efficient of inter-rater reliability (or consistency) between three independent measurements obtained from each of the techniques was determined by Cronbach's co-efficient alpha (α C). The correlation between the mean Pdt and Ptt values recorded by standardized algometer and the sphygmomanometer technique and nerve stimulator technique was performed using Pearson Correlation. An r >0.5 and a two-tailed significance of 0.7) for the three techniques. There was a good correlation with r >0.65 (P simple, efficient, repeatable measure of pain intensity and can be used as suitable alternatives to standard algometers.

  12. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes

    Directory of Open Access Journals (Sweden)

    Dmitry eSamigullin

    2015-01-01

    Full Text Available At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers—which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal—has hitherto been technically impossible. With the aim of quantifying both Ca2+ currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 рА and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 µM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  13. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes.

    Science.gov (United States)

    Samigullin, Dmitry; Fatikhov, Nijaz; Khaziev, Eduard; Skorinkin, Andrey; Nikolsky, Eugeny; Bukharaeva, Ellya

    2014-01-01

    At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers-which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal-has hitherto been technically impossible. With the aim of quantifying both Ca(2+) currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 pA and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 μM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  14. Functional neuromuscular junctions formed by embryonic stem cell-derived motor neurons.

    Directory of Open Access Journals (Sweden)

    Joy A Umbach

    Full Text Available A key objective of stem cell biology is to create physiologically relevant cells suitable for modeling disease pathologies in vitro. Much progress towards this goal has been made in the area of motor neuron (MN disease through the development of methods to direct spinal MN formation from both embryonic and induced pluripotent stem cells. Previous studies have characterized these neurons with respect to their molecular and intrinsic functional properties. However, the synaptic activity of stem cell-derived MNs remains less well defined. In this study, we report the development of low-density co-culture conditions that encourage the formation of active neuromuscular synapses between stem cell-derived MNs and muscle cells in vitro. Fluorescence microscopy reveals the expression of numerous synaptic proteins at these contacts, while dual patch clamp recording detects both spontaneous and multi-quantal evoked synaptic responses similar to those observed in vivo. Together, these findings demonstrate that stem cell-derived MNs innervate muscle cells in a functionally relevant manner. This dual recording approach further offers a sensitive and quantitative assay platform to probe disorders of synaptic dysfunction associated with MN disease.

  15. Morphometric characterization of the neuromuscular junction of rodents intoxicated with 2,4-dithiobiuret: evidence that nerve terminal recycling processes contribute to muscle weakness

    International Nuclear Information System (INIS)

    Rheuben, Mary B.; Autio, Dawn M.; Xu Youfen; Atchison, William D.

    2004-01-01

    2,4-Dithiobiuret (DTB) causes ascending motor weakness when given chronically to rodents. In muscles of animals with DTB-induced weakness, quantal release of acetylcholine (ACh) is impaired. We examined in detail the structural changes that occurred at neuromuscular junctions and their associated Schwann cells of extensor digitorum longus (EDL) muscles of male rats treated with DTB to the onset of muscle weakness, 5-8 days. Our objective was to assess the involvement of the Schwann cells and to determine the most likely primary targets of DTB. At the onset of muscle weakness, nerve terminals exhibited some enlarged regions, but did not sprout. Terminal Schwann cells became flatter and expanded to cover most of the endplate. The extent of invasion of the synaptic cleft by Schwann cell processes was not significantly different from controls; extension of Schwann cell sprouts away from the junction was not seen. Thus, the morphology of the Schwann cells, although clearly affected by DTB, does not suggest that they contribute directly to the physiological defects of DTB-treated terminals. Abnormal tubulovesicular structures or tangles of neurofilaments were clustered in the centers of about 25% of treated terminals. Fewer synaptic vesicles occupied the region opposite the postsynaptic folds. Vesicle volumes were variable and included some very large vesicles, corresponding with the variable MEPP amplitudes reported previously for terminals of DTB-treated rodents. The postsynaptic area stained by rhodamine-labeled α-bungarotoxin expanded with terminal swelling, apparently by unpleating of the postsynaptic folds. No loss of ACh receptors or spread of ACh receptors beyond terminal boundaries was detected. Morphometric data are consistent with the conclusion that DTB affects, either directly or indirectly, vesicular release of ACh and the subsequent vesicular recycling process

  16. Metabolic stabilization of acetylcholine receptors in vertebrate neuromuscular junction by muscle activity

    International Nuclear Information System (INIS)

    Rotzler, S.; Brenner, H.R.

    1990-01-01

    The effects of muscle activity on the growth of synaptic acetylcholine receptor (AChR) accumulations and on the metabolic AChR stability were investigated in rat skeletal muscle. Ectopic end plates induced surgically in adult soleus muscle were denervated early during development when junctional AChR number and stability were still low and, subsequently, muscles were either left inactive or they were kept active by chronic exogenous stimulation. AChR numbers per ectopic AChR cluster and AChR stabilities were estimated from the radioactivity and its decay with time, respectively, of end plate sites whose AChRs had been labeled with 125 I-alpha-bungarotoxin (alpha-butx). The results show that the metabolic stability of the AChRs in ectopic clusters is reversibly increased by muscle activity even when innervation is eliminated very early in development. 1 d of stimulation is sufficient to stabilize the AChRs in ectopic AChR clusters. Muscle stimulation also produced an increase in the number of AChRs at early denervated end plates. Activity-induced cluster growth occurs mainly by an increase in area rather than in AChR density, and for at least 10 d after denervation is comparable to that in normally developing ectopic end plates. The possible involvement of AChR stabilization in end plate growth is discussed

  17. Repouso da junção neuromuscular no tratamento de crises miastênicas e colinérgicas Management of the myasthenic and cholinergic crisis by neuromuscular junction rest

    Directory of Open Access Journals (Sweden)

    J. Lamartine de Assis

    1968-06-01

    second group, in addition to this management, were submitted to prolonged curarization by galamine (Flaxedil by intramuscular injection; all of them presented an initial curare supersensitivity which always decreased shortly. In both methods the reinstitution of the drug therapy was progressive. The respirator weanned of progressively and the patients were kept under observation for adequate ventilation. The doses were variable but subsequent doses of antimyasthenic medications were determined by clinical findings and response to the tensilon or prostigmine tests. The doses were increased or decreased accordingly in each individual case, rapid changes of drug doses to perfect adjustment being undesirable in this transition period. Partial or temporary remission occurred in some patients. Others were able to sustain satisfactory ventilation for a long period or definitively. Most of the crisis improved and most of the patients benefited from the therapeutic method of the neuromuscular junction rest. There was a remarkable reduction in the mortality rate from the crisis. One patient had a thymoma which was malignant; in spite of this the evolution of this case has been good after the treatment. Those patients who had immediate good response to the treatment of the crisis had a favorable fellow up, even a complete remission. Respiratory infections were very common in spite of all cares. Culture of tracheal secretions and wound exsudates were made. Bactericidal and broad-spectrum antibiotics were used, depending of the laboratory report cf patient's sensitivity. Physiotherapy besides other prophylactic measures was used against bronchopneumonia. Atelectasis was a common complication in the crisis and all efforts to prevent it were made, including daily clinical examination of pulmonary conditions, Vt,, blood pressure and bed side chest films. The routine use of atropine sulfate promoved inspissation of bronchial secretions, plugging of the bronchi, and attendant atelectasis

  18. Presynaptic inhibition of spontaneous acetylcholine release mediated by P2Y receptors at the mouse neuromuscular junction.

    Science.gov (United States)

    De Lorenzo, S; Veggetti, M; Muchnik, S; Losavio, A

    2006-09-29

    At the neuromuscular junction, ATP is co-released with the neurotransmitter acetylcholine (ACh) and once in the synaptic space, it is degraded to the presynaptically active metabolite adenosine. Intracellular recordings were performed on diaphragm fibers of CF1 mice to determine the action of extracellular ATP (100 muM) and the slowly hydrolysable ATP analog 5'-adenylylimidodiphosphate lithium (betagamma-imido ATP) (30 muM) on miniature end-plate potential (MEPP) frequency. We found that application of ATP and betagamma-imido ATP decreased spontaneous secretion by 45.3% and 55.9% respectively. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A(1) adenosine receptor antagonist and alpha,beta-methylene ADP sodium salt (alphabeta-MeADP), which is an inhibitor of ecto-5'-nucleotidase, did not prevent the inhibitory effect of ATP, demonstrating that the nucleotide is able to modulate spontaneous ACh release through a mechanism independent of the action of adenosine. Blockade of Ca(2+) channels by both, Cd(2+) or the combined application of nitrendipine and omega-conotoxin GVIA (omega-CgTx) (L-type and N-type Ca(2+) channel antagonists, respectively) prevented the effect of betagamma-imido ATP, indicating that the nucleotide modulates Ca(2+) influx through the voltage-dependent Ca(2+) channels related to spontaneous secretion. betagamma-Imido ATP-induced modulation was antagonized by the non-specific P2 receptor antagonist suramin and the P2Y receptor antagonist 1-amino-4-[[4-[[4-chloro-6-[[3(or4)-sulfophenyl] amino]-1,3,5-triazin-2-yl]amino]-3-sulfophenyl] amino]-9,10-dihydro-9,10-dioxo-2-anthracenesulfonic acid (reactive blue-2), but not by pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt (PPADS), which has a preferential antagonist effect on P2X receptors. Pertussis toxin and N-ethylmaleimide (NEM), which are blockers of G(i/o) proteins, prevented the action of the nucleotide, suggesting that the effect is mediated by P2Y receptors

  19. Schwann cells sense and control acetylcholine spillover at the neuromuscular junction by α7 nicotinic receptors and butyrylcholinesterase.

    Science.gov (United States)

    Petrov, Konstantin A; Girard, Emmanuelle; Nikitashina, Alexandra D; Colasante, Cesare; Bernard, Véronique; Nurullin, Leniz; Leroy, Jacqueline; Samigullin, Dmitry; Colak, Omer; Nikolsky, Evgenii; Plaud, Benoit; Krejci, Eric

    2014-09-03

    Terminal Schwann cells (TSCs) are key components of the mammalian neuromuscular junction (NMJ). How the TSCs sense the synaptic activity in physiological conditions remains unclear. We have taken advantage of the distinct localization of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at the NMJ to bring out the function of different ACh receptors (AChRs). AChE is clustered by the collagen Q in the synaptic cleft and prevents the repetitive activation of muscle nicotinic AChRs. We found that BChE is anchored at the TSC by a proline-rich membrane anchor, the small transmembrane protein anchor of brain AChE. When BChE was specifically inhibited, ACh release was significant depressed through the activation of α7 nAChRs localized on the TSC and activated by the spillover of ACh. When both AChE and BChE were inhibited, the spillover increased and induced a dramatic reduction of ACh release that compromised the muscle twitch triggered by the nerve stimulation. α7 nAChRs at the TSC may act as a sensor for spillover of ACh adjusted by BChE and may represent an extrasynaptic sensor for homeostasis at the NMJ. In myasthenic rats, selective inhibition of AChE is more effective in rescuing muscle function than the simultaneous inhibition of AChE and BChE because the concomitant inhibition of BChE counteracts the positive action of AChE inhibition. These results show that inhibition of BChE should be avoided during the treatment of myasthenia and the pharmacological reversal of residual curarization after anesthesia. Copyright © 2014 the authors 0270-6474/14/3411870-14$15.00/0.

  20. Validation of simple and inexpensive algometry using sphygmomanometer cuff and neuromuscular junction monitor with standardized laboratory algometer

    Science.gov (United States)

    Durga, Padmaja; Wudaru, Sreedhar Reddy; Khambam, Sunil Kumar Reddy; Chandra, Shobha Jagadish; Ramachandran, Gopinath

    2016-01-01

    Background and Aims: The availability, ergonomics and economics prohibit the routine use of algometers in clinical practice and research by the anesthesiologists. A simple bedside technique of quantitative pain measurement would enable the routine use of algometry. We proposed to validate simple pain provocation using sphygmomanometer cuff and the electric stimulation of neuromuscular junction monitor (TOF-guard, Organon Teknika) to measure pain against a standardized laboratory pressure algometer. Material and Methods: Pain detection threshold (Pdt) and pain tolerance threshold (Ptt) were measured in forty healthy volunteers of both genders, using the above three techniques. All measurements were repeated three times. The co-efficient of inter-rater reliability (or consistency) between three independent measurements obtained from each of the techniques was determined by Cronbach's co-efficient alpha (α C). The correlation between the mean Pdt and Ptt values recorded by standardized algometer and the sphygmomanometer technique and nerve stimulator technique was performed using Pearson Correlation. An r >0.5 and a two-tailed significance of algometer and the tested techniques. Results: There was a good inter-rater reliability (α C > 0.7) for the three techniques. There was a good correlation with r >0.65 (P algometer and the two techniques being tested as alternatives for algometer to measure pain. Conclusion: The sphygmomanometer cuff technique and electrical stimulation with the peripheral nerve stimulator to measure pain threshold and tolerance provide a simple, efficient, repeatable measure of pain intensity and can be used as suitable alternatives to standard algometers. PMID:27006546

  1. Age-related Differences in Dystrophin: Impact on Force Transfer Proteins, Membrane Integrity, and Neuromuscular Junction Stability.

    Science.gov (United States)

    Hughes, David C; Marcotte, George R; Marshall, Andrea G; West, Daniel W D; Baehr, Leslie M; Wallace, Marita A; Saleh, Perrie M; Bodine, Sue C; Baar, Keith

    2017-05-01

    The loss of muscle strength with age has been studied from the perspective of a decline in muscle mass and neuromuscular junction (NMJ) stability. A third potential factor is force transmission. The purpose of this study was to determine the changes in the force transfer apparatus within aging muscle and the impact on membrane integrity and NMJ stability. We measured an age-related loss of dystrophin protein that was greatest in the flexor muscles. The loss of dystrophin protein occurred despite a twofold increase in dystrophin mRNA. Importantly, this disparity could be explained by the four- to fivefold upregulation of the dystromir miR-31. To compensate for the loss of dystrophin protein, aged muscle contained increased α-sarcoglycan, syntrophin, sarcospan, laminin, β1-integrin, desmuslin, and the Z-line proteins α-actinin and desmin. In spite of the adaptive increase in other force transfer proteins, over the 48 hours following lengthening contractions, the old muscles showed more signs of impaired membrane integrity (fourfold increase in immunoglobulin G-positive fibers and 70% greater dysferlin mRNA) and NMJ instability (14- to 96-fold increases in Runx1, AchRδ, and myogenin mRNA). Overall, these data suggest that age-dependent alterations in dystrophin leave the muscle membrane and NMJ more susceptible to contraction-induced damage even before changes in muscle mass are obvious. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Technique of the computed tomography examination of skeletal muscle in neuromuscular diseases

    International Nuclear Information System (INIS)

    Rodiek, S.O.; Kuether, G.; Technische Univ. Muenchen

    1985-01-01

    Computed tomography provides a complete view of morphological alterations in skeletal muscle caused by neuromuscular diseases. A good image quality of the lower as well as of the upper limbs is obtained by choosing a small scanning-field and an appropriate scanning-position. The arms are best examined one by one. In follow-up studies muscular atrophy can be documented by planimetric and densimetric measurements. Furthermore CT-scanning is a convenient method for selecting suitable muscles for muscle biopsy. (orig.) [de

  3. Long-term Low-Intensity Endurance Exercise along with Blood-Flow Restriction Improves Muscle Mass and Neuromuscular Junction Compartments in Old Rats

    Directory of Open Access Journals (Sweden)

    Mohammad-Ali Bahreini Pour

    2017-11-01

    Full Text Available Background: During the aging process, muscle atrophy and neuromuscular junction remodeling are inevitable. The present study aimed to clarify whether low-intensity aerobic exercise along with limb blood-flow restriction (BFR could improve aging-induced muscle atrophy and nicotinic acetylcholine receptors (nAChRs at the neuromuscular junction. Methods: Forty-eight male Wistar rats, aged 23–24 months, were randomly divided into control, sham (Sh: subjected to surgery without BFR, BFR (subjected to BFR, exercise (Ex: subjected to 10 weeks of low-intensity exercise, Sh+Ex, and BFR+Ex groups. Forty-eight hours after the last training session, the animals were sacrificed and their soleus and extensor digitorum longus (EDL muscles were removed. The hypertrophy index was calculated, and molecular parameters were measured using western blotting. Statistical analysis was done with ANOVA using SPSS (version 20, with a P<0.05 as the level of significance. Results: The control and Sh groups showed weight gain (P=0.001, whereas the Ex, Sh+Ex, and BFR+Ex groups had significant weight loss (P<0.001. The hypertrophy index of the soleus was significantly higher in the BFR+Ex group than in the control, Sh, and BFR groups (P<0.001. BFR+Ex induced significant hypertrophic effects on the EDL (P<0.001 vs. the control, Sh, Ex, and Sh+Ex groups, and P=0.006 vs. the BFR group. BFR+Ex also increased nAChRs in the soleus (P=0.02 vs. the control and Sh groups and the EDL (P=0.008 vs. the control and Sh groups. Conclusion: BFR plus mild exercise is a safe method with potential beneficial effects in protecting and augmenting muscle mass and nAChR clustering at the neuromuscular junction in old rats.

  4. FER-1/Dysferlin promotes cholinergic signaling at the neuromuscular junction in C. elegans and mice

    Directory of Open Access Journals (Sweden)

    Predrag Krajacic

    2013-10-01

    Dysferlin is a member of the evolutionarily conserved ferlin gene family. Mutations in Dysferlin lead to Limb Girdle Muscular Dystrophy 2B (LGMD2B, an inherited, progressive and incurable muscle disorder. However, the molecular mechanisms underlying disease pathogenesis are not fully understood. We found that both loss-of-function mutations and muscle-specific overexpression of C. elegans fer-1, the founding member of the Dysferlin gene family, caused defects in muscle cholinergic signaling. To determine if Dysferlin-dependent regulation of cholinergic signaling is evolutionarily conserved, we examined the in vivo physiological properties of skeletal muscle synaptic signaling in a mouse model of Dysferlin-deficiency. In addition to a loss in muscle strength, Dysferlin −/− mice also exhibited a cholinergic deficit manifested by a progressive, frequency-dependent decrement in their compound muscle action potentials following repetitive nerve stimulation, which was observed in another Dysferlin mouse model but not in a Dysferlin-independent mouse model of muscular dystrophy. Oral administration of Pyridostigmine bromide, a clinically used acetylcholinesterase inhibitor (AchE.I known to increase synaptic efficacy, reversed the action potential defect and restored in vivo muscle strength to Dysferlin −/− mice without altering muscle pathophysiology. Our data demonstrate a previously unappreciated role for Dysferlin in the regulation of cholinergic signaling and suggest that such regulation may play a significant pathophysiological role in LGMD2B disease.

  5. A Novel Egr-1-Agrin Pathway and Potential Implications for Regulation of Synaptic Physiology and Homeostasis at the Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Ryen MacDonald

    2017-08-01

    Full Text Available Synaptic transmission requires intricate coordination of the components involved in processing of incoming signals, formation and stabilization of synaptic machinery, neurotransmission and in all related signaling pathways. Changes to any of these components cause synaptic imbalance and disruption of neuronal circuitry. Extensive studies at the neuromuscular junction (NMJ have greatly aided in the current understanding of synapses and served to elucidate the underlying physiology as well as associated adaptive and homeostatic processes. The heparan sulfate proteoglycan agrin is a vital component of the NMJ, mediating synaptic formation and maintenance in both brain and muscle, but very little is known about direct control of its expression. Here, we investigated the relationship between agrin and transcription factor early growth response-1 (Egr-1, as Egr-1 regulates the expression of many genes involved in synaptic homeostasis and plasticity. Using chromatin immunoprecipitation (ChIP, cell culture with cell lines derived from brain and muscle, and animal models, we show that Egr-1 binds to the AGRN gene locus and suppresses its expression. When compared with wild type (WT, mice deficient in Egr-1 (Egr-1−/− display a marked increase in AGRN mRNA and agrin full-length and cleavage fragment protein levels, including the 22 kDa, C-terminal fragment in brain and muscle tissue homogenate. Because agrin is a crucial component of the NMJ, we explored possible physiological implications of the Egr-1-agrin relationship. In the diaphragm, Egr-1−/− mice display increased NMJ motor endplate density, individual area and area of innervation. In addition to increased density, soleus NMJs also display an increase in fragmented and faint endplates in Egr-1−/− vs. WT mice. Moreover, the soleus NMJ electrophysiology of Egr-1−/− mice revealed increased quantal content and motor testing showed decreased movement and limb muscle strength compared with

  6. Immunoglobulins from Animal Models of Motor Neuron Disease and from Human Amyotrophic Lateral Sclerosis Patients Passively Transfer Physiological Abnormalities to the Neuromuscular Junction

    Science.gov (United States)

    Apel, Stanley H.; Engelhardt, Jozsef I.; Garcia, Jesus; Stefani, Enrico

    1991-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating human disease of upper and lower motoneurons of unknown etiology. In support of the potential role of autoimmunity in ALS, two immune-mediated animal models of motoneuron disease have been developed that resemble ALS with respect to the loss of motoneurons, the presence of IgG within motoneurons and at the neuromuscular junction, and with respect to altered physiology of the motor nerve terminal. To provide direct evidence for the primary role of humoral immunity, passive transfer with immunoglobulins from the two animal models and human ALS was carried out. Mice injected with serum or immunoglobulins from the animal disease models and human ALS but not controls demonstrated IgG in motoneurons and at the neuromuscular junction. The mice also demonstrated an increase in miniature end-plate potential (mepp) frequency, with normal amplitude and time course and normal resting membrane potential, indicating an increased resting quantal release of acetylcholine from the nerve terminal. The ability to transfer motoneuron dysfunction with serum immunoglobulins provides evidence for autoimmune mechanisms in the pathogenesis of both the animal models and human ALS.

  7. Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis

    Science.gov (United States)

    Baehr, Leslie M.; West, Daniel W.D.; Marcotte, George; Marshall, Andrea G.; De Sousa, Luis Gustavo; Baar, Keith; Bodine, Sue C.

    2016-01-01

    Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength. PMID:26826670

  8. Neuromuscular blockade in children

    Directory of Open Access Journals (Sweden)

    Almeida João Fernando Lourenço de

    2000-01-01

    Full Text Available Neuromuscular blocking agents (NMBAs have been widely used to control patients who need to be immobilized for some kind of medical intervention, such as an invasive procedure or synchronism with mechanical ventilation. The purpose of this monograph is to review the pharmacology of the NMBAs, to compare the main differences between the neuromuscular junction in neonates, infants, toddlers and adults, and moreover to discuss their indications in critically ill pediatric patients. Continuous improvement of knowledge about NMBAs pharmacology, adverse effects, and the many other remaining unanswered questions about neuromuscular junction and neuromuscular blockade in children is essential for the correct use of these drugs. Therefore, the indication of these agents in pediatrics is determined with extreme judiciousness. Computorized (Medline 1990-2000 and active search of articles were the mechanisms used in this review.

  9. Comparative effects of clindamycin and lincomycin on end-plate currents and quantal content at the neuromuscular junction.

    Science.gov (United States)

    Fiekers, J F; Henderson, F; Marshall, I G; Parsons, R L

    1983-11-01

    The pre- and postjunctional effects of the lincosamide antibiotics, clindamycin and lincomycin, were studied in voltage-clamped transected twitch fibers of costocutaneous muscles of garter snakes (species Thamnophis). Miniature end-plate currents and end-plate currents (EPCs) were recorded over a wide voltage range for each antibiotic. The amplitude and kinetics of these currents were studied and estimates of the quantal content of evoked transmitter release determined. High concentrations of clindamycin (2 X 10(-4) M) and lincomycin (2 X 10(-3) M) produced significant depression of EPC amplitude and a nonlinearity in the EPC-voltage relationships. The time constant of EPC decay was accelerated in clindamycin and the relationship between the time constant of EPC decay and membrane potential remained a single exponential function with a concentration-dependent loss of the voltage dependence. In contrast to clindamycin, lincomycin produced biphasic EPCs which consisted of two components, one faster and one slower than the control decay rate. The relative amplitude and decay rate of each component was both concentration and voltage dependent. Either increasing the concentration of lincomycin or membrane hyperpolarization decreased the amplitude ratio, iota slow/iota fast, and increased the ratio of the respective time constants, tau slow/tau fast. Clindamycin affected EPC decay amplitude and quantal content in the same concentration range, whereas lincomycin affected EPC decay at concentrations 20 times less than those required to reduce EPC amplitude and quantal content. These results suggest that the neuromuscular blocking effects of clindamycin involve both pre-and postjunctional sites, whereas the effects of lincomycin are primarily on the postjunctional receptor-channel complex.

  10. MAPK3 at the Autism-Linked Human 16p11.2 Locus Influences Precise Synaptic Target Selection at Drosophila Larval Neuromuscular Junctions.

    Science.gov (United States)

    Park, Sang Mee; Park, Hae Ryoun; Lee, Ji Hye

    2017-02-01

    Proper synaptic function in neural circuits requires precise pairings between correct pre- and post-synaptic partners. Errors in this process may underlie development of neuropsychiatric disorders, such as autism spectrum disorder (ASD). Development of ASD can be influenced by genetic factors, including copy number variations (CNVs). In this study, we focused on a CNV occurring at the 16p11.2 locus in the human genome and investigated potential defects in synaptic connectivity caused by reduced activities of genes located in this region at Drosophila larval neuromuscular junctions, a well-established model synapse with stereotypic synaptic structures. A mutation of rolled , a Drosophila homolog of human mitogen-activated protein kinase 3 ( MAPK3 ) at the 16p11.2 locus, caused ectopic innervation of axonal branches and their abnormal defasciculation. The specificity of these phenotypes was confirmed by expression of wild-type rolled in the mutant background. Albeit to a lesser extent, we also observed ectopic innervation patterns in mutants defective in Cdk2, Gα q , and Gp93, all of which were expected to interact with Rolled MAPK3. A further genetic analysis in double heterozygous combinations revealed a synergistic interaction between rolled and Gp93 . In addition, results from RT-qPCR analyses indicated consistently reduced rolled mRNA levels in Cdk2 , Gα q , and Gp93 mutants. Taken together, these data suggest a central role of MAPK3 in regulating the precise targeting of presynaptic axons to proper postsynaptic targets, a critical step that may be altered significantly in ASD.

  11. Purinoceptors in neuromuscular transmission

    NARCIS (Netherlands)

    Henning, RH

    1997-01-01

    At the neuromuscular junction, P-2-purinoceptors mediate the actions of the co-transmitter ATP and P-1-purinoceptors, those of its degradation product adenosine. The classification of the subtypes of P-1- and P-2-purinoceptors and their signal transduction routes is presented. Purinoceptor mediated

  12. Excitatory effect of the A2A adenosine receptor agonist CGS-21680 on spontaneous and K+-evoked acetylcholine release at the mouse neuromuscular junction.

    Science.gov (United States)

    Palma, A G; Muchnik, S; Losavio, A S

    2011-01-13

    The mechanism of action of the A2A adenosine receptor agonist 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680) in the facilitation of spontaneous (isotonic and hypertonic condition) and K+-evoked acetylcholine (ACh) release was investigated in the mouse diaphragm muscles. At isotonic condition, the CGS-21680-induced excitatory effect on miniature end-plate potential (MEPP) frequency was not modified in the presence of CdCl2 and in a medium free of Ca2+ (0Ca2+-EGTA), but it was abolished after buffering the rise of intracellular Ca2+ with 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra(acetoxy-methyl) (BAPTA-AM) and when the Ca2+-ATPase inhibitor thapsigargin was used to deplete intracellular Ca2+ stores. CGS-21680 did not have a direct effect on the Ca2+-independent neurotransmitter-releasing machinery, since the modulatory effect on the hypertonic response was also occluded by BAPTA-AM and thapsigargin. CGS-21680 facilitation on K+-evoked ACh release was not altered by the P/Q-type voltage-dependent calcium channel (VDCC) blocker ω-Agatoxin IVA, but it was completely prevented by both, the L-type VDCC blocker nitrendipine (which is known to immobilize their gating charges), or thapsigargin, suggesting that the effects of CGS-21680 on L-type VDCC and thapsigargin-sensitive internal stores are associated. We found that the VDCC pore blocker Cd2+ (2 mM Ca2+ or 0Ca2+-EGTA) failed to affect the CGS-21680 effect in high K+ whereas nitrendipine in 0Ca2+-EGTA+Cd2+ occluded its action. The blockade of Ca2+ release from endoplasmic reticulum with ryanodine antagonized the facilitating effect of CGS-21680 in control and high K+ concentration. It is concluded that, at the mouse neuromuscular junction, activation of A2A receptors facilitates spontaneous and K+-evoked ACh release by an external Ca2+-independent mechanism but that involves mobilization of Ca2+ from internal stores: during spontaneous ACh release

  13. Neuromuscular Disorders

    Science.gov (United States)

    Neuromuscular disorders affect the nerves that control your voluntary muscles. Voluntary muscles are the ones you can ... function and your ability to breathe. Examples of neuromuscular disorders include Amyotrophic lateral sclerosis Multiple sclerosis Myasthenia ...

  14. Neuromuscular Scoliosis

    Science.gov (United States)

    ... Radiation Exposure in Scoliosis Kyphosis Adolescent Back Pain Spondylolysis For Adolescents For Adults Common Questions & Glossary Resources ... Radiation Exposure in Scoliosis Kyphosis Adolescent Back Pain Spondylolysis For Adolescents For Adults Neuromuscular Scoliosis Neuromuscular scoliosis ...

  15. Practical approach to the patient with acute neuromuscular weakness.

    Science.gov (United States)

    Nayak, Rajeev

    2017-07-16

    Acute neuromuscular paralysis (ANMP) is a clinical syndrome characterized by rapid onset muscle weakness progressing to maximum severity within several days to weeks (less than 4 wk). Bulbar and respiratory muscle weakness may or may not be present. It is a common neurological emergency which requires immediate and careful investigations to determine the etiology because accurate diagnosis has significant impact on therapy and prognosis. Respiratory failure caused by neuromuscular weakness is considered as more critical than lung disease because its development may be insidious or subtle until sudden decompensation leads to life threatening hypoxia. Also, the arterial blood gas finding of severe hypoxemia, hypercapnia, and acidosis may not be apparent until respiratory failure is profound. Hence, the requirement for respiratory assistance should also be intensively and promptly investigated in all patients with neuromuscular disease. The disorder is classified based on the site of defect in motor unit pathway, i.e ., anterior horn cells, nerve root, peripheral nerve, neuromuscular junction or muscle. Identification of the cause is primarily based on a good medical history and detailed clinical examination supplemented with neurophysiologic investigations and sometimes few specific laboratory tests. Medical history and neurological examination should be focused on the onset, progression, pattern and severity of muscle weakness as well as cranial nerves testing and tests for autonomic dysfunction. Associated non neurological features like fever, rash or other skin lesions etc. should also be noted. Globally, Guillain-Barré syndrome is the most frequent cause of ANMP and accounts for the majority of cases of respiratory muscles weakness associated with neuromuscular disorders. Newly acquired neuromuscular weakness in intensive care unit patients consist of critical illness polyneuropathy, critical illness myopathy and drug induced neuromuscular weakness which may

  16. Partial neuromuscular blockade in humans enhances muscle blood flow during exercise independently of muscle oxygen uptake and acetylcholine receptor blockade

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Krustrup, Peter; Iaia, F Marcello

    2009-01-01

    This study examined the role of acetylcholine for skeletal muscle blood flow during exercise by use of the competitive neuromuscular blocking agent cisatracurium in combination with the acetylcholine receptor blocker glycopyrrone. Nine healthy male subjects performed a 10-min bout of one...... conductance during exercise, events that are not associated with either acetylcholine or an increased oxygen demand. The results do not support an essential role for acetylcholine, released form the neuromuscular junction, in exercise hyperaemia or for the enhanced blood flow during neuromuscular blockade...

  17. High gender -specific susceptibility to curare- a neuromuscular blocking agent

    Directory of Open Access Journals (Sweden)

    Santosh K Maurya

    2013-01-01

    Full Text Available Curare, a selective skeletal muscle relaxant, has been used clinically to reduce shivering and as an anesthetic auxiliary in abdominal surgery. It is also widely used in animal experiments to block neuromuscular junction activity. Effective doses of curare diminish muscle contraction without affecting brain function, but at higher doses it is known to be lethal. However, the exact dose of curare initiating muscle relaxation vs. lethal effect has not been fully characterized in mice. In this study we carefully examined the dose-response for achieving muscle inactivity over lethality in both male and female mice (C57BL6/J. The most striking finding of this study is that female mice were highly susceptible to curare; both the EDm and LDm were at least 3-fold lower than male littermates. This study shows that gender-specific differences can be an important factor when administering skeletal muscle relaxants, particularly curare or other analogous agents targeted to the neuromuscular junction.

  18. Examination of a Junction-Box Adhesion Test for Use in Photovoltaic Module Qualification (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Miller, D. C.; Wohlgemuth, J. H.

    2012-08-01

    Engineering robust adhesion of the junction-box (j-box) is a hurdle typically encountered by photovoltaic (PV) module manufacturers during product development. There are historical incidences of adverse effects (e.g., fires) caused when the j-box/adhesive/module system has failed in the field. The addition of a weight to the j-box during the 'damp heat' IEC qualification test is proposed to verify the basic robustness of its adhesion system. The details of the proposed test will be described, in addition to the preliminary results obtained using representative materials and components. The described discovery experiments examine moisture-cured silicone, foam tape, and hot-melt adhesives used in conjunction with PET or glass module 'substrates.' To be able to interpret the results, a set of material-level characterizations was performed, including thermogravimetric analysis, differential scanning calorimetry, and dynamic mechanical analysis. PV j-boxes were adhered to a substrate, loaded with a prescribed weight, and then placed inside an environmental chamber (at 85C, 85% relative humidity). Some systems did not remain attached through the discovery experiments. Observed failure modes include delamination (at the j-box/adhesive or adhesive/substrate interface) and phase change/creep. The results are discussed in the context of the application requirements, in addition to the plan for the formal experiment supporting the proposed modification to the qualification test.

  19. Examination of a Junction-Box Adhesion Test for Use in Photovoltaic Module Qualification: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Miller, D. C.; Wohlgemuth, J. H.

    2012-08-01

    Engineering robust adhesion of the junction-box (j-box) is a hurdle typically encountered by photovoltaic (PV) module manufacturers during product development. There are historical incidences of adverse effects (e.g., fires) caused when the j-box/adhesive/module system has failed in the field. The addition of a weight to the j-box during the 'damp heat' IEC qualification test is proposed to verify the basic robustness of its adhesion system. The details of the proposed test will be described, in addition to the preliminary results obtained using representative materials and components. The described discovery experiments examine moisture-cured silicone, foam tape, and hot-melt adhesives used in conjunction with PET or glass module 'substrates.' To be able to interpret the results, a set of material-level characterizations was performed, including thermogravimetric analysis, differential scanning calorimetry, and dynamic mechanical analysis. PV j-boxes were adhered to a substrate, loaded with a prescribed weight, and then placed inside an environmental chamber (at 85C, 85% relative humidity). Some systems did not remain attached through the discovery experiments. Observed failure modes include delamination (at the j-box/adhesive or adhesive/substrate interface) and phase change/creep. The results are discussed in the context of the application requirements, in addition to the plan for the formal experiment supporting the proposed modification to the qualification test.

  20. Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan (Oxyuranus scutellatus) by F(ab0)2 and whole IgG antivenoms

    OpenAIRE

    Herrera Vega, María; de Cássia de O. Collaço, Rita; Villalta, Mauren; Segura Ruiz, Álvaro; Vargas Arroyo, Mariángela; Wright, Christine E.; Paiva, Owen K.; Matainaho, Teatulohi; Jensen, Simon D.; León Montero, Guillermo; Williams, David J.; Rodrigues Simioni, Lea; Gutiérrez, José María

    2016-01-01

    The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21 °C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent add...

  1. Neutralization Of The Neuromuscular Inhibition Of Venom And Taipoxin From The Taipan (oxyuranus Scutellatus) By F(ab ') 2 And Whole Igg Antivenoms

    OpenAIRE

    Herrera; Maria; de O Collaco; Rita de Cassia; Villalta; Mauren; Segura; Alvaro; Vargas; Mariangela; Wright; Christine E.; Paiva; Owen K.; Matainaho; Teatulohi; Jensen; Simon D.; Leon; Guillermo; Williams; David J.; Rodrigues-Simioni; Lea; Maria Gutierrez; Jose

    2016-01-01

    The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21 degrees C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independ...

  2. Neuromuscular complications in cancer.

    Science.gov (United States)

    Grisold, W; Grisold, A; Löscher, W N

    2016-08-15

    Cancer is becoming a treatable and even often curable disease. The neuromuscular system can be affected by direct tumor invasion or metastasis, neuroendocrine, metabolic, dysimmune/inflammatory, infections and toxic as well as paraneoplastic conditions. Due to the nature of cancer treatment, which frequently is based on a DNA damaging mechanism, treatment related toxic side effects are frequent and the correct identification of the causative mechanism is necessary to initiate the proper treatment. The peripheral nervous system is conventionally divided into nerve roots, the proximal nerves and plexus, the peripheral nerves (mono- and polyneuropathies), the site of neuromuscular transmission and muscle. This review is based on the anatomic distribution of the peripheral nervous system, divided into cranial nerves (CN), motor neuron (MND), nerve roots, plexus, peripheral nerve, the neuromuscular junction and muscle. The various etiologies of neuromuscular complications - neoplastic, surgical and mechanic, toxic, metabolic, endocrine, and paraneoplastic/immune - are discussed separately for each part of the peripheral nervous system. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. The undesirable effects of neuromuscular blocking drugs

    DEFF Research Database (Denmark)

    Claudius, C; Garvey, L H; Viby-Mogensen, J

    2009-01-01

    Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

  4. Neuromuscular Scoliosis

    Science.gov (United States)

    ... irregular spinal curvature caused by disorders of the brain, spinal cord, and muscular system. Nerves and muscles are unable to maintain appropriate balance / alignment of the spine and trunk. Neuromuscular curves are often associated with pelvic obliquity, ...

  5. Doenças neuromusculares Neuromuscular disorders

    Directory of Open Access Journals (Sweden)

    Umbertina C. Reed

    2002-08-01

    differential diagnosis among the main neuromuscular disorders in children, that include the diseases affecting the motor unity, i.e. spinal motor neurons, peripheral nerves, neuromuscular junction and muscular fibers. Sources: the review of the clinical aspects that should be considered for a prompt differential diagnosis among several neuromuscular disorders as well as between those and the main causes of secondary muscular hypotonia due to central nervous system or systemic disturbances is based on the clinical experience acquired along the last 12 years in following-up children with Neuromuscular Disorders attended at the outpatient Service of Neuromuscular Disorders at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. In addition, it is based on Medline and on the review of the most recent numbers of Neuromuscular Disorders, the official journal of the World Muscle Society. Summary of the findings: most of neuromuscular disorders are genetic conditions in children and the most common of them are X-linked Progressive Muscular Dystrophy of Duchenne, Spinal Muscular Atrophy, Congenital Muscular Dystrophy, Myotonic Dystrophy and Congenital Myopathies. Conclusions: due to the phenomenal development in human molecular genetics the pathogenesis of several neuromuscular disorders in children has been clarified over the last decade. Nowadays many new diagnostic methods, including techniques of fetal diagnosis, and a more objective genotype-phenotype correlation as well as classification are available.

  6. Effects of nitric oxide on neuromuscular properties of developing zebrafish embryos.

    Directory of Open Access Journals (Sweden)

    Michael Jay

    Full Text Available Nitric oxide is a bioactive signalling molecule that is known to affect a wide range of neurodevelopmental processes. However, its functional relevance to neuromuscular development is not fully understood. Here we have examined developmental roles of nitric oxide during formation and maturation of neuromuscular contacts in zebrafish. Using histochemical approaches we show that elevating nitric oxide levels reduces the number of neuromuscular synapses within the axial swimming muscles whilst inhibition of nitric oxide biosynthesis has the opposite effect. We further show that nitric oxide signalling does not change synapse density, suggesting that the observed effects are a consequence of previously reported changes in motor axon branch formation. Moreover, we have used in vivo patch clamp electrophysiology to examine the effects of nitric oxide on physiological maturation of zebrafish neuromuscular junctions. We show that developmental exposure to nitric oxide affects the kinetics of spontaneous miniature end plate currents and impacts the neuromuscular drive for locomotion. Taken together, our findings implicate nitrergic signalling in the regulation of zebrafish neuromuscular development and locomotor maturation.

  7. Autoradiographic localization of voltage-dependent sodium channels on the mouse neuromuscular junction using 125I-alpha scorpion toxin. I. Preferential labeling of glial cells on the presynaptic side

    International Nuclear Information System (INIS)

    Boudier, J.L.; Jover, E.; Cau, P.

    1988-01-01

    Alpha-scorpion toxins bind specifically to the voltage-sensitive sodium channel in excitable membranes, and binding is potential-dependent. The radioiodinated toxin II from the scorpion Androctonus australis Hector (alpha ScTx) was used to localize voltage-sensitive sodium channels on the presynaptic side of mouse neuromuscular junctions (NMJ) by autoradiography using both light and electron microscopy. Silver grain localization was analyzed by the cross-fire method. At the light-microscopic level, grain density over NMJ appeared 6-8x higher than over nonjunctional muscle membrane. The specificity of labeling was verified by competition/displacement with an excess of native alpha ScTx. Labeling was also inhibited by incubation in depolarizing conditions, showing its potential-dependence. At the electron-microscopic level, analysis showed that voltage-sensitive sodium channels labeled with alpha ScTx were almost exclusively localized on membranes, as expected. Due to washout after incubation, appreciable numbers of binding sites were not found on the postsynaptic membranes. However, on the presynaptic side, alpha ScTx-labeled voltage-sensitive sodium channels were localized on the membrane of non-myelin-forming Schwann cells covering NMJ. The axonal presynaptic membrane was not labeled. These results show that voltage-sensitive sodium channels are present on glial cells in vivo, as already demonstrated in vitro. It is proposed that these glial channels could be indirectly involved in the ionic homeostasis of the axonal environment

  8. [Characteristics of neuromuscular scoliosis].

    Science.gov (United States)

    Putzier, M; Groß, C; Zahn, R K; Pumberger, M; Strube, P

    2016-06-01

    Usually, neuromuscular scolioses become clinically symptomatic relatively early and are rapidly progressive even after the end of growth. Without sufficient treatment they lead to a severe reduction of quality of life, to a loss of the ability of walking, standing or sitting as well as to an impairment of the cardiopulmonary system resulting in an increased mortality. Therefore, an intensive interdisciplinary treatment by physio- and ergotherapists, internists, pediatricians, orthotists, and orthopedists is indispensable. In contrast to idiopathic scoliosis the treatment of patients with neuromuscular scoliosis with orthosis is controversially discussed, whereas physiotherapy is established and essential to prevent contractures and to maintain the residual sensorimotor function.Frequently, the surgical treatment of the scoliosis is indicated. It should be noted that only long-segment posterior correction and fusion of the whole deformity leads to a significant improvement of the quality of life as well as to a prevention of a progression of the scoliosis and the development of junctional problems. The surgical intervention is usually performed before the end of growth. A prolonged delay of surgical intervention does not result in an increased height but only in a deformity progression and is therefore not justifiable. In early onset neuromuscular scolioses guided-growth implants are used to guarantee the adequat development. Because of the high complication rates, further optimization of these implant systems with regard to efficiency and safety have to be addressed in future research.

  9. Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail.

    Science.gov (United States)

    Tokuyama, Minami A; Xu, Cindy; Fisher, Rebecca E; Wilson-Rawls, Jeanne; Kusumi, Kenro; Newbern, Jason M

    2018-01-15

    Peripheral nerves exhibit robust regenerative capabilities in response to selective injury among amniotes, but the regeneration of entire muscle groups following volumetric muscle loss is limited in birds and mammals. In contrast, lizards possess the remarkable ability to regenerate extensive de novo muscle after tail loss. However, the mechanisms underlying reformation of the entire neuromuscular system in the regenerating lizard tail are not completely understood. We have tested whether the regeneration of the peripheral nerve and neuromuscular junctions (NMJs) recapitulate processes observed during normal neuromuscular development in the green anole, Anolis carolinensis. Our data confirm robust axonal outgrowth during early stages of tail regeneration and subsequent NMJ formation within weeks of autotomy. Interestingly, NMJs are overproduced as evidenced by a persistent increase in NMJ density 120 and 250 days post autotomy (DPA). Substantial Myelin Basic Protein (MBP) expression could also be detected along regenerating nerves indicating that the ability of Schwann cells to myelinate newly formed axons remained intact. Overall, our data suggest that the mechanism of de novo nerve and NMJ reformation parallel, in part, those observed during neuromuscular development. However, the prolonged increase in NMJ number and aberrant muscle differentiation hint at processes specific to the adult response. An examination of the coordinated exchange between peripheral nerves, Schwann cells, and newly synthesized muscle of the regenerating neuromuscular system may assist in the identification of candidate molecules that promote neuromuscular recovery in organisms incapable of a robust regenerative response. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Presynaptic muscarinic acetylcholine autoreceptors (M1, M2 and M4 subtypes), adenosine receptors (A1 and A2A) and tropomyosin-related kinase B receptor (TrkB) modulate the developmental synapse elimination process at the neuromuscular junction.

    Science.gov (United States)

    Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria A; Santafé, Manel; Tomàs, Josep

    2016-06-23

    The development of the nervous system involves an initially exuberant production of neurons that make an excessive number of synaptic contacts. The initial overproduction of synapses promotes connectivity. Hebbian competition between axons with different activities (the least active are punished) leads to the loss of roughly half of the overproduced elements and this refines connectivity and increases specificity. The neuromuscular junction is innervated by a single axon at the end of the synapse elimination process and, because of its relative simplicity, has long been used as a model for studying the general principles of synapse development. The involvement of the presynaptic muscarinic ACh autoreceptors may allow for the direct competitive interaction between nerve endings through differential activity-dependent acetylcholine release in the synaptic cleft. Then, the most active ending may directly punish the less active ones. Our previous results indicate the existence in the weakest axons on the polyinnervated neonatal NMJ of an ACh release inhibition mechanism based on mAChR coupled to protein kinase C and voltage-dependent calcium channels. We suggest that this mechanism plays a role in the elimination of redundant neonatal synapses. Here we used confocal microscopy and quantitative morphological analysis to count the number of brightly fluorescent axons per endplate in P7, P9 and P15 transgenic B6.Cg-Tg (Thy1-YFP)16 Jrs/J mice. We investigate the involvement of individual mAChR M1-, M2- and M4-subtypes in the control of axonal elimination after the Levator auris longus muscle had been exposed to agonist and antagonist in vivo. We also analysed the role of adenosine receptor subtypes (A1 and A2A) and the tropomyosin-related kinase B receptor. The data show that postnatal axonal elimination is a regulated multireceptor mechanism that guaranteed the monoinnervation of the neuromuscular synapses. The three receptor sets considered (mAChR, AR and TrkB receptors

  11. Anesthetic consideration for neuromuscular diseases.

    Science.gov (United States)

    Katz, Jeffery A; Murphy, Glenn S

    2017-06-01

    The aim of this review is to examine data relating to perioperative management of the patient with neuromuscular disorders RECENT FINDINGS: Patients with pre-existing neuromuscular disorders are at risk for a number of postoperative complications that are related to anesthetic drugs that are administered intraoperatively. Careful preoperative assessment is necessary to reduce morbidity and mortality. In particular, the risk of postoperative respiratory failure and need for long-term ventilation should be reviewed with patients. The use of succinylcholine should be avoided in muscular dystrophies, motor neuron diseases, and intrinsic muscle disease due to a risk of malignant hyperthermia, hyperkalemia, rhabdomyolysis, and cardiac arrest. The use of quantitative neuromuscular monitoring should be strongly considered whenever nondepolarizing neuromuscular blocking agents are administered. A number of case series and reports have been recently published demonstrating that sugammadex can be safely used in patients with neuromuscular disease; the risk of residual neuromuscular is nearly eliminated when this agent is administered intraoperatively. Careful assessment and management of patients with underlying neuromuscular diseases is required to reduce postoperative complications. This article reviews the anesthetic implications of patients undergoing surgery with neuromuscular disorder.

  12. Neuromuscular NMDA Receptors Modulate Developmental Synapse Elimination.

    Science.gov (United States)

    Personius, Kirkwood E; Slusher, Barbara S; Udin, Susan B

    2016-08-24

    At birth, each mammalian skeletal muscle fiber is innervated by multiple motor neurons, but in a few weeks, all but one of those axons retracts (Redfern, 1970) and differential activity between inputs controls this phenomenon (Personius and Balice-Gordon, 2001; Sanes and Lichtman, 2001; Personius et al., 2007; Favero et al., 2012). Acetylcholine, the primary neuromuscular transmitter, has long been presumed to mediate this activity-dependent process (O'Brien et al., 1978), but glutamatergic transmission also occurs at the neuromuscular junction (Berger et al., 1995; Grozdanovic and Gossrau, 1998; Mays et al., 2009). To test the role of neuromuscular NMDA receptors, we assessed their contribution to muscle calcium fluxes in mice and tested whether they influence removal of excess innervation at the end plate. Developmental synapse pruning was slowed by reduction of NMDA receptor activation or expression and by reduction of glutamate production. Conversely, pruning is accelerated by application of exogenous NMDA. We also found that NMDA induced increased muscle calcium only during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play previously unsuspected roles in neuromuscular activity and synaptic pruning during development. In normal adult muscle, each muscle fiber is innervated by a single axon, but at birth, fibers are multiply innervated. Elimination of excess connections requires neural activity; because the neuromuscular junction (NMJ) is a cholinergic synapse, acetylcholine has been assumed to be the critical mediator of activity. However, glutamate receptors are also expressed at the NMJ. We found that axon removal in mice is slowed by pharmacological and molecular manipulations that decrease signaling through neuromuscular NMDA receptors, whereas application of exogenous NMDA at the NMJ accelerates synapse elimination and increases muscle calcium levels during the first 2 postnatal weeks. Therefore, neuromuscular NMDA receptors play

  13. Comparative investigation of the pharmacology of fish and mammalian neuromuscular systems

    International Nuclear Information System (INIS)

    Gant, D.B.

    1985-01-01

    Neuromuscular pharmacology has been extensively studied in mammals but there have been few investigations examining the neuromuscular systems of fish. In situ experiments have shown that the basic cholinergic characteristics of fish neuromuscular junctions are different from those of mammals. In order to further understand the nature of these differences, the nicotinic acetylcholine receptors (AChR) of rat and buffalo sculpin (Enophrys bison) neuromuscular junctions and the AChR of electric ray (Torpedo california) electroplax, were investigated using receptor binding analysis. A rapid filtration assay was utilized to measure [ 125 I]α-BGT binding to tissue membranes. Scatchard analysis of [ 175 I]α-BGT binding was performed on sculpin pectoral muscle rat gastrocnemius, rat denervated gastrocnemius, and Torpedo electroplax. The affinity constant was similar for all tissues studied. In competition studies, d-tubocurarine had the highest affinity for the [ 125 I]-α-BGT binding site in all tissues, illustrating the nicotinic nature of the binding sites. Acetylcholine had high affinity for the rat gastrocnemius binding site and low affinity for the sculpin pectoral muscle and Torpedo electroplax binding site. Atropine had high affinity for the sculpin pectoral muscle binding site when compared to the rate gastrocnemius and Torpedo electroplax binding site, indicating that the sculpin pectoral site may have some mixed muscarinic-nicitinic characteristics. These results indicate that there are definite qualitative as well as quantitative differences between the fish skeletal muscle nicotinic receptor and the nicotinic receptor of fish electroplax and rat skeletal muscle

  14. Re-examination of the possible role of Golgi tendon organ and muscle spindle reflexes in proprioceptive neuromuscular facilitation muscle stretching.

    Science.gov (United States)

    Chalmers, Gordon

    2004-01-01

    Literature concerning the theoretical role of spinal reflex circuits and their sensorimotor signals in proprioceptive neuromuscular facilitation (PNF) muscle stretching techniques was examined. Reviewed data do not support the assertion commonly made in PNF literature that contraction of a stretched muscle prior to further stretch, or contraction of opposing muscles during muscle stretch, produces relaxation of the stretched muscle. Further, following contraction of a stretched muscle, inhibition of the stretch reflex response lasts only 1 s. Studies examined suggested that decreases in the response amplitude of the Hoffmann and muscle stretch reflexes following a contraction of a stretched muscle are not due to the activation of Golgi tendon organs, as commonly purported, but instead may be due to presynaptic inhibition of the muscle spindle sensory signal. The current view on the complex manner by which the spinal cord processes proprioceptive signals was discussed. The ability of acute PNF stretching procedures to often produce a joint range of motion greater than that observed with static stretching must be explained by mechanisms other than the spinal processing of proprioceptive information. Studies reviewed indicate that changes in the ability to tolerate stretch and/or the viscoelastic properties of the stretched muscle, induced by PNF procedures, are possible mechanisms.

  15. Residual Neuromuscular Blockade in the Critical Care Setting.

    Science.gov (United States)

    Stawicki, Nicole; Gessner, Patty

    2018-01-01

    Residual neuromuscular blockade is a widespread challenge for providers in the acute care setting that, if left unrecognized or untreated, places patients at higher risk for morbidity and mortality. The condition is estimated to occur in 26% to 88% of patients undergoing general anesthesia. The role of the advanced practice nurse in the acute care setting is to facilitate a safe recovery process by identifying early signs of deterioration and supporting the patient until full muscular strength has returned. This article discusses the prevalence of residual neuromuscular blockade and associated complications and patient risk factors. A review is included of the current uses for neuromuscular blockade, pathophysiology of the neuromuscular junction, pharmacologic characteristics of neuromuscular blocking agents (including drug-drug interactions), monitoring modalities, and effectiveness of reversal agents. Treatment recommendations pertinent to residual neuromuscular blockade are outlined. ©2018 American Association of Critical-Care Nurses.

  16. Cut-loading: a useful tool for examining the extent of gap junction tracer coupling between retinal neurons.

    Science.gov (United States)

    Choi, Hee Joo; Ribelayga, Christophe P; Mangel, Stuart C

    2012-01-12

    In addition to chemical synaptic transmission, neurons that are connected by gap junctions can also communicate rapidly via electrical synaptic transmission. Increasing evidence indicates that gap junctions not only permit electrical current flow and synchronous activity between interconnected or coupled cells, but that the strength or effectiveness of electrical communication between coupled cells can be modulated to a great extent(1,2). In addition, the large internal diameter (~1.2 nm) of many gap junction channels permits not only electric current flow, but also the diffusion of intracellular signaling molecules and small metabolites between interconnected cells, so that gap junctions may also mediate metabolic and chemical communication. The strength of gap junctional communication between neurons and its modulation by neurotransmitters and other factors can be studied by simultaneously electrically recording from coupled cells and by determining the extent of diffusion of tracer molecules, which are gap junction permeable, but not membrane permeable, following iontophoretic injection into single cells. However, these procedures can be extremely difficult to perform on neurons with small somata in intact neural tissue. Numerous studies on electrical synapses and the modulation of electrical communication have been conducted in the vertebrate retina, since each of the five retinal neuron types is electrically connected by gap junctions(3,4). Increasing evidence has shown that the circadian (24-hour) clock in the retina and changes in light stimulation regulate gap junction coupling(3-8). For example, recent work has demonstrated that the retinal circadian clock decreases gap junction coupling between rod and cone photoreceptor cells during the day by increasing dopamine D2 receptor activation, and dramatically increases rod-cone coupling at night by reducing D2 receptor activation(7,8). However, not only are these studies extremely difficult to perform on

  17. Post-Junctional Modulatory Effects of Hemicholinium on Isolated ...

    African Journals Online (AJOL)

    Conclusion: HC-3 has antimuscarinic actions on Ach- and carbacholinduced responses; a post-junctional action at the neuromuscular junction and differing anticholinesterase activities with DFP and physostigmine but not edrophonium. KEY WORDS: Post-Junctional, Anti-Muscarinic, Anti-Cholinesterase Jnl of Medical ...

  18. Influência da procainamida sobre o bloqueio neuromuscular produzido pelo rocurônio e investigação sobre o mecanismo de ação da procainamida na junção neuromuscular Influencia de la procainamida sobre el bloqueo neuromuscular producido por el rocuronio e investigación sobre el mecanismo de acción de la procainamida en la junción neuromuscular Influence of procainamide on the neuromuscular blockade caused by rocuronium and investigation on the mechanism of action of procainamide on the neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Thalita Duque Martins

    2007-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A potencialização da procainamida sobre o bloqueio neuromuscular produzido pela d-tubocurarina já está comprovada, porém o mecanismo é controverso. O objetivo do estudo foi avaliar a influência da procainamida no bloqueio neuromuscular produzido pelo rocurônio e investigar os mecanismos desta interação. MÉTODO: Foram utilizados 15 ratos (250 a 300 g em preparação descrita por Bülbring. Formaram-se os seguintes grupos (n = 5 cada: procainamida - 20 µg.mL-1 (Grupo I; rocurônio - 4 µg.mL-1 (Grupo II e rocurônio - 4 µg.mL-1 e procainamida - 20 µg.mL-1 (Grupo III. Avaliaram-se: 1 a amplitude das contrações musculares sob estimulação indireta em cada grupo, antes e após a adição dos fármacos; 2 os potenciais de placa terminal em miniatura (PPTM; 3 a eficácia da 4-aminopiridina na reversão do bloqueio neuromuscular. O mecanismo da interação foi estudado em Biventer cervicis (n = 5 e diafragma de rato desnervado (n = 5, observando-se a influência da procainamida na resposta à acetilcolina antes e após a adição da procainamida. RESULTADOS: A procainamida isoladamente não alterou as respostas neuromusculares. O bloqueio produzido com o Grupo III foi de 68,6% ± 7,1%, com diferença significativa (p = 0,0067 em relação ao Grupo II (10,4% ± 4,5%, revertido pela 4-aminopiridina. A procainamida ocasionou aumento na freqüência dos PPTM, seguido de bloqueio revertido pela 4-aminopiridina. Em Biventer cervicis a procainamida aumentou a resposta à ação de contração da acetilcolina, resultado não observado com o diafragma desnervado. CONCLUSÕES: A procainamida potencializou o bloqueio produzido pelo rocurônio. As alterações observadas com PPTM e Biventer cervicis identificaram ação pré-sináptica. O antagonismo da 4-aminopiridina sobre o bloqueio dos PPTM sugeriu dessensibilização dos receptores pela procainamida.JUSTIFICATIVA Y OBJETIVOS: La potenciación de la procainamida sobre

  19. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Karen K Y Ling

    2010-11-01

    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  20. Clinical detectable tension in the growing body: new and revisited signs in clinical examination in children with postural problems and spinal deformities. Restoration of lordosis on the thoracolumbar junction can correct sagittal and coronal plane deformity; a new (revisited) linked approach on the treatment and etiology of adolescent spinal deformities.

    Science.gov (United States)

    van Loon, P J M

    2008-01-01

    Unclear etiology in scoliotic and kyphotic deformities of the spine is responsible for uncertainty in treatment options. Normal all-day factors can be of importance. Newly developed or revisited clinical examination of sitting and supine children and consequent testing of neuro-muscular tightness shows to be useful in understanding the different spinal deformations and postural problems during growth and point to neuromuscular tension in growth. The goal is: -Better understanding of the role and individual characteristics of the central nervous system, especially the cord and roots in proper and improper growth of the human spine. -Clarifying that preservation of lordosis and good function at the thoracolumbar junction at the end of growth can be of value for normal configuration and function of the spine in adult life. -Present obvious important and consistent clinical observations in children in sitting and supine position with early and advanced adolescent deformities, by photographic studies and video fragments. Use of work on growth and deformation of the spine by Milan Roth on uncoupled neuro-osseous growth and other historical literature. -Relate these clinical findings and background literature with common knowledge about adolescent spinal deformities and mechanical laws on tensile and compressive forces in structures. Overview of relevant clinical tests in the growing child presented with deformities show possible correlation with the proposed internal balancing problem (uncoupled neuro-osseous growth) researched by Roth. Concomitant radiological and MRI signs are shown. Around 1900 most orthopaedic surgeons and anatomists saw relationship between the new habitude of children to sit for prolonged periods in schools and spinal deformities. A physiological explanation as adaptations needed by the total neuromuscular system ("the growing system") was widely postulated (Hueter-Volkmann principle) and subject in research but a concise theory was not achieved

  1. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.

    Science.gov (United States)

    Lee, Young Il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-08-15

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precede the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Sleep in Neuromuscular Diseases.

    Science.gov (United States)

    Fermin, Anna Monica; Afzal, Umair; Culebras, Antonio

    2016-03-01

    Sleep disorders in neuromuscular disorders are generally caused by respiratory dysfunction associated with these diseases. Hypoventilation in neuromuscular diseases results from both respiratory muscle weakness and reduced chemoreceptor sensitivity, which is required for ventilatory drive. This condition results in repeated arousals, sleep fragmentation, and nocturnal hypoxemia, manifesting most commonly as excessive daytime somnolence. Polysomnography can identify sleep disordered breathing in patients with neuromuscular disorders and treatment with noninvasive ventilation may improve quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Genome Editing of Monogenic Neuromuscular Diseases

    Science.gov (United States)

    Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N.

    2017-01-01

    IMPORTANCE Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. OBJECTIVES To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. EVIDENCE REVIEW PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, andmyotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9–mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1

  4. Hexosamine Biosynthetic Pathway Mutations Cause Neuromuscular Transmission Defect

    Science.gov (United States)

    Senderek, Jan; Müller, Juliane S.; Dusl, Marina; Strom, Tim M.; Guergueltcheva, Velina; Diepolder, Irmgard; Laval, Steven H.; Maxwell, Susan; Cossins, Judy; Krause, Sabine; Muelas, Nuria; Vilchez, Juan J.; Colomer, Jaume; Mallebrera, Cecilia Jimenez; Nascimento, Andres; Nafissi, Shahriar; Kariminejad, Ariana; Nilipour, Yalda; Bozorgmehr, Bita; Najmabadi, Hossein; Rodolico, Carmelo; Sieb, Jörn P.; Steinlein, Ortrud K.; Schlotter, Beate; Schoser, Benedikt; Kirschner, Janbernd; Herrmann, Ralf; Voit, Thomas; Oldfors, Anders; Lindbergh, Christopher; Urtizberea, Andoni; von der Hagen, Maja; Hübner, Angela; Palace, Jacqueline; Bushby, Kate; Straub, Volker; Beeson, David; Abicht, Angela; Lochmüller, Hanns

    2011-01-01

    Neuromuscular junctions (NMJs) are synapses that transmit impulses from motor neurons to skeletal muscle fibers leading to muscle contraction. Study of hereditary disorders of neuromuscular transmission, termed congenital myasthenic syndromes (CMS), has helped elucidate fundamental processes influencing development and function of the nerve-muscle synapse. Using genetic linkage, we find 18 different biallelic mutations in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in 13 unrelated families with an autosomal recessive CMS. Consistent with these data, downregulation of the GFPT1 ortholog gfpt1 in zebrafish embryos altered muscle fiber morphology and impaired neuromuscular junction development. GFPT1 is the key enzyme of the hexosamine pathway yielding the amino sugar UDP-N-acetylglucosamine, an essential substrate for protein glycosylation. Our findings provide further impetus to study the glycobiology of NMJ and synapses in general. PMID:21310273

  5. The Role of AMPK in Neuromuscular Biology and Disease.

    Science.gov (United States)

    Dial, Athan G; Ng, Sean Y; Manta, Alexander; Ljubicic, Vladimir

    2018-03-20

    AMP-activated protein kinase (AMPK) is a primary regulator of cellular metabolism. Recent studies have revealed that AMPK also mediates the maintenance and plasticity of α-motoneurons, the neuromuscular junction, and skeletal muscle. Furthermore, AMPK stimulation by either genetic, pharmacological, or physiological approaches elicits beneficial phenotypic remodeling in neuromuscular disorders (NMDs). Here, we review the role of AMPK as a governor of neuromuscular biology, and present evidence for AMPK as an effective molecular target for therapeutic pursuit in the context of the most prevalent NMDs, including Duchenne muscular dystrophy, spinal muscular atrophy, and myotonic dystrophy type 1. This information may be useful for engineering AMPK-targeted pharmacological- or lifestyle-based strategies to treat disorders of the neuromuscular system. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Nanotube junctions

    Science.gov (United States)

    Crespi, Vincent Henry; Cohen, Marvin Lou; Louie, Steven Gwon Sheng; Zettl, Alexander Karlwalter

    2003-01-01

    The present invention comprises a new nanoscale metal-semiconductor, semiconductor-semiconductor, or metal-metal junction, designed by introducing topological or chemical defects in the atomic structure of the nanotube. Nanotubes comprising adjacent sections having differing electrical properties are described. These nanotubes can be constructed from combinations of carbon, boron, nitrogen and other elements. The nanotube can be designed having different indices on either side of a junction point in a continuous tube so that the electrical properties on either side of the junction vary in a useful fashion. For example, the inventive nanotube may be electrically conducting on one side of a junction and semiconducting on the other side. An example of a semiconductor-metal junction is a Schottky barrier. Alternatively, the nanotube may exhibit different semiconductor properties on either side of the junction. Nanotubes containing heterojunctions, Schottky barriers, and metal-metal junctions are useful for microcircuitry.

  7. BIOLOGY OF SOME NEUROMUSCULAR DISORDERS

    Directory of Open Access Journals (Sweden)

    Gerta Vrbova

    2004-12-01

    unit is slower. The rate of maturation is critical for the survival of both motoneurone and muscle and that events that interfere with the time course of maturation cause both motoneurone and muscle fibre death. The proposal that the SMN gene/protein is involved in the process to developmental changes in cells and therefore crucial for their survival is put forward. The understanding of the developmental changes and their influence on motoneurone and muscle survival may help to devise therapeutic interventions. These may include a protection of the motoneurone cell body during a critical period of its development by reducing its excitability or enhancing its defences by upregulating heat shock proteins, b stabilizing neuromuscular junctions to enhance and prolong the retrograde influences from the muscle that affect motoneurone survival, c protecting muscle fibres from apoptosis, as well as stimulating their maturation by activity appropriate to their younger age that results from their delayed development.These approaches should be considered in addition to or in conjunction with possible interference with the gene and its product.In order to understand and possibly interfere/treat neuromuscular disorders it is important to analyze the biological events that may be causing the disability. In this presentation I would illustrate such attempts on two examples of genetically determined neuromuscular diseases: 1 Duchenne muscular dystrophy, and 2 Spinal muscular atrophy.

  8. Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission

    Science.gov (United States)

    Chaouch, Amina; Porcelli, Vito; Cox, Daniel; Edvardson, Shimon; Scarcia, Pasquale; De Grassi, Anna; Pierri, Ciro L.; Cossins, Judith; Laval, Steven H.; Griffin, Helen; Müller, Juliane S.; Evangelista, Teresinha; Töpf, Ana; Abicht, Angela; Huebner, Angela; von der Hagen, Maja; Bushby, Kate; Straub, Volker; Horvath, Rita; Elpeleg, Orly; Palace, Jacqueline; Senderek, Jan; Beeson, David; Palmieri, Luigi; Lochmüller, Hanns

    2016-01-01

    Background and Objective Congenital myasthenic syndromes are rare inherited disorders characterized by fatigable weakness caused by malfunction of the neuromuscular junction. We performed whole exome sequencing to unravel the genetic aetiology in an English sib pair with clinical features suggestive of congenital myasthenia. Methods We used homozygosity mapping and whole exome sequencing to identify the candidate gene variants. Mutant protein expression and function were assessed in vitro and a knockdown zebrafish model was generated to assess neuromuscular junction development. Results We identified a novel homozygous missense mutation in the SLC25A1 gene, encoding the mitochondrial citrate carrier. Mutant SLC25A1 showed abnormal carrier function. SLC25A1 has recently been linked to a severe, often lethal clinical phenotype. Our patients had a milder phenotype presenting primarily as a neuromuscular (NMJ) junction defect. Of note, a previously reported patient with different compound heterozygous missense mutations of SLC25A1 has since been shown to suffer from a neuromuscular transmission defect. Using knockdown of SLC25A1 expression in zebrafish, we were able to mirror the human disease in terms of variable brain, eye and cardiac involvement. Importantly, we show clear abnormalities in the neuromuscular junction, regardless of the severity of the phenotype. Conclusions Based on the axonal outgrowth defects seen in SLC25A1 knockdown zebrafish, we hypothesize that the neuromuscular junction impairment may be related to pre-synaptic nerve terminal abnormalities. Our findings highlight the complex machinery required to ensure efficient neuromuscular function, beyond the proteomes exclusive to the neuromuscular synapse. PMID:26870663

  9. Neuromuscular Disorders - Multiple Languages

    Science.gov (United States)

    ... Health Information Translations Spanish (español) Expand Section Neuromuscular Disorders: MedlinePlus Health Topic - English ... Health Information Translations Characters not displaying correctly on this page? See language display issues . Return to the MedlinePlus Health Information ...

  10. [Residual neuromuscular blockade].

    Science.gov (United States)

    Fuchs-Buder, T; Schmartz, D

    2017-06-01

    Even small degrees of residual neuromuscular blockade, i. e. a train-of-four (TOF) ratio >0.6, may lead to clinically relevant consequences for the patient. Especially upper airway integrity and the ability to swallow may still be markedly impaired. Moreover, increasing evidence suggests that residual neuromuscular blockade may affect postoperative outcome of patients. The incidence of these small degrees of residual blockade is relatively high and may persist for more than 90 min after a single intubating dose of an intermediately acting neuromuscular blocking agent, such as rocuronium and atracurium. Both neuromuscular monitoring and pharmacological reversal are key elements for the prevention of postoperative residual blockade.

  11. Neuromuscular disorders in acute leukemia and lymphoma treatment

    Directory of Open Access Journals (Sweden)

    E. A. Politova

    2014-07-01

    Full Text Available Different mechanisms of neuromuscular complications, their clinical presentation, methods of diagnosis, prognosis and treatment options arepresented. The material is presented according to the level of nervous system damage, with inclusion of different clinical entities. Authors revieweda wide range of disease – disease of the spinal cord, peripheral nerves and plexus, neuromuscular junction and muscle – as a result of chemotherapy and radiation therapy. Systemic effects of drugs on peripheral nervous system, various departments of which can be simultaneously involved in the pathological process, were also highlighted.

  12. FUNCTIONS OF A NEUROMUSCULAR CENTRE

    Directory of Open Access Journals (Sweden)

    Janez Zidar

    2004-12-01

    Full Text Available Main functions of a neuromuscular (NM centre are making diagnosis, treatment and counselling. Some other functions, e. g. forming a register and epidemiological endeavours, could be added. All these activities are expected to be achieved by multidisciplinary approach with the idea that members use the same guidelines and share the same knowledge.NM diseases affect lower levels of the nervous system that is motor units (motor cells in the brainstem and spinal cord, nerve roots, cranial and peripheral nerves, neuromuscular junction, and muscles. There are many such diseases; a few are more common others are rare.Rational approach in making a diagnosis can be divided into several steps. The process begins with a person with clinical symptoms and signs which raise the suspicion of NM disease. The first step is the description of the predominant pattern of muscular wasting and weakness (e. g. limb-girdle, distal, ocular, facio-scapulo-humeral. Each of these syndromes require a differential diagnosis within the motor unit territory what is achieved by means of EMG and muscle biopsy. The latter is even more important to define the nature of the abnormality. Disease nature can also be determined biochemically and, as NM disorders are commonly genetically determined, at the molecular genetic level. Treatment modalities include drugs (causative and symptomatic and other measures such as promoting and maintaining good general health, preventing skeletal deformities, physiotherapy, orthoses, surgery, and prevention of respiratory and cardiac functions. Counselling is mainly by social workers that focus on the practical aspects of coping with illness and disability and by genetic counsellors who gave advise on family planning.

  13. Gap junctions.

    Science.gov (United States)

    Goodenough, Daniel A; Paul, David L

    2009-07-01

    Gap junctions are aggregates of intercellular channels that permit direct cell-cell transfer of ions and small molecules. Initially described as low-resistance ion pathways joining excitable cells (nerve and muscle), gap junctions are found joining virtually all cells in solid tissues. Their long evolutionary history has permitted adaptation of gap-junctional intercellular communication to a variety of functions, with multiple regulatory mechanisms. Gap-junctional channels are composed of hexamers of medium-sized families of integral proteins: connexins in chordates and innexins in precordates. The functions of gap junctions have been explored by studying mutations in flies, worms, and humans, and targeted gene disruption in mice. These studies have revealed a wide diversity of function in tissue and organ biology.

  14. Hereditary neuromuscular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  15. Hereditary neuromuscular diseases

    International Nuclear Information System (INIS)

    Oezsarlak, O.; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J.

    2001-01-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible

  16. Computed tomography (CT) in neuromuscular disorders

    International Nuclear Information System (INIS)

    Novak, M.; Ambler, Z.

    1997-01-01

    For 24 patients with confirmed neuromuscular disorders, the clinical picture of the disease was complemented with CT examination. It is concluded, in accordance with the literature, that CT has a supplementary value as regards the extent and degree of disorder of the affected muscle groups. The basic pathological picture includes muscular atrophies, dystrophies, hypertrophies, and their combinations. The CT images are non-specific for the individual neuromuscular disorders and are of minor importance in the diagnostic process. 1 tab., 7 figs., 6 refs

  17. Expression of cAMP-responsive element binding proteins (CREBs) in fast- and slow-twitch muscles: a signaling pathway to account for the synaptic expression of collagen-tailed subunit (ColQ) of acetylcholinesterase at the rat neuromuscular junction.

    Science.gov (United States)

    Choi, Roy C Y; Chen, Vicky P; Luk, Wilson K W; Yung, Amanda W Y; Ng, Alice H M; Dong, Tina T X; Tsim, Karl W K

    2013-03-25

    The gene encoding the collagen-tailed subunit (ColQ) of acetylcholinesterase (AChE) contains two distinct promoters that drive the production of two ColQ mRNAs, ColQ-1 and ColQ-1a, in slow- and fast-twitch muscles, respectively. ColQ-1a is expressed at the neuromuscular junction (NMJ) in fast-twitch muscle, and this expression depends on trophic factors supplied by motor neurons signaling via a cAMP-dependent pathway in muscle. To further elucidate the molecular basis of ColQ-1a's synaptic expression, here we investigated the expression and localization of cAMP-responsive element binding protein (CREB) at the synaptic and extra-synaptic regions of fast- and slow-twitch muscles from adult rats. The total amount of active, phosphorylated CREB (P-CREB) present in slow-twitch soleus muscle was higher than that in fast-twitch tibialis muscle, but P-CREB was predominantly expressed in the fast-twitch muscle at NMJs. In contrast, P-CREB was detected in both synaptic and extra-synaptic regions of slow-twitch muscle. These results reveal, for the first time, the differential distribution of P-CREB in fast- and slow-twitch muscles, which might support the crucial role of cAMP-dependent signaling in controlling the synapse-specific expression of ColQ-1a in fast-twitch muscles. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Functional Connectivity under Optogenetic Control Allows Modeling of Human Neuromuscular Disease.

    Science.gov (United States)

    Steinbeck, Julius A; Jaiswal, Manoj K; Calder, Elizabeth L; Kishinevsky, Sarah; Weishaupt, Andreas; Toyka, Klaus V; Goldstein, Peter A; Studer, Lorenz

    2016-01-07

    Capturing the full potential of human pluripotent stem cell (PSC)-derived neurons in disease modeling and regenerative medicine requires analysis in complex functional systems. Here we establish optogenetic control in human PSC-derived spinal motorneurons and show that co-culture of these cells with human myoblast-derived skeletal muscle builds a functional all-human neuromuscular junction that can be triggered to twitch upon light stimulation. To model neuromuscular disease we incubated these co-cultures with IgG from myasthenia gravis patients and active complement. Myasthenia gravis is an autoimmune disorder that selectively targets neuromuscular junctions. We saw a reversible reduction in the amplitude of muscle contractions, representing a surrogate marker for the characteristic loss of muscle strength seen in this disease. The ability to recapitulate key aspects of disease pathology and its symptomatic treatment suggests that this neuromuscular junction assay has significant potential for modeling of neuromuscular disease and regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Temporal and spatial requirements of unplugged/MuSK function during zebrafish neuromuscular development.

    Directory of Open Access Journals (Sweden)

    Lili Jing

    2010-01-01

    Full Text Available One of the earliest events in neuromuscular junction (NMJ development is the accumulation of acetylcholine receptor (AChR at the center of muscle cells. The unplugged/MuSK (muscle specific tyrosine kinase gene is essential to initiate AChR clustering but also to restrict approaching growth cones to the muscle center, thereby coordinating pre- and postsynaptic development. To determine how unplugged/MuSK signaling coordinates these two processes, we examined the temporal and spatial requirements of unplugged/MuSK in zebrafish embryos using heat-shock inducible transgenes. Here, we show that despite its expression in muscle cells from the time they differentiate, unplugged/MuSK activity is first required just prior to the appearance of AChR clusters to simultaneously induce AChR accumulation and to guide motor axons. Furthermore, we demonstrate that ectopic expression of unplugged/MuSK throughout the muscle membrane results in wildtype-like AChR prepattern and neuromuscular synapses in the central region of muscle cells. We propose that AChR prepatterning and axonal guidance are spatio-temporally coordinated through common unplugged/MuSK signals, and that additional factor(s restrict unplugged/MuSK signaling to a central muscle zone critical for establishing mid-muscle synaptogenesis.

  20. Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review.

    Science.gov (United States)

    Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N

    2016-11-01

    Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. Multiple proof

  1. Non-quantal acetylcholine release at the neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Vyskočil, František; Malomouzh, A. I.; Nikolsky, E. E.

    2009-01-01

    Roč. 58, č. 6 (2009), s. 763-784 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA500110905 Institutional research plan: CEZ:AV0Z50110509 Keywords : acetylcholine * non-quantal release * nitric oxide Subject RIV: ED - Physiology Impact factor: 1.430, year: 2009

  2. MRI in neuromuscular disorders

    International Nuclear Information System (INIS)

    Fischmann, Arne

    2014-01-01

    Neuromuscular disorders are caused by damage of the skeletal muscles or supplying nerves, in many cases due to a genetic defect, resulting in progressive disability, loss of ambulation and often a reduced life expectancy. Previously only supportive care and steroids were available as treatments, but several novel therapies are under development or in clinical trial phase. Muscle imaging can detect specific patterns of involvement and facilitate diagnosis and guide genetic testing. Quantitative MRT can be used to monitor disease progression either to monitor treatment or as a surrogate parameter for clinical trails. Novel imaging sequences can provide insights into disease pathology and muscle metabolism. (orig.)

  3. Neuromuscular Blocking Agents and Neuromuscular Dysfunction Acquired in Critical Illness: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Price, David R; Mikkelsen, Mark E; Umscheid, Craig A; Armstrong, Ehrin J

    2016-11-01

    The relationship between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness remains unclear. We examined the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, and critical illness myopathy. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and bibliographies of included studies were searched from database inception until September 24, 2015. Randomized controlled trials and prospective observational studies examining the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, or critical illness myopathy. One author screened titles/abstracts. Two authors independently reviewed full text and extracted data from included studies. Meta-analysis was performed using the DerSimonian-Laird random effects model (OpenMetaAnalyst 10.10 for OS.X). We assessed reporting bias with funnel plots and heterogeneity with the I statistic. Of 2,170 titles/abstracts screened, 99 full texts were selected for review, yielding one randomized controlled trial and 18 prospective observational studies, for a total of 2,254 patients. The randomized controlled trial did not show an association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness (odds ratio, 1.21; 95% CI, 0.67-2.19), but pooled data from all included studies suggested a modest association (odds ratio, 1.25; 95% CI, 1.06-1.48; I = 16%). Funnel plots suggested reporting bias, and sensitivity analyses showed a disproportionate contribution from critical illness polyneuropathy/critical illness myopathy and severe sepsis/septic shock studies. This meta-analysis suggests a modest association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness; limitations include studies with a high risk of bias and a

  4. Perineal neuromuscular fatigue.

    Science.gov (United States)

    Deffieux, X; Hubeaux, K; Damphousse, M; Raibaut, P; Sheikh Ismael, S; Thoumie, P; Amarenco, G; Lapeyre, E; Jousse, M

    2006-07-01

    The physiology of urinary continence during stress is complex and the role of passive and active mechanisms remains unclear. Coughing leads to a contraction of urethral rhabdomyosphincter and pelvic floor muscles leading to a positive urethro-vesical gradient and continence. Neuromuscular fatigue can involve all striated muscles, including rhabdomyosphincter, peri-urethral and pelvic floor muscles. This article reviews results of studies assessing perineal muscular fatigue in urinary incontinence. A systematic review of the literature (Medline, Pascal and Embase) with use of the MESH keywords fatigue, stress, urinary incontinence, pelvic floor, urethra, urethral pressure, and muscle. Animal models have shown that the pelvic muscles (iliococcygeus and pubococcygeous) exhibit more neuromuscular fatigue than classical skeletal striated muscles (i.e. soleus muscle). Although the human external urethral sphincter is considered to be a highly fatigue-resistant muscle with its high proportion of slow muscle fibers, repeated coughing seems to lead to decreased urethral pressure in numerous women affected with stress urinary incontinence. In this case, "urethral fatigue" might be a possibility. Although few studies have focused on perineal muscular fatigue, such increased fatigue in pelvic floor muscles may play a role in the pathophysiologic features of stress urinary incontinence in women.

  5. Effect of calcium on excitatory neuromuscular transmission in the crayfish

    Science.gov (United States)

    Bracho, H.; Orkand, R. K.

    1970-01-01

    1. The effects of varying the external Ca concentration from 1·8 to 30 mM/l. (⅛-2 times normal) have been studied at the in vitro crayfish excitatory neuromuscular junction. Electrophysiological techniques were used to record transmembrane junctional potentials from muscle fibres and extracellular junctional currents from the vicinity of nerve terminals. 2. The excitatory junctional potential amplitude was proportional to [Ca]0n, where n varied between 0·68 and 0·94 (mean 0·82) when [Ca]0 was varied from 1·8 to 15 mM/l. 3. The increase in junctional potential amplitude on raising [Ca]0 resulted primarily from an increase in the average number of quanta of excitatory transmitter released from the presynaptic nerve terminal by the nerve impulse. 4. The size of the quanta, synaptic delay, presynaptic potential and electrical properties of the muscle membrane were little affected by changes in calcium concentration in the range studied. PMID:5498460

  6. Factors that affect the onset of action of non-depolarizing neuromuscular blocking agents.

    Science.gov (United States)

    Kim, Yong Byum; Sung, Tae-Yun; Yang, Hong Seuk

    2017-10-01

    Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric anesthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action. Factors that affect the onset time include the potency of the NMBDs, the rate of NMBDs reaching the effect site, the onset time by dose control, metabolism and elimination of NMBDs, buffered diffusion to the effect site, nicotinic acetylcholine receptor subunit affinity, drugs that affect acetylcholine (ACh) production and release at the neuromuscular junction, drugs that inhibit plasma cholinesterase, presynaptic receptors responsible for ACh release at the neuromuscular junction, anesthetics or drugs that affect muscle contractility, site and methods for monitoring neuromuscular function, individual variability, and coexisting disease. NMBDs with rapid onset without major adverse events are expected in the next few years, and the development of lower potency NMBDs will continue. Anesthesiologists should be aware of the use of NMBDs in the management of anesthesia. The choice of NMBD and determination of the appropriate dosage to modulate neuromuscular blockade characteristics such as onset time and duration of neuromuscular blockade should be considered along with factors that affect the effects of the NMBDs. In this review, we discuss the factors that affect the onset time of NMBDs.

  7. Clinical neuropsychiatric and neuromuscular manifestations in systemic lupus erythematosus.

    Science.gov (United States)

    Omdal, R; Mellgren, S I; Husby, G

    1988-01-01

    Thirty patients with SLE were studied retrospectively and subjected to clinical neurological examination. The accumulated neurological manifestations from the beginning of the disease until the time of examination were thus collected. Twenty-five patients (83%) had experienced neuropsychiatric manifestations while 11 patients (37%) had neuromuscular manifestations. The most frequent single symptom was migraine which had occurred in 40% of the patients. This was followed by severe protracted headache in 20%, vertigo in 20%, and psychiatric problems in 17%. Carpal tunnel syndrome and muscular weakness both occurring in 23% of the patients were the most prevalent neuromuscular manifestations, followed by myositis in 10%.

  8. Neuromuscular Electrical Stimulation and Anabolic Signaling in Patients with Stroke.

    Science.gov (United States)

    Mettler, Joni A; Bennett, Sydney M; Doucet, Barbara M; Magee, Dillon M

    2017-12-01

    Stroke results in limited ability to produce voluntary muscle contraction and movement on one side of the body, leading to further muscle wasting and weakness. Neuromuscular electrical stimulation is often used to facilitate involuntary muscle contraction; however, the effect of neuromuscular electrical stimulation on muscle growth and strengthening processes in hemiparetic muscle is not clear. This study examined the skeletal muscle anabolic response of an acute bout of neuromuscular electrical stimulation in individuals with chronic stroke and healthy older adults. Eleven individuals (59.8 ± 2.7 years old) were divided into a chronic stroke group (n = 5) and a healthy older adult control group (n = 6). Muscle biopsies were obtained before and after stimulation from the vastus lateralis of the hemiparetic leg for the stroke group and the right leg for the control group. The neuromuscular electrical stimulation protocol consisted of a 60-minute, intermittent stimulation train at 60 Hz. Phosphorylation of mammalian target of rapamycin and ribosomal protein S6 kinase beta-1 were analyzed by Western blot. An acute bout of neuromuscular electrical stimulation increased phosphorylation of mammalian target of rapamycin (stroke: 56.0%; control: 51.4%; P = .002) and ribosomal protein S6 kinase beta-1 (stroke: 131.2%; control: 156.3%; P = .002) from resting levels to post-neuromuscular electrical stimulation treatment, respectively. Phosphorylated protein content was similar between stroke and control groups at both time points. Findings suggest that paretic muscles of patients with chronic stroke may maintain ability to stimulate protein synthesis machinery in response to neuromuscular electrical stimulation. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. Neuromuscular disease classification system

    Science.gov (United States)

    Sáez, Aurora; Acha, Begoña; Montero-Sánchez, Adoración; Rivas, Eloy; Escudero, Luis M.; Serrano, Carmen

    2013-06-01

    Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic patterns.

  10. Carabelli's trait revisited: an examination of mesiolingual features at the enamel-dentine junction and enamel surface of Pan and Homo sapiens upper molars.

    Science.gov (United States)

    Ortiz, Alejandra; Skinner, Matthew M; Bailey, Shara E; Hublin, Jean-Jacques

    2012-10-01

    Carabelli's trait is a morphological feature that frequently occurs on the mesiolingual aspect of Homo sapiens upper molars. Similar structures also referred to as Carabelli's trait have been reported in apes and fossil hominins. However, the morphological development and homology of these mesiolingual structures among hominoids are poorly understood. In this study, we employ micro-computed tomography to image the enamel-dentine junction (EDJ) and outer enamel surface (OES) of Pan (n = 48) and H. sapiens (n = 52) upper molars. We investigate the developmental origin of mesiolingual features in these taxa and establish the relative contribution of the EDJ and enamel cap to feature expression. Results demonstrate that mesiolingual features of H. sapiens molars develop at the EDJ and are similarly expressed at the OES. Morphological variation at both surfaces in this taxon can satisfactorily be assessed using standards for Carabelli's trait developed by the Arizona State University Dental Anthropology System (ASUDAS). Relative to H. sapiens, Pan has an even greater degree of correspondence in feature expression between the EDJ and OES. Morphological manifestations in Pan molars are not necessarily limited to the protocone and are best characterized by a lingual cingulum that cannot be captured by the ASUDAS. Cusp-like structures, similar to those seen in marked Carabelli's trait expressions in H. sapiens, were not found in Pan. This study provides a foundation for further analyses on the evolutionary history of mesiolingual dental traits within the hominoid lineage. It also highlights the wealth of morphological data that can be obtained at the EDJ for understanding tooth development and for characterizing tooth crown variation in worn fossil teeth. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Validation of the ICF core set for neuromuscular diseases

    NARCIS (Netherlands)

    Bos, Isaac; Stallinga, H. A.; Middel, B.; Kuks, J. B. M.; Wynia, K.

    Background. Understanding of the consequences of a neuromuscular disease (NMD) can improve when a valid sample of disease-specific categories based on the International Classification of Functioning, Disabilities, and Health (ICF) is available. Objective. To examine the content validity of the

  12. Validation of the ICF core set for neuromuscular diseases

    NARCIS (Netherlands)

    K. Wynia; J.B. Kuks; H.A. Stallinga; B. Middel; I. Bos

    2013-01-01

    BACKGROUND: Understanding of the consequences of a neuromuscular disease (NMD) can improve when a valid sample of disease-specific categories based on the International Classification of Functioning, Disabilities, and Health (ICF) is available. OBJECTIVE: To examine the content validity of the

  13. Volume of the effect compartment in simulations of neuromuscular block

    NARCIS (Netherlands)

    Nigrovic, Vladimir; Proost, Johannes H.; Amann, Anton; Bhatt, Shashi B.

    2005-01-01

    Background: The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants. Methods: The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent

  14. Intrauterine neuromuscular blockade in fetus.

    Science.gov (United States)

    Fan, S Z; Huang, F Y; Lin, S Y; Wang, Y P; Hsieh, F J

    1990-03-01

    Antenatal intrauterine fetal therapy has now become the target of numerous invasive diagnostic and therapeutic maneuvers. Fetal motion during intrauterine fetal therapy not only makes these procedures technically more difficult but also increases the likelihood of trauma to the umbilical vessels and the fetus. Combination of high doses of sedatives, tranquilizers, and narcotics rarely results in adequate suppression of fetal movement. Such medication puts the mother at risk of respiratory depression, regurgitation and aspiration. The use of pancuronium or atracurium to temporarily arrest fetal movement in ten fetus is reported. After an initial ultrasound assessment of fetal lie, placental location, and umbilical cord insertion site, the fetal weight was calculated by the ultrasound parameters of biparietal diameter and abdominal circumference. Under ultrasound guidance, we injected pancuronium 0.15 mg/kg or atracurium 1.0 mg/kg using a 23-gauge spinal needle into the fetal gluteal muscle. Short-term paralysis of the fetus was induced in all cases. Fetal movement stopped by sonographic observation within 5.8 +/- 2.3 min in the pancuronium group and 4.7 +/- 1.8 min in the atracurium group. Fetal movements returned both to maternal sensation or ultrasonic observation by 92 +/- 23 min in the first group and 36 +/- 11 min in the second group. No adverse effect of the relaxant has been observed in any of the mothers. There was no evidence of local soft tissue, nerve or muscle damage at the site of injection on initial examination of the neonates after delivery. The use of neuromuscular relaxant in fetus was a safe and useful method.

  15. Muscle ultrasound in neuromuscular disorders.

    NARCIS (Netherlands)

    Pillen, S.; Arts, I.M.P.; Zwarts, M.J.

    2008-01-01

    Muscle ultrasound is a useful tool in the diagnosis of neuromuscular disorders, as these disorders result in muscle atrophy and intramuscular fibrosis and fatty infiltration, which can be visualized with ultrasound. Several prospective studies have reported high sensitivities and specificities in

  16. Palliative care in neuromuscular diseases

    NARCIS (Netherlands)

    de Visser, Marianne; Oliver, David J.

    2017-01-01

    Purpose of review Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness. Neuromuscular disorders (NMDs) are characterized by progressive muscle weakness, leading to pronounced and incapacitating

  17. Vocational perspectives and neuromuscular disorders

    NARCIS (Netherlands)

    Andries, F; Wevers, CWJ; Wintzen, AR; Busch, HFM; Howeler, CJ; deJager, AEJ; Padberg, GW; deVisser, M; Wokke, JHJ

    The present study analyses the actual occupational situation, vocational handicaps and past labour career of a group of about 1000 Dutch patients suffering from a neuromuscular disorder (NMD). On the basis of the likelihood of a substantial employment history and sufficient numbers of patients, four

  18. Vocational perspectives and neuromuscular disorders

    NARCIS (Netherlands)

    Andries, F.; Wevers, C. W.; Wintzen, A. R.; Busch, H. F.; Höweler, C. J.; de Jager, A. E.; Padberg, G. W.; de Visser, M.; Wokke, J. H.

    1997-01-01

    The present study analyses the actual occupational situation, vocational handicaps and past labour career of a group of about 1000 Dutch patients suffering from a neuromuscular disorder (NMD). On the basis of the likelihood of a substantial employment history and sufficient numbers of patients, four

  19. Neuromuscular disease and respiratory physiology in children: putting lung function into perspective.

    Science.gov (United States)

    Fauroux, Brigitte; Khirani, Sonia

    2014-08-01

    Neuromuscular diseases represent a heterogeneous group of disorders of the muscle, nerve or neuromuscular junction. The respiratory muscles are rarely spared in neuromuscular diseases even if the type of muscle involvement, severity and time course greatly varies among the different diseases. Diagnosis of respiratory muscle weakness is crucial because of the importance of respiratory morbidity and mortality. Presently, routine respiratory evaluation is based on non-invasive volitional tests, such as the measurement of lung volumes, spirometry and the maximal static pressures, which may be difficult or impossible to obtain in some young children. Other tools or parameters are thus needed to assess the respiratory muscle weakness and its consequences in young children. The measurement of oesogastric pressures can be helpful as they allow the diagnosis and quantification of paradoxical breathing, as well as the assessment of the strength of the inspiratory and expiratory muscles by means of the oesophageal pressure during a maximal sniff and of the gastric pressure during a maximal cough. Sleep assessment should also be part of the respiratory evaluation of children with neuromuscular disease with at least the recording of nocturnal gas exchange if polysomnography is not possible or unavailable. This improvement in the assessment of respiratory muscle performance may increase our understanding of the respiratory pathophysiology of the different neuromuscular diseases, improve patient care, and guide research and innovative therapies by identifying and validating respiratory parameters. © 2014 Asian Pacific Society of Respirology.

  20. Phenomenological approach to bistable behavior of Josephson junctions

    International Nuclear Information System (INIS)

    Nishi, K.; Nara, S.; Hamanaka, K.

    1985-01-01

    The interaction of unbiased Josephson junction with external electromagnetic field in the presence of externally applied uniform magnetic field is theoretically examined by means of phenomenological treatment. It is proposed that an irradiated junction with suitably chosen parameters shows a bistable behavior of voltage across the junction as a function of the radiation intensity

  1. Design junctions

    DEFF Research Database (Denmark)

    Jørgensen, Ulrik

    2012-01-01

    This article discusses the question: Are weak signals independent of framing and interactions with the environment? The response proposed here is that many of the developments identified by efforts to detect and interpret weak signals are the result of designed interventions that define the reper......This article discusses the question: Are weak signals independent of framing and interactions with the environment? The response proposed here is that many of the developments identified by efforts to detect and interpret weak signals are the result of designed interventions that define...... given to weak signals are strongly influenced by design choices made at the outset. In this sense design is a constitutive element of both the environment and signal detection/use. An example of how design is constitutive of both context and understanding can be found in the history of hospital hygiene....... This case study illustrates how dominant regimes of practice, established through the conception of pathogen bacteria and antibacterial treatments and disinfection, are now creating signals that call into question fundamental design of hygiene practices. By examining the epistemic assumptions of scientific...

  2. Intercellular junctions in rabbit eye ora serrata.

    Science.gov (United States)

    Nobeschi, L; Freymuller, E; Smith, R L

    2006-10-01

    Summary The aim of this study was to describe and localize the intercellular junctions in the ora serrata region of albino and pigmented rabbit eyes. Eyes of albino and pigmented rabbits were fixed and processed for transmission electron microscopy. Light and electron microscope examination was carried out on semithin and ultrathin sections. The ora serrata region showed adherens, gap and tight junctions in the retinal and ciliary margins of albino and pigmented rabbit eyes. In the retinal margin, zonulae adherens between Müller cells and photoreceptors are associated with tight junctions. In the ciliary margin, epithelial cells are joined by adherens, gap and tight junctions localized between apical and apicolateral cell membranes. Tight junctions appear as zonulae occludens in the non-pigmented apicolateral cell membranes and as tight focal junctions between pigmented and non-pigmented apical cell membranes. Between the ciliary and retinal margins there are adherens and tight focal junctions which attach pigmented apical cell membranes to adjacent cells. There were no differences in the distribution of intercellular junctions between albino and pigmented rabbits.

  3. Myths and facts in neuromuscular pharmacology - New developments in reversing neuromuscular blockade

    NARCIS (Netherlands)

    Fink, H.; Hollmann, M. W.

    2012-01-01

    Pharmacologic reversal of neuromuscular blockade is a topic nor very well acknowledged and controversially discussed. Reasons for this are numerous and include missing perception of the potential complications of residual neuromuscular paralysis including an increased morbidity and mortality, as

  4. Neuromuscular disorders and chronic ventilation.

    Science.gov (United States)

    Alexiou, Stamatia; Piccione, Joseph

    2017-08-01

    Morbidity and mortality have decreased in patients with neuromuscular disease due to implementation of therapies to augment cough and improve ventilation. Infants with progressive neuromuscular disease will eventually develop respiratory complications as a result of muscle weakness and their inability to compensate during periods of increased respiratory loads. The finding of nocturnal hypercapnia is often the trigger for initiating non-invasive ventilation and studies have shown that its use not only may improve sleep-disordered breathing, but also that it may have an effect on daytime function, symptoms related to hypercapnia, and partial pressure of CO 2 . It is important to understand the respiratory physiology of this population and to understand the benefits and limitations of assisted ventilation. Copyright © 2017. Published by Elsevier Ltd.

  5. [Respiratory treatments in neuromuscular disease].

    Science.gov (United States)

    Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A

    2014-10-01

    In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  6. Neuromuscular blockade in the elderly.

    Science.gov (United States)

    Stankiewicz-Rudnicki, Michał

    2016-01-01

    The aim of the presented review is to highlight the clinical problem of postoperative residual curarization (PORC) following general anaesthesia in the elderly. Possible complications of PORC are described along with age-induced changes in pharmacokinetics of long and intermediate-acting neuromuscular blocking agents. This is intended to facilitate the selection and to promote appropriate intraoperative use of muscle relaxants in patients over the age of 65 years.

  7. Dengue-associated neuromuscular complications

    OpenAIRE

    Ravindra Kumar Garg; Hardeep Singh Malhotra; Amita Jain; Kiran Preet Malhotra

    2015-01-01

    Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evo...

  8. Recent advances in neuromuscular block during anesthesia.

    Science.gov (United States)

    Boon, Martijn; Martini, Christian; Dahan, Albert

    2018-01-01

    Muscle relaxation is a routine part of anesthesia and has important advantages. However, the lingering effects of muscle relaxants in the postoperative period have historically been associated with postoperative adverse events. Neuromuscular reversal, together with neuromuscular monitoring, is a recognized strategy to reduce the rate of postoperative residual relaxation but has only marginally improved outcome in the past few decades. Sugammadex, a novel reversal agent with unique encapsulating properties, has changed the landscape of neuromuscular reversal and opened up new opportunities to improve patient care. By quickly and completely reversing any depth of neuromuscular block, it may reduce the rate of residual relaxation and improve respiratory recovery. In addition, sugammadex has made the use of deep neuromuscular block possible during surgery. Deep neuromuscular block may improve surgical working conditions and allow for a reduction in insufflation pressures during selected laparoscopic procedures. However, whether and how this may impact outcomes is not well established.

  9. Molecular electronic junction transport

    DEFF Research Database (Denmark)

    Solomon, Gemma C.; Herrmann, Carmen; Ratner, Mark

    2012-01-01

    Whenasinglemolecule,oracollectionofmolecules,isplacedbetween two electrodes and voltage is applied, one has a molecular transport junction. We discuss such junctions, their properties, their description, and some of their applications. The discussion is qualitative rather than quantitative......, and focuses on mechanism, structure/function relations, regimes and mechanisms of transport, some molecular regularities, and some substantial challenges facing the field. Because there are many regimes and mechanisms in transport junctions, we will discuss time scales, geometries, and inelastic scattering...

  10. Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming.

    Science.gov (United States)

    Silva, Anjana; Hodgson, Wayne C; Isbister, Geoffrey K

    2017-04-19

    Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information. We searched MEDLINE (from 1946) and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded no randomised placebo-controlled trials of antivenom for neuromuscular dysfunction. There were several randomised and non-randomised comparative trials that compared two or more doses of the same or different antivenom, and numerous cohort studies and case reports. The majority of studies available had deficiencies including poor case definition, poor study design, small sample size or no objective measures of paralysis. A number of studies demonstrated the efficacy of antivenom in human envenoming by clearing circulating venom. Studies of snakes with primarily pre-synaptic neurotoxins, such as kraits ( Bungarus spp.) and taipans ( Oxyuranus spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species ( Naja spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this.

  11. Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction

    OpenAIRE

    Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

    2015-01-01

    [Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used t...

  12. Innervation and neuromuscular control in ageing skeletal muscle

    Science.gov (United States)

    Rice, Charles L.

    2015-01-01

    Abstract Changes in the neuromuscular system affecting the ageing motor unit manifest structurally as a reduction in motor unit number secondary to motor neuron loss; fibre type grouping due to repeating cycles of denervation‐reinnervation; and instability of the neuromuscular junction that may be due to either or both of a gradual perturbation in postsynaptic signalling mechanisms necessary for maintenance of the endplate acetylcholine receptor clusters or a sudden process involving motor neuron death or traumatic injury to the muscle fibre. Functionally, these changes manifest as a reduction in strength and coordination that precedes a loss in muscle mass and contributes to impairments in fatigue. Regular muscle activation in postural muscles or through habitual physical activity can attenuate some of these structural and functional changes up to a point along the ageing continuum. On the other hand, regular muscle activation in advanced age (>75 years) loses its efficacy, and at least in rodents may exacerbate age‐related motor neuron death. Transgenic mouse studies aimed at identifying potential mechanisms of motor unit disruptions in ageing muscle are not conclusive due to many different mechanisms converging on similar motor unit alterations, many of which phenocopy ageing muscle. Longitudinal studies of ageing models and humans will help clarify the cause and effect relationships and thus, identify relevant therapeutic targets to better preserve muscle function across the lifespan. PMID:26437581

  13. Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae Venom in Vitro

    Directory of Open Access Journals (Sweden)

    Alejandro Carbajal-Saucedo

    2014-01-01

    Full Text Available In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake venom (MLV in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1–30 µg/mL neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05. In mouse phrenic nerve-diaphragm preparations, MLV (1–10 µg/mL promoted a slight increase in the amplitude of twitch-tension (3 µg/mL, followed by neuromuscular blockade (n = 4; the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min, without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal to 28 ± 2.5 (t15 and 12 ± 2 (t60. The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL was also significantly less negative with MLV (10 µg/mL. Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.

  14. PCBS AND TIGHT JUNCTION EXPRESSION

    OpenAIRE

    Eum, Sung Yong; András, Ibolya E.; Couraud, Pierre-Olivier; Hennig, Bernhard; Toborek, Michal

    2008-01-01

    Polychlorinated biphenyl (PCB) congeners exhibit a broad range of adverse biological effects including neurotoxicity. The mechanisms by which PCBs cause neurotoxic effects are still not completely understood. The blood-brain barrier (BBB) is a physical and metabolic barrier separating brain microenvironment from the peripheral circulation and is mainly composed of endothelial cells connected by tight junctions. We examined the effects of several highly-chlorinated PCB congeners on expression ...

  15. Muscle edema in MR imaging of neuromuscular diseases

    International Nuclear Information System (INIS)

    Schedel, H.; Reimers, C.D.; Vogl, T.; Witt, T.N.

    1995-01-01

    The purpose of this study was to examine the frequency of muscle edema and the diagnostic usefulness of Gd-DTPA in neuromuscular diseases. 144 consecutive patients with various generalized neuromuscular diseases were examined by MR imaging. Areas of high signal intensity, relative to normal muscle, were seen in 36% of T2-weighted images, whereas the corresponding T1-weighted images showed normal or lower signal intensities. These edema-like abnormalities -enlargement of the extracellular fluid space-were found more often in inflammatory and metabolic myopathies, but were also seen in degenerative myopathies. Contrast-enhanced T1-weighted images in 25 patients were not more sensitive than plain T2-weighted images. (orig.)

  16. Deep neuromuscular blockade leads to a larger intraabdominal volume during laparoscopy

    DEFF Research Database (Denmark)

    Lindekaer, Astrid Listov; Halvor Springborg, Henrik; Istre, Olav

    2013-01-01

    for measuring the intra-abdominal space available to the surgeon during laproscopy, in order to examine whether the relaxation produced by deep neuromuscular blockade can increase the working surgical space sufficiently to permit a reduction in the CO2 insufflation pressure. Using the laproscopic grasper......, the distance from the promontory to the skin is measured at two different insufflation pressures: 8 mm Hg and 12 mm Hg. After the initial measurements, a neuromuscular blocking agent (rocuronium) is administered to the patient and the intra-abdominal volume is measured again. Pilot data collected from 15...... patients shows that the intra-abdominal space at 8 mm Hg with blockade is comparable to the intra-abdominal space measured at 12 mm Hg without blockade. The impact of neuromuscular blockade was not correlated with patient height, weight, BMI, and age. Thus, using neuromuscular blockade to maintain a steady...

  17. Kinship and interaction in neuromuscular pharmacology

    NARCIS (Netherlands)

    Schiere, Sjouke

    2006-01-01

    The background of this thesis is presented in the introductory chapters and stafts with a brief history of neuromuscular relaxants. It is followed by a short description of the neuromuscular physiology and pharmacology in chapters 2 and 3, respectively. In chapter 4 the aim of the thesis is

  18. Anaesthesia in children with inherited neuromuscular diseases

    OpenAIRE

    Simić Dušica; Bogićević Dragana; Milojević Irina; Budić Ivana; Marković Marija

    2010-01-01

    Children with inherited neuromuscular diseases often require anaesthesia for diagnostic or therapy procedures. These patients have an increased risk of perioperative complications due to the nature of the disease and medications administered during anaesthesia. Many anaesthetics and muscle relaxants can aggravate the underlying disease and trigger life-threatening reactions (cardiorespiratory complications, malignant hyperthermia). Besides, the neuromuscular disorders are associated wit...

  19. Neuromuscular blockade during laparoscopic ventral herniotomy

    DEFF Research Database (Denmark)

    Medici, Roar; Madsen, Matias V; Asadzadeh, Sami

    2015-01-01

    INTRODUCTION: Laparoscopic herniotomy is the preferred technique for some ventral hernias. Several factors may influence the surgical conditions, one being the depth of neuromuscular blockade (NMB) applied. We hypothesised that deep neuromuscular blockade defined as a post-tetanic count below eight...

  20. Sugammadex Improves Neuromuscular Function in Patients ...

    African Journals Online (AJOL)

    2018-02-23

    Feb 23, 2018 ... with a modified gamma-cyclodextrin structure offers a viable alternative to the traditional decurarization by cholinesterase inhibitors in the context of the use of steroidal neuromuscular blocking agents. Sugammadex shows its effects through encapsulation of the steroidal neuromuscular blockers, its effects ...

  1. Neuromuscular blockade during laparoscopic ventral herniotomy

    DEFF Research Database (Denmark)

    Medici, Roar; Madsen, Matias V; Asadzadeh, Sami

    2015-01-01

    INTRODUCTION: Laparoscopic herniotomy is the preferred technique for some ventral hernias. Several factors may influence the surgical conditions, one being the depth of neuromuscular blockade (NMB) applied. We hypothesised that deep neuromuscular blockade defined as a post-tetanic count below eig...

  2. Reduced neuromuscular performance in amenorrheic elite endurance athletes

    DEFF Research Database (Denmark)

    Tornberg, Åsa B; Melin, Anna; Manderson Koivula, Fiona

    2017-01-01

    INTRODUCTION: Secondary functional hypothalamic amenorrhea (SFHA) is common among female athletes, especially in weight-sensitive sports. The aim of this study was to investigate the link between SFHA and neuromuscular performance in elite endurance athletes. METHODS: Sixteen eumenorrheic (EUM......) and 14 SFHA athletes from national teams and competitive clubs participated. Methods included gynecological examination; body composition (DXA);; resting metabolic rate and work efficiency; exercise capacity; knee muscular strength (KMS) and knee muscular endurance (KME); reaction time (RT); blood...

  3. Beneficial effect of adipokinetic hormone on neuromuscular paralysis in insect body elicited by braconid wasp venom.

    Science.gov (United States)

    Shaik, Haq Abdul; Mishra, Archana; Kodrík, Dalibor

    2017-06-01

    The effect of Habrobracon hebetor venom and the role of the adipokinetic hormone (AKH) in poisoned adult females of the firebug Pyrrhocoris apterus were studied 24 and 48h after treatments. Venom application elicited total neuromuscular paralysis in firebugs, but the co-application of venom and Pyrap-AKH significantly reduced paralysis (up to 3.2 times) compared to the application of venom only. Although the mechanisms of their action are unknown, both agents might affect neuromuscular junctions. Venom application significantly increased the expression of both P. apterus Akh genes (Pyrap-Akh 5.4 times and Peram-Cah-II 3.6 times), as well as the level of AKHs in the central nervous system (2.5 times) and haemolymph (3.0 times). In the haemolymph, increased AKH levels might have led to the mobilization of stored lipids, which increased 1.9 times, while the level of free carbohydrates remained unchanged. Total metabolism, monitored by carbon dioxide production, significantly declined in paralysed P. apterus individuals (1.4 times and 1.9 times, 24 and 48h after the treatment, respectively), probably because of a malfunction of the muscular system. The results suggest an active role of AKH in the defence mechanism against the stress elicited by neuromuscular paralysis, and the possible involvement of this hormone in neuronal/neuromuscular signalling. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia

    Science.gov (United States)

    Pannérec, Alice; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S.; Feige, Jerome N.

    2016-01-01

    Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process. PMID:27019136

  5. Neuromuscular Monitoring in the Perioperative Period.

    Science.gov (United States)

    Murphy, Glenn S

    2018-02-01

    Neuromuscular monitoring devices were introduced into clinical practice in the 1970s. Qualitative neuromuscular monitors, or peripheral nerve stimulators, provide an electrical stimulus to a motor nerve and the response of corresponding muscle subjectively evaluated. A standard peripheral nerve stimulator provides several patterns of nerve stimulation, including train-of-four (TOF), double-burst, tetanic, and post-tetanic count. Qualitative (and quantitative) monitors are needed to determine onset of neuromuscular blockade, maintain the required depth of muscle relaxation during the surgical procedure, and assess an appropriate dose of reversal agent. However, absence of fade measured with a peripheral nerve stimulator does not exclude residual neuromuscular block; TOF ratios as low as 0.4-0.6 may be present when fade is no longer observed. In addition, the risk of incomplete neuromuscular recovery may be influenced by monitoring site. The adductor pollicis is more sensitive to the effects of neuromuscular blocking agents (compared to the muscles surrounding the eye), and monitoring at this site may more accurately reflect recovery of pharyngeal muscles (the last muscles to recover from the effects of neuromuscular blocking agents, in which dysfunction may persist even at a TOF ratio of 1.0). Quantitative monitors are devices that measure and quantify the degree of muscle weakness and display the results numerically. Several different technologies have been developed, including mechanomyography, electromyography, acceleromyography, kineograph, and phonomyography. Lower doses of anticholinesterases may be used to effectively reverse neuromuscular blockade at TOF ratios of 0.4-0.6; quantitative monitoring is required to determine that this level of neuromuscular recovery has occurred. As clinical tests of muscle strength, peripheral nerve stimulators are unable to determine whether full recovery of neuromuscular function is present at the end of the surgical

  6. Characterization of cervical neuromuscular response to head-neck perturbation in active young adults.

    Science.gov (United States)

    Alsalaheen, Bara; Bean, Ryan; Almeida, Andrea; Eckner, James; Lorincz, Matthew

    2018-04-01

    The majority of studies examining the role of cervical muscles on head-neck kinematics focused on musculoskeletal attributes (e.g. strength). Cervical neuromuscular response to perturbation may represent a divergent construct that has not been examined under various perturbation conditions. This study examined the association between cervical musculoskeletal attributes and cervical neuromuscular response of the sternocleidomastoid (SCM) to perturbation. Furthermore, this study examined the effect of anticipation and preload on the SCM neuromuscular response. Nineteen participants completed measurement of SCM muscle size, cervical flexion maximal voluntary isometric contraction, and the neuromuscular response of the SCM to cervical perturbation. Cervical perturbation was delivered by dropping a 1.59 kg mass from a loading apparatus. The impulsive load was delivered under four conditions: (1) Anticipated perturbation with no preload (A-NP), (2) Unanticipated perturbation with no preload (U-NP), (3) Anticipated perturbation with preload (A-P), and (4) Unanticipated perturbation with preload (U-P). None of the cervical musculoskeletal attributes were correlated with the SCM cervical neuromuscular response. This study demonstrated significant effect of preloading and anticipation on baseline EMG amplitude and EMG onset latency for the SCM. Furthermore, there was a significant effect of preloading on average EMG response amplitude for the SCM. The findings of this study indicate that cervical neuromuscular response of the SCM is different from musculoskeletal attributes and is influenced by perturbation conditions. These findings provide conceptual support to examine the neuromuscular response of the SCM in mitigating head-neck kinematics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Spatial distribution and molecular dynamics of dystrophin glycoprotein components at the neuromuscular junctionin vivo.

    Science.gov (United States)

    Aittaleb, Mohamed; Martinez-Pena Y Valenzuela, Isabel; Akaaboune, Mohammed

    2017-05-15

    A bimolecular fluorescence complementation (BiFC) approach was used to study the molecular interactions between different components of the postsynaptic protein complex at the neuromuscular junction of living mice. We show that rapsyn forms complex with both α-dystrobrevin and α-syntrophin at the crests of junctional folds. The linkage of rapsyn to α-syntrophin and/or α-dystrobrevin is mediated by utrophin, a protein localized at acetylcholine receptor (AChR)-rich domains. In mice deficient in α-syntrophin, in which utrophin is no longer present at the synapse, rapsyn interaction with α-dystrobrevin was completely abolished. This interaction was completely restored when either utrophin or α-syntrophin was introduced into muscles deficient in α-syntrophin. However, in neuromuscular junctions deficient in α-dystrobrevin, in which utrophin is retained, complex formation between rapsyn and α-syntrophin was unaffected. Using fluorescence recovery after photobleaching, we found that α-syntrophin turnover is 5-7 times faster than that of AChRs, and loss of α-dystrobrevin has no effect on rapsyn and α-syntrophin half-life, whereas the half-life of AChR was significantly altered. Altogether, these results provide new insights into the spatial distribution of dystrophin glycoprotein components and their dynamics in living mice. © 2017. Published by The Company of Biologists Ltd.

  8. 21 CFR 882.5860 - Implanted neuromuscular stimulator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted neuromuscular stimulator. 882.5860... neuromuscular stimulator. (a) Identification. An implanted neuromuscular stimulator is a device that provides... Administration on or before July 13, 1999 for any implanted neuromuscular stimulator that was in commercial...

  9. Learning disabilities in neuromuscular disorders: a springboard for adult life.

    Science.gov (United States)

    Astrea, Guja; Battini, Roberta; Lenzi, Sara; Frosini, Silvia; Bonetti, Silvia; Moretti, Elena; Perazza, Silvia; Santorelli, Filippo M; Pecini, Chiara

    2016-10-01

    Although the presence of cognitive deficits in Duchenne muscular dystrophy or myotonic dystrophy DM1 is well established in view of brain-specific expression of affected muscle proteins, in other neuromuscular disorders, such as congenital myopathies and limb-girdle muscular dystrophies, cognitive profiles are poorly defined. Also, there are limited characterization of the cognitive profile of children with congenital muscular dystrophies, notwithstanding the presence of cerebral abnormality in some forms, and in spinal muscular atrophies, with the exception of distal spinal muscular atrophy (such as the DYN1CH1- associated form). Starting from the Duchenne muscular dystrophy, which may be considered a kind of paradigm for the co-occurrence of learning disabilities in the contest of a progressive muscular involvement, the findings of neuropsychological (or cognitive) dysfunctions in several forms of neuromuscular diseases will be examined and reviewed.

  10. Magnetic resonance imaging (MRI) in the diagnosis of neuromuscular diseases

    International Nuclear Information System (INIS)

    Schalke, B.C.G.; Rohkamm, R.; Kaiser, W.

    1990-01-01

    In the last few years imaging procedures became also important in the diagnosis of neuromuscular diseases. We examined more than 150 patients with different neuromuscular diseases with MRI. Conventional diagnostic procedures like EMG, muscle biopsy can not be replaced by imaging procedures. MRI gives the chance to get additional diagnostic informations. It is possible to determine exact distribution and intensity of pathological changes in the muscle. Inflammatory muscle diseases can be differrentiated by T1/T2 values from atrophic/dystrophic diseases. The resolving power is very high and allows the exact detection of affected areas even in a single muscle. This can help to reduce false negative muscle biopsies. This is very useful in children and young adults. MRI can be used for the early detection of genetic myopathies and neuropathies. MRI allows to examine all muscles, including the heart, bone artefacts are absent. Heart muscle involvement in neuromuscular diseases can directly be shown by this method without any risk for the patient. In addition P-spectroscopy can be done for better understanding of pathogenesis, especially if the exact distribution of pathological changes is known. (author)

  11. Quantum Junction Solar Cells

    KAUST Repository

    Tang, Jiang

    2012-09-12

    Colloidal quantum dot solids combine convenient solution-processing with quantum size effect tuning, offering avenues to high-efficiency multijunction cells based on a single materials synthesis and processing platform. The highest-performing colloidal quantum dot rectifying devices reported to date have relied on a junction between a quantum-tuned absorber and a bulk material (e.g., TiO 2); however, quantum tuning of the absorber then requires complete redesign of the bulk acceptor, compromising the benefits of facile quantum tuning. Here we report rectifying junctions constructed entirely using inherently band-aligned quantum-tuned materials. Realizing these quantum junction diodes relied upon the creation of an n-type quantum dot solid having a clean bandgap. We combine stable, chemically compatible, high-performance n-type and p-type materials to create the first quantum junction solar cells. We present a family of photovoltaic devices having widely tuned bandgaps of 0.6-1.6 eV that excel where conventional quantum-to-bulk devices fail to perform. Devices having optimal single-junction bandgaps exhibit certified AM1.5 solar power conversion efficiencies of 5.4%. Control over doping in quantum solids, and the successful integration of these materials to form stable quantum junctions, offers a powerful new degree of freedom to colloidal quantum dot optoelectronics. © 2012 American Chemical Society.

  12. Neuromuscular complications of diabetes mellitus.

    Science.gov (United States)

    Bril, Vera

    2014-06-01

    Diabetes mellitus has become a modern global epidemic, with steadily increasing prevalence rates related to lifestyle such that 27% of individuals aged 65 years or older have diabetes mellitus, 95% of whom have type 2. This article reviews the effects of diabetes mellitus on the neuromuscular system. Diabetes mellitus leads to diverse forms of peripheral neuropathy as the major neuromuscular complication. Both focal and diffuse types of neuropathy can develop, with the most common form being diabetic sensorimotor polyneuropathy. Small fibers are damaged early in the development of diabetic sensorimotor polyneuropathy and are not assessed by nerve conduction studies. Small fiber damage occurs even in the prediabetes stage. No disease-modifying therapy for diabetic sensorimotor polyneuropathy is available at this time, but this complication can be limited in patients who have type 1 diabetes mellitus with strict glycemic control; the same outcome is not clearly observed in patients who have type 2 diabetes mellitus. Recently, the evidence base for symptomatic treatments of painful diabetic sensorimotor polyneuropathy underwent systematic review. Effective evidence-based treatments include some anticonvulsants (eg, pregabalin, gabapentin), antidepressants (eg, amitriptyline, duloxetine), opioids (eg, morphine sulfate, oxycodone), capsaicin cream, and transcutaneous electrical nerve stimulation. This article reviews the increasing prevalence of diabetes mellitus and diabetic sensorimotor polyneuropathy and discusses recent consensus opinion on the objective confirmation needed for the diagnosis in the clinical research setting. The evidence from clinical trials shows that intensive glycemic control reduces prevalence of diabetic sensorimotor polyneuropathy in patients with type 1 diabetes mellitus, but variable outcomes are observed in patients with type 2 diabetes mellitus. Finally, despite the lack of disease-modifying treatment, effective evidence-based therapy can

  13. Classification of Neuromuscular Disorders Based an Clinical Criteria , Molocular and Immunohistochemisty Analysis in Tehran Pateints

    Directory of Open Access Journals (Sweden)

    Kimia Kahrizi

    2005-10-01

    Full Text Available Objective: Neuromuscular disordres are a gorup of heterogenous inherited diseases. More than 150 types of these group of disorders have been known.The criticals that were used for classification of these disease include: age of onset, clinical course, disease progression and type of inheritance. Neuromuscular disorders have been classified in four categories: Myopaties (Muscular dystrophies Neuropathy (Charcot-Marie-Tooth dieseas, Motor neuron junction (Myasthenia Syndrome Motor neuron disorder (Spinal muscular atrophy. Objective of this study was classification of neuromuscular disorders based on clinical criteria, molecular and immunohistochemical analysis that reffered to Genetic Research Center. As a result of neuromuscular disorders was the second most common disabilities, more investigation in this group of disorders is necessary in Iranian population so this study was performed for the first time in Iranian patients. Materials & Methods: Total of 143 patient with neuromuscular deficiency that clinical, EMG and muscle enzymes have been tested and also in some cases molecular and immunohistochemical analysis was performed. Results: 82 patients with myotonic dystrophy, 19 patients with DMD/BMD, 6 patients with congenital muscular dystrophy, 3 patients with FSHD, 10 patients with SMA, 2 patients with CMS and 21 patients with LGMD. For the other cases we need more molecular and definite clinical analysis. Conclusion: For some cases that DM1 was not confirmed, study of DM2 is recommended. In patients with LGMD that analysis with 5 Abs were normal we advised multiple western blot for them (including calpain, sarcoglycans, dysferlin. Study of congenital muscular dystrophy besides merosin analysis, investigation for the other involved protein and molecular testing for mutation detection is considrable.

  14. Deep Neuromuscular Blockade Improves Laparoscopic Surgical Conditions

    DEFF Research Database (Denmark)

    Rosenberg, Jacob; Herring, W Joseph; Blobner, Manfred

    2017-01-01

    INTRODUCTION: Sustained deep neuromuscular blockade (NMB) during laparoscopic surgery may facilitate optimal surgical conditions. This exploratory study assessed whether deep NMB improves surgical conditions and, in doing so, allows use of lower insufflation pressures during laparoscopic cholecys...

  15. Neuromuscular complications of immune checkpoint inhibitor therapy.

    Science.gov (United States)

    Kolb, Noah A; Trevino, Christopher R; Waheed, Waqar; Sobhani, Fatemeh; Landry, Kara K; Thomas, Alissa A; Hehir, Mike

    2018-01-17

    Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

  16. Deep Neuromuscular Blockade Improves Laparoscopic Surgical Conditions

    DEFF Research Database (Denmark)

    Rosenberg, Jacob; Herring, W Joseph; Blobner, Manfred

    2017-01-01

    INTRODUCTION: Sustained deep neuromuscular blockade (NMB) during laparoscopic surgery may facilitate optimal surgical conditions. This exploratory study assessed whether deep NMB improves surgical conditions and, in doing so, allows use of lower insufflation pressures during laparoscopic cholecys......INTRODUCTION: Sustained deep neuromuscular blockade (NMB) during laparoscopic surgery may facilitate optimal surgical conditions. This exploratory study assessed whether deep NMB improves surgical conditions and, in doing so, allows use of lower insufflation pressures during laparoscopic...

  17. The extremity function index (EFI), a disability severity measure for neuromuscular diseases: psychometric evaluation.

    Science.gov (United States)

    Bos, Isaäc; Wynia, Klaske; Drost, Gea; Almansa, Josué; Kuks, Jan B M

    2018-06-01

    To adapt and to combine the self-report Upper Extremity Functional Index and Lower Extremity Function Scale, for the assessment of disability severity in patients with a neuromuscular disease and to examine its psychometric properties in order to make it suitable for indicating disease severity in neuromuscular diseases. A cross-sectional postal survey study was performed among patients diagnosed with a neuromuscular disease. Patients completed both adapted extremity function scales, questionnaires for psychometric evaluation, and disease-specific questions. Confirmatory factor analysis was performed, and reliability and validity were examined. Response rate was 70% (n = 702). The Extremity Function Index model with a two-factor structure - for upper and lower extremities - showed an acceptable fit. The Extremity Function Index scales showed good internal consistency (alphas: 0.97-0.98). The known-groups validity test confirmed that Extremity Function Index scales discriminate between categories of "Extent of limitations" and "Quality of Life." Convergent and divergent validity tests confirmed that Extremity Function Index scales measure the physical impact of neuromuscular diseases. Relative validity tests showed that the Extremity Function Index scales performed well in discriminating between subgroups of patients with increasing "Extent of limitations" compared to concurrent measurement instruments. The Extremity Function Index proved to be a sound and easy to apply self-report disability severity measurement instrument in neuromuscular diseases. Implications for rehabilitation The Extremity Function Index reflects the functioning of all muscles in the upper and lower extremities involved in activities of daily living. The Extremity Function Index is an easy to administer and patient-friendly disability severity measurement instrument that has the ability to evaluate differences in disability severity between relevant neuromuscular disease subgroups. The

  18. Eccentric Exercise to Enhance Neuromuscular Control.

    Science.gov (United States)

    Lepley, Lindsey K; Lepley, Adam S; Onate, James A; Grooms, Dustin R

    Neuromuscular alterations are a major causal factor of primary and secondary injuries. Though injury prevention programs have experienced some success, rates of injuries have not declined, and after injury, individuals often return to activity with functionality below clinical recommendations. Considering alternative therapies to the conventional concentric exercise approach, such as one that can target neuromuscular injury risk and postinjury alterations, may provide for more effective injury prevention and rehabilitation protocols. Peer-reviewed sources available on the Web of Science and MEDLINE databases from 2000 through 2016 were gathered using searches associated with the keywords eccentric exercise, injury prevention, and neuromuscular control. Eccentric exercise will reduce injury risk by targeting specific neural and morphologic alterations that precipitate neuromuscular dysfunction. Clinical review. Level 4. Neuromuscular control is influenced by alterations in muscle morphology and neural activity. Eccentric exercise beneficially modifies several underlying factors of muscle morphology (fiber typing, cross-sectional area, working range, and pennation angle), and emerging evidence indicates that eccentric exercise is also beneficial to peripheral and central neural activity (alpha motorneuron recruitment/firing, sarcolemma activity, corticospinal excitability, and brain activation). There is mounting evidence that eccentric exercise is not only a therapeutic intervention influencing muscle morphology but also targets unique alterations in neuromuscular control, influencing injury risk.

  19. Evidence-Based Systematic Review: Effects of Neuromuscular Electrical Stimulation on Swallowing and Neural Activation

    Science.gov (United States)

    Clark, Heather; Lazarus, Cathy; Arvedson, Joan; Schooling, Tracy; Frymark, Tobi

    2009-01-01

    Purpose: To systematically review the literature examining the effects of neuromuscular electrical stimulation (NMES) on swallowing and neural activation. The review was conducted as part of a series examining the effects of oral motor exercises (OMEs) on speech, swallowing, and neural activation. Method: A systematic search was conducted to…

  20. [Effect of ropivacaine combined with pancuronium on neuromuscular transmission and effectiveness of neostigmine and 4-aminopyridine for blockade reversal: experimental study].

    Science.gov (United States)

    Braga, Angélica de Fátima; Carvalho, Vanessa Henriques; Braga, Franklin Sarmento; Potério, Gloria Maria Braga; Santos, Filipe Nadir Caparica

    2015-01-01

    The local anesthetic effects on neuromuscular junction and its influence on blockade produced by nondepolarizing neuromuscular blockers are still under-investigated; however, this interaction has been described in experimental studies and in humans. The aim of this study was to evaluate in vitro the interaction between ropivacaine and pancuronium, the influence on transmission and neuromuscular blockade, and the effectiveness of neostigmine and 4-aminopyridine to reverse the blockade. Rats were divided into groups (n=5) according to the study drug: ropivacaine (5μgmL(-1)); pancuronium (2μg.mL(-1)); ropivacaine+pancuronium. Neostigmine and 4-aminopyridine were used at concentrations of 2μgmL(-1) and 20μgmL(-1), respectively. The effects of ropivacaine on membrane potential and miniature end-plate potential, the amplitude of diaphragm responses before and 60minutes after the addition of ropivacaine (degree of neuromuscular blockade with pancuronium and with the association of pancuronium-ropivacaine), and the effectiveness of neostigmine and 4-aminopyridine on neuromuscular block reversal were evaluated. Ropivacaine did not alter the amplitude of muscle response (the membrane potential), but decreased the frequency and amplitude of the miniature end-plate potential. Pancuronium blockade was potentiated by ropivacaine, and partially and fully reversed by neostigmine and 4-aminopyridine, respectively. Ropivacaine increased the neuromuscular block produced by pancuronium. The complete antagonism with 4-aminopyridine suggests presynaptic action of ropivacaine. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  1. Junction-FET dosimeter

    International Nuclear Information System (INIS)

    Tomimasu, T.; Yamazaki, T.

    1976-01-01

    The performance of a new junction-FET dosimeter and its application to the beam profile measurement are presented. One of the two junction FET's making up an astable multivibrator is used as a small-size (approx.0.4x0.4 mm) high-level dose detector. The irradiated dose can be estimated by the amount of the decrease of the oscillator period of the multivibrator. The distinct advantages in its small size and superior resistive property to radiation effect enable us to measure the cross-sectional profile of the electron beam from a linac with high spatial resolution of about 0.4 mm

  2. Tunable Nitride Josephson Junctions.

    Energy Technology Data Exchange (ETDEWEB)

    Missert, Nancy A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Henry, Michael David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lewis, Rupert M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Howell, Stephen W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolfley, Steven L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Brunke, Lyle Brent [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolak, Matthaeus [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-12-01

    We have developed an ambient temperature, SiO2/Si wafer - scale process for Josephson junctions based on Nb electrodes and Ta x N barriers with tunable electronic properties. The films are fabricated by magnetron sputtering. The electronic properties of the TaxN barriers are controlled by adjusting the nitrogen flow during sputtering. This technology offers a scalable alternative to the more traditional junctions based on AlOx barriers for low - power, high - performance computing.

  3. Knee joint biomechanics and neuromuscular control during gait before and after total knee arthroplasty are sex-specific.

    Science.gov (United States)

    Astephen Wilson, Janie L; Dunbar, Michael J; Hubley-Kozey, Cheryl L

    2015-01-01

    The future of total knee arthroplasty (TKA) surgery will involve planning that incorporates more patient-specific characteristics. Despite known biological, morphological, and functional differences between men and women, there has been little investigation into knee joint biomechanical and neuromuscular differences between men and women with osteoarthritis, and none that have examined sex-specific biomechanical and neuromuscular responses to TKA surgery. The objective of this study was to examine sex-associated differences in knee kinematics, kinetics and neuromuscular patterns during gait before and after TKA. Fifty-two patients with end-stage knee OA (28 women, 24 men) underwent gait and neuromuscular analysis within the week prior to and one year after surgery. A number of sex-specific differences were identified which suggest a different manifestation of end-stage knee OA between the sexes. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Selective Neuromuscular Denervation in Taiwanese Severe SMA Mouse Can Be Reversed by Morpholino Antisense Oligonucleotides.

    Directory of Open Access Journals (Sweden)

    Te-Lin Lin

    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive motor neuron disease caused by deficiency of the survival of motor neuron (SMN protein, which leads to synaptic defects and spinal motor neuron death. Neuromuscular junction (NMJ abnormalities have been found to be involved in SMA pathogenesis in the SMNΔ7 SMA mouse model. However, whether similar NMJ pathological findings present in another commonly used mouse model, the Taiwanese SMA mouse, has not been fully investigated. To examine the NMJs of the Taiwanese severe SMA mouse model (Smn-/-; SMN2tg/0, which is characterized by severe phenotype and death before postnatal day (P 9, we investigated 25 axial and appendicular muscles from P1 to P9. We labelled the muscles with anti-neurofilament and anti-synaptophysin antibodies for nerve terminals and α-bungarotoxin for acetylcholine receptors (AChRs. We found that severe NMJ denervation (<50% fully innervated endplates selectively occurred in the flexor digitorum brevis 2 and 3 (FDB-2/3 muscles from P5, and an increased percentage of fully denervated endplates correlated with SMA progression. Furthermore, synaptophysin signals were absent at the endplate compared to control littermate mice, suggesting that vesicle transport might only be affected at the end stage. Subsequently, we treated the Taiwanese severe SMA mice with morpholino (MO antisense oligonucleotides (80 μg/g via subcutaneous injection at P0. We found that MO significantly reversed the NMJ denervation in FDB-2/3 muscles and extended the survival of Taiwanese severe SMA mice. We conclude that early NMJ denervation in the FDB-2/3 muscles of Taiwanese severe SMA mice can be reversed by MO treatment. The FDB-2/3 muscles of Taiwanese severe SMA mice provide a very sensitive platform for assessing the effectiveness of drug treatments in SMA preclinical studies.

  5. Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning

    DEFF Research Database (Denmark)

    Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel

    2017-01-01

    and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel....... A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. OBJECTIVE: The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual...... departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff's knowledge and skills, patient care...

  6. Neuromuscular Adaptations to Reduced Use

    Science.gov (United States)

    Ploutz-Snyder, Lori

    2009-01-01

    This viewgraph presentation reviews the studies done to reduce neuromuscular strength loss during unilateral lower limb suspension (ULLS). Since there are animals that undergo fairly long periods of muscular disuse without any or minimal muscular atrophy, there is an answer to that might be applicable to human in situations that require no muscular use to diminish the effects of muscular atrophy. Three sets of ULLS studies were reviewed indicated that muscle strength decreased more than the muscle mass. The study reviewed exercise countermeasures to combat the atrophy, including: ischemia maintained during Compound muscle action potential (CMAP), ischemia and low load exercise, Japanese kaatsu, and the potential for rehabilitation or situations where heavy loading is undesirable. Two forms of countermeasures to unloading have been successful, (1) high-load resistance training has maintained muscle mass and strength, and low load resistance training with blood flow restriction (LL(sub BFR)). The LL(sub BFR) has been shown to increase muscle mass and strength. There has been significant interest in Tourniquet training. An increase in Growth Hormone(GH) has been noted for LL(sub BFR) exercise. An experimental study with 16 subjects 8 of whom performed ULLS, and 8 of whom performed ULLS and LL(sub BFR) exercise three times per week during the ULLS. Charts show the results of the two groups, showing that performing LL(sub BFR) exercise during 30 days of ULLS can maintain muscle size and strength and even improve muscular endurance.

  7. Doped semiconductor nanocrystal junctions

    Energy Technology Data Exchange (ETDEWEB)

    Borowik, Ł.; Mélin, T., E-mail: thierry.melin@isen.iemn.univ-lille1.fr [Institut d’Electronique, de Microélectronique et de Nanotechnologie, CNRS-UMR8520, Avenue Poincaré, F-59652 Villeneuve d’Ascq (France); Nguyen-Tran, T.; Roca i Cabarrocas, P. [Laboratoire de Physique des Interfaces et des Couches Minces, CNRS-UMR7647, Ecole Polytechnique, F-91128 Palaiseau (France)

    2013-11-28

    Semiconductor junctions are the basis of electronic and photovoltaic devices. Here, we investigate junctions formed from highly doped (N{sub D}≈10{sup 20}−10{sup 21}cm{sup −3}) silicon nanocrystals (NCs) in the 2–50 nm size range, using Kelvin probe force microscopy experiments with single charge sensitivity. We show that the charge transfer from doped NCs towards a two-dimensional layer experimentally follows a simple phenomenological law, corresponding to formation of an interface dipole linearly increasing with the NC diameter. This feature leads to analytically predictable junction properties down to quantum size regimes: NC depletion width independent of the NC size and varying as N{sub D}{sup −1/3}, and depleted charge linearly increasing with the NC diameter and varying as N{sub D}{sup 1/3}. We thus establish a “nanocrystal counterpart” of conventional semiconductor planar junctions, here however valid in regimes of strong electrostatic and quantum confinements.

  8. Flow mechanotransduction regulates traction forces, intercellular forces, and adherens junctions

    Science.gov (United States)

    Ting, Lucas H.; Jahn, Jessica R.; Jung, Joon I.; Shuman, Benjamin R.; Feghhi, Shirin; Han, Sangyoon J.; Rodriguez, Marita L.

    2012-01-01

    Endothelial cells respond to fluid shear stress through mechanotransduction responses that affect their cytoskeleton and cell-cell contacts. Here, endothelial cells were grown as monolayers on arrays of microposts and exposed to laminar or disturbed flow to examine the relationship among traction forces, intercellular forces, and cell-cell junctions. Cells under laminar flow had traction forces that were higher than those under static conditions, whereas cells under disturbed flow had lower traction forces. The response in adhesion junction assembly matched closely with changes in traction forces since adherens junctions were larger in size for laminar flow and smaller for disturbed flow. Treating the cells with calyculin-A to increase myosin phosphorylation and traction forces caused an increase in adherens junction size, whereas Y-27362 cause a decrease in their size. Since tugging forces across cell-cell junctions can promote junctional assembly, we developed a novel approach to measure intercellular forces and found that these forces were higher for laminar flow than for static or disturbed flow. The size of adherens junctions and tight junctions matched closely with intercellular forces for these flow conditions. These results indicate that laminar flow can increase cytoskeletal tension while disturbed flow decreases cytoskeletal tension. Consequently, we found that changes in cytoskeletal tension in response to shear flow conditions can affect intercellular tension, which in turn regulates the assembly of cell-cell junctions. PMID:22447948

  9. Diagnostics of neuromuscular diseases with the aid of computerized tomography

    International Nuclear Information System (INIS)

    Visser, M. de; Verbeeten, B.J. Jr.

    1988-01-01

    In this article the diagnosis of neuromuscular diseases with the aid of computerized tomography is treated. Computerized tomography of skeletal muscles give no information which is pathognomonic for particular diseases. But the technique can be used in the following aspects: to choose a muscle for a biopsy; when it is not possible to examine the function of a muscle, a CT scan can visualize morphological deviations; in the differentiation of muscle hypertrophy and pseudo-hypertrophy. For some cases as Becker-type muscular dystrophy, facioscapulohumeral dystrophy and Kugelberg-Welander type spinal muscular atrophy computerized tomography gives characteristic images. 10 refs.; 6 figs

  10. Phase-dependent noise in Josephson junctions

    Science.gov (United States)

    Sheldon, Forrest; Peotta, Sebastiano; Di Ventra, Massimiliano

    2018-03-01

    In addition to the usual superconducting current, Josephson junctions (JJs) support a phase-dependent conductance related to the retardation effect of tunneling quasi-particles. This introduces a dissipative current with a memory-resistive (memristive) character that should also affect the current noise. By means of the microscopic theory of tunnel junctions we compute the complete current autocorrelation function of a Josephson tunnel junction and show that this memristive component gives rise to both a previously noted phase-dependent thermal noise, and an undescribed non-stationary, phase-dependent dynamic noise. As experiments are approaching ranges in which these effects may be observed, we examine the form and magnitude of these processes. Their phase dependence can be realized experimentally as a hysteresis effect and may be used to probe defects present in JJ based qubits and in other superconducting electronics applications.

  11. Anormalidades neuromuscular no desuso, senilidade e caquexia Neuromuscular abnormalities in disuse, cachexia and ageing

    Directory of Open Access Journals (Sweden)

    João Aris Kouyoumdjian

    1993-09-01

    Full Text Available É feita revisão de literatura sobre as principais alterações do sistema neuromuscular no desuso, senilidade e caquexia no ser humano e em modelos animais. A diminuição do diâmetro das fibras musculares após período de inatividade/imobilidade (desuso deve-se à perda de miofibrilas periféricas não ocorrendo formação de core-targetóides ou diminuição da atividade da miofosforilase, próprias da desnervação; mantêm-se a liberação espontânea de acetilcolina e fatores tróficos na junção mio-neural; em geral são afetadas preferencialmente fibras II, que podem assumir forma angular. Existe um processo contínuo intrínseco de envelhecimento de nervos e músculos, com desnervação e reinervação lenta e progressiva; o número de unidades motoras se reduz após 60 anos, sem ocorrência de atividade elétrica desnervatória; a quantidade de acetilcolina liberada nos neurônios terminais e a capacidade máxima de utilização de oxigênio estão diminuídas; a redução da capacidade oxidativa mitocondrial pode explicar o aumento de fibras I, mantendo-se o equilíbrio energético. Após poucas semanas de caquexia as fibras musculares podem ter o diâmetro reduzido em 30%, essa redução ocorre em ordem decrescente nos músculos dos membros inferiores, superiores e tronco; existe atrofia II preferencial com fibras angulares ocasionais, redução de RNA/síntese proteica, mantendo-se DNA normal.Cachexia, ageing and disuse and their effects on the human and animals neuromuscular system are reviewed. Disuse induces reduction of muscle fibers (mainly II diameter with peripheral myofibrils lost; there is no core-targetoid or even reduction on myophosphorilase activity, both typical of denervation; the acetylcholine spontaneous release and trophic factors on myoneural junction are maintained; muscle fibers could change to angular shape. Ageing affects nerve and muscle by a continuous and progressive process of denervation and reinner

  12. Vocational perspectives and neuromuscular disorders.

    Science.gov (United States)

    Andries, F; Wevers, C W; Wintzen, A R; Busch, H F; Höweler, C J; de Jager, A E; Padberg, G W; de Visser, M; Wokke, J H

    1997-09-01

    The present study analyses the actual occupational situation, vocational handicaps and past labour career of a group of about 1000 Dutch patients suffering from a neuromuscular disorder (NMD). On the basis of the likelihood of a substantial employment history and sufficient numbers of patients, four types of NMD were selected: dystrophia myotonica (DM), hereditary motor and sensory neuropathy, (HMSN), spinal muscular atrophy (SMA) and myasthenia gravis (MG). Results show that a labour career is in reach of most NMD patients, even for those with severe limitations. It is concluded that physical limitations seem not to be decisive in that respect. The loss of the quality of communication, the loss of mental abilities and the effect of the diseases on the facial expression, as with some DM patients, are also important for chances on the labour market. Though the labour participation of NMD patients tends to decrease after the age of 34, the availability of work adaptations makes it possible to prolong the labour career. Analysis of the actual work situation of NMD patients shows that both disorder-related limitations and work characteristics play an important role in the amount of physical work problems encountered. It is argued that physical labour has to be regarded as generally unsuitable for NMD patients. This has implications for the sort and level of education to be attained by NMD patients. Career counselling as a focus point for the choice of an educational programme may improve labour market opportunities as well as quality of employment of NMD patients. Allowing for and accepting the possible effects of the disorder in the work situation are considered to be important in respect to labour participation and work satisfaction of workers with NMD. Reducing time pressure demands and increasing the freedom to organize one's work, are measures to be given especial consideration.

  13. Protein defects in neuromuscular diseases

    Directory of Open Access Journals (Sweden)

    Vainzof M.

    2003-01-01

    Full Text Available Muscular dystrophies are a heterogeneous group of genetically determined progressive disorders of the muscle with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is highly variable, ranging from severe congenital forms with rapid progression to milder forms with later onset and a slower course. In recent years, several proteins from the sarcolemmal muscle membrane (dystrophin, sarcoglycans, dysferlin, caveolin-3, from the extracellular matrix (alpha2-laminin, collagen VI, from the sarcomere (telethonin, myotilin, titin, nebulin, from the muscle cytosol (calpain 3, TRIM32, from the nucleus (emerin, lamin A/C, survival motor neuron protein, and from the glycosylation pathway (fukutin, fukutin-related protein have been identified. Mutations in their respective genes are responsible for different forms of neuromuscular diseases. Protein analysis using Western blotting or immunohistochemistry with specific antibodies is of the utmost importance for the differential diagnosis and elucidation of the physiopathology of each genetic disorder involved. Recent molecular studies have shown clinical inter- and intra-familial variability in several genetic disorders highlighting the importance of other factors in determining phenotypic expression and the role of possible modifying genes and protein interactions. Developmental studies can help elucidate the mechanism of normal muscle formation and thus muscle regeneration. In the last fifteen years, our research has focused on muscle protein expression, localization and possible interactions in patients affected by different forms of muscular dystrophies. The main objective of this review is to summarize the most recent findings in the field and our own contribution.

  14. 21 CFR 882.5810 - External functional neuromuscular stimulator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External functional neuromuscular stimulator. 882.5810 Section 882.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External functional neuromuscular stimulator. (a) Identification. An external functional neuromuscular...

  15. Neuromuscular transmission and muscle fatigue changes by nanostructured oxygen.

    Science.gov (United States)

    Ivannikov, Maxim V; Sugimori, Mutsuyuki; Llinás, Rodolfo R

    2017-04-01

    Oxygen (O 2 ) nanobubbles offer a new method for tissue oxygenation. The effects of O 2 nanobubbles on transmission at neuromuscular junctions (NMJs) and muscle function were explored in murine diaphragm. Electrophysiological parameters, NMJ ultrastructure, muscle force, and muscle fatigue were studied during superfusion with solutions with different oxygen levels or oxygen nanobubbles. High frequency nerve stimulation of muscles superfused with O 2 nanobubble solution slowed neurotransmission decline over those with either control or hyperoxic solution. O 2 nanobubble solution increased the amplitude of evoked end plate potentials and quantal content but did not affect spontaneous activity. Electron microscopy of stimulated O 2 nanobubble treated NMJs showed accumulation of large synaptic vesicles and endosome-like structures. O 2 nanobubble solution had no effects on isometric muscle force, but it significantly decreased fatigability and maximum force recovery time in nerve stimulated muscles. O 2 nanobubbles increase neurotransmission and reduce the probability of neurotransmission failure in muscle fatigue. Muscle Nerve 55: 555-563, 2017. © 2016 Wiley Periodicals, Inc.

  16. Research highlights of partial neuromuscular disorders

    Directory of Open Access Journals (Sweden)

    Cheng ZHANG

    2014-05-01

    Full Text Available In order to understand the latest progression on neuromuscular disorders for clinicians, this review screened and systemized the papers on neuromuscular disorders which were collected by PubMed from January 2013 to February 2014. This review also introduced the clinical diagnosis and treatment hightlights on glycogen storage disease type Ⅱ (GSD Ⅱ, Duchenne muscular dystrophy (DMD, amyotrophic lateral sclerosis (ALS and spinal muscular atrophy (SMA. The important references will be useful for clinicians. doi: 10.3969/j.issn.1672-6731.2014.05.004

  17. Neuromuscular Exercise Post Partial Medial Meniscectomy

    DEFF Research Database (Denmark)

    Hall, Michelle; Hinman, Rana S; Wrigley, Tim V

    2015-01-01

    : An assessor-blinded, randomised controlled trial including people aged 30-50 years with no to mild pain following medial arthroscopic partial meniscectomy was conducted. Participants were randomly allocated to either a 12-week neuromuscular exercise program that targeted neutral lower limb alignment......PURPOSE: To evaluate the effects of a 12-week, home-based, physiotherapist-guided neuromuscular exercise program on the knee adduction moment (an indicator of mediolateral knee load distribution) in people with a medial arthroscopic partial meniscectomy within the past 3-12 months. METHODS...

  18. Performance and neuromuscular adaptations following differing ratios of concurrent strength and endurance training

    OpenAIRE

    Jones, Thomas W.; Howatson, Glyn; Russell, Mark; French, Duncan N.

    2013-01-01

    The interference effect attenuates strength and hypertrophic responses when strength and endurance training are conducted concurrently; however, the influence of training frequency on these responses remain unclear when varying ratios of concurrent strength and endurance training are performed. Therefore, the purpose of the study was to examine the strength, limb girth, and neuromuscular adaptations to varying ratios of concurrent strength and endurance training. Tw...

  19. Mirror Visual Feedback Induces Lower Neuromuscular Activity in Children with Spastic Hemiparetic Cerebral Palsy

    Science.gov (United States)

    Feltham, Max G.; Ledebt, Annick; Deconinck, Frederik J. A.; Savelsbergh, Geert J. P.

    2010-01-01

    The study examined the effects of mirror feedback information on neuromuscular activation during bimanual coordination in eight children with spastic hemiparetic cerebral palsy (SHCP) and a matched control group. The "mirror box" creates a visual illusion, which gives rise to a visual perception of a zero lag, symmetric movement between the two…

  20. Neuromuscular adaptations to 4 weeks of intensive drop jump training in well-trained athletes

    DEFF Research Database (Denmark)

    Alkjær, Tine; Meyland, Jacob; Raffalt, Peter C

    2013-01-01

    This study examined the effects of 4 weeks of intensive drop jump training in well-trained athletes on jumping performance and underlying changes in biomechanics and neuromuscular adaptations. Nine well-trained athletes at high national competition level within sprinting and jumping disciplines...

  1. Fractional order junctions

    Science.gov (United States)

    Machado, J. Tenreiro

    2015-01-01

    Gottfried Leibniz generalized the derivation and integration, extending the operators from integer up to real, or even complex, orders. It is presently recognized that the resulting models capture long term memory effects difficult to describe by classical tools. Leon Chua generalized the set of lumped electrical elements that provide the building blocks in mathematical models. His proposal of the memristor and of higher order elements broadened the scope of variables and relationships embedded in the development of models. This paper follows the two directions and proposes a new logical step, by generalizing the concept of junction. Classical junctions interconnect system elements using simple algebraic restrictions. Nevertheless, this simplistic approach may be misleading in the presence of unexpected dynamical phenomena and requires including additional "parasitic" elements. The novel γ -junction includes, as special cases, the standard series and parallel connections and allows a new degree of freedom when building models. The proposal motivates the search for experimental and real world manifestations of the abstract conjectures.

  2. Stabilization of acetylcholine receptors at the neuromuscular synapse: the role of the nerve.

    Science.gov (United States)

    Ramsay, D A; Drachman, D B; Drachman, R J; Stanley, E F

    1992-05-29

    The majority of acetylcholine receptors (AChRs) at innervated neuromuscular junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent muscles. In addition to the stable AChRs, approximately 18% of AChRs at these innervated junctions are rapidly turned over (RTOs), with half lives of less than 24 h. We have postulated that RTOs may be precursors of stable AChRs, and that the motor nerve may influence their stabilization. This hypothesis was tested by: (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii) denervating one SM muscle in each mouse, and (iii) following the fate of the labeled AChRs through a 5-day period when RTOs were either stabilized or degraded. The hypothesis predicts that denervation should preclude stabilization of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The results showed a highly significant (P less than 0.002) deficit of stable AChRs in denervated as compared with innervated muscles. Control experiments excluded the possibility that this deficit could be attributed to independent accelerated degradation of either RTOs or pre-existing stable AChRs. The observed deficit was quantitatively consistent with the deficit predicted by a mathematical model based on interruption of stabilization following denervation. We conclude that: (i) the observed deficit after denervation of NMJs is due to failure of stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are precursors of stable AChRs; (iii) stabilization occurs after the insertion of AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs. The concept of receptor stabilization has important implications for understanding the biology of the neuromuscular junction and post-synaptic plasticity.

  3. Neuromuscular hamartoma arising in the brachial plexus

    International Nuclear Information System (INIS)

    Lai, P.H.; Chen, C.; Yeh, L.R.; Pan, H.B.; Ho, J.T.; Hsu, S.S.; Lin, S.L.

    2004-01-01

    We report a case brachial plexus neuromuscular hamartoma (choristoma) in a 28-year-old man who complained of numbness of the left hand and forearm for several years. MRI revealed a circumscribed, rounded mass in the left brachial plexus. The patient is well 2 years after surgery, with no neurological deficit. (orig.)

  4. Neuromuscular contributions to age-related weakness

    Science.gov (United States)

    Age-related physiological change of neuromuscular function is not a linear process and is likely influenced by various biological and behavioral factors (e.g., genetics, nutrition, physical activity level, comorbidities, etc.). These factors contribute to heterogeneity among older adults, which chal...

  5. Dynamic Flexibility and Proprioceptive Neuromuscular Facilitation.

    Science.gov (United States)

    Hardy, Lew; Jones, David

    1986-01-01

    Two experiments are described which investigated whether results obtained in studies of static flexibility tranfer to dynamic flexibility. In both experiments, subjects were assigned to a group receiving proprioceptive neuromuscular facilitation training, ballistic stretching technique training or a control group. Results are presented and…

  6. Sugammadex Improves Neuromuscular Function in Patients ...

    African Journals Online (AJOL)

    2018-02-23

    Feb 23, 2018 ... aminoglycosides), history of allergy to neuromuscular blocking agents, opioids or other drugs, and alcohol and drug dependence. Patients were divided into two ... titration microcalorimetry investigated the likelihood of the formation of complexes between sugammadex and other steroidal and nonsteroidal ...

  7. MRC Centre Neuromuscular Biobank (Newcastle and London): Supporting and facilitating rare and neuromuscular disease research worldwide.

    Science.gov (United States)

    Reza, Mojgan; Cox, Daniel; Phillips, Lauren; Johnson, Diana; Manoharan, Vaishnavi; Grieves, Michael; Davis, Becky; Roos, Andreas; Morgan, Jennifer; Hanna, Michael G; Muntoni, Francesco; Lochmüller, Hanns

    2017-11-01

    Neuromuscular diseases are both genetic and acquired conditions resulting in progressive muscle weakness and wasting which lead to disability and reduced survival. The availability of high-quality human biomaterial is crucial to support biomedical research with potential applications at all stages of development, from molecular pathophysiology to drug discovery, clinical trials and evaluation of biomarkers. Although significant progress has been made over the last few years in the diagnosis of these rare conditions, the genetic defect and underlying pathological abnormality remain unknown in approximately 1/3 of cases. Moreover, to date no definitive cure is available for most neuromuscular disorders, nor are there sufficiently reliable and specific biomarkers to monitor disease progression and response to treatment. This is in part due to the rarity and genetic heterogeneity of neuromuscular diseases and the lack of access to patient samples. The availability of the national MRC Centre Biobank for Neuromuscular Diseases in Newcastle and London has addressed this bottleneck and supported neuromuscular research. Nine years after the establishment of the MRC Centre Biobank, many high profile research publications have highlighted the positive impact of neuromuscular biobanking for translational research and proven this facility to be a unique repository source for diagnostics, basic science research, industry, drug development, and therapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. O uso de bloqueadores neuromusculares no Brasil El uso de bloqueadores neuromusculares en Brasil Neuromuscular blockers in Brazil

    Directory of Open Access Journals (Sweden)

    Maria Cristina Simões de Almeida

    2004-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Dados estatísticos referentes ao uso de bloqueadores neuromusculares no Brasil são desconhecidos. Este trabalho se propõe a análise estatística desse tópico. MÉTODO: Foram compiladas 831 respostas de um questionário preenchido em parte por anestesiologistas presentes ao 48º Congresso Brasileiro de Anestesiologia em Recife, 2001 e em parte via Internet, por anestesiologistas cujos endereços eletrônicos constam na página da Sociedade Brasileira de Anestesiologia (www.sba.com.br. Foram analisados os seguintes dados: tempo de contato com a especialidade, região onde atuam os anestesiologistas, uso de bloqueadores neuromusculares (BNM em ordem de preferência, indicações do uso de succinilcolina, uso do monitor da transmissão neuromuscular, critérios para se considerar o paciente descurarizado, uso de neostigmina, forma de administração dos BNM e descrição de complicações observadas. RESULTADOS: A maioria dos anestesiologistas em questão exerce a profissão há mais de 11 anos e o maior número de respostas foi proveniente da região sudeste do Brasil. O BNM mais empregado é o atracúrio, seguido de pancurônio e succinilcolina. A succinilcolina é mais empregada na indução rápida e em crianças (80% e 25% respectivamente. Monitores da transmissão neuromuscular, 53% dos anestesiologistas nunca usam, e como critério de recuperação, 92% consideram o paciente descurarizado mediante sinais clínicos. Em 45% das vezes os profissionais empregam a neostigmina de forma rotineira, e 94% administra os BNM sob forma de bolus. Cerca de 30% registra ter havido complicação decorrente do uso de BNM. As complicações mais apontadas foram o bloqueio prolongado, o broncoespasmo grave e a curarização residual. CONCLUSÕES: O atracúrio é o bloqueador neuromuscular mais empregado no Brasil, há percentual alto de uso da succinilcolina em situações não emergenciais, o uso de monitores da transmiss

  9. Cementoenamel junction: An insight

    Directory of Open Access Journals (Sweden)

    Kharidi Laxman Vandana

    2014-01-01

    Full Text Available The location and nature of cemento-enamel junction (CEJ are more than descriptive terms used simply to describe some aspects of tooth morphology; however, CEJ gains a lot of clinical significance due to various measurements dependent on it. It may be necessary to determine the location and pathological changes occurring at CEJ to make a diagnosis and treat diseases pertaining to epithelial attachment and gingival margin. However, the information related to CEJ is not discussed commonly. Hence, the present review paper provides an insight on CEJ in both primary and permanent dentition.

  10. The human myotendinous junction

    DEFF Research Database (Denmark)

    Knudsen, A B; Larsen, M; Mackey, Abigail

    2015-01-01

    The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never...... been described in three dimensions (3D). The aim of this study was to describe the ultrastructure of the human MTJ and render 3D reconstructions. Fourteen subjects (age 25 ± 3 years) with isolated injury of the anterior cruciate ligament (ACL), scheduled for reconstruction with a semitendinosus...

  11. The neuromuscular approach towards interdisciplinary cooperation in medicine.

    Science.gov (United States)

    Yurchenko, Maksim; Hubálková, Hana; Klepáček, Ivo; Machoň, Vladimír; Mazánek, Jiří

    2014-02-01

    The contemporary approach of dentistry towards interdisciplinary cooperation is based on the neuromuscular concept. In recent years many authors have pointed out a correlation between orthopaedic and dental findings. Furthermore, there is an intimate biomechanical interrelationship of occlusion with cerebral fluid circulation, left and right equilibrium, gaze stabilisation and headache. The influence of a dental occlusion and temporomandibular joint (TMJ) status on general health has been widely analysed in the current scientific literature. The aim of this analytic study was to display the deep relationship between dentistry and other fields of medicine, and to show the necessity of wide cooperation between dentists and physicians. This study was based on a review of 41 sources, including specialised articles and books. The significance of different anatomical and physiological preconditions (occlusion, muscles and TMJ status) was considered and evaluated separately. However, as a result of modern concepts of general body health, extending cooperation between different fields of medicine is essential. The practical application of the principles of neuromuscular dentistry enables one to increase greatly the treatment efficiency of aches in muscles, headaches, postural dysfunctions as well as of many other diseases. However, the dentist's contribution to the development of an interdisciplinary approach is underestimated. Many theoretical aspects of the interdisciplinary relationship have not been sufficiently examined, hence the practical consequences remain unclear. Further research in the field is urgently needed. © 2013 FDI World Dental Federation.

  12. Neuromuscular compensation mechanisms in vocal fold paralysis and paresis.

    Science.gov (United States)

    Dewan, Karuna; Vahabzadeh-Hagh, Andrew; Soofer, Donna; Chhetri, Dinesh K

    2017-07-01

    Vocal fold paresis and paralysis are common conditions. Treatment options include augmentation laryngoplasty and voice therapy. The optimal management for this condition is unclear. The objective of this study was to assess possible neuromuscular compensation mechanisms that could potentially be used in the treatment of vocal fold paresis and paralysis. In vivo canine model. In an in vivo canine model, we examined three conditions: 1) unilateral right recurrent laryngeal nerve (RLN) paresis and paralysis, 2) unilateral superior laryngeal nerve (SLN) paralysis, and 3) unilateral vagal nerve paresis and paralysis. Phonatory acoustics and aerodynamics were measured in each of these conditions. Effective compensation was defined as improved acoustic and aerodynamic profile. The most effective compensation for all conditions was increasing RLN activation and decreasing glottal gap. Increasing RLN activation increased the percentage of possible phonatory conditions that achieved phonation onset. SLN activation generally led to decreased number of total phonation onset conditions within each category. Differential effects of SLN (cricothyroid [CT] muscle) activation were seen. Ipsilateral SLN activation could compensate for RLN paralysis; normal CT compensated well in unilateral SLN paralysis; and in vagal paresis/paralysis, contralateral SLN and RLN displayed antagonistic relationships. Methods to improve glottal closure should be the primary treatment for large glottal gaps. Neuromuscular compensation is possible for paresis. This study provides insights into possible compensatory mechanisms in vocal fold paresis and paralysis. NA Laryngoscope, 127:1633-1638, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Guidance of matter waves through Y-junctions

    Energy Technology Data Exchange (ETDEWEB)

    Kevrekidis, P.G.; Frantzeskakis, D.J.; Theocharis, G.; Kevrekidis, I.G

    2003-10-27

    We discuss the concept of Y-junctions for matter waves and investigate their guidance properties, focusing on the case of Bose-Einstein condensates with attractive interatomic interactions. We examine both discrete and continuous models, respectively relevant to Y-junctions formed in optical lattices (OL) and magnetic traps (MT). We find a strong dependence of the transmitted fraction of the condensate (in the OL case) on the angle with a maximum (per arm) of approximately 30%. In the MT case, we show that the presence of the junction's wedge can prevent collapse of the original condensate.

  14. Mixing in T-junctions

    NARCIS (Netherlands)

    Kok, Jacobus B.W.; van der Wal, S.

    1996-01-01

    The transport processes that are involved in the mixing of two gases in a T-junction mixer are investigated. The turbulent flow field is calculated for the T-junction with the k- turbulence model by FLOW3D. In the mathematical model the transport of species is described with a mixture fraction

  15. Fluid Flow at Branching Junctions

    OpenAIRE

    Sochi, Taha

    2013-01-01

    The flow of fluids at branching junctions plays important kinematic and dynamic roles in most biological and industrial flow systems. The present paper highlights some key issues related to the flow of fluids at these junctions with special emphasis on the biological flow networks particularly blood transportation vasculature.

  16. Terahertz pulse driven Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Camerlingo, Carlo, E-mail: c.camerlingo@cib.na.cnr.it [CNR - Consiglio Nazionale delle Ricerche, Istituto di Cibernetica ' E. Caianiello' , Via Campi Flegrei 34, I-80078 Pozzuoli (Italy)

    2011-09-15

    Theoretical model of the ac Josephson effect in pulsed current driven junctions. Evaluation of the voltage response of a THz pulsed radiation driven Josephson junction. The pulsed current bias induces steps in the junction I/V characteristics for voltages depending on the pulse rate. Working principles of a fast response detector for THz pulsed radiation. The voltage response of a Josephson junction to a pulsed terahertz current is evaluated in the limit of a negligible junction capacitance (overdamped limit). The time-dependent superconductor phase difference across the junction is calculated in the framework of the standard resistive shunted junction model by using a perturbative method. The pulsed current bias affects the time average value of the voltage across the junction and current steps are induced in the current-voltage characteristics for voltage values depending on the pulse repetition rate. The current step height is proportional to the square of the pulse time width ({tau}) to the period (T) ratio. A fast response detector for pulsed Terahertz radiation is proposed, with an expected responsivity of the order of 0.1 V/W and an equivalent noise power of about 3 x 10{sup -10} W/Hz{sup 1/2}.

  17. Electron transport in molecular junctions

    DEFF Research Database (Denmark)

    Jin, Chengjun

    This thesis addresses the electron transport in molecular junctions, focusing on the energy level alignment and correlation effects. Various levels of theory have been applied to study the structural and electronic effects in different molecular junctions, starting from the single particle density...

  18. Topological Properties of Superconducting Junctions

    NARCIS (Netherlands)

    Pikulin, D.I.; Nazarov, Y.V.

    Motivated by recent developments in the field of one-dimensional topological superconductors, we investigate the topological properties of s-matrix of generic superconducting junctions where dimension should not play any role. We argue that for a finite junction the s-matrix is always topologically

  19. Neuromuscular adaptations to training, injury and passive interventions: implications for running economy.

    Science.gov (United States)

    Bonacci, Jason; Chapman, Andrew; Blanch, Peter; Vicenzino, Bill

    2009-01-01

    has also been observed. Muscle activity during running after cycling has yet to be fully investigated, and to date, the effect of alterations in muscle coordination on running economy is largely unknown. Stretching, which is another mode of training, may induce acute neuromuscular effects but does not appear to alter running economy. There are also factors other than training structure that may influence running economy and neuromuscular adaptations. For example, passive interventions such as shoes and in-shoe orthoses, as well as the presence of musculoskeletal injury, may be considered important modulators of neuromuscular control and run performance. Alterations in muscle activity and running economy have been reported with different shoes and in-shoe orthoses; however, these changes appear to be subject-specific and non-systematic. Musculoskeletal injury has been associated with modifications in lower limb neuromuscular control, which may persist well after an athlete has returned to activity. The influence of changes in neuromuscular control as a result of injury on running economy has yet to be examined thoroughly, and should be considered in future experimental design and training analysis.

  20. Ion bipolar junction transistors.

    Science.gov (United States)

    Tybrandt, Klas; Larsson, Karin C; Richter-Dahlfors, Agneta; Berggren, Magnus

    2010-06-01

    Dynamic control of chemical microenvironments is essential for continued development in numerous fields of life sciences. Such control could be achieved with active chemical circuits for delivery of ions and biomolecules. As the basis for such circuitry, we report a solid-state ion bipolar junction transistor (IBJT) based on conducting polymers and thin films of anion- and cation-selective membranes. The IBJT is the ionic analogue to the conventional semiconductor BJT and is manufactured using standard microfabrication techniques. Transistor characteristics along with a model describing the principle of operation, in which an anionic base current amplifies a cationic collector current, are presented. By employing the IBJT as a bioelectronic circuit element for delivery of the neurotransmitter acetylcholine, its efficacy in modulating neuronal cell signaling is demonstrated.

  1. RNAi-Mediated Reverse Genetic Screen IdentifiedDrosophilaChaperones Regulating Eye and Neuromuscular Junction Morphology.

    Science.gov (United States)

    Raut, Sandeep; Mallik, Bhagaban; Parichha, Arpan; Amrutha, Valsakumar; Sahi, Chandan; Kumar, Vimlesh

    2017-07-05

    Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes. Ubiquitous actin5C -Gal4-mediated RNAi knockdown revealed that ∼50% of the chaperones are essential in Drosophila Knocking down these genes in eyes revealed that ∼30% of the essential chaperones are crucial for eye development. Using neuron-specific knockdown, immunocytochemistry, and robust behavioral assays, we identified a new set of chaperones that play critical roles in the regulation of Drosophila NMJ structural organization. Together, our data present the first classification and comprehensive analysis of Drosophila chaperones. Our screen identified a new set of chaperones that regulate eye and NMJ morphogenesis. The outcome of the screen reported here provides a useful resource for further elucidating the role of individual chaperones in Drosophila eye morphogenesis and synaptic development. Copyright © 2017 Raut et al.

  2. RNAi-Mediated Reverse Genetic Screen Identified Drosophila Chaperones Regulating Eye and Neuromuscular Junction Morphology

    Directory of Open Access Journals (Sweden)

    Sandeep Raut

    2017-07-01

    Full Text Available Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes. Ubiquitous actin5C-Gal4-mediated RNAi knockdown revealed that ∼50% of the chaperones are essential in Drosophila. Knocking down these genes in eyes revealed that ∼30% of the essential chaperones are crucial for eye development. Using neuron-specific knockdown, immunocytochemistry, and robust behavioral assays, we identified a new set of chaperones that play critical roles in the regulation of Drosophila NMJ structural organization. Together, our data present the first classification and comprehensive analysis of Drosophila chaperones. Our screen identified a new set of chaperones that regulate eye and NMJ morphogenesis. The outcome of the screen reported here provides a useful resource for further elucidating the role of individual chaperones in Drosophila eye morphogenesis and synaptic development.

  3. Calcium dependence of uni-quantal release latencies and quantal content at mouse neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Samigullin, D.; Bukharaeva, E. A.; Vyskočil, František; Nikolsky, E. E.

    2005-01-01

    Roč. 54, č. 1 (2005), s. 129-132 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA5011411; GA ČR(CZ) GA305/02/1333 Grant - others:RFBR(RU) 05-04-49723; Russian Science Support Foundation(RU) 1063.2003.4; GA-(RU) MK-2153.2003.04 Institutional research plan: CEZ:AV0Z50110509 Keywords : quantal release * synaptic latency * calcium Subject RIV: ED - Physiology Impact factor: 1.806, year: 2005

  4. Cholinergic regulation of the evoked quantal release at frog neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Nikolsky, E. E.; Vyskočil, František; Bukharaeva, E. A.; Samigullin, D.; Magazanik, L. G.

    2004-01-01

    Roč. 560, č. 1 (2004), s. 77-88 ISSN 0022-3751 R&D Projects: GA AV ČR IAA5011411; GA ČR GA305/02/1333 Institutional research plan: CEZ:AV0Z5011922 Keywords : acetylcholine * quantal * synapse Subject RIV: ED - Physiology Impact factor: 4.346, year: 2004

  5. Temperature effect on carbachol-induced depression of spontaneous quantal transmitter release in frog neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Strunsky, E. G.; Borisover, M. D.; Nikolsky, E. E.; Vyskočil, František

    2001-01-01

    Roč. 26, 8-9 (2001), s. 891-897 ISSN 0364-3190 R&D Projects: GA AV ČR IAA7011902; GA MŠk OK 267 Grant - others:RFBR(RU) 99-04-48286; EU(XX) Nesting Institutional research plan: CEZ:AV0Z5011922 Keywords : carbachol * temperature * acetylcholine release Subject RIV: ED - Physiology Impact factor: 1.638, year: 2001

  6. The effect of palytoxin on neuromuscular junctions in the anococcygeus muscle of the rat.

    Science.gov (United States)

    Amir, I; Harris, J B; Zar, M A

    1997-06-01

    Palytoxin, a highly toxic natural product isolated from zoanthids of the genus Palythoa, is accumulated by a wide range of fishes and marine invertebrates used as food in the Indo-Pacific. It is responsible for many incidents of human morbidity and mortality. The toxin is a potent smooth muscle spasmogen. The cause of the contraction of smooth muscle is unclear, but recent work strongly suggests that it is primarily initiated by the release of neurotransmitters from the motor innervation of the smooth muscle. We show here that palytoxin caused the swelling of the muscle cells and some internal organelles of the anococcygeus muscle of the rat, but no substantial structural damage to the tissue. Axons and Schwann cells were also swollen but the most dramatic feature was the depletion of synaptic vesicles from putative release sites in the axons. Some axons were physically damaged following exposure to the toxin, but this was relatively uncommon (< 10% of all axons studied). In the majority of axons there was no damage to nerve terminal membranes, but there was damage to mitochondria. The depletion of vesicles involved all types-clear, dense-cored, large and small. Our observations and pharmacological data gathered elsewhere, provide a neuropathological basis for the spasmogenic activity of palytoxin.

  7. Pre- and postsynaptic effects of the calcium channel blocker verapamil at neuromuscular junctions

    Czech Academy of Sciences Publication Activity Database

    Sharifullina, R.; Afzalov, R. A.; Talantova, M. V.; Vyskočil, František; Giniatullin, R. A.

    2002-01-01

    Roč. 32, č. 3 (2002), s. 309-315 ISSN 0097-0549 R&D Projects: GA AV ČR IAA7011902; GA ČR GA202/02/1213; GA ČR GA305/02/1333 Institutional research plan: CEZ:AV0Z5011922 Keywords : verapamil * cholinoreceptors * calcium channels Subject RIV: ED - Physiology

  8. ATP but not adenosine inhibits nonquantal acetylcholine release at the mouse neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Galkin, A. V.; Giniatullin, R. A.; Mukhtarov, M. R.; Švandová, Iva; Grishin, S. N.; Vyskočil, František

    2001-01-01

    Roč. 13, č. 11 (2001), s. 2047-2053 ISSN 0953-816X R&D Projects: GA AV ČR IAA7011902; GA MŠk OK 267 Grant - others:INTAS(BE) 99-1147; RFBI(XX) 99-48298 Institutional research plan: CEZ:AV0Z5011922 Keywords : motor nerve ending * purinergic receptors * staurosporin Subject RIV: ED - Physiology Impact factor: 3.919, year: 2001

  9. Glutamate regulation of non-quantal release of acetylcholine in the rat neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Malomouzh, A. I.; Mukhtarov, M. R.; Nikolsky, E. E.; Vyskočil, František; Lieberman, E. M.; Urazaev, A. K.

    2003-01-01

    Roč. 85, č. 1 (2003), s. 206-213 ISSN 0022-3042 R&D Projects: GA AV ČR IAA7011902; GA ČR GA305/02/1333; GA ČR GA202/02/1213 Institutional research plan: CEZ:AV0Z5011922; CEZ:MSM 113100003 Keywords : muscle endplate * nitric oxide * N-methyl-D-aspartate receptor Subject RIV: CG - Electrochemistry Impact factor: 4.825, year: 2003

  10. Possible mechanisms of action of Gymnodinium breve toxin at the mammalian neuromuscular junction.

    Science.gov (United States)

    Shinnick-Gallagher, P.

    1980-01-01

    1 The mechanism of action of a crude fraction of Gymnodinium breve toxin (GBTX) was investigated by intracellular recording techniques in the rat phrenic nerve diaphragm preparation. 2 GBTX (2 micrograms/ml) decreased the input resistance of the muscle membrane concomitantly with a depolarization of the resting membrane potential. 3 A low sodium solution reversed or prevented a GBTX-induced membrane depolarization. 4 Tetrodotoxin (TTX) antagonized a GBTX-induced increase in miniature endplate potential (m.e.p.p.) frequency and repolarized a GBTX-depolarized membrane. Pretreatment with TTX prevented GBTX effects. 5 GBTX reversibly reduced depolarizations produced by bath applied acetylcholine (ACh). The membrane depolarization was not responsible for the depression of ACh responses. 6 These findings suggest that GBTX increases m.e.p.p. frequency and depolarizes the resting membrane potential by increasing sodium permeability. The reduction of ACh-induced depolarizations suggests that GBTX may be acting at some site on the ACh receptor. PMID:7190452

  11. Interaction of glutamate- and adenosine-induced decrease of acetylcholine quantal release at frog neuromuscular junction

    Czech Academy of Sciences Publication Activity Database

    Adámek, S.; Shakirzyanova, V.; Malomouzh, A. I.; Naumenko, N. V.; Vyskočil, František

    2010-01-01

    Roč. 59, č. 5 (2010), s. 803-810 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA500110905; GA ČR GA202/09/0806 Institutional research plan: CEZ:AV0Z50110509 Keywords : Endplate potentials * Guanylyl cyclase Subject RIV: ED - Physiology Impact factor: 1.646, year: 2010

  12. [Mediator liberation at the neuromuscular junctions of rhythmically stimulated frog sartorius muscles].

    Science.gov (United States)

    Zefirov, A L; Zemskova, S N

    1979-08-01

    Synapses of large fibers seem to have a more obvious initial increase followed by a greater decrease in quantum content (m) of EPPs than the small fibers. The total amount of neurotransmitter released during EPPs reproduction was much greater in the large fibres. The calculation of binomial parameters of transmitter release showed that n parameter repeated the dynamics of m, while the P parameter gradually increased. The initial uptake of P and increase of n was more obvious in verve endings of the large muscle fibres. The findings suggest an unequal length of synaptic contact.

  13. CLINICAL APPROACH TO THE DIAGNOSTIC EVALUATION OF HERDITARY AND ACQUIRED NEUROMUSCULAR DISEASES

    Science.gov (United States)

    McDonald, Craig M.

    2012-01-01

    SYNOPSIS In the context of a neuromuscular disease diagnostic evaluation, the clinician still must be able to obtain a relevant patient and family history and perform focused general, musculoskeletal, neurologic and functional physical examinations to direct further diagnostic evaluations. Laboratory studies for hereditary neuromuscular diseases include relevant molecular genetic studies. The EMG and nerve conduction studies remain an extension of the physical examination and help to guide further diagnostic studies such as molecular genetic studies, and muscle and nerve biopsies. All diagnostic information needs to be interpreted not in isolation, but within the context of relevant historical information, family history, physical examination findings, and laboratory data, electrophysiologic findings, pathologic findings, and molecular genetic findings if obtained. PMID:22938875

  14. Influence of intense neuromuscular blockade on surgical conditions during laparotomy

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Donatsky, Anders Meller; Jensen, Bente Rona

    2015-01-01

    neuromuscular block on surgical conditions with a subjective rating scale, force needed to close the fascia, incidences of abdominal contractions while suctioning the lungs, width of the wound diastase and operating time as outcome parameters. RESULTS: In all six pigs no abdominal contractions occurred while...... neuromuscular block suctioning the lungs elicited brief periods of abdominal EMG activity. No difference was found in the force needed to close the fascia when comparing no neuromuscular block with intense neuromuscular block. Furthermore, no significant differences were found in the width of the diastase...... not influence the force needed to close the fascia....

  15. Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning

    DEFF Research Database (Denmark)

    Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel

    2017-01-01

    BACKGROUND: Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an......-learning module can increase anesthetists' use of neuromuscular monitoring. TRIAL REGISTRATION: Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x)....

  16. Urgencias en patología neuromuscular Emergencies in neuromuscular pathology

    OpenAIRE

    T. Ayuso; I. Jericó

    2008-01-01

    La debilidad muscular aguda (DMA) es el síntoma predominante de las urgencias neuromusculares, especialmente si afecta a la musculatura respiratoria u orofaríngea. La DMA es un síndrome plurietiológico y con distintos niveles lesionales en la unidad motora. Dentro del amplio grupo de enfermedades neuromusculares, las que con mayor frecuencia provocan DMA e insuficiencia respiratoria son el síndrome de Guillain-Barré (SGB) y la miastenia gravis (MG). El SGB constituye la causa más frecuente de...

  17. Autoantibodies to neurotransmitter receptors and ion channels: from neuromuscular to neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Pilar eMartinez-Martinez

    2013-09-01

    Full Text Available Changes of voltage-gated ion channels and ligand-gated receptor channels caused by mutation or autoimmune attack are the cause of so-called channelopathies in the central and peripheral nervous system. We present the pathophysiology of channelopathies of the neuromuscular junction in terms of loss-of-function and gain-of-function principles. Autoantibodies generally have reduced access to the CNS, but in some cases this is enough to cause disease. A review is provided of recent findings implicating autoantibodies against ligand–activated receptor channels and potassium channels in psychiatric and neurological disorders, including schizophrenia and limbic encephalitis. The emergence of channelopathy-related neuropsychiatric disorders has implications for research and practice.

  18. The prevalence and severity of disease-related disabilities and their impact on quality of life in neuromuscular diseases.

    Science.gov (United States)

    Bos, Isaac; Wynia, Klaske; Almansa, Josué; Drost, Gea; Kremer, Berry; Kuks, Jan

    2018-03-08

    People with neuromuscular disease experience lower quality of life levels than people from the general population. We examined the prevalence and severity of a broad range of neuromuscular disease-related disabilities and their impact on health-related quality of life. A cross-sectional postal survey study was conducted among patients diagnosed with neuromuscular disease. Patients completed the Neuromuscular Disease Impact Profile, a disease-related disability impact questionnaire, and two generic health-related quality of life questionnaires: the medical outcome study Short Form Questionnaire and the World Health Organization Quality of Life-bref. The impact of disabilities on quality of life was estimated using multiple regression analyses. Six hundred sixty two patients (68% response rate) completed the questionnaires. There were no differences in quality of life between diagnosis-based subgroups. 'Impairments in muscle functions' had the highest prevalence and severity scores in the total sample and diagnosis-based subgroups. Neuromuscular disease-related disabilities showed strong and independent associations with all aspects of health-related quality of life. 'Impairments in mental functions and pain' was the most important predictor of health-related quality of life followed by 'restrictions in participation in life situations'. Although 'impairment in muscle functions' is the most prevalent and severe disability, the 'impairments in mental functions and pain' have a strong association with health-related quality of life in patients with a neuromuscular disease. Implications for rehabilitation Disease-related disabilities have a strong and independent associations with all aspects of health-related quality of life. Although health-related domains of quality of life are affected by the neuromuscular disease, the general quality of life is quite good. The most prevalent and severe disability in total group and diagnosis-based subgroups is 'impairments in

  19. Excess junction current of silicon solar cells

    Science.gov (United States)

    Wang, E. Y.; Legge, R. N.; Christidis, N.

    1973-01-01

    The current-voltage characteristics of n(plus)-p silicon solar cells with 0.1, 1.0, 2.0, and 10 ohm-cm p-type base materials have been examined in detail. In addition to the usual I-V measurements, we have studied the temperature dependence of the slope of the I-V curve at the origin by the lock-in technique. The excess junction current coefficient (Iq) deduced from the slope at the origin depends on the square root of the intrinsic carrier concentration. The Iq obtained from the I-V curve fitting over the entire forward bias region at various temperatures shows the same temperature dependence. This result, in addition to the presence of an aging effect, suggest that the surface channel effect is the dominant cause of the excess junction current.

  20. Dissipation and traversal time in Josephson junctions

    International Nuclear Information System (INIS)

    Cacciari, Ilaria; Ranfagni, Anedio; Moretti, Paolo

    2010-01-01

    The various ways of evaluating dissipative effects in macroscopic quantum tunneling are re-examined. The results obtained by using functional integration, while confirming those of previously given treatments, enable a comparison with available experimental results relative to Josephson junctions. A criterion based on the shortening of the semiclassical traversal time τ of the barrier with regard to dissipation can be established, according to which Δτ/τ > or approx. N/Q, where Q is the quality factor of the junction and N is a numerical constant of order unity. The best agreement with the experiments is obtained for N=1.11, as it results from a semiempirical analysis based on an increase in the potential barrier caused by dissipative effects.

  1. Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density: A study in 417 older women.

    Science.gov (United States)

    Belavý, Daniel L; Armbrecht, Gabriele; Blenk, Tilo; Bock, Oliver; Börst, Hendrikje; Kocakaya, Emine; Luhn, Franziska; Rantalainen, Timo; Rawer, Rainer; Tomasius, Frederike; Willnecker, Johannes; Felsenberg, Dieter

    2016-02-01

    We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Adenosine receptors and muscarinic receptors cooperate in acetylcholine release modulation in the neuromuscular synapse.

    Science.gov (United States)

    Santafe, M M; Priego, M; Obis, T; Garcia, N; Tomàs, M; Lanuza, M A; Tomàs, J

    2015-07-01

    Adenosine receptors (ARs) are present in the motor terminals at the mouse neuromuscular junction. ARs and the presynaptic muscarinic acetylcholine receptors (mAChRs) share the functional control of the neuromuscular junction. We analysed their mutual interaction in transmitter release modulation. In electrophysiological experiments with unaltered synaptic transmission (muscles paralysed by blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB), we found that: (i) a collaborative action between different AR subtypes reduced synaptic depression at a moderate activity level (40 Hz); (ii) at high activity levels (100 Hz), endogenous adenosine production in the synaptic cleft was sufficient to reduce depression through A1 -type receptors (A1 Rs) and A2 A-type receptors (A2 A Rs); (iii) when the non-metabolizable 2-chloroadenosine (CADO) agonist was used, both the quantal content and depression were reduced; (iv) the protective effect of CADO on depression was mediated by A1 Rs, whereas A2 A Rs seemed to modulate A1 Rs; (v) ARs and mAChRs absolutely depended upon each other for the modulation of evoked and spontaneous acetylcholine release in basal conditions and in experimental conditions with CADO stimulation; (vi) the purinergic and muscarinic mechanisms cooperated in the control of depression by sharing a common pathway although the purinergic control was more powerful than the muscarinic control; and (vii) the imbalance of the ARs created by using subtype-selective and non-selective inhibitory and stimulatory agents uncoupled protein kinase C from evoked transmitter release. In summary, ARs (A1 Rs, A2 A Rs) and mAChRs (M1 , M2 ) cooperated in the control of activity-dependent synaptic depression and may share a common protein kinase C pathway. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Acute Effects of Static and Proprioceptive Neuromuscular Facilitation Stretching on Muscle Strength and Power Output.

    Science.gov (United States)

    Marek, Sarah M; Cramer, Joel T; Fincher, A Louise; Massey, Laurie L; Dangelmaier, Suzanne M; Purkayastha, Sushmita; Fitz, Kristi A; Culbertson, Julie Y

    2005-06-01

    Context: Stretching is commonly used as a technique for injury prevention in the clinical setting. Our findings may improve the understanding of the neuromuscular responses to stretching and help clinicians make decisions for rehabilitation progression and return to play.Objective: To examine the short-term effects of static and proprioceptive neuromuscular facilitation stretching on peak torque (PT), mean power output (MP), active range of motion (AROM), passive range of motion (PROM), electromyographic (EMG) amplitude, and mechanomyographic (MMG) amplitude of the vastus lateralis and rectus femoris muscles during voluntary maximal concentric isokinetic leg extensions at 60 and 300 degrees .s.Design: A randomized, counterbalanced, cross-sectional, repeated-measures design.Setting: A university human research laboratory.Patients or Other Participants: Ten female (age, 23 +/- 3 years) and 9 male (age, 21 +/- 3 years) apparently healthy and recreationally active volunteers.Intervention(s): Four static or proprioceptive neuromuscular facilitation stretching exercises to stretch the leg extensor muscles of the dominant limb during 2 separate, randomly ordered laboratory visits.Main Outcome Measure(s): The PT and MP were measured at 60 and 300 degrees .s, EMG and MMG signals were recorded, and AROM and PROM were measured at the knee joint before and after the stretching exercises.Results: Static and proprioceptive neuromuscular facilitation stretching reduced PT (P = .051), MP (P = .041), and EMG amplitude (P = .013) from prestretching to poststretching at 60 and 300 degrees .s (P proprioceptive neuromuscular facilitation stretching. The MMG amplitude increased in the rectus femoris muscle in response to the static stretching at 60 degrees .s (P = .031), but no other changes in MMG amplitude were observed (P > .05).Conclusions: Both static and proprioceptive neuromuscular facilitation stretching caused similar deficits in strength, power output, and muscle activation at

  4. The use of an online support group for neuromuscular disorders: a thematic analysis of message postings.

    Science.gov (United States)

    Meade, Oonagh; Buchanan, Heather; Coulson, Neil

    2017-06-08

    People affected by neuromuscular disorders can experience adverse psychosocial consequences and difficulties accessing information and support. Online support groups provide new opportunities for peer support. The aim of this study was to understand how contributors used the message board function of a newly available neuromuscular disorders online support group. Message postings (n = 1951) from the first five months of the message board of a newly formed online support group for neuromuscular disorders hosted by a charitable organization were analyzed using inductive thematic analysis. Members created a sense of community through disclosing personal information, connecting with people with similar illness experiences or interests, welcoming others and sharing aspirations for the development of a resourceful community. Experiences, emotional reactions and support were shared in relation to: delayed diagnosis; symptom interpretation; illness management and progression; the isolating impact of rare disorders; and the influence of social and political factors on illness experiences. This study provided a novel insight into individuals' experiences of accessing a newly available online support group for rare conditions hosted by a charitable organization. The findings highlight how the online support group provided an important peer support environment for members to connect with others, exchange information and support and engender discussion on political and social issues unique to living with often-rare neuromuscular disorders. Online support groups may therefore provide an important and easily accessible support outlet for people with neuromuscular disorders as well as a platform for empowering members to raise awareness about the impact of living with these conditions. Further research is needed to examine member motivations for using such groups and any effects of participation in greater detail. Implications for rehabilitation Online support groups may

  5. The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of kratom leaves (Mitragyna speciosa Korth.).

    Science.gov (United States)

    Chittrakarn, Somsmorn; Keawpradub, Niwat; Sawangjaroen, Kitja; Kansenalak, Supaporn; Janchawee, Benjamas

    2010-06-16

    The effects of pure alkaloid, mitragynine and a methanolic extract of kratom leaves were investigated on neuromuscular junction and compound nerve action potential. Wistar rats were killed by cervical dislocation and decapitated. The phrenic nerve-hemidiaphragms, hemidiaphragms and sciatic nerve were isolated. Kratom methanolic extract present at 0.1-1 mg/mL and mitragynine (0.0156 mg/mL) decreased the muscle twitch on the isolated phrenic nerve-hemidiaphragm and hemidiaphragm preparation. Muscle relaxation caused by kratom extract (1 mg/mL) was greater than the effect of mitragynine. Pancuronium and succinylcholine potentiated the effect of kratom extract. It also had a direct relaxation effect on the hemidiaphragm muscle. The muscle relaxation caused by kratom extract was not antagonized by neostigmine, tetraethylammonium and calcium chloride. High concentrations of kratom extract (10-40 mg/mL) and mitragynine (2 mg/mL) blocked the nerve conduction, amplitude and duration of compound nerve action potential. The mechanism of action of kratom extract might not act as a competitive antagonist of acetylcholine yet its dominant effect was at the neuromuscular junction and not at the skeletal muscle or somatic nerve. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Effectiveness of neuromuscular electrical stimulation for management of shoulder subluxation post-stroke: a systematic review with meta-analysis.

    Science.gov (United States)

    Lee, Jae-Hyoung; Baker, Lucinda L; Johnson, Robert E; Tilson, Julie K

    2017-11-01

    To examine the effectiveness of neuromuscular electrical stimulation (NMES) for the management of shoulder subluxation after stroke including assessment of short (1 hour or less) and long (more than one hour) daily treatment duration. MEDLINE, CENTRAL, CINAHL, WOS, KoreaMed, RISS and reference lists from inception to January 2017 Review methods: We considered randomized controlled trials that reported neuromuscular electrical stimulation for the treatment of shoulder subluxation post-stroke. Two reviewers independently selected trials for inclusion, assessed trial quality, and extracted data. Eleven studies were included (432 participants); seven studies were good quality, four were fair. There was a significant treatment effect of neuromuscular electrical stimulation for reduction of subluxation for persons with acute and subacute stroke (SMD:-1.11; 95% CI:-1.53, -0.68) with either short (SMD:-0.91; 95% CI:-1.43, -0.40) or long (SMD:-1.49; 95% CI:-2.31, -0.67) daily treatment duration. The effect for patients with chronic stroke was not significant (SMD:-1.25; 95% CI:-2.60, 0.11). There was no significant effect of neuromuscular electrical stimulation on arm function or shoulder pain. This meta-analysis suggests a beneficial effect of neuromuscular electrical stimulation, with either short or long daily treatment duration, for reducing shoulder subluxation in persons with acute and subacute stroke. No significant benefits were observed for persons with chronic stroke or for improving arm function or reducing shoulder pain.

  7. The impact of neuromuscular electrical stimulation on recovery after intensive, muscle damaging, maximal speed training in professional team sports players.

    Science.gov (United States)

    Taylor, Tom; West, Daniel J; Howatson, Glyn; Jones, Chris; Bracken, Richard M; Love, Thomas D; Cook, Christian J; Swift, Eamon; Baker, Julien S; Kilduff, Liam P

    2015-05-01

    During congested fixture periods in team sports, limited recovery time and increased travel hinder the implementation of many recovery strategies; thus alternative methods are required. We examined the impact of a neuromuscular electrical stimulation device on 24-h recovery from an intensive training session in professional players. Twenty-eight professional rugby and football academy players completed this randomised and counter-balanced study, on 2 occasions, separated by 7 days. After baseline perceived soreness, blood (lactate and creatine kinase) and saliva (testosterone and cortisol) samples were collected, players completed a standardised warm-up and baseline countermovement jumps (jump height). Players then completed 60 m × 50 m maximal sprints, with 5 min recovery between efforts. After completing the sprint session, players wore a neuromuscular electrical stimulation device or remained in normal attire (CON) for 8 h. All measures were repeated immediately, 2 and 24-h post-sprint. Player jump height was reduced from baseline at all time points under both conditions; however, at 24-h neuromuscular electrical stimulation was significantly more recovered (mean±SD; neuromuscular electrical stimulation -3.2±3.2 vs. CON -7.2±3.7%; P0.05). Neuromuscular electrical stimulation improves recovery from intensive training in professional team sports players. This strategy offers an easily applied recovery strategy which may have particular application during sleep and travel. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  8. Imaging of cervicothoracic junction trauma

    Directory of Open Access Journals (Sweden)

    Wongwaisayawan S

    2013-01-01

    Full Text Available Sirote Wongwaisayawan,1 Ruedeekorn Suwannanon,2 Rathachai Kaewlai11Department of Radiology, Ramathibodi Hospital and Mahidol University, Bangkok, Thailand; 2Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, ThailandAbstract: Cervicothoracic junction trauma is an important cause of morbidity and mortality in trauma patients. Imaging has played an important role in identifying injuries and guiding appropriate, timely therapy. Computed tomography is currently a method of choice for diagnosing cervicothoracic junction trauma, in which the pattern of injuries often suggests possible mechanisms and potential injuries. In this article, the authors describe and illustrate common and uncommon injuries that can occur in the cervicothoracic junction.Keywords: cervicothoracic junction, cervical spine, trauma, imaging, radiology

  9. The Control of Junction Flows

    National Research Council Canada - National Science Library

    Smith, Charles

    1997-01-01

    An experimental study of the effects of spatially-limited (i.e. localized) surface suction on unsteady laminar and turbulent junction flows was performed using hydrogen bubble flow visualization and Particle Image Velocimetry (PIV...

  10. Classification of neuromuscular blocking agents in a new neuromuscular preparation of the chick in vitro

    NARCIS (Netherlands)

    Riezen, H. van

    1968-01-01

    A neuromuscular preparation of the chick is described: 1. 1. The sciatic nerve-tibilis anterior muscle preparation of the 2–10 days old chick fulfils all criteria of an assay preparation and differentiates between curare-like and decamethonium-like agents. 2. 2. The preparation responds to

  11. Intercellular junctions in nerve-free hydra

    DEFF Research Database (Denmark)

    McDowall, A W; Grimmelikhuijzen, C J

    1980-01-01

    Epithelial cells of nerve-free hydra contain septate and gap junctions. In thin sections the gap junctions are characterized by a gap of 3-4 nm. Freeze-fracture demonstrates the presence of septate junctions and two further types of structures: (i) the "E-type" or "inverted" gap junctions...

  12. Josephson junctions with ferromagnetic interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Wild, Georg Hermann

    2012-03-04

    We report on the fabrication of superconductor/insulator/ferromagnetic metal/superconductor (Nb/AlO{sub x}/Pd{sub 0.82}Ni{sub 0.18}/Nb) Josephson junctions (SIFS JJs) with high critical current densities, large normal resistance times area products, and high quality factors. For these junctions, a transition from 0- to {pi}-coupling is observed for a thickness d{sub F}=6 nm of the ferromagnetic Pd{sub 0.82}Ni{sub 0.18} interlayer. The magnetic field dependence of the critical current of the junctions demonstrates good spatial homogeneity of the tunneling barrier and ferromagnetic interlayer. Magnetic characterization shows that the Pd{sub 0.82}Ni{sub 0.18} has an out-of-plane anisotropy and large saturation magnetization indicating negligible dead layers at the interfaces. A careful analysis of Fiske modes up to about 400 GHz provides valuable information on the junction quality factor and the relevant damping mechanisms. Whereas losses due to quasiparticle tunneling dominate at low frequencies, at high frequencies the damping is explained by the finite surface resistance of the junction electrodes. High quality factors of up to 30 around 200 GHz have been achieved. They allow to study the junction dynamics, in particular the switching probability from the zero-voltage into the voltage state with and without microwave irradiation. The experiments with microwave irradiation are well explained within semi-classical models and numerical simulations. In contrast, at mK temperature the switching dynamics without applied microwaves clearly shows secondary quantum effects. Here, we could observe for the first time macroscopic quantum tunneling in Josephson junctions with a ferromagnetic interlayer. This observation excludes fluctuations of the critical current as a consequence of an unstable magnetic domain structure of the ferromagnetic interlayer and affirms the suitability of SIFS Josephson junctions for quantum information processing.

  13. Peltier cooling in molecular junctions

    Science.gov (United States)

    Cui, Longji; Miao, Ruijiao; Wang, Kun; Thompson, Dakotah; Zotti, Linda Angela; Cuevas, Juan Carlos; Meyhofer, Edgar; Reddy, Pramod

    2018-02-01

    The study of thermoelectricity in molecular junctions is of fundamental interest for the development of various technologies including cooling (refrigeration) and heat-to-electricity conversion1-4. Recent experimental progress in probing the thermopower (Seebeck effect) of molecular junctions5-9 has enabled studies of the relationship between thermoelectricity and molecular structure10,11. However, observations of Peltier cooling in molecular junctions—a critical step for establishing molecular-based refrigeration—have remained inaccessible. Here, we report direct experimental observations of Peltier cooling in molecular junctions. By integrating conducting-probe atomic force microscopy12,13 with custom-fabricated picowatt-resolution calorimetric microdevices, we created an experimental platform that enables the unified characterization of electrical, thermoelectric and energy dissipation characteristics of molecular junctions. Using this platform, we studied gold junctions with prototypical molecules (Au-biphenyl-4,4'-dithiol-Au, Au-terphenyl-4,4''-dithiol-Au and Au-4,4'-bipyridine-Au) and revealed the relationship between heating or cooling and charge transmission characteristics. Our experimental conclusions are supported by self-energy-corrected density functional theory calculations. We expect these advances to stimulate studies of both thermal and thermoelectric transport in molecular junctions where the possibility of extraordinarily efficient energy conversion has been theoretically predicted2-4,14.

  14. Neuromuscular electrical stimulation for thromboprophylaxis: A systematic review.

    Science.gov (United States)

    Hajibandeh, S; Hajibandeh, S; Antoniou, G A; Scurr, J R H; Torella, F

    2015-10-01

    To evaluate the effect of neuromuscular electrical stimulation on lower limb venous blood flow and its role in thromboprophylaxis. Systematic review of randomised and non-randomised studies evaluating neuromuscular electrical stimulation, and reporting one or more of the following outcomes: incidence of venous thromboembolism, venous blood flow and discomfort profile. Twenty-one articles were identified. Review of these articles showed that neuromuscular electrical stimulation increases venous blood flow and is generally associated with an acceptable tolerability, potentially leading to good patient compliance. Ten comparative studies reported DVT incidence, ranging from 2% to 50% with neuromuscular electrical stimulation and 6% to 47.1% in controls. There were significant differences, among included studies, in terms of patient population, neuromuscular electrical stimulation delivery, diagnosis of venous thromboembolism and blood flow measurements. Neuromuscular electrical stimulation increases venous blood flow and is well tolerated, but current evidence does not support a role for neuromuscular electrical stimulation in thromboprophylaxis. Randomised controlled trials are required to investigate the clinical utility of neuromuscular electrical stimulation in this setting. © The Author(s) 2015.

  15. Medical back belt with integrated neuromuscular electrical stimulation

    NARCIS (Netherlands)

    Bottenberg, E. (Eliza); Brinks, G.J. (Ger); Hesse, J. (Jenny)

    2014-01-01

    The medical back belt with integrated neuromuscular electrical stimulation is anorthopedic device, which has two main functions. The first function is to stimulate the backmuscles by using a neuromuscular electrical stimulation device that releases regular,electrical impulses. The second function of

  16. ATRACURIUM-INDUCED NEUROMUSCULAR BLOCK IN THE ISOLATED ARM

    NARCIS (Netherlands)

    ERIKSSON, LI; VANDENBROM, RHG; LENNMARKEN, C; AGOSTON, S

    1992-01-01

    A modification of the isolated arm technique was applied in 10 females under opioid-based i.v. anaesthesia for comparison of the offset of an atracurium-induced neuromuscular block in an isolated arm to an arm with maintained circulation. The neuromuscular blocking effect of a bolus dose of

  17. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    International Nuclear Information System (INIS)

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies

  18. Neuromuscular Manifestations of West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    A. Arturo eLeis

    2012-03-01

    Full Text Available The most common neuromuscular manifestation of West Nile virus (WNV infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis to four limbs (quadriparesis, with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis, motor axons (polyradiculitis, peripheral nerve (Guillain-Barré syndrome, brachial plexopathy. In addition, involvement of spinal sympathetic neurons and ganglia provides a plausible explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neu¬ropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms. Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies. Human experience with these agents seems promising based on anecdotal

  19. Acute neuromuscular weakness associated with dengue infection

    Directory of Open Access Journals (Sweden)

    Harmanjit Singh Hira

    2012-01-01

    Full Text Available Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK were tested. In addition, two patients underwent nerve conduction velocity (NCV test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2 nd to 4 th day of illness in 11 of 12 patients. In one patient, it developed on 10 th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients.

  20. Electronic thermometry in tunable tunnel junction

    Energy Technology Data Exchange (ETDEWEB)

    Maksymovych, Petro

    2016-03-15

    A tunable tunnel junction thermometry circuit includes a variable width tunnel junction between a test object and a probe. The junction width is varied and a change in thermovoltage across the junction with respect to the change in distance across the junction is determined. Also, a change in biased current with respect to a change in distance across the junction is determined. A temperature gradient across the junction is determined based on a mathematical relationship between the temperature gradient, the change in thermovoltage with respect to distance and the change in biased current with respect to distance. Thermovoltage may be measured by nullifying a thermoelectric tunneling current with an applied voltage supply level. A piezoelectric actuator may modulate the probe, and thus the junction width, to vary thermovoltage and biased current across the junction. Lock-in amplifiers measure the derivatives of the thermovoltage and biased current modulated by varying junction width.

  1. Effects of regular Tai Chi practice and jogging on neuromuscular reaction during lateral postural control in older people.

    Science.gov (United States)

    Wang, Shao-Jun; Xu, Dong-Qing; Li, Jing-Xian

    2017-01-01

    This study examined the effects of regular Tai Chi practice and jogging on the neuromuscular activity of the trunk, hip, and ankle joint muscles of older people during lateral postural perturbation. A total of 42 older people participated in the study and formed the Tai Chi, jogging, and sedentary control groups. Electromyography signals were collected from the peroneus longus, anterior tibialis, gluteus medius, and erector spinae during unpredictable mediolateral perturbation. The Tai Chi group exhibited significantly faster latencies of the tibialis anterior and erector spinae than the control group. The jogging group showed a significantly shorter neuromuscular reaction time of the erector spinae than the control group. No significant difference was observed between the Tai Chi and jogging groups. Long-term regular Tai Chi practice enhanced the neuromuscular reaction of the erector spinae and tibialis anterior to lateral perturbation and will help timely posture correction when lateral postural distributions occur.

  2. The immediate effects of proprioceptive neuromuscular facilitation with taping on gait parameters in patients with chronic stroke.

    Science.gov (United States)

    Park, Shin-Jun

    2017-11-01

    [Purpose] The purpose of the present study was to examine the immediate effects of simultaneous application of proprioceptive neuromuscular facilitation (PNF) and elastic taping (T), and the removal of the elastic tape, on the gait parameters of stroke patients. [Subjects and Methods] Twenty stroke patients were divided into a proprioceptive neuromuscular facilitation group (PNFG, n=7), a taping group (TG, n=6), and a proprioceptive neuromuscular facilitation with taping group (PNFTG, n=7). Relevant interventions were applied for 30 minutes, the tape was removed, and gait parameters were evaluated. [Results] Only the intervention of the PNFTG yielded significant differences in patient cadence, speed, and stride length. [Conclusion] The simultaneous application of PNF and taping for 30 minutes has carryover effects that can improve stroke patients' gait ability, even after the removal of the tape.

  3. Desarrollo neuromuscular en la atrofia muscular espinal

    OpenAIRE

    Martínez Hernàndez, Rebeca

    2012-01-01

    INTRODUCCIÓN: La atrofia muscular espinal (AME) es una enfermedad neuromuscular infantil caracterizada por la muerte de las neuronas motoras del asta anterior de la médula espinal. Como consecuencia de ello hay una degeneración y atrofia muscular, por lo que los pacientes mueren a menudo de insuficiencias respiratorias graves. La AME se clasifica en tres tipos principales según el grado de gravedad, la edad de aparición y las pautas motoras. Se trata de una enfermedad con patrón de herencia a...

  4. RADIOLOGICAL EVALUATION OF CRANIOVERTEBRAL JUNCTION ANOMALIES

    Directory of Open Access Journals (Sweden)

    Joji Reddy

    2015-08-01

    Full Text Available INTRODUCTION: Detailed discussions of the CVJ are conspicuously absent in many standard textbooks and chapters addressing the skull or cervical spine, since it lies in between these regions . CVJ anomalies are common in India subcontinent. OBJECTIVES : To outline the normal anatomy and various abnormalities of craniovertebral junction. To evaluate the most common developmental and acquired craniovertebral junction abnormalities . CRANIOMETRY AND DIAGNOSIS: Radiological evaluation of CVJ requir es identification of only a few anatomic structures. Over the years multiple lines , planes and angles have been described for assessment of CVJ relationship , initially with radiography and later with polytomography. Two lines have remained particularly use ful for evaluation of CVJ relationship with virtually any imaging modality: the chamberlain`s line and weckenheim ’ s clivus base line . Two angles also continue to be useful: the welcher basal angle and atlanto occipital joint axis angle. PATIENTS AND METHOD S: The prospective study of craniovertebral junction anomalies was carried out at Kurnool medical college , Governament general hospital Kurnool from NOV 2012 to AUG 2014. The patients are subjected to clinical evaluation and radiological evaluation. OBSERV ATIONS AND RESULTS : In our study there is male predominance with male to female ratio of 2:1 . Majority of patients are in the age group of 11 - 40 (73.26%. The commonest symptom seen is weakness of extremities ( 70% with associated numbness (50%. On clinica l examination pyramidal tract involvement noticed in 70% of cases. Basilar invagination is the most common followed by Atlantoocoipital assimilation (40% and AAD (30% . CONCLUSION : Computed tomography and magnetic resonance imaging are invalvable adjuncts to the plain radiographs in the evaluation of the craniovertebral junction anomalies. Chamberlain’s line and McGregor line are the most commonly applied craniometric measurements

  5. Combined application of neuromuscular electrical stimulation and voluntary muscular contractions.

    Science.gov (United States)

    Paillard, Thierry

    2008-01-01

    Electromyostimulation (EMS) and voluntary muscle contraction (VC) constitute different modes of muscle activation and induce different acute physiological effects on the neuromuscular system. Long-term application of each mode of muscle activation can produce different muscle adaptations. It seems theoretically possible to completely or partially cumulate the muscle adaptations induced by each mode of muscle activation applied separately. This work consisted of examining the literature concerning the muscle adaptations induced by long-term application of the combined technique (CT) [i.e. EMS is combined with VC - non-simultaneously] compared with VC and/or EMS alone in healthy subjects and/or athletes and in post-operative knee-injured subjects. In general, CT induced greater muscular adaptations than VC whether in sports training or rehabilitation. This efficiency would be due to the fact that CT can facilitate cumulative effects of training completely or partially induced by VC and EMS practiced alone. CT also provides a greater improvement of the performance of complex dynamic movements than VC. However, EMS cannot improve coordination between different agonistic and antagonistic muscles and thus does not facilitate learning the specific coordination of complex movements. Hence, EMS should be combined with specific sport training to generate neuromuscular adaptations, but also allow the adjustment of motor control during a voluntary movement. Likewise, in a therapeutic context, CT was particularly efficient to accelerate recovery of muscle contractility during a rehabilitation programme. Strength loss and atrophy inherent in a traumatism and/or a surgical operation would be more efficiently compensated with CT than with VC. Furthermore, CT also restored more functional abilities than VC. Finally, in a rehabilitation context, EMS is complementary to voluntary exercise because in the early phase of rehabilitation it elicits a strength increase, which is necessary

  6. Aerobic influence on neuromuscular function and tolerance during passive hyperthermia.

    Science.gov (United States)

    Morrison, Shawnda A; Sleivert, Gordon G; Cheung, Stephen

    2006-10-01

    To determine the role of aerobic fitness on central neuromuscular activation and maximal voluntary contractile force during hyperthermia. Thirty-seven healthy males in three distinct groups based on aerobic fitness and training history were passively heated using a liquid conditioning garment in a hot (35 degrees C, 50% RH) environment with the intention of testing neuromuscular function with whole-body hyperthermia. Of these initial participants, 11 of the 13 highly fit (HF; VO2max = 71.2 +/- 5.9 mL x kg(-1) x min(-1), body fat = 5.6 +/- 1.9%), 11 of the 13 moderately fit (MF; 57.2 +/- 4.2 mL x kg(-1) x min(-1), 11 +/- 3.4%), and 4 of the 11 lower-fit (LF; 49.6 +/- 1.1 mL x kg(-1) x min(-1), 19.4 +/- 2.6%) individuals tolerated heating to 39.0 degrees C, with the remainder terminating the experimental protocol early. Maximal force output and voluntary activation were examined during a 10-s maximal isometric knee extension. Passive heating attenuated force production (-61.7 +/- 69.6 N change from initial values) and decreased voluntary activation (8.6 (12.6), 18.1 (12.4), and 6.1 (3.1)% for HF, MF, and LF training groups, respectively). Cardiovascular strain moderately increased to 60 +/- 14% (P heating (98 +/- 15, 99 +/- 7, and 79 +/- 5 mm Hg for HF, MF, and LF, respectively; P heating to 39.0 degrees C (and above) differed between the HF and MF compared with LF, despite no difference in their psychophysical rankings of thermal sensations and/or (dis)comfort. Low aerobic fitness and activity level are associated with a decreased tolerance to passive hyperthermia. However, at high body temperatures, maximum force production and voluntary activation were impaired to an equal level regardless of training status.

  7. NEUROMUSCULAR AND CARDIOVASCULAR EFFECTS OF NEOSTIGMINE AND METHYL-ATROPINE ADMINISTERED AT DIFFERENT DEGREES OF ROCURONIUM-INDUCED NEUROMUSCULAR BLOCK

    NARCIS (Netherlands)

    VANDENBROEK, L; PROOST, JH; WIERDA, JMKH; NJOO, MD; HENNIS, PJ

    1994-01-01

    The neuromuscular and cardiovascular effects of neostigmine, 40 mug kg-1, and methyl-atropine, 7 mug kg-1, administered at different degrees of rocuronium-induced (600 mug kg-1) neuromuscular block were evaluated. In one group of patients spontaneous recovery was awaited (Group A; n = 20).

  8. Shoulder Taping and Neuromuscular Control.

    Science.gov (United States)

    Snodgrass, Suzanne J; Farrell, Scott F; Tsao, Henry; Osmotherly, Peter G; Rivett, Darren A; Chipchase, Lucy S; Schabrun, Siobhan M

    2018-03-23

      Scapular taping can offer clinical benefit to some patients with shoulder pain; however, the underlying mechanisms are unclear. Understanding these mechanisms may guide the development of treatment strategies for managing neuromusculoskeletal shoulder conditions.   To examine the mechanisms underpinning the benefits of scapular taping.   Descriptive laboratory study.   University laboratory.   A total of 15 individuals (8 men, 7 women; age = 31.0 ± 12.4 years, height = 170.9 ± 7.6 cm, mass = 73.8 ± 14.4 kg) with no history of shoulder pain.   Scapular taping.   Surface electromyography (EMG) was used to assess the (1) magnitude and onset of contraction of the upper trapezius (UT), lower trapezius (LT), and serratus anterior relative to the contraction of the middle deltoid during active shoulder flexion and abduction and (2) corticomotor excitability (amplitude of motor-evoked potentials from transcranial magnetic stimulation) of these muscles at rest and during isometric abduction. Active shoulder-flexion and shoulder-abduction range of motion were also evaluated. All outcomes were measured before taping, immediately after taping, 24 hours after taping with the original tape on, and 24 hours after taping with the tape removed.   Onset of contractions occurred earlier immediately after taping than before taping during abduction for the UT (34.18 ± 118.91 milliseconds and 93.95 ± 106.33 milliseconds, respectively, after middle deltoid contraction; P = .02) and during flexion for the LT (110.02 ± 109.83 milliseconds and 5.94 ± 92.35 milliseconds, respectively, before middle deltoid contraction; P = .06). These changes were not maintained 24 hours after taping. Mean motor-evoked potential onset of the middle deltoid was earlier at 24 hours after taping (tape on = 7.20 ± 4.33 milliseconds) than before taping (8.71 ± 5.24 milliseconds, P = .008). We observed no differences in peak root mean square EMG activity or corticomotor excitability of

  9. Experienced stigmatization reduced quality of life of patients with a neuromuscular disease : a cross-sectional study

    NARCIS (Netherlands)

    van der Beek, Kyra M.; Bos, Isäac; Middel, Berrie; Wynia, Klaske

    2013-01-01

    Objective: To examine the influence of stigma on the quality of life of patients with a neuromuscular disease. Design: Cross-sectional postal survey. Setting: Outpatient clinic of the Department of Neurology, University Hospital Groningen, the Netherlands. Subjects: Patients diagnosed with a

  10. Neuromuscular Responses to Conditioned Soccer Sessions Assessed Via GPS-Embedded Accelerometers: Insights Into Tactical Periodization.

    Science.gov (United States)

    Buchheit, Martin; Lacome, Mathieu; Cholley, Yannick; Simpson, Ben M

    2017-09-05

    To 1) examine the reliability of field-based running-specific measures of neuromuscular function assessed via GPS-embedded accelerometers and 2) examine their responses to three typical conditioned sessions (i.e., Strength, Endurance and Speed) in elite soccer players. Before and immediately after each session, vertical jump (CMJ) and adductors squeeze strength (Groin) performances were recorded. Players also performed a 4-min run at 12 km/h followed by 4 ~60-m runs (run =12 s, r =33 s). GPS (15-Hz) and accelerometer (100 Hz) data collected during the four runs + the recovery periods excluding the last recovery period were used to derive vertical stiffness (K), peak loading force (peak force over all the foot-strikes, Fpeak) and propulsion efficiency (i.e., ratio between velocity and force loads, Vl/Fl). Typical errors were small (CMJ, Groin, K and Vl/Fl) and moderate (Fpeak), with moderate (Fpeak), high (K and Vl/Fl) and very high ICC (CMJ and Groin). After all sessions, there were small decreases in Groin and increases in K, while changes in F were all unclear. In contrast, the CMJ and Vl/Fl ratio responses were session-dependent: small increase in CMJ after Speed and Endurance, but unclear changes after Strength; the Vl/Fl ratio increased largely after Strength, while there was a small and a moderate decrease after the Endurance and Speed, respectively. Running-specific measures of neuromuscular function assessed in the field via GPS-embedded accelerometers show acceptable levels of reliability. While the three sessions examined may be associated with limited neuromuscular fatigue, changes in neuromuscular performance and propulsion-efficiency are likely session objective-dependent.

  11. NEUROMUSCULAR CONTROL IN LUMBAR DISORDERS

    Directory of Open Access Journals (Sweden)

    Ville Leinonen

    2004-03-01

    Full Text Available Impaired motor and sensory functions have been associated with low back pain (LBP. This includes disturbances in a wide range of sensorimotor control e.g. sensory dysfunctions, impaired postural responses and psychomotor control. However, the physiological mechanisms, clinical relevance and characteristics of these findings in different spinal pathologies require further clarification. The purposes of this study were to investigate postural control, lumbar muscle function, movement perception and associations between these findings in healthy volunteers (n=35, patients with lumbar disc herniation (n=20 and lumbar spinal stenosis (LSS, n=26. Paraspinal muscle responses for sudden upper limb loading and muscle activation during flexion-extension movement and the lumbar endurance test were measured by surface electromyography (EMG. Postural stability was measured on a force platform during two- and one-footed standing. Lumbar movement perception was assessed in a motorised trunk rotation unit in the seated position. In addition, measurements of motor-(MEP and somatosensory evoked potentials (SEP and needle EMG examination of lumbar multifidus muscles were performed in the LSS patients. Clinical and questionnaire data were also recorded. A short latency paraspinal muscle response (~50 ms for sudden upper limb loading was observed. The latency of the response was shortened by expectation (p=0.017. The response latency for unexpected loading was similar in healthy persons and disc herniation patients but the latency was not shortened by expectation in the patients (p = 0.014. Also impaired postural control (p < 0.05 and lumbar movement perception (p = 0.012 were observed in disc herniation patients. The impaired lumbar movement perception (p=0.054 and anticipatory muscle activation (p = 0.043 tended to be restored after successful surgery but postural control had still not recovered after 3 months of follow-up. The majority of LSS patients were unable

  12. Prevalence of complications in neuromuscular scoliosis surgery

    DEFF Research Database (Denmark)

    Sharma, Shallu; Wu, Chunsen; Andersen, Thomas

    2013-01-01

    PURPOSE: Our objectives were primarily to review the published literature on complications in neuromuscular scoliosis (NMS) surgery and secondarily, by means of a meta-analysis, to determine the overall pooled rates (PR) of various complications associated with NMS surgery. METHODS: PubMed and Em......PURPOSE: Our objectives were primarily to review the published literature on complications in neuromuscular scoliosis (NMS) surgery and secondarily, by means of a meta-analysis, to determine the overall pooled rates (PR) of various complications associated with NMS surgery. METHODS: Pub.......71 %) followed by implant complications (PR = 12.51 %), infections (PR = 10.91 %), neurological complications (PR = 3.01 %) and pseudoarthrosis (PR = 1.88 %). Revision, removal and extension of implant had highest PR (7.87 %) followed by malplacement of the pedicle screws (4.81 %). Rates of individual studies....... In regard to surgical complications affiliated with various surgical techniques in NMS, the level of evidence of published literature ranges between 2+ to 2-; the subsequent recommendations are level C. CONCLUSION: NMS patients have diverse and high complication rates after scoliosis surgery. High PRs...

  13. Neuromuscular imaging in inherited muscle diseases

    International Nuclear Information System (INIS)

    Wattjes, Mike P.; Kley, Rudolf A.; Fischer, Dirk

    2010-01-01

    Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. (orig.)

  14. Next generation sequencing in neuromuscular diseases

    Science.gov (United States)

    Efthymiou, S; Manole, A; Houlden, H

    2016-01-01

    Purpose of review Neuromuscular diseases are clinically and genetically heterogeneous and probably contains the greatest proportion of causative Mendelian defects than any other group of conditions. These disorders affect muscle and/or nerves with neonatal, childhood or adulthood onset, with significant disability and early mortality. Along with heterogeneity, unidentified and often very large genes, require complementary and comprehensive methods in routine molecular diagnosis. Inevitably this leads to increased diagnostic delays and challenges in the interpretation of genetic variants. Recent findings The application of next-generation sequencing, as a research and diagnostic strategy has made significant progress into solving many of these problems. The analysis of these data is by no means simple and the clinical input is essential to interpret results. Summary In this review, we describe using examples the recent advances in the genetic diagnosis of neuromuscular disorders, in research and clinical practice and the latest developments that are underway in NGS. We also discuss the latest collaborative initiatives such as the Genomics England genome sequencing project that combine rare disease clinical phenotyping with genomics, with the aim of defining the vast majority of rare disease genes in patients as well as modifying risks and pharmacogenomics factors. PMID:27588584

  15. Neuromuscular imaging in inherited muscle diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wattjes, Mike P. [VU University Medical Center, Department of Radiology, De Boelelaan 1117, HV, Amsterdam (Netherlands); Kley, Rudolf A. [Klinken Bergmannsheil, Ruhr-University, Department of Neurology, Neuromuscular Centre Ruhrgebiet, Bochum (Germany); Fischer, Dirk [University Hospital of Basel, Department of Neurology, Basel (Switzerland); University Children' s Hospital Basel, Department of Neuropaediatrics, Basel (Switzerland)

    2010-10-15

    Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. (orig.)

  16. Neuromuscular Dysfunction in Experimental Sepsis and Glutamine.

    Science.gov (United States)

    Çankayalı, İlkin; Boyacılar, Özden; Demirağ, Kubilay; Uyar, Mehmet; Moral, Ali Reşat

    2016-05-01

    Electrophysiological studies show that critical illness polyneuromyopathy appears in the early stage of sepsis before the manifestation of clinical findings. The metabolic response observed during sepsis causes glutamine to become a relative essential amino acid. We aimed to assess the changes in neuromuscular transmission in the early stage of sepsis after glutamine supplementation. Animal experimentation. Twenty male Sprague-Dawley rats were randomized into two groups. Rats in both groups were given normal feeding for one week. In the study group, 1 g/kg/day glutamine was added to normal feeding by feeding tube for one week. Cecal ligation and perforation (CLP) surgery was performed at the end of one week. Before and 24 hours after CLP, compound muscle action potentials were recorded from the gastrocnemius muscle. Latency measurements before and 24 hours after CLP were 0.68±0.05 ms and 0.80±0.09 ms in the control group and 0.69±0.07 ms and 0.73±0.07 ms in the study group (p<0.05). Since enteral glutamine prevented compound muscle action potentials (CMAP) latency prolongation in the early phase of sepsis, it was concluded that enteral glutamine replacement might be promising in the prevention of neuromuscular dysfunction in sepsis; however, further studies are required.

  17. Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

    Directory of Open Access Journals (Sweden)

    İlkin Çankayalı

    2016-06-01

    Full Text Available Background: Electrophysiological studies show that critical illness polyneuromyopathy appears in the early stage of sepsis before the manifestation of clinical findings. The metabolic response observed during sepsis causes glutamine to become a relative essential amino acid. Aims: We aimed to assess the changes in neuromuscular transmission in the early stage of sepsis after glutamine supplementation. Study Design: Animal experimentation. Methods: Twenty male Sprague-Dawley rats were randomized into two groups. Rats in both groups were given normal feeding for one week. In the study group, 1 g/kg/day glutamine was added to normal feeding by feeding tube for one week. Cecal ligation and perforation (CLP surgery was performed at the end of one week. Before and 24 hours after CLP, compound muscle action potentials were recorded from the gastrocnemius muscle. Results: Latency measurements before and 24 hours after CLP were 0.68±0.05 ms and 0.80±0.09 ms in the control group and 0.69±0.07 ms and 0.73±0.07 ms in the study group (p<0.05. Conclusion: Since enteral glutamine prevented compound muscle action potentials (CMAP latency prolongation in the early phase of sepsis, it was concluded that enteral glutamine replacement might be promising in the prevention of neuromuscular dysfunction in sepsis; however, further studies are required.

  18. Neuromuscular fatigue during high-intensity intermittent exercise in individuals with intellectual disability.

    Science.gov (United States)

    Borji, Rihab; Sahli, Sonia; Zarrouk, Nidhal; Zghal, Firas; Rebai, Haithem

    2013-12-01

    This study examined neuromuscular fatigue after high-intensity intermittent exercise in 10 men with mild intellectual disability (ID) in comparison with 10 controls. Both groups performed three maximal voluntary contractions (MVC) of knee extension with 5 min in-between. The highest level achieved was selected as reference MVC. The fatiguing exercise consists of five sets with a maximal number of flexion-extension cycles at 80% of the one maximal repetition (1RM) for the right leg at 90° with 90 s rest interval between sets. The MVC was tested again after the last set. Peak force and electromyography (EMG) signals were measured during the MVC tests. Root Mean Square (RMS) and Median Frequency (MF) were calculated. Neuromuscular efficiency (NME) was calculated as the ratio of peak force to the RMS. Before exercise, individuals with ID had a lower MVC (psport train ID individuals, they should consider this nervous system weakness. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Muscle synergies and complexity of neuromuscular control during gait in cerebral palsy.

    Science.gov (United States)

    Steele, Katherine M; Rozumalski, Adam; Schwartz, Michael H

    2015-12-01

    Individuals with cerebral palsy (CP) have impaired movement due to a brain injury near birth. Understanding how neuromuscular control is altered in CP can provide insight into pathological movement. We sought to determine if individuals with CP demonstrate reduced complexity of neuromuscular control during gait compared with unimpaired individuals and if changes in control are related to functional ability. Muscle synergies during gait were retrospectively analyzed for 633 individuals (age range 3.9-70y): 549 with CP (hemiplegia, n=122; diplegia, n=266; triplegia, n=73; quadriplegia, n=88) and 84 unimpaired individuals. Synergies were calculated using non-negative matrix factorization from surface electromyography collected during previous clinical gait analyses. Synergy complexity during gait was compared with diagnosis subtype, functional ability, and clinical examination measures. Fewer synergies were required to describe muscle activity during gait in individuals with CP compared with unimpaired individuals. Changes in synergies were related to functional impairment and clinical examination measures including selective motor control, strength, and spasticity. Individuals with CP use a simplified control strategy during gait compared with unimpaired individuals. These results were similar to synergies during walking among adult stroke survivors, suggesting similar neuromuscular control strategies between these clinical populations. © 2015 Mac Keith Press.

  20. Single-molecule detection of dihydroazulene photo-thermal reaction using break junction technique

    Science.gov (United States)

    Huang, Cancan; Jevric, Martyn; Borges, Anders; Olsen, Stine T.; Hamill, Joseph M.; Zheng, Jue-Ting; Yang, Yang; Rudnev, Alexander; Baghernejad, Masoud; Broekmann, Peter; Petersen, Anne Ugleholdt; Wandlowski, Thomas; Mikkelsen, Kurt V.; Solomon, Gemma C.; Brøndsted Nielsen, Mogens; Hong, Wenjing

    2017-05-01

    Charge transport by tunnelling is one of the most ubiquitous elementary processes in nature. Small structural changes in a molecular junction can lead to significant difference in the single-molecule electronic properties, offering a tremendous opportunity to examine a reaction on the single-molecule scale by monitoring the conductance changes. Here, we explore the potential of the single-molecule break junction technique in the detection of photo-thermal reaction processes of a photochromic dihydroazulene/vinylheptafulvene system. Statistical analysis of the break junction experiments provides a quantitative approach for probing the reaction kinetics and reversibility, including the occurrence of isomerization during the reaction. The product ratios observed when switching the system in the junction does not follow those observed in solution studies (both experiment and theory), suggesting that the junction environment was perturbing the process significantly. This study opens the possibility of using nano-structured environments like molecular junctions to tailor product ratios in chemical reactions.

  1. Neuromuscular electrical stimulation for the prevention of venous thromboembolism.

    Science.gov (United States)

    Ravikumar, Raveena; Williams, Katherine J; Babber, Adarsh; Moore, Hayley M; Lane, Tristan Ra; Shalhoub, Joseph; Davies, Alun H

    2017-01-01

    Objective Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, is a significant cause of morbidity and mortality, affecting one in 1000 adults per year. Neuromuscular electrical stimulation is the transcutaneous application of electrical impulses to elicit muscle contraction, preventing venous stasis. This review aims to investigate the evidence underlying the use of neuromuscular electrical stimulation in thromboprophylaxis. Methods The Medline and Embase databases were systematically searched, adhering to PRISMA guidelines, for articles relating to electrical stimulation and thromboprophylaxis. Articles were screened according to a priori inclusion and exclusion criteria. Results The search strategy identified 10 randomised controlled trials, which were used in three separate meta-analyses: five trials compared neuromuscular electrical stimulation to control, favouring neuromuscular electrical stimulation (odds ratio of deep vein thrombosis 0.29, 95% confidence interval 0.13-0.65; P = .003); three trials compared neuromuscular electrical stimulation to heparin, favouring heparin (odds ratio of deep vein thrombosis 2.00, 95% confidence interval 1.13-3.52; P = .02); three trials compared neuromuscular electrical stimulation as an adjunct to heparin versus heparin only, demonstrating no significant difference (odds ratio of deep vein thrombosis 0.33, 95% confidence interval 0.10-1.14; P = .08). Conclusion Neuromuscular electrical stimulation significantly reduces the risk of deep vein thrombosis compared to no prophylaxis. It is inferior to heparin in preventing deep vein thrombosis and there is no evidence for its use as an adjunct to heparin.

  2. Surgical advances in the treatment of neuromuscular scoliosis.

    Science.gov (United States)

    Canavese, Federico; Rousset, Marie; Le Gledic, Benoit; Samba, Antoine; Dimeglio, Alain

    2014-04-18

    Neuromuscular disorders are a group of diseases affecting the neuro-musculo-skeletal system. Children with neuromuscular disorders frequently develop progressive spinal deformities with cardio-respiratory compromise in the most severe cases. The incidence of neuromuscular scoliosis is variable, inversely correlated with ambulatory abilities and with a reported risk ranging from 80% to 100% in non-ambulatory patients. As surgical and peri-operative techniques have improved, more severely affected children with complex neuromuscular deformities and considerable co-morbidities are now believed to be candidates for extensive surgery for spinal deformity. This article aimed to provide a comprehensive review of how neuromuscular spinal deformities can affect normal spine balance and how these deformities can be treated with segmental instrumentation and sub-laminar devices. Older concepts have been integrated with newer scientific data to provide the reader with a basis for better understanding of how treatment of neuromuscular scoliosis has evolved over the past few decades. Recent advances, as well as challenges that remain to be overcome, in the surgical treatment of neuromuscular curves with sub-laminar devices and in the management of post-operative infections are outlined.

  3. Microstructure of Josephson junctions: Effect on supercurrent transport in YBCO grain boundary and barrier layer junctions

    International Nuclear Information System (INIS)

    Merkle, K.L.; Huang, Y.

    1998-01-01

    The electric transport of high-temperature superconductors, such as YBa 2 Cu 3 O 7-x (YBCO), can be strongly restricted by the presence of high-angle grain boundaries (GB). This weak-link behavior is governed by the macroscopic GB geometry and the microscopic grain boundary structure and composition at the atomic level. Whereas grain boundaries present a considerable impediment to high current applications of high T c materials, there is considerable commercial interest in exploiting the weak-link-nature of grain boundaries for the design of microelectronic devices, such as superconducting quantum interference devices (SQUIDs). The Josephson junctions which form the basis of this technology can also be formed by introducing artificial barriers into the superconductor. The authors have examined both types of Josephson junctions by EM techniques in an effort to understand the connection between microstructure/chemistry and electrical transport properties. This knowledge is a valuable resource for the design and production of improved devices

  4. Effects of sugammadex on incidence of postoperative residual neuromuscular blockade

    DEFF Research Database (Denmark)

    Brueckmann, B; Sasaki, N; Grobara, P

    2015-01-01

    BACKGROUND: This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. METHODS: Adult patients undergoing abdominal surgery received rocuronium, followed...... by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual...... neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio

  5. Neuromuscular hamartoma: imaging features of a rare paediatric craniofacial tumour

    International Nuclear Information System (INIS)

    Oeppen, Rachel S.; Harden, Stephen P.; Argent, Julie D.

    2003-01-01

    Neuromuscular hamartoma (also referred to as neuromuscular choristoma or benign triton tumour) has not previously been described in the radiological literature. It is a rare benign lesion composed of mature elements of striated muscle and neural tissue. We report a case of neuromuscular hamartoma involving the skull base, nasopharynx, orbit and maxilla in a 2.5-year-old child who presented with facial swelling. The CT and MRI appearances of this unusual soft-tissue tumour are emphasized, together with a discussion of the pathological findings, differential diagnosis and review of the literature. (orig.)

  6. Gravitation at the Josephson Junction

    Directory of Open Access Journals (Sweden)

    Victor Atanasov

    2018-01-01

    Full Text Available A geometric potential from the kinetic term of a constrained to a curved hyperplane of space-time quantum superconducting condensate is derived. An energy conservation relation involving the geometric field at every material point in the superconductor is demonstrated. At a Josephson junction the energy conservation relation implies the possibility of transforming electric energy into geometric field energy, that is, curvature of space-time. Experimental procedures to verify that the Josephson junction can act as a voltage-to-curvature converter are discussed.

  7. Computed tomography of muscles in neuromuscular disease

    International Nuclear Information System (INIS)

    Serratrice, G.

    1986-01-01

    137 patients with neuromuscular diseases were studied by CT scan. Four levels were chosen: mid-calf, mid-thigh, pelvic girdle, and spinal muscles. The scans were compared with normal control scans taken from the same sites. The patients were divided into those with myogenic diseases and those with neurogenic diseases. Of the 102 patients with myogenic changes, 17 had X-linked dystrophy, 13 had facio-scapulo-humeral dystrophy, 22 had limb girdle dystrophy, 19 had myotonic dystrophy, 14 had inflammatory muscle diseases, and 17 had miscellaneous muscular diseases. Of the 35 patients with neurogenic changes, 8 had amyotrophic lateral sclerosis (ALS), 16 had chronic spinal amyotrophies, 9 had peripheral neuropathies, and 2 had Friedreich's disease. The analysis of muscles changes (volume, outline, density) was established on the following muscles: tibialis anterior, peroneus, soleus, gastrocnemius mediale, gastrocnemius laterale, quadriceps, semitendinosus, semimembranosus, sartorius, adductor, gracilis, gluteus, spine extensors, and psoas

  8. Effects of calcium chloride coadministered with neostigmine on neuromuscular blockade recovery: A double-blind randomised study.

    Science.gov (United States)

    Ju, Jae-Woo; Kim, Hyun-Chang; Yoon, Sehee; Hong, Deok Man; Park, Hee-Pyoung

    2017-09-01

    Ionised calcium plays an important role in neuromuscular transmission, but its effects on the reversal of nondepolarising neuromuscular blockade have not been fully evaluated. We examined whether calcium chloride coadministered with neostigmine could enhance the rate of neuromuscular recovery. Randomised double-blind trial. A tertiary teaching hospital. In total, 53 patients undergoing elective surgery under general anaesthesia with neuromuscular monitoring by acceleromyography using a TOF-Watch SX monitor. Patients were randomly allocated to receive either 5 mg kg of calcium chloride (calcium group, n = 26) or the same volume of normal saline (control group, n = 27) coadministered with 25 μg kg of neostigmine and 15 μg kg of atropine at the end of surgery. The primary end point was the neuromuscular recovery time [time from neostigmine administration to recovery of the TOF ratio (TOFr) to 0.9]. Secondary end points included the TOFr at 5, 10 and 20 min after neostigmine administration and the incidence of postoperative residual curarisation (PORC), defined as a TOFr less than 0.9 at each time point. The neuromuscular recovery time was significantly faster in the calcium group than in the control group (median [Q1 to Q3]; 5.0 [3.0 to 7.0] vs. 6.7 [5.7 to 10.0] min, respectively; P = 0.007). At 5 min after neostigmine administration, the TOFr was higher [87 (74 to 100) vs. 68 (51 to 81)%, respectively; P = 0.002] and the incidence of PORC was lower (50.0 vs. 81.5%, respectively; P = 0.016) in the calcium group than in the control group. There were no differences between the two groups with respect to the TOFr or incidence of PORC at 10 and 20 min after neostigmine administration. Calcium chloride coadministered with neostigmine enhanced neuromuscular recovery in the early period of nondepolarising neuromuscular blockade reversal.

  9. Electronic noise of superconducting tunnel junction detectors

    International Nuclear Information System (INIS)

    Jochum, J.; Kraus, H.; Gutsche, M.; Kemmather, B.; Feilitzsch, F. v.; Moessbauer, R.L.

    1994-01-01

    The optimal signal to noise ratio for detectors based on superconducting tunnel junctions is calculated and compared for the cases of a detector consisting of one single tunnel junction, as well as of series and of parallel connections of such tunnel junctions. The influence of 1 / f noise and its dependence on the dynamical resistance of tunnel junctions is discussed quantitatively. A single tunnel junction yields the minimum equivalent noise charge. Such a tunnel junction exhibits the best signal to noise ratio if the signal charge is independent of detector size. In case, signal charge increases with detector size, a parallel or a series connection of tunnel junctions would provide the optimum signal to noise ratio. The equivalent noise charge and the respective signal to noise ratio are deduced as functions of tunnel junction parameters such as tunneling time, quasiparticle lifetime, etc. (orig.)

  10. C-terminal agrin fragment is inversely related to neuromuscular fatigue in older men.

    Science.gov (United States)

    Stout, Jeffrey R; Fragala, Maren S; Hoffman, Jay R; Robinson, Edward H; Mccormack, William P; Townsend, Jeremy R; Jatjner, Adam R; Emerson, Nadia S; Oliveira, Leonardo P; Fukuda, David H

    2015-01-01

    The aim of this study was to examine the relationship between serum C-terminal agrin fragment (CAF) concentrations and neuromuscular fatigue in older adults. Twenty-two healthy older men and women volunteered for this study. Resting fasted blood samples were collected and prepared for measurement of serum CAF concentration by a commercially available ELISA kit. The onset of neuromuscular fatigue was measured by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at fatigue threshold (PWCFT ) test. A significant inverse correlation for men was observed between CAF and PWCFT (r = -0.602; P = 0.05), but not for women (r = 0.208; P = 0.54). After controlling for age and body mass index, significant correlations (r = -0.69; P = 0.042) remained for men, but not for women (r = 0.12; P = 0.76). These data suggest that serum CAF concentrations were significantly related to the onset of neuromuscular fatigue independent of age and BMI in men only. © 2014 Wiley Periodicals, Inc.

  11. The effects of dynamic exercise using the proprioceptive neuromuscular facilitation pattern on posture in healthy adults.

    Science.gov (United States)

    Cho, Misuk; Gong, Wontae

    2017-06-01

    [Purpose] The purpose of this study is to examine the effects of dynamic exercise utilizing the proprioceptor neuromuscular facilitation pattern accompanied by abdominal drawing-in exercises on posture in healthy adults. [Subjects and Methods] The total number of subjects were 32; 16 were randomly placed in the training group, and the remaining 16 made up the control group. The subjects in the training group conducted 5 sets of dynamic exercises utilizing the proprioceptor neuromuscular facilitation patterns each day, 3 times a week for 6 weeks. Using BackMapper, their trunk inclination, trunk imbalance, pelvic position, pelvic torsion, pelvic rotation and the position of their scapula were evaluated. [Results] When the training group's posture pre-test and post-test were compared in this study, there was a statistical significance in trunk inclination, pelvic position, pelvic torsion, pelvic rotation and the position of their scapula. [Conclusion] Dynamic exercise utilizing the proprioceptor neuromuscular facilitation patterns increased the posture that are the basis of trunk stabilization.

  12. Treatment of postoperative infection after posterior spinal fusion and instrumentation in a patient with neuromuscular scoliosis.

    Science.gov (United States)

    Ghattas, Paul J; Mehlman, Charles T; Eichten, David

    2014-02-01

    According to the literature, patients with neuromuscular scoliosis have a higher rate of infection after spinal fusion. No randomized controlled trials have been completed to assess the optimal treatment and related outcomes for patients with infections after posterior spinal fusion. In this article, we examine the data and report a case in which a vacuum-assisted closure (VAC) device was used as definitive treatment for a deep wound infection after posterior spinal fusion and instrumentation in a patient with neuromuscular scoliosis. Our patient, a 17-year-old adolescent girl with progressive neuromuscular scoliosis, underwent posterior spinal fusion with instrumentation and bone graft from T2 to sacrum without complication. One month after surgery, she presented with a draining wound. She underwent repeat surgical irrigation and debridement with subsequent use of a wound VAC. The wound VAC was used for more than 2 months, until skin closure was complete. The deep polymicrobial wound infection was treated successfully and definitively with a wound VAC. This case report suggests that good long-term outcomes can be achieved with use of a wound VAC for definitive closure, with possible avoidance of other secondary surgeries requiring skin grafts or flaps for wound closure.

  13. Gap junctions and motor behavior

    DEFF Research Database (Denmark)

    Kiehn, Ole; Tresch, Matthew C.

    2002-01-01

    The production of any motor behavior requires coordinated activity in motor neurons and premotor networks. In vertebrates, this coordination is often assumed to take place through chemical synapses. Here we review recent data suggesting that electrical gap-junction coupling plays an important role...... to the production of motor behavior in adult mammals....

  14. Gap Junctions and Chagas Disease

    Science.gov (United States)

    Adesse, Daniel; Goldenberg, Regina Coeli; Fortes, Fabio S.; Jasmin; Iacobas, Dumitru A.; Iacobas, Sanda; de Carvalho, Antonio Carlos Campos; de Narareth Meirelles, Maria; Huang, Huan; Soares, Milena B.; Tanowitz, Herbert B.; Garzoni, Luciana Ribeiro; Spray, David C.

    2013-01-01

    Gap junction channels provide intercellular communication between cells. In the heart, these channels coordinate impulse propagation along the conduction system and through the contractile musculature, thereby providing synchronous and optimal cardiac output. As in other arrhythmogenic cardiac diseases, chagasic cardiomyopathy is associated with decreased expression of the gap junction protein connexin43 (Cx43) and its gene. Our studies of cardiac myocytes infected with Trypanosoma cruzi have revealed that synchronous contraction is greatly impaired and gap junction immunoreactivity is lost in infected cells. Such changes are not seen for molecules forming tight junctions, another component of the intercalated disc in cardiac myocytes. Transcriptomic studies of hearts from mouse models of Chagas disease and from acutely infected cardiac myocytes in vitro indicate profound remodelling of gene expression patterns involving heart rhythm determinant genes, suggesting underlying mechanisms of the functional pathology. One curious feature of the altered expression of Cx43 and its gene expression is that it is limited in both extent and location, suggesting that the more global deterioration in cardiac function may result in part from spread of damage signals from more seriously compromised cells to healthier ones. PMID:21884887

  15. Neuromuscular and biomechanical characteristics do not vary across the menstrual cycle.

    Science.gov (United States)

    Abt, John P; Sell, Timothy C; Laudner, Kevin G; McCrory, Jean L; Loucks, Tammy L; Berga, Sarah L; Lephart, Scott M

    2007-07-01

    Research examining the menstrual cycle and its relationship to ACL injury has focused on determining the incidence of ACL injury during the different phases of the menstrual cycle and assessing the changes in neuromuscular and biomechanical characteristics between these phases. Conflicting results warrant further investigation to determine if neuromuscular and biomechanical characteristics respond in a similar pattern to the fluctuating estradiol and progesterone. The purpose of this study was to determine if changes in the levels of estradiol and progesterone significantly altered fine motor coordination, postural stability, knee strength, and knee joint kinematics and kinetics between the menses, post-ovulatory, and mid-luteal phases of the menstrual cycle. Ten healthy and physically active females (Age: 21.4 +/- 1.4 years, Height: 1.67 +/- 0.06 m, Mass: 59.9 +/- 7.4 kg), who did not use oral contraceptives, were recruited from the local university population. Single-leg postural stability, fine motor coordination, knee strength, knee biomechanics, and serum estradiol and progesterone were assessed at the menses, post-ovulatory, and mid-luteal phases of the menstrual cycle. Levels of estradiol were significantly higher during the post-ovulatory (P = 0.016) and mid-luteal phases (P hamstring - quadriceps strength ratio at 60 degrees s(-1) (P = 0.748) or 180 degrees s(-1) (P = 0.789), knee flexion excursion (P = 0.6), knee valgus excursion (P = 0.899), peak proximal tibial anterior shear force (P = 0.797), flexion moment at peak proximal tibial anterior shear force (P = 0.698), or valgus moment at peak proximal tibial anterior shear force (P = 0.924). The results of the current study suggest neuromuscular and biomechanical characteristics are not influenced by estradiol and progesterone fluctuations. All neuromuscular and biomechanical characteristics remained invariable between testing sessions despite concentration changes in estradiol and progesterone.

  16. Aging and limb alter the neuromuscular control of goal-directed movements.

    Science.gov (United States)

    Kwon, MinHyuk; Chen, Yen-Ting; Fox, Emily J; Christou, Evangelos A

    2014-06-01

    The purpose of this study was to determine whether the neuromuscular control of goal-directed movements is different for young and older adults with the upper and lower limbs. Twenty young (25.1 ± 3.9 years) and twenty older adults (71.5 ± 4.8 years) attempted to accurately match the displacement of their limb to a spatiotemporal target during ankle dorsiflexion or elbow flexion movements. We quantified neuromuscular control by examining the movement endpoint accuracy and variability, and the antagonistic muscle activity using surface electromyography (EMG). Our results indicate that older adults exhibit impaired endpoint accuracy with both limbs due to greater time variability. In addition, older adults exhibit greater EMG burst and lower EMG burst variability as well as lower coactivation of the antagonistic muscles. The impaired accuracy of older adults during upper limb movements was related to lower coactivation of the antagonistic muscles, whereas their impaired accuracy during lower limb movements was related to the amplified EMG bursts. The upper limb exhibited greater movement control than the lower limb, and different neuromuscular parameters were related to the accuracy and consistency for each limb. Greater endpoint error during upper limb movements was related to lower coactivation of the antagonistic muscles, whereas greater endpoint error during lower limb movements was related to the amplified EMG bursts. These findings indicate that the age-associated impairments in movement control are associated with altered activation of the involved antagonistic muscles. In addition, independent of age, the neuromuscular control of goal-directed movements is different for the upper and lower limbs.

  17. Neuromuscular Effects of Common Krait (Bungarus caeruleus Envenoming in Sri Lanka.

    Directory of Open Access Journals (Sweden)

    Anjana Silva

    2016-02-01

    Full Text Available We aimed to investigate neurophysiological and clinical effects of common krait envenoming, including the time course and treatment response.Patients with definite common krait (Bungarus caeruleus bites were recruited from a Sri Lankan hospital. All patients had serial neurological examinations and stimulated concentric needle single-fibre electromyography (sfEMG of orbicularis oculi in hospital at 6 wk and 6-9 mth post-bite.There were 33 patients enrolled (median age 35 y; 24 males. Eight did not develop neurotoxicity and had normal sfEMG. Eight had mild neurotoxicity with ptosis, normal sfEMG; six received antivenom and all recovered within 20-32 h. Seventeen patients developed severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness. All 17 received Indian polyvalent antivenom a median 3.5 h post-bite (2.8-7.2 h, which cleared unbound venom from blood. Despite this, the paralysis worsened requiring intubation and ventilation within 7 h post-bite. sfEMG showed markedly increased jitter and neuromuscular blocks within 12 h. sfEMG abnormalities gradually improved over 24 h, corresponding with clinical recovery. Muscle recovery occurred in ascending order. Myotoxicity was not evident, clinically or biochemically, in any of the patients. Patients were extubated a median 96 h post-bite (54-216 h. On discharge, median 8 days (4-12 days post-bite, patients were clinically normal but had mild sfEMG abnormalities which persisted at 6 wk post-bite. There were no clinical or neurophysiological abnormalities at 6-9 mth.Common krait envenoming causes rapid onset severe neuromuscular paralysis which takes days to recover clinically consistent with sfEMG. Subclinical neuromuscular dysfunction lasts weeks but was not permanent. Antivenom effectively cleared venom but did not prevent worsening or reverse neuromuscular paralysis.

  18. Recovery from mivacurium-induced neuromuscular blockade is not affected by anticonvulsant therapy.

    Science.gov (United States)

    Jellish, W S; Thalji, Z; Brundidge, P K; Tempelhoff, R

    1996-01-01

    Long-term chronic anticonvulsant therapy produces a resistance to the effects of all nondepolarizing neuromuscular blocking agents studied to date. Since the metabolism of mivacurium is unique among the nondepolarizing neuromuscular blocking agents, the effect of anticonvulsants on its recovery parameters was examined. Forty-five patients were separated into three groups based on the number of chronic anticonvulsant medications the subjects were taking: subjects in group 1, the control group, took no anticonvulsant medication; group 2 subjects took one medication; and group 3 subjects took two medications. Mivacurium, 0.15 mg/kg i.v., was administered after induction of general anesthesia with thiopental sodium, 4-6 mg/kg, and fentanyl 2-4 micrograms/kg i.v. Maintenance anesthesia consisted of N2O in O2. 0.2-0.3% end-tidal isoflurane, and a fentanyl infusion. The evoked compound electromyograph (ECEMG) of the adductor pollicis-brevis muscle was measured for time of onset, T-1 (time at which ECEMG signal reaches 5, 25, 50, and 75% of baseline), TR (TOF ratio), and recovery index. T-1 at 25% was 18.2 +/- 1.8, 20.7 +/- 1.9, and 21.5 +/- 1.4 min for groups 1, 2, and 3, respectively, with TR at 25% being 23.7 +/- 2.3, 26.9 +/- 2.4, and 27.3 +/- 2.3 min. No significant differences were noted in neuromuscular recovery between groups at any time point. These results fail to demonstrate the resistance to the nondepolarizing neuromuscular blockade of mivacurium that has been observed with other nondepolarizing agents.

  19. Deep neuromuscular blockade and low insufflation pressure during laparoscopic hysterectomy

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Istre, Olav; Springborg, Henrik Halvor

    2017-01-01

    INTRODUCTION: Establishment of sufficient muscle relaxation is essential in laparoscopic surgery. During laparoscopy, surgeons can experience abdominal contractions in their patients. Deep neuromuscular block (NMB) has the potential to prevent such episodes. In this study, we explored if deep NMB...

  20. The role of proprioception and neuromuscular stability in carpal instabilities.

    Science.gov (United States)

    Hagert, E; Lluch, A; Rein, S

    2016-01-01

    Carpal stability has traditionally been defined as dependent on the articular congruity of joint surfaces, the static stability maintained by intact ligaments, and the dynamic stability caused by muscle contractions resulting in a compression of joint surfaces. In the past decade, a fourth factor in carpal stability has been proposed, involving the neuromuscular and proprioceptive control of joints. The proprioception of the wrist originates from afferent signals elicited by sensory end organs (mechanoreceptors) in ligaments and joint capsules that elicit spinal reflexes for immediate joint stability, as well as higher order neuromuscular influx to the cerebellum and sensorimotor cortices for planning and executing joint control. The aim of this review is to provide an understanding of the role of proprioception and neuromuscular control in carpal instabilities by delineating the sensory innervation and the neuromuscular control of the carpus, as well as descriptions of clinical applications of proprioception in carpal instabilities. © The Author(s) 2015.

  1. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    Science.gov (United States)

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  2. Neuromuscular function during a forward lunge in meniscectomized patients

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Damgaard, Jacob; Roos, Ewa M.

    2012-01-01

    This study aimed to investigate differences in knee joint kinematics, ground reaction force kinetics and neuromuscular activity including muscle coactivation, and medial versus lateral muscle activity during a forward lunge between the operated and contralateral legs of meniscectomized patients...

  3. Exploring employment in consultation reports of patients with neuromuscular diseases

    NARCIS (Netherlands)

    Minis, M.A.H; Cup, E.H.C.; Heerkens, Y.H.; Engels, J.A.; Engelen, B.G.M. van; Oostendorp, R.A.B.

    2012-01-01

    Minis MA, Cup EH, Heerkens YF, Engels JA, van Engelen BG, Oostendorp RA. Exploring employment in consultation reports of patients with neuromuscular diseases. OBJECTIVES: To explore consultation reports for patient and employment characteristics and recommendations on employment regarding patients

  4. [Neuromuscular relaxation and CCMDP. The Zilgrei and Feldenkrais methods 2].

    Science.gov (United States)

    Santoro, F; Maiorana, C; Faccin, C

    1989-10-31

    The Authors show two neuromuscular release methods employed in the treatment of cranio-cervico-mandibular syndrome; these methods work at the place of origin of the pathology resolving the symptoms in different districts of the body.

  5. Dynamics of pi-junction interferometer circuits

    DEFF Research Database (Denmark)

    Kornkev, V.K.; Mozhaev, P.B.; Borisenko, I.V.

    2002-01-01

    The pi-junction superconducting circuit dynamics was studied by means of numerical simulation technique. Parallel arrays consisting of Josephson junctions of both 0- and pi-type were studied as a model of high-T-c grain-boundary Josephson junction. The array dynamics and the critical current...... dependence on magnetic field are discussed. Experimental results for dc interferometers with 0 and pi high-T-c bi-crystal Josephson junctions are reported and discussed in comparison with numerical simulation....

  6. Guyana Junction, globalisation, localisation, and the production of East Indianness

    NARCIS (Netherlands)

    Kruijf, J.G. de

    2006-01-01

    Guyana Junction involves the analysis of the construction of East Indian ethnic and religious distinction in Guyana. It is a book in which the author endeavours to examine the manner in which Indian ethnic/religious culture as well as Indian tainted personal meaning and practice are produced and

  7. Neuromuscular fatigue and recovery profiles in individuals with intellectual disability

    OpenAIRE

    Borji , Rihab; Zghal , Firas; Zarrouk , Nidhal; Martin , Vincent; Sahli , Sonia; Rebai , Haithem

    2017-01-01

    International audience; Purpose: This study aimed to explore neuromuscular fatigue and recovery profiles in individuals with intellectual disability (ID) after exhausting submaximal contraction.Methods: Ten men with ID were compared to 10 men without ID. The evaluation of neuromuscular function consisted in brief (3 s) isometric maximal voluntary contraction (IMVC) of the knee extension superimposed with electrical nerve stimulation before, immediately after, and during 33 min after an exhaus...

  8. Management of Cardiac Involvement in NeuroMuscular Diseases: Review

    OpenAIRE

    Bouhouch, Rachida; Elhouari, Tarik; Oukerraj, Latifa; Fellat, Ibtissam; Zarzur, Jamila; Bennani, Rajaa; Arharbi, Mhamed

    2008-01-01

    Neuromuscular Diseases are a heterogeneous molecular, clinical and prognosis group. Progress has been achieved in the understanding and classification of these diseases. Cardiac involvement in neuromuscular diseases namely conduction disorders, ventricular dilatation and dilated cardiomyopathy with its impact on prognosis, is often dissociated from the peripheral myopathy. Therefore, close surveillance is mandatory in the affected patients. In this context, preventive therapy (beta-blockers a...

  9. Modelling and Analysis of Long Josephson Junctions

    NARCIS (Netherlands)

    Visser, T.P.P.

    2002-01-01

    For various reasons people have been interested in Josephson junctions. Ranging from "understanding nature" to building quantum computers. In this thesis we focus on a special type of junction (the long junction) and to a special type of problem fluxon dynamics.

  10. Soliton bunching in annular Josephson junctions

    DEFF Research Database (Denmark)

    Vernik, I.V; Lazarides, Nickos; Sørensen, Mads Peter

    1996-01-01

    By studying soliton (fluxon) motion in long annular Josephson junctions it is possible to avoid the influence of the boundaries and soliton-soliton collisions present in linear junctions. A new experimental design consisting of a niobium coil placed on top of an annular junction has been used...

  11. Traumatic Tear of the Latissimus Dorsi Myotendinous Junction

    Science.gov (United States)

    Friedman, Michael V.; Stensby, J. Derek; Hillen, Travis J.; Demertzis, Jennifer L.; Keener, Jay D.

    2015-01-01

    A case of a latissimus dorsi myotendinous junction strain in an avid CrossFit athlete is presented. The patient developed acute onset right axillary burning and swelling and subsequent palpable pop with weakness while performing a “muscle up.” Magnetic resonance imaging examination demonstrated a high-grade tear of the right latissimus dorsi myotendinous junction approximately 9 cm proximal to its intact humeral insertion. There were no other injuries to the adjacent shoulder girdle structures. Isolated strain of the latissimus dorsi myotendinous junction is a very rare injury with a scarcity of information available regarding its imaging appearance and preferred treatment. This patient was treated conservatively and was able to resume active CrossFit training within 3 months. At 6 months postinjury, he had only a mild residual functional deficit compared with his preinjury level. PMID:26502450

  12. Ageing and neurotrophic signalling effects on diaphragm neuromuscular function

    Science.gov (United States)

    Greising, Sarah M; Ermilov, Leonid G; Sieck, Gary C; Mantilla, Carlos B

    2015-01-01

    The age-related mechanisms underlying sarcopenia are largely unknown. We hypothesize that age-related neuromuscular changes depend on brain-derived neurotrophic factor (BDNF) acting through the tropomyosin-related kinase receptor B (TrkB). Maximal specific force and neuromuscular transmission failure were assessed at 6, 18 and 24 months following control, BDNF or phosphoprotein phosphatase 1 derivative (1NMPP1) treatment in male TrkBF616A mice. Phosphoprotein phosphatase-1 derivatives such as 1NMPP1 inhibit TrkB kinase activity as a result of this single amino acid mutation in the ATP binding domain. Maximal twitch and isometric tetanic force were reduced at 24 months compared to 6 and 18 months (P Neuromuscular transmission failure significantly increased at 18 and 24 months compared to 6 months (age × treatment interaction: P Neuromuscular transmission was improved following BDNF at 6 and 18 months and was impaired only at 6 months following 1NMPP1 treatment. Age and inhibition of TrkB kinase activity had similar effects on neuromuscular transmission failure, supporting a critical role for BDNF/TrkB signalling on neuromuscular changes in ageing. These results suggest that an age-related loss of endogenous BDNF precedes reductions in TrkB kinase activity in the diaphragm muscle. PMID:25630263

  13. Plexin-Semaphorin Signaling Modifies Neuromuscular Defects in a Drosophila Model of Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Stuart J. Grice

    2018-02-01

    Full Text Available Dominant mutations in GARS, encoding the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS, cause peripheral nerve degeneration and Charcot-Marie-Tooth disease type 2D (CMT2D. This genetic disorder exemplifies a recurring paradigm in neurodegeneration, in which mutations in essential genes cause selective degeneration of the nervous system. Recent evidence suggests that the mechanism underlying CMT2D involves extracellular neomorphic binding of mutant GlyRS to neuronally-expressed proteins. Consistent with this, our previous studies indicate a non-cell autonomous mechanism, whereby mutant GlyRS is secreted and interacts with the neuromuscular junction (NMJ. In this Drosophila model for CMT2D, we have previously shown that mutant gars expression decreases viability and larval motor function, and causes a concurrent build-up of mutant GlyRS at the larval neuromuscular presynapse. Here, we report additional phenotypes that closely mimic the axonal branching defects of Drosophila plexin transmembrane receptor mutants, implying interference of plexin signaling in gars mutants. Individual dosage reduction of two Drosophila Plexins, plexin A (plexA and B (plexB enhances and represses the viability and larval motor defects caused by mutant GlyRS, respectively. However, we find plexB levels, but not plexA levels, modify mutant GlyRS association with the presynaptic membrane. Furthermore, increasing availability of the plexB ligand, Semaphorin-2a (Sema2a, alleviates the pathology and the build-up of mutant GlyRS, suggesting competition for plexB binding may be occurring between these two ligands. This toxic gain-of-function and subversion of neurodevelopmental processes indicate that signaling pathways governing axonal guidance could be integral to neuropathology and may underlie the non-cell autonomous CMT2D mechanism.

  14. Influence of phospholipasic inhibition on neuromuscular activity of Bothrops fonsecai snake venom.

    Science.gov (United States)

    Schezaro-Ramos, Raphael; Collaço, Rita de Cássia O; Randazzo-Moura, Priscila; Rocha, Thalita; Cogo, José Carlos; Rodrigues-Simioni, Léa

    2017-05-01

    Bothrops fonsecai (B. fonsecai), a pitviper endemic to southeastern Brazil, has a venom mainly composed by snake venom phospholipases (PLA 2 ) and metalloproteases, compounds that could interfere with neuromuscular junction in vitro. In this work, we investigated the role of PLA 2 in the myotoxicity and neuromuscular blockade caused by B. fonsecai venom using different procedures frequently associated with PLA 2 activity inhibition: 24 °C bath temperature, Ca 2+ - Sr 2+ replacement and chemical modification with p-bromophenacyl bromide (p-BPB). Mice extensor digitorum longus preparations (EDL) were incubated with usual or modified Tyrode solution (prepared with Ca 2+ or Sr 2+ respectively) at 24 °C or 37 °C (as controls) and in addition of B. fonsecai venom (100 μg/mL) alone or after its incubation with buffer (24 h, 23 °C) on the absence (alkylation control) and presence of p-BPB; all muscle were processed for histological analysis. The PLA 2 , proteolytic and amidolytic activities under the same conditions (24 °C or 37 °C, Ca 2+ - Sr 2+ replacement, absence or presence p-BPB) were also assessed. The B. fonsecai venom caused total neuromuscular blockade after 100 min of incubation, in Ca 2+ Tyrode solution at 37 °C (usual conditions); on Sr 2+ Tyrode solution (37 °C) the twitch height were 31.7 ± 7.4% of basal, and at 24 °C (Ca 2+ Tyrode solution) were 53.6 ± 7.0% of basal. The alkylation of PLA 2 with p-BPB promoted a great blockade decrease at 100 min of incubation (88.7 ± 5.7% of basal), but it was also observed on alkylation control preparations (66.2 ± 6.6%). The venom produced 50% of blockade at 40.5 ± 5.9 min, in Ca 2+ Tyrode solution at 37 °C. The protocols delayed the time for 50% blockade: 105.7 ± 7.1 min (at 24 °C, in Ca 2+ Tyrode solution) and 71.1 ± 9.0 min (at 37 °C, in Sr 2+ Tyrode solution). Regarding p-BPB incubation and alkylation control preparations, 50% of blockade was not reached

  15. Objective neuromuscular monitoring of neuromuscular blockade in Denmark: an online-based survey of current practice.

    Science.gov (United States)

    Söderström, C M; Eskildsen, K Z; Gätke, M R; Staehr-Rye, A K

    2017-07-01

    Neuromuscular blocking agents are commonly used during general anaesthesia but can lead to postoperative residual neuromuscular blockade and associated morbidity. With appropriate objective neuromuscular monitoring (objNMM) residual blockade can be avoided. In this survey, we investigated the use of objNMM in Denmark. We conducted an anonymous Internet-based survey distributed through e-mails to Danish public anaesthesia departments. The survey consisted of 15-17 short questions regarding the use of objNMM. A total of 653 (27%) anaesthetists from 90% of the hospitals answered the questionnaire. ObjNMM was always used by 58% of the anaesthetists and 86% used objNMM at least 75% of the times. Despite the frequent use, 75% of the anaesthetists experienced difficulties with objNMM in at least 25% of the cases. The likelihood of using objNMM was higher among nurse anaesthetists vs. anaesthesiologists (odds ratio (OR) 2.24 [95% confidence interval (CI): 1.62-3.08]), if the department had an employee with special interest in objNMM (OR 1.66 [95% CI: 1.12-2.47]), if the anaesthetist had < 5 years of experience (OR 1.88 [95% CI: 1.29-2.73]), or if experiencing difficulties with objNMM < 25% of the cases (OR 1.60 [95% CI: 1.00-2.57]). In this survey, Danish anaesthetists frequently, in an international perspective, use objNMM, but the use is often associated with technical difficulties. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  16. HEMODYNAMIC AND LACTIC ACID RESPONSES TO PROPRIOCEPTIVE NEUROMUSCULAR FACILITATION EXERCISE

    Directory of Open Access Journals (Sweden)

    Zuhal Gültekin

    2006-09-01

    Full Text Available The hemodynamic and metabolic responses to proprioceptive neuromuscular facilitation (PNF exercise were examined in 32 male university students (aged 19-28 years. Ten repetitions of PNF exercises were applied to the subjects' dominant upper extremities in the following order: as an agonist pattern flexion, adduction and external rotation; and as an antagonist pattern extension, abduction and internal rotation. Heart rate (HR, systolic blood pressure (SBP, diastolic blood pressure (DBP, double product (DP, and blood lactate concentration (La were determined before, immediately after, and at 1st, 3rd, and 5th minutes after PNF exercise. A one-way ANOVA with repeated measures indicated significant differences in HR, SBP, DBP, DP and La immediately after PNF exercise. HR increased from 81 (±10 to 108 (±15 b·min-1 (p < 0.01, SBP increased from 117 (±10 to 125 (±11 mmHg (p < 0.01, DBP increased from 71 (±10 to 75 (±8 mmHg (p < 0.01, DP increased from 96 (±16 to 135 (±24 (p < 0.01, and La increased from 0.69 (±0.31 to 3.99 (±14.63 mmol·L-1 (p < 0.01. Thus PNF exercise resulted in increased hemodynamic responses and blood lactate concentration that indicate a high strain on the cardiovascular system and anaerobic metabolism in healthy subjects

  17. Flexible 2D layered material junctions

    Science.gov (United States)

    Balabai, R.; Solomenko, A.

    2018-03-01

    Within the framework of the methods of the electron density functional and the ab initio pseudopotential, we have obtained the valence electron density spatial distribution, the densities of electron states, the widths of band gaps, the charges on combined regions, and the Coulomb potentials for graphene-based flexible 2D layered junctions, using author program complex. It is determined that the bending of the 2D layered junctions on the angle α leads to changes in the electronic properties of these junctions. In the graphene/graphane junction, there is clear charge redistribution with different signs in the regions of junctions. The presence in the heterojunctions of charge regions with different signs leads to the formation of potential barriers. The greatest potential jump is in the graphene/fluorographene junction. The greatest value of the band gap width is in the graphene/graphane junction.

  18. Polyglucosan Bodies in Placental Extravillious Trophoblast for the Diagnosis of Fatal Perinatal Neuromuscular Type Glycogen Storage Disease Type IV.

    Science.gov (United States)

    Yu, Weiming; Brundler, Marie-Anne; Wright, James R

    2017-01-01

    The fatal infantile neuromuscular type is the most severe form of glycogen storage disease type IV. We report a case of a 22-day-old female neonate born at 34 weeks gestation with polyhyramnios, fetal hydrops, and severe hypotonia. Placental examination revealed numerous periodic acid schiff (PAS)-positive diastase-resistant polyglucosan bodies in the cytoplasm of extravillous trophoblast predominantly in the placental basal plate. Muscle biopsy and autopsy findings supported a diagnosis of neuromuscular-type glycogen storage disease IV with extensive involvement of skeletal muscle, heart, and liver. The diagnosis was confirmed by molecular genetic testing. We could only find one prior report in the English literature that describes placental pathological changes. Our findings suggest that placental examination can be a useful adjunct for early diagnosis, as placentas are often received for pathological examination shortly after birth and usually before a diagnostic muscle biopsy can be performed. Pathologists need to be aware of characteristic placental features.

  19. Josephson junctions and dark energy

    Science.gov (United States)

    Jetzer, Philippe; Straumann, Norbert

    2006-08-01

    In a recent paper Beck and Mackey [C. Beck, M.C. Mackey, astro-ph/0603397] argue that the argument we gave in our paper [Ph. Jetzer, N. Straumann, Phys. Lett. B 606 (2005) 77, astro-ph/0411034] to disprove their claim that dark energy can be discovered in the Lab through noise measurements of Josephson junctions is incorrect. In particular, they emphasize that the measured noise spectrum in Josephson junctions is a consequence of the fluctuation dissipation theorem, while our argument was based on equilibrium statistical mechanics. In this note we show that the fluctuation dissipation relation does not depend upon any shift of vacuum (zero-point) energies, and therefore, as already concluded in our previous paper, dark energy has nothing to do with the proposed measurements.

  20. Josephson junctions and dark energy

    International Nuclear Information System (INIS)

    Jetzer, Philippe; Straumann, Norbert

    2006-01-01

    In a recent paper Beck and Mackey [C. Beck, M.C. Mackey, astro-ph/0603397] argue that the argument we gave in our paper [Ph. Jetzer, N. Straumann, Phys. Lett. B 606 (2005) 77, astro-ph/0411034] to disprove their claim that dark energy can be discovered in the Lab through noise measurements of Josephson junctions is incorrect. In particular, they emphasize that the measured noise spectrum in Josephson junctions is a consequence of the fluctuation dissipation theorem, while our argument was based on equilibrium statistical mechanics. In this note we show that the fluctuation dissipation relation does not depend upon any shift of vacuum (zero-point) energies, and therefore, as already concluded in our previous paper, dark energy has nothing to do with the proposed measurements

  1. Josephson junctions and dark energy

    Energy Technology Data Exchange (ETDEWEB)

    Jetzer, Philippe [Institute for Theoretical Physics, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich (Switzerland)]. E-mail: jetzer@physik.unizh.ch; Straumann, Norbert [Institute for Theoretical Physics, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich (Switzerland)

    2006-08-03

    In a recent paper Beck and Mackey [C. Beck, M.C. Mackey, astro-ph/0603397] argue that the argument we gave in our paper [Ph. Jetzer, N. Straumann, Phys. Lett. B 606 (2005) 77, astro-ph/0411034] to disprove their claim that dark energy can be discovered in the Lab through noise measurements of Josephson junctions is incorrect. In particular, they emphasize that the measured noise spectrum in Josephson junctions is a consequence of the fluctuation dissipation theorem, while our argument was based on equilibrium statistical mechanics. In this note we show that the fluctuation dissipation relation does not depend upon any shift of vacuum (zero-point) energies, and therefore, as already concluded in our previous paper, dark energy hathing to do with the proposed measurements.

  2. Superconducting tunnel-junction refrigerator

    International Nuclear Information System (INIS)

    Melton, R.G.; Paterson, J.L.; Kaplan, S.B.

    1980-01-01

    The dc current through an S 1 -S 2 tunnel junction, with Δ 2 greater than Δ 1 , when biased with eV 1 +Δ 2 , will lower the energy in S 1 . This energy reduction will be shared by the phonons and electrons. This device is shown to be analogous to a thermoelectric refrigerator with an effective Peltier coefficient π* approx. Δ 1 /e. Tunneling calculations yield the cooling power P/sub c/, the electrical power P/sub e/ supplied by the bias supply, and the cooling efficiency eta=P/sub c//P/sub e/. The maximum cooling power is obtained for eV= +- (Δ 2 -Δ 1 ) and t 1 =T 1 /T/sub c/1 approx. 0.9. Estimates are made of the temperature difference T 2 -T 1 achievable in Al-Pb and Sn-Pb junctions with an Al 2 O 3 tunneling barrier. The performance of this device is shown to yield a maximum cooling efficiency eta approx. = Δ 1 /(Δ 2 -Δ 1 ) which can be compared with that available in an ideal Carnot refrigerator of eta=T 1 /(T 2 -T 1 ). The development of a useful tunnel-junction refrigerator requires a tunneling barrier with an effective thermal conductance per unit area several orders of magnitude less than that provided by the A1 2 O 3 barrier in the Al-Pb and Sn-Pb systems

  3. Squeezed States in Josephson Junctions.

    Science.gov (United States)

    Hu, X.; Nori, F.

    1996-03-01

    We have studied quantum fluctuation properties of Josephson junctions in the limit of large Josephson coupling energy and small charging energy, when the eigenstates of the system can be treated as being nearly localized. We have considered(X. Hu and F. Nori, preprints.) a Josephson junction in a variety of situations, e.g., coupled to one or several of the following elements: a capacitor, an inductor (in a superconducting ring), and an applied current source. By solving an effective Shrödinger equation, we have obtained squeezed vacuum (coherent) states as the ground states of a ``free-oscillating'' (linearly-driven) Josephson junction, and calculated the uncertainties of its canonical momentum, charge, and coordinate, phase. We have also shown that the excited states of the various systems we consider are similar to the number states of a simple harmonic oscillator but with different fluctuation properties. Furthermore, we have obtained the time-evolution operators for these systems. These operators can make it easier to calculate the time-dependence of the expectation values and fluctuations of various quantities starting from an arbitrary initial state.

  4. Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different neuromuscular mechanisms: Preliminary report

    Directory of Open Access Journals (Sweden)

    Parker Stephen W

    2005-02-01

    Full Text Available Abstract Background Vestibular rehabilitation (VR is a well-accepted exercise program intended to remedy balance impairment caused by damage to the peripheral vestibular system. Alternative therapies, such as Tai Chi (TC, have recently gained popularity as a treatment for balance impairment. Although VR and TC can benefit people with vestibulopathy, the degree to which gait improvements may be related to neuromuscular adaptations of the lower extremities for the two different therapies are unknown. Methods We examined the relationship between lower extremity neuromuscular function and trunk control in 36 older adults with vestibulopathy, randomized to 10 weeks of either VR or TC exercise. Time-distance measures (gait speed, step length, stance duration and step width, lower extremity sagittal plane mechanical energy expenditures (MEE, and trunk sagittal and frontal plane kinematics (peak and range of linear and angular velocity, were measured. Results Although gait time-distance measures were improved in both groups following treatment, no significant between-groups differences were observed for the MEE and trunk kinematic measures. Significant within groups changes, however, were observed. The TC group significantly increased ankle MEE contribution and decreased hip MEE contribution to total leg MEE, while no significant changes were found within the VR group. The TC group exhibited a positive relationship between change in leg MEE and change in trunk velocity peak and range, while the VR group exhibited a negative relationship. Conclusion Gait function improved in both groups consistent with expectations of the interventions. Differences in each group's response to therapy appear to suggest that improved gait function may be due to different neuromuscular adaptations resulting from the different interventions. The TC group's improvements were associated with reorganized lower extremity neuromuscular patterns, which appear to promote a faster

  5. Stem cell route to neuromuscular therapies.

    Science.gov (United States)

    Partridge, Terence A

    2003-02-01

    As applied to skeletal muscle, stem cell therapy is a reincarnation of myoblast transfer therapy that has resulted from recent advances in the cell biology of skeletal muscle. Both strategies envisage the reconstruction of damaged muscle from its precursors, but stem cell therapy employs precursors that are earlier in the developmental hierarchy. It is founded on demonstrations of apparently multipotential cells in a wide variety of tissues that can assume, among others, a myogenic phenotype. The main demonstrated advantage of such cells is that they are capable of colonizing many tissues, including skeletal and cardiac muscle via the blood vascular system, thereby providing the potential for a body-wide distribution of myogenic progenitors. From a practical viewpoint, the chief disadvantage is that such colonization has been many orders of magnitude too inefficient to be useful. Proposals for overcoming this drawback are the subject of much speculation but, so far, relatively little experimentation. This review attempts to give some perspective to the status of the stem cell as a therapeutic instrument for neuromuscular disease and to identify issues that need to be addressed for application of this technology.

  6. Neuromuscular Fatigue During 200 M Breaststroke

    Directory of Open Access Journals (Sweden)

    Ana Conceição

    2014-03-01

    Full Text Available The aims of this study were: i to analyze activation patterns of four upper limb muscles (duration of the active and non-active phase in each lap of 200m breaststroke, ii quantify neuromuscular fatigue, with kinematics and physiologic assessment. Surface electromyogram was collected for the biceps brachii, deltoid anterior, pectoralis major and triceps brachii of nine male swimmers performing a maximal 200m breaststroke trial. Swimming speed, SL, SR, SI decreased from the 1st to the 3rd lap. SR increased on the 4th lap (35.91 ± 2.99 stroke·min-1. Peak blood lactate was 13.02 ± 1.72 mmol·l-1 three minutes after the maximal trial. The EMG average rectified value (ARV increased at the end of the race for all selected muscles, but the deltoid anterior and pectoralis major in the 1st lap and for biceps brachii, deltoid anterior and triceps brachii in the 4th lap. The mean frequency of the power spectral density (MNF decreased at the 4th lap for all muscles. These findings suggest the occurrence of fatigue at the beginning of the 2nd lap in the 200m breaststroke trial, characterized by changes in kinematic parameters and selective changes in upper limb muscle action. There was a trend towards a non-linear fatigue state.

  7. Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

    Directory of Open Access Journals (Sweden)

    Andreas Totzeck

    2016-09-01

    Full Text Available Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

  8. Peristalsis and propulsion of colonic content can occur after blockade of major neuroneuronal and neuromuscular transmitters in isolated guinea pig colon.

    Science.gov (United States)

    Sia, T C; Brookes, S J; Dinning, P G; Wattchow, D A; Spencer, N J

    2013-12-01

    We recently identified hexamethonium-resistant peristalsis in the guinea pig colon. We showed that, following acute blockade of nicotinic receptors, peristalsis recovers, leading to normal propagation velocities of fecal pellets along the colon. This raises the fundamental question: what mechanisms underlie hexamethonium-resistant peristalsis? We investigated whether blockade of the major receptors that underlie excitatory neuromuscular transmission is required for hexamethonium-resistant peristalsis. Video imaging of colonic wall movements was used to make spatiotemporal maps and determine the velocity of peristalsis. Propagation of artificial fecal pellets in the guinea pig distal colon was studied in hexamethonium, atropine, ω-conotoxin (GVIA), ibodutant (MEN-15596), and TTX. Hexamethonium and ibodutant alone did not retard peristalsis. In contrast, ω-conotoxin abolished peristalsis in some preparations and reduced the velocity of propagation in all remaining specimens. Peristalsis could still occur in some animals in the presence of hexamethonium + atropine + ibodutant + ω-conotoxin. Peristalsis never occurred in the presence of TTX. The major finding of the current study is the unexpected observation that peristalsis can occur after blockade of the major excitatory neuroneuronal and neuromuscular transmitters. Also, the colon retained an intrinsic polarity in the presence of these antagonists and was only able to expel pellets in an aboral direction. The nature of the mechanism(s)/neurotransmitter(s) that generate(s) peristalsis and facilitate(s) natural fecal pellet propulsion, after blockade of major excitatory neurotransmitters, at the neuroneuronal and neuromuscular junction remains to be identified.

  9. Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

    Science.gov (United States)

    Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

    2016-06-01

    Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Computerized tomography, magnetic resonance tomography, and magnetic resonance spectroscopy in neuromuscular disease

    International Nuclear Information System (INIS)

    Rodiek, S.O.

    1987-01-01

    This book is about imaging and the tissue characterization of skeletal muscles in vivo. It tries to answer the following questions: 1. Which examination techniques yield the highest quality of imaging results? 2. Which are the typical characteristics of a healthy skeletal muscle? 3. What alterations can be verified in skeletal muscles suffering neuromuscular disease - and are these specific of the disease? 4. What are the common traits of imaging techniques and what are the differences between them - and how can one make aimed use of these techniques?. With 56 figs., 21 tabs [de

  11. Pharmacokinetic studies of neuromuscular blocking agents: Good Clinical Research Practice (GCRP)

    DEFF Research Database (Denmark)

    Viby-Mogensen, J.; Østergaard, D.; Donati, F.

    2000-01-01

    Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design......Good Clinical Research Practice (GCRP), neuromuscular blocking agents, pharmacokinetics, pharmacokinetic/pharmacodynamic modeling, population pharmacokinetics, statistics, study design...

  12. Intraoperative neuromuscular monitoring site and residual paralysis.

    Science.gov (United States)

    Thilen, Stephan R; Hansen, Bradley E; Ramaiah, Ramesh; Kent, Christopher D; Treggiari, Miriam M; Bhananker, Sanjay M

    2012-11-01

    Residual paralysis is common after general anesthesia involving administration of neuromuscular blocking drugs (NMBDs). Management of NMBDs and reversal is frequently guided by train-of-four (TOF) monitoring. We hypothesized that monitoring of eye muscles is associated with more frequent residual paralysis than monitoring at the adductor pollicis. This prospective cohort study enrolled 180 patients scheduled for elective surgery with anticipated use of NMBDs. Collected variables included monitoring site, age, gender, weight, body mass index, American Society of Anesthesiologists physical status class, type and duration of surgery, type of NMBDs, last and total dose administered, TOF count at time of reversal, dose of neostigmine, and time interval between last dose of NMBDs to quantitative measurement. Upon postanesthesia care unit admission, we measured TOF ratios by acceleromyography at the adductor pollicis. Residual paralysis was defined as a TOF ratio less than 90%. Multivariable logistic regression was used to account for unbalances between the two groups and to adjust for covariates. 150 patients received NMBDs and were included in the analysis. Patients with intraoperative TOF monitoring of eye muscles had significantly greater incidence of residual paralysis than patients monitored at the adductor pollicis (P paralysis was observed in 51/99 (52%) and 11/51 (22%) of patients, respectively. The crude odds ratio was 3.9 (95% CI: 1.8-8.4), and the adjusted odds ratio was 5.5 (95% CI: 2.1-14.5). Patients having qualitative TOF monitoring of eye muscles had a greater than 5-fold higher risk of postoperative residual paralysis than those monitored at the adductor pollicis.

  13. Neuromuscular transmission in the athymic nude mouse.

    Science.gov (United States)

    Schofield, G G; Marshall, I G

    1980-10-01

    No major differences were observed in the mechanical properties of diaphragm, extensor digitorum longus and soleus muscles from athymic nude and control mice. Denervated soleus muscles from nudes and controls showed no significant differences in their sensitivities to the cholinoceptor agonists acetylcholine and carbachol, either in the absence or presence of the anticholinesterase, physostigmine, suggesting that postjunctional receptor function is essentially normal. Phrenic nerve-diaphragm preparations from nudes were less sensitive to the twitch-augmenting effects of neostigmine. No difference in the time course of endplate potentials (epps) between nudes and controls was seen either in the absence or presence of neostigmine. Hence the observed differences in twitch augmentation are unlikely to be due to differences in acetylcholinesterase activity in the two muscles. In normal mice miniature endplate potential (mepp) amplitude decreased and mepp frequency increased with age. These changes were associated with an increase in muscle fibre diameter and a concomitant decrease in membrane resistance. Such changes did not occur in nude mice; thus mepp amplitude remained, high as in young normal muscle. It is suggested that the thymus may play a role in muscle development and that the effects on neuromuscular transmission are secondary to changes in development. In cut diaphragm muscles transmitter reversal potentials in nudes and controls were not different. Although there was no difference in the amplitude of the first epp of a train, or in the immediately releasable acetylcholine store, the quantal content of the first epp, the probability of transmitter release, the total nerve terminal acetylcholine store and the transmitter mobilization rate were all reduced. It is considered probable that all the measurable differences in transmitter release can be explained in terms of the nude muscle fibre diameter being small and being associated with a small nerve terminal

  14. Redox homeostasis and age-related deficits in neuromuscular integrity and function.

    Science.gov (United States)

    Sakellariou, Giorgos K; Lightfoot, Adam P; Earl, Kate E; Stofanko, Martin; McDonagh, Brian

    2017-12-01

    Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age-related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this 'epidemic' problem, the primary biochemical and molecular mechanisms underlying age-related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age-associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age-related muscle atrophy and weakness. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  15. Is deep neuromuscular blockade beneficial in laparoscopic surgery?

    DEFF Research Database (Denmark)

    Madsen, M. V.; Staehr-Rye, A K; Claudius, C

    2016-01-01

    BACKGROUND: Deep neuromuscular blockade during laparoscopic surgery may provide some clinical benefit. We present the 'Pro-' argument in this paired position paper. METHODS: We reviewed recent evidence from a basic database of references which we agreed on with the 'Con-' side, and present...... this in narrative form. We have shared our analysis and text with the authors of the 'Con-' side of these paired position papers during the preparation of the manuscripts. RESULTS: There are a few low risk of bias studies indicating that use of deep neuromuscular blockade improve surgical conditions and improve...... patient outcomes such as post-operative pain in laparoscopic surgery. CONCLUSION: Our interpretation of recent findings is that there is reason to believe that there may be some patient benefit of deep neuromuscular blockade in this context, and more detailed study is needed....

  16. Neuromuscular economy, strength, and endurance in healthy elderly men.

    Science.gov (United States)

    Cadore, Eduardo Lusa; Pinto, Ronei Silveira; Alberton, Cristine Lima; Pinto, Stephanie Santana; Lhullier, Francisco Luiz Rodrigues; Tartaruga, Marcus Peikriszwili; Correa, Cleiton Silva; Almeida, Ana Paula Viola; Silva, Eduardo Marczwski; Laitano, Orlando; Kruel, Luiz Fernando Martins

    2011-04-01

    Declines in muscular strength resulting from reduced neural activity may influence the reduction in aerobic capacity in older men. However, there has been little investigation into the relationship between muscular strength and economy of movement during aerobic exercise in elderly subjects. Thus, the purpose of this study was to investigate the possible relationship between strength, aerobic performance, and neuromuscular economy in older men. Twenty-eight aged men (65 ± 4 years old) were evaluated in dynamic (1 repetition maximum test), isometric strength (maximal voluntary contraction), and rate of force development. Peak oxygen uptake, maximal workload, and ventilatory threshold were determined during a ramp protocol on a cycle ergometer. Throughout the same protocol, the neuromuscular economy (electromyographic signal) of the vastus lateralis was measured. Significant correlations were found between muscular strength, cardiorespiratory fitness, and neuromuscular economy (r = 0.43-0.64, p economy of movement are associated with muscular strength during aging.

  17. Effects of neuromuscular training (NEMEX-TJR) on patient-reported outcomes and physical function in severe primary hip or knee osteoarthritis

    DEFF Research Database (Denmark)

    Ageberg, Eva; Nilsdotter, Anna; Kosek, Eva

    2013-01-01

    The benefits of exercise in mild and moderate knee or hip osteoarthritis (OA) are apparent, but the evidence in severe OA is less clear. We recently reported that neuromuscular training was well tolerated and feasible in patients with severe primary hip or knee OA. The aims of this controlled...... before-and-after study were to compare baseline status to an age-matched population-based reference group and to examine the effects of neuromuscular training on patient-reported outcomes and physical function in patients with severe primary OA of the hip or knee....

  18. [Occipitocervical junction: Aanatomy, craniometry and pathology].

    Science.gov (United States)

    Furtner, J; Woitek, R; Asenbaum, U; Prayer, D; Schueller-Weidekamm, C

    2016-04-01

    The occipitocervical junction comprises of the occiput condyles, the atlas, and the axis. The radiological evaluation of this region is supported by craniometric measurement methods which are based on predefined anatomical landmarks. The main pathologies of the occipitocervical junction are traumatic injuries, congenital anomalies or normal variants, infections, arthropathies, and tumors. In this article, the anatomy of the occipitocervical junction as well as the most important craniometric measurement methods are explained. Moreover various pathologies and similar appearing normal variants are presented.

  19. Method for shallow junction formation

    Science.gov (United States)

    Weiner, Kurt H.

    1996-01-01

    A doping sequence that reduces the cost and complexity of forming source/drain regions in complementary metal oxide silicon (CMOS) integrated circuit technologies. The process combines the use of patterned excimer laser annealing, dopant-saturated spin-on glass, silicide contact structures and interference effects creates by thin dielectric layers to produce source and drain junctions that are ultrashallow in depth but exhibit low sheet and contact resistance. The process utilizes no photolithography and can be achieved without the use of expensive vacuum equipment. The process margins are wide, and yield loss due to contact of the ultrashallow dopants is eliminated.

  20. Josephson junctions as heterodyne detectors

    International Nuclear Information System (INIS)

    Taur, Y.; Claassen, J.H.; Richards, P.L.

    Heterodyne detection with a point-contact Josephson junction has been investigated both experimentally and theoretically. The measured performance of the device at 36 GHz is in good agreement with the theory. By operating vanadium point contacts at 1.4 K, the authors have achieved a single-sideband (SSB) mixer noise temperature of 54 K with a conversion gain of 1.35 and a signal bandwidth on the order of 1 GHz. A potentially impressive performance for these devices at submillimeter wavelengths can be extrapolated from the results

  1. Josephson junctions as heterodyne detectors

    International Nuclear Information System (INIS)

    Taur, Y.; Claassen, J.H.; Richards, P.L.

    1974-01-01

    Heterodyne detection with a point-contact Josephson junction has been investigated both experimentally and theoretically. The measured performance of the device at 36 GHz is in good agreement with the theory. By operating vanadium point contacts at 1.4 K, a single-sideband (SSB) mixer noise temperature of 54 K with a conversion gain of 1.35 and a signal bandwidth on the order of 1 GHz has been achieved. From the results one can extrapolate a potentially impressive performance for these devices at submillimeter wavelengths

  2. Exercise Therapy in Spinobulbar Muscular Atrophy and Other Neuromuscular Disorders

    DEFF Research Database (Denmark)

    Dahlqvist, Julia Rebecka; Vissing, John

    2016-01-01

    There is no curative treatment for most neuromuscular disorders. Exercise, as a treatment for these diseases, has therefore received growing attention. When executed properly, exercise can maintain and improve health and reduce the risk of cardiovascular disease, obesity, and diabetes. In persons...... in patients with neuromuscular diseases associated with weakness and wasting. We review studies that have investigated different types of exercise in both myopathies and motor neuron diseases, with particular emphasis on training of persons affected by spinobulbar muscular atrophy (SBMA). Finally, we provide...

  3. Magnetic resonance imaging of myoedema in neuromuscular diseases

    International Nuclear Information System (INIS)

    Schedel, H.; Vogel, T.; Lissner, J.; Reimers, C.C.

    1992-01-01

    Magnetic resonance imaging was done in 100 patients suffering from various generalized neuromuscular diseases. 30 (30%) showed higher signal intensities on T2-weighted images compared to T1-weighted images without contrast medium, indicating muscle edema. In inflammatory myopathies diffuse and severe muscle edema were found, whereas local and slight or moderate muscle edema were unspecific findings. In 10 patients also contrast enhanced T1-weighted images were done, showing no more sensitivity than T2-weighted images. In conclusion, we think that magnetic resonance imaging may contribute to differential diagnosis of neuromuscular diseases. (orig.) [de

  4. Neuromuscular activity and knee kinematics in adolescents with patellofemoral pain

    DEFF Research Database (Denmark)

    Rathleff, Michael Skovdal; Samani, Afshin; Olesen, Jens Lykkegaard

    2013-01-01

    This study aimed to investigate the neuromuscular control of the knee during stair descent among female adolescents with patellofemoral pain (PFP) and to report its association with self-reported clinical status assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS).......This study aimed to investigate the neuromuscular control of the knee during stair descent among female adolescents with patellofemoral pain (PFP) and to report its association with self-reported clinical status assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS)....

  5. Neuromuscular exercise as treatment of degenerative knee disease

    DEFF Research Database (Denmark)

    Ageberg, Eva; Roos, Ewa M.

    2015-01-01

    Exercise is recommended as first-line treatment of degenerative knee disease. Our hypothesis is that neuromuscular exercise is feasible and at least as effective as tradionally used strength or aerobic training, but aims to more closely target the sensorimotor deficiencies and functional...... instability associated with the degenerative knee disease than traditionally used training methods.SUMMARY FOR TABLE OF CONTENTS PAGECurrent data suggests that the effect from neuromuscular exercise on pain and function is comparable to the effects seen from other forms of exercise....

  6. Efectos del vendaje neuromuscular sobre la flexibilidad del raquis lumbar

    OpenAIRE

    A.M. Labrador-Cerrato; P. Ortega Sánchez-Diezma; G. Lanzas Melendo; C. Gutiérrez-Ortega

    2015-01-01

    Introducción: El vendaje neuromuscular es una técnica que produce una estimulación muy selectiva sobre la piel a través de la aplicación de unas vendas elásticas especiales con el fin de lograr cambios propioceptivos, aumento o inhibición del tono muscular y mitigación de algias, entre otros. Objetivos: Comprobar si la aplicación del vendaje neuromuscular permite aumentar la flexión del raquis lumbar comparándola con otras técnicas de vendaje placebo (esparadrapo rígido convencional; Omniplas...

  7. Neuromuscular hip biomechanics and pathology in the athlete.

    Science.gov (United States)

    Torry, Michael R; Schenker, Mara L; Martin, Hal D; Hogoboom, Doug; Philippon, Marc J

    2006-04-01

    Although hip arthroscopic techniques have been developed and evolved over the last 5 to 10 years to help active athletes, the mechanisms of athletic hip injuries across various sports are not well understood. The purpose of this article is to review the literature related to the osseous and ligamentous support as well as the neuromuscular control strategies associated with hip joint mechanics. The neuromuscular contributions to hip stability and mobility with respect to gait will be provided because this data represents the largest body of knowledge regarding hip function. Further, this article will present and describe probable mechanisms of injury in sporting activities most often associated with hip injury in the young athlete.

  8. An anterior cruciate ligament injury does not affect the neuromuscular function of the non-injured leg except for dynamic balance and voluntary quadriceps activation

    NARCIS (Netherlands)

    Zult, Tjerk; Gokeler, Alli; van Raay, Jos J. A. M.; Brouwer, Reinoud W.; Zijdewind, Inge; Hortobagyi, Tibor

    The function of the anterior cruciate ligament (ACL) patients' non-injured leg is relevant in light of the high incidence of secondary ACL injuries on the contralateral side. However, the non-injured leg's function has only been examined for a selected number of neuromuscular outcomes and often

  9. Graphene Josephson Junction Microwave Detector

    Science.gov (United States)

    Fong, Kin Chung; Walsh, Evan; Lee, Gil-Ho; Efetov, Dmitri; Crossno, Jesse; Ranzani, Leonardo; Ohki, Thomas; Kim, Philip; Englund, Dirk

    Modern readout schemes for superconducting qubits have predominately relied on weak microwave signal detection and discrimination. Most schemes are based on heterodyne or homodyne receiver systems and only a few have demonstrated direct detection of microwave photons. The challenges of direct detection stem from the low energy of microwave photons and existing detector efficiency. We have designed, fabricated, and measured a graphene-based Josephson junction (gJJ) microwave detector. Exploiting its low electronic thermal conductivity and specific heat, an electron temperature rise on the order of 0.1 K due to a time average of about 10 photons in the graphene thermal photodetector is readout via a Josephson junction embedded in an 8 GHz microwave cavity. We will estimate the quantum efficiency and dark count probability of the gJJ microwave single photon detectors. This document does not contain technology or technical data controlled under either the U.S. International Traffic in Arms Regulations or the U.S. Export Administration Regulations.

  10. [The eyelid-cheek junction].

    Science.gov (United States)

    Volpei, Ch; Fernandez, J; Chignon-Sicard, B

    2017-10-01

    The eyelid-cheek junction is a key area which generates many comments: from looking tired to looking good or rested, without forgetting charm, beauty, and a youthful appearance. In spite of many interesting medical and surgical procedures, treating this area is sometimes difficult and results are not always up to our expectations. Standardized blepharoplasty, which has often been improperly used, has shown its limits. Since the latest refinements, lipostructure has revolutionised blepharoplasty and serving as a reference, it has become an established technique. Subperiostal mediofacial lift allows outstanding results at the cost of a certain technical aggressiveness. Aesthetic medicine proposes worthy alternative and/or appropriate complementary solutions. Different procedures we dispose of have been reviewed together with their assets and their limits. A codification of therapeutic indications is proposed. The positioning of the eyelid-cheek clinical junction in relation with the low orbital bone rim influences our strategy in choosing the appropriate technique. Copyright © 2017. Published by Elsevier Masson SAS.

  11. Spectroscopy of Deep Traps in Cu2S-CdS Junction Structures

    Directory of Open Access Journals (Sweden)

    Eugenijus Gaubas

    2012-12-01

    Full Text Available Cu2S-CdS junctions of the polycrystalline material layers have been examined by combining the capacitance deep level transient spectroscopy technique together with white LED light additional illumination (C-DLTS-WL and the photo-ionization spectroscopy (PIS implemented by the photocurrent probing. Three types of junction structures, separated by using the barrier capacitance characteristics of the junctions and correlated with XRD distinguished precipitates of the polycrystalline layers, exhibit different deep trap spectra within CdS substrates.

  12. Bipolar junction transistor models for circuit simulation of cosmic-ray-induced soft errors

    Science.gov (United States)

    Benumof, R.; Zoutendyk, J.

    1984-01-01

    This paper examines bipolar junction transistor models suitable for calculating the effects of large excursions of some of the variables determining the operation of a transistor. Both the Ebers-Moll and Gummel-Poon models are studied, and the junction and diffusion capacitances are evaluated on the basis of the latter model. The most interesting result of this analysis is that a bipolar junction transistor when struck by a cosmic particle may cause a single event upset in an electronic circuit if the transistor is operated at a low forward base-emitter bias.

  13. Hemodynamic and lactic Acid responses to proprioceptive neuromuscular facilitation exercise.

    Science.gov (United States)

    Gültekin, Zuhal; Kin-Isler, Ayse; Sürenkök, Ozgür

    2006-01-01

    The hemodynamic and metabolic responses to proprioceptive neuromuscular facilitation (PNF) exercise were examined in 32 male university students (aged 19-28 years). Ten repetitions of PNF exercises were applied to the subjects' dominant upper extremities in the following order: as an agonist pattern flexion, adduction and external rotation; and as an antagonist pattern extension, abduction and internal rotation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), double product (DP), and blood lactate concentration (La) were determined before, immediately after, and at 1(st), 3(rd), and 5(th) minutes after PNF exercise. A one-way ANOVA with repeated measures indicated significant differences in HR, SBP, DBP, DP and La immediately after PNF exercise. HR increased from 81 (±10) to 108 (±15) b·min(-1) (p < 0.01), SBP increased from 117 (±10) to 125 (±11) mmHg (p < 0.01), DBP increased from 71 (±10) to 75 (±8) mmHg (p < 0.01), DP increased from 96 (±16) to 135 (±24) (p < 0.01), and La increased from 0.69 (±0.31) to 3.99 (±14.63) mmol·L(-1) (p < 0.01). Thus PNF exercise resulted in increased hemodynamic responses and blood lactate concentration that indicate a high strain on the cardiovascular system and anaerobic metabolism in healthy subjects. Key PointsPNF exercises resulted in increased hemodynamic responses.Repeated PNF exercises resulted in an increased blood lactate concentration.

  14. Computed tomography of the skeletal muscles in neuromuscular diseases

    International Nuclear Information System (INIS)

    Nagao, Hideo; Takahashi, Mitsugi; Habara, Shinji; Nagai, Yoshinao; Matsuda, Hiroshi

    1986-01-01

    Computed tomographic (CT) scans of the shoulder girdle, upper arm, waist, pelvic girdle, thigh, and lower leg were obtained in a total of 21 patients with neuromuscular diseases, including 10 with Duchenne muscle dystrophy (DMD), 3 with Fukushima type congenital muscular dystrophy (FCMD), 3 with Werdnig-Hoffmann's disease (WH), 3 with autosomal recessive muscular dystrophy in childhood (childhood MC), one with nemaline myopathy (NM), and one with myositis ossificans circumscripta (MOC). Age-dependent changes in CT findings were examined in the 10 DMD patients ranging in age from 3 to 15 years. Each muscle of the shoulder girdle and upper arm was seen as a low density area on CT in patients 9 years of age when the arms are difficult to elevate. Changes in the m. quadriceps femoris occurring in all the patients were visible earlist on CT, followed by those in the m. gluteus maximus, m. gastrocnemius, and m. soleus. CT scans of the thigh was thus considered most useful in diagnosing DMD. CT scans of the lower leg showed low density areas in the m. gastrocnemius and m. soleus in both WH and FCMD patients, while a low density area seen in the m. gluteus maximum on CT was restricted to FCMD patients. This suggests the potential of CT in the differentiation of WH from FCMD. In patients with childhood ARMD, there were various CT findings including normal and extremely low density areas. CT findings in NM patients were similar to those in DMD patients. High density areas were seen along the fascia of the trunk in MOC patients. (Namekawa, K.)

  15. Anormalidades neuromuscular no desuso, senilidade e caquexia

    Directory of Open Access Journals (Sweden)

    João Aris Kouyoumdjian

    1993-09-01

    Full Text Available É feita revisão de literatura sobre as principais alterações do sistema neuromuscular no desuso, senilidade e caquexia no ser humano e em modelos animais. A diminuição do diâmetro das fibras musculares após período de inatividade/imobilidade (desuso deve-se à perda de miofibrilas periféricas não ocorrendo formação de core-targetóides ou diminuição da atividade da miofosforilase, próprias da desnervação; mantêm-se a liberação espontânea de acetilcolina e fatores tróficos na junção mio-neural; em geral são afetadas preferencialmente fibras II, que podem assumir forma angular. Existe um processo contínuo intrínseco de envelhecimento de nervos e músculos, com desnervação e reinervação lenta e progressiva; o número de unidades motoras se reduz após 60 anos, sem ocorrência de atividade elétrica desnervatória; a quantidade de acetilcolina liberada nos neurônios terminais e a capacidade máxima de utilização de oxigênio estão diminuídas; a redução da capacidade oxidativa mitocondrial pode explicar o aumento de fibras I, mantendo-se o equilíbrio energético. Após poucas semanas de caquexia as fibras musculares podem ter o diâmetro reduzido em 30%, essa redução ocorre em ordem decrescente nos músculos dos membros inferiores, superiores e tronco; existe atrofia II preferencial com fibras angulares ocasionais, redução de RNA/síntese proteica, mantendo-se DNA normal.

  16. Effects of hamstring-emphasized neuromuscular training on strength and sprinting mechanics in football players.

    Science.gov (United States)

    Mendiguchia, J; Martinez-Ruiz, E; Morin, J B; Samozino, P; Edouard, P; Alcaraz, P E; Esparza-Ros, F; Mendez-Villanueva, A

    2015-12-01

    The objective of this study was to examine the effects of a neuromuscular training program combining eccentric hamstring muscle strength, plyometrics, and free/resisted sprinting exercises on knee extensor/flexor muscle strength, sprinting performance, and horizontal mechanical properties of sprint running in football (soccer) players. Sixty footballers were randomly assigned to an experimental group (EG) or a control group (CG). Twenty-seven players completed the EG and 24 players the CG. Both groups performed regular football training while the EG performed also a neuromuscular training during a 7-week period. The EG showed a small increases in concentric quadriceps strength (ES = 0.38/0.58), a moderate to large increase in concentric (ES = 0.70/0.74) and eccentric (ES = 0.66/0.87) hamstring strength, and a small improvement in 5-m sprint performance (ES = 0.32). By contrast, the CG presented lower magnitude changes in quadriceps (ES = 0.04/0.29) and hamstring (ES = 0.27/0.34) concentric muscle strength and no changes in hamstring eccentric muscle strength (ES = -0.02/0.11). Thus, in contrast to the CG (ES = -0.27/0.14), the EG showed an almost certain increase in the hamstring/quadriceps strength functional ratio (ES = 0.32/0.75). Moreover, the CG showed small magnitude impairments in sprinting performance (ES = -0.35/-0.11). Horizontal mechanical properties of sprint running remained typically unchanged in both groups. These results indicate that a neuromuscular training program can induce positive hamstring strength and maintain sprinting performance, which might help in preventing hamstring strains in football players. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Neuromuscular Control Deficits and the Risk of Subsequent Injury after a Concussion: A Scoping Review.

    Science.gov (United States)

    Howell, David R; Lynall, Robert C; Buckley, Thomas A; Herman, Daniel C

    2018-05-01

    An emerging area of research has identified that an increased risk of musculoskeletal injury may exist upon returning to sports after a sport-related concussion. The mechanisms underlying this recently discovered phenomenon, however, remain unknown. One theorized reason for this increased injury risk includes residual neuromuscular control deficits that remain impaired despite clinical recovery. Thus, the objectives of this review were: (1) to summarize the literature examining the relationship between concussion and risk of subsequent injury and (2) to summarize the literature for one mechanism with a theorized association with this increased injury risk, i.e., neuromuscular control deficits observed during gait after concussion under dual-task conditions. Two separate reviews were conducted consistent with both specified objectives. Studies published before 9 December, 2016 were identified using PubMed, Web of Science, and Academic Search Premier (EBSCOhost). Inclusion for the objective 1 search included dependent variables of quantitative measurements of musculoskeletal injury after concussion. Inclusion criteria for the objective 2 search included dependent variables pertaining to gait, dynamic balance control, and dual-task function. A total of 32 studies were included in the two reviews (objective 1 n = 10, objective 2 n = 22). According to a variety of study designs, athletes appear to have an increased risk of sustaining a musculoskeletal injury following a concussion. Furthermore, dual-task neuromuscular control deficits may continue to exist after patients report resolution of concussion symptoms, or perform normally on other clinical concussion tests. Therefore, musculoskeletal injury risk appears to increase following a concussion and persistent motor system and attentional deficits also seem to exist after a concussion. While not yet experimentally tested, these motor system and attentional deficits may contribute to the risk of sustaining a

  18. Cause of exercise associated muscle cramps (EAMC)--altered neuromuscular control, dehydration or electrolyte depletion?

    Science.gov (United States)

    Schwellnus, M P

    2009-06-01

    Exercise Associated Muscle Cramps (EAMC) is one of the most common conditions that require medical attention during or immediately after sports events. Despite the high prevalence of this condition the aetiology of EAMC in athletes is still not well understood. The purpose of this review is to examine current scientific evidence in support of (1) the "electrolyte depletion" and "dehydration" hypotheses and (2) the "altered neuromuscular control" hypothesis in the aetiology of EAMC. In this review, scientific evidence will, as far as possible, be presented using evidence-based medicine criteria. This is particularly relevant in this field, as the quality of experimental methodology varies considerably among studies that are commonly cited in support of hypotheses to explain the aetiology of EAMC. Scientific evidence in support of the "electrolyte depletion" and "dehydration" hypotheses for the aetiology of EAMC comes mainly from anecdotal clinical observations, case series totalling 18 cases, and one small (n = 10) case-control study. Results from four prospective cohort studies do not support these hypotheses. In addition, the "electrolyte depletion" and "dehydration" hypotheses do not offer plausible pathophysiological mechanisms with supporting scientific evidence that could adequately explain the clinical presentation and management of EAMC. Scientific evidence for the "altered neuromuscular control" hypothesis is based on evidence from research studies in human models of muscle cramping, epidemiological studies in cramping athletes, and animal experimental data. Whilst it is clear that further evidence to support the "altered neuromuscular control" hypothesis is also required, research data are accumulating that support this as the principal pathophysiological mechanism for the aetiology of EAMC.

  19. Differences in neuromuscular strategies between landing and cutting tasks in female basketball and soccer athletes.

    Science.gov (United States)

    Cowley, Hanni R; Ford, Kevin R; Myer, Gregory D; Kernozek, Thomas W; Hewett, Timothy E

    2006-01-01

    High school female athletes are most likely to sustain a serious knee injury during soccer or basketball, 2 sports that often involve a rapid deceleration before a change of direction or while landing from a jump. To determine if female high school basketball and soccer players show neuromuscular differences during landing and cutting tasks and to examine neuromuscular differences between tasks and between dominant and nondominant sides. A 3-way mixed factorial design investigating the effects of sport (basketball, soccer), task (jumping, cutting), and side (dominant, nondominant). Laboratory. Thirty high school female athletes who listed either basketball or soccer as their only sport of participation (basketball: n = 15, age = 15.1 +/- 1.7 years, experience = 6.9 +/- 2.2 years, height = 165.3 +/- 7.9 cm, mass = 61.8 +/- 9.3 kg; soccer: n = 15, age = 14.8 +/- 0.8 years, experience = 8.8 +/- 2.5 years, height = 161.8 +/- 4.1 cm, mass = 54.6 +/- 7.6 kg). Ground reaction forces, stance time, valgus angles, and valgus moments were assessed during (1) a drop vertical jump with an immediate maximal vertical jump and (2) an immediate side-step cut at a 45 degrees angle. Basketball athletes had greater ground reaction forces (P vertical jump, whereas soccer players had greater ground reaction forces (P vertical jump. Greater valgus moments (P = .006) were noted on the dominant side during cutting. Our subjects demonstrated differences in ground reaction forces and stance times during 2 movements associated with noncontact anterior cruciate ligament injuries. Knee valgus moment and angle were significantly influenced by the type of movement performed. Sport-specific neuromuscular training may be warranted, with basketball players focusing on jumping and landing and soccer players focusing on unanticipated cutting maneuvers.

  20. Dysarthria and dysphagia are highly prevalent among various types of neuromuscular diseases.

    Science.gov (United States)

    Knuijt, Simone; Kalf, Johanna G; de Swart, Bert J M; Drost, Gea; Hendricks, Henk T; Geurts, Alexander C H; van Engelen, Baziel G M

    2014-01-01

    Patients with a neuromuscular disease (NMD) can present with dysarthria and/or dysphagia. Literature regarding prevalence rates of dysarthria and dysphagia is scarce. The purpose of this study was to determine prevalence rates, severity and co-presence of dysarthria and dysphagia in adult patients with NMD. Two groups of adult patients with NMD were included: 102 consecutive outpatients (the "unselected cohort") and 118 consecutive patients who were referred for multidisciplinary assessment (the "selected cohort"). An experienced speech-language pathologist examined each patient in detail. The pooled prevalence of dysarthria was 46% (95% CI: 36.5-55.9) and 62% (95% CI: 53.3-70.8) in the unselected and selected cohorts, respectively. The pooled prevalence of dysphagia was 36% (95% CI: 27.1-45.7) and 58% (95% CI: 49.4-67.2) in the unselected and selected cohorts, respectively. There was a modest but significant association between the presence of dysarthria and dysphagia (rs = 0.40; p dysarthria was moderate to severe in 15% of the dysarthric patients. The prevalence rates of dysarthria and dysphagia among patients with various types of NMD are high. Physicians should therefore be aware of this prevalence and consider referring NMD patients to a speech-language pathologist. IMPLICATONS OF REHABILITATION: Both dysarthria and dysphagia are highly prevalent among patients with neuromuscular diseases; moreover, although often mild, these disorders can occur relatively early in the course of the disease. Clinicians should routinely check for signs and symptoms related to dysarthria and/or dysphagia in patients who present with a neuromuscular disease, preferably using standardised instruments.

  1. Sport-specific functional movement can simulate aspects of neuromuscular fatigue occurring in team sports.

    Science.gov (United States)

    Wilke, Jan; Fleckenstein, Johannes; Krause, Frieder; Vogt, Lutz; Banzer, Winfried

    2016-06-01

    Fatigue protocols have been used over the years to examine muscular exhaustion. As an alternative to approaches in laboratory settings, functional agility protocols claiming to mimic the multifaceted loads of athletic activity have been proposed. This study aimed to examine the effects of a functional agility short-term fatigue protocol (FAST-FP) on neuromuscular function. Twenty-eight healthy sports students (15 males, aged 24.3 ± 2.4 years) completed the FAST-FP, which consists of four components: three counter-movement jumps (90% of individual maximum), a 20-s bout of step-ups, three bodyweight squats and an agility run. Tasks were repeated until the participants no longer achieved the required jump height in two consecutive sets. Outcomes (pre-post) encompassed subjective exhaustion (visual analogue scale [VAS]), maximum isometric voluntary force of the knee extensors (MIVF), reactive strength index (RSI), mean power frequency (MPF, measured using surface electromyography) and maximum knee range of motion (ROM). Post-intervention, VAS (+54 mm) increased significantly, while MIVF (-6.1%), RSI (-10.7%) and MPF (-4.1%) were reduced (p  0.05). The FAST-FP induces small-to-moderate impairments in neuromuscular function and considerable self-perceived fatigue. Current evidence on exhaustion developing in team sports suggests that this magnitude of fatigue is similar. The protocol might thus be valuable in the evaluation of treatments counteracting post-match fatigue in team sports.

  2. Multiplication in Silicon p-n Junctions

    DEFF Research Database (Denmark)

    Moll, John L.

    1965-01-01

    Multiplication values were measured in the collector junctions of silicon p-n-p and n-p-n transistors before and after bombardment by 1016 neutrons/cm2. Within experimental error there was no change either in junction fields, as deduced from capacitance measurements, or in multiplication values...

  3. Gap junctions and connexin-interacting proteins

    NARCIS (Netherlands)

    Giepmans, Ben N G

    2004-01-01

    Gap junctions form channels between adjacent cells. The core proteins of these channels are the connexins. Regulation of gap junction communication (GJC) can be modulated by connexin-associating proteins, such as regulatory protein phosphatases and protein kinases, of which c-Src is the

  4. Sex differences in neuromuscular fatigability in response to load carriage in the field in British Army recruits.

    Science.gov (United States)

    O'Leary, Thomas J; Saunders, Samantha C; McGuire, Stephen J; Izard, Rachel M

    2017-10-23

    Women are resistant to neuromuscular fatigue compared to men in response to a range of exercise tasks. The sex differences in the neuromuscular responses to load carriage have yet to be investigated. Prospective cohort study. Twenty-three male and 19 female British Army recruits completed a 9.7km loaded march within 90min, with the weight carried dependent on military trade (16±2kg for men and 15±1kg for women). Isometric maximal voluntary contraction (MVC) force of the knee extensors and vertical jump (VJ) height were examined pre- and post-loaded march to examine neuromuscular fatigue. Heart rate (HR) was recorded throughout and ratings of perceived exertion (RPE) was recorded following the march. HR was higher for women (173±9bmin -1 , 83±6% heart rate reserve) than men (158±8bmin -1 , 72±6% heart rate reserve) (p≤0.001). RPE following the march was also higher for women than men (6±2 vs 4±2, respectively, ploss in MVC force was greater for men than women (-12±9% vs -9±13%, respectively, p=0.031), however VJ height was impaired to a similar extent (-5±11% vs -5±6%, respectively, p=0.582). The greater physiological stress during load carriage for women compared to men did not translate to a greater severity of knee extensor muscle fatigue, with women demonstrating fatigue resistance. Copyright © 2017. Published by Elsevier Ltd.

  5. An anterior cruciate ligament injury does not affect the neuromuscular function of the non-injured leg except for dynamic balance and voluntary quadriceps activation.

    Science.gov (United States)

    Zult, Tjerk; Gokeler, Alli; van Raay, Jos J A M; Brouwer, Reinoud W; Zijdewind, Inge; Hortobágyi, Tibor

    2017-01-01

    The function of the anterior cruciate ligament (ACL) patients' non-injured leg is relevant in light of the high incidence of secondary ACL injuries on the contralateral side. However, the non-injured leg's function has only been examined for a selected number of neuromuscular outcomes and often without appropriate control groups. We measured a broad array of neuromuscular functions between legs of ACL patients and compared outcomes to age, sex, and physical activity matched controls. Thirty-two ACL-deficient patients (208 ± 145 days post-injury) and active and less-active controls (N = 20 each) participated in the study. We measured single- and multi-joint neuromuscular function in both legs in each group and expressed the overall neuromuscular function in each leg by calculating a mean z-score across all neuromuscular measures. A group by leg MANOVA and ANOVA were performed to examine group and leg differences for the selected outcomes. After an ACL injury, duration (-4.3 h/week) and level (Tegner activity score of -3.9) of sports activity decreased and was comparable to less-active controls. ACL patients showed bilateral impairments in the star excursion balance test compared to both control groups (P ≤ 0.004) and for central activation ratio compared to active controls (P ≤ 0.002). There were between-leg differences within each group for maximal quadriceps and hamstring strength, voluntary quadriceps activation, star excursion balance test performance, and single-leg hop distance (all P quadriceps force accuracy and variability, knee joint proprioception, and static balance. Overall neuromuscular function (mean z-score) did not differ between groups, but ACL patients' non-injured leg displayed better neuromuscular function than the injured leg (P quadriceps activation, ACL patients had no bilateral neuromuscular deficits despite reductions in physical activity after injury. Therapists can use the non-injured leg as a reference to assess the

  6. Neuromuscular Electrical Stimulation for Motor Restoration in Hemiplegia

    Science.gov (United States)

    Knutson, Jayme S.; Fu, Michael J.; Sheffler, Lynne R.; Chae, John

    2015-01-01

    Synopsis This article reviews the most common therapeutic and neuroprosthetic applications of neuromuscular electrical stimulation (NMES) for upper and lower extremity stroke rehabilitation. Fundamental NMES principles and purposes in stroke rehabilitation are explained. NMES modalities used for upper and lower limb rehabilitation are described and efficacy studies are summarized. The evidence for peripheral and central mechanisms of action is also summarized. PMID:26522909

  7. Neuromuscular stimulation after stroke: from technology to clinical deployment

    NARCIS (Netherlands)

    IJzerman, Maarten Joost; Renzenbrink, Gerbert J.; Geurts, Alexander C.H.

    2009-01-01

    Since the early 1960s, electrical or neuromuscular electrical stimulation (NMES) has been used to support the rehabilitation of stroke patients. One of the earliest applications of NMES included the use of external muscle stimulation to correct drop-foot after stroke. During the last few decades

  8. Neuromuscular stimulation after stroke: from technology to clinical deployment.

    NARCIS (Netherlands)

    IJzerman, M.J.; Renzenbrink, G.J.; Geurts, A.C.H.

    2009-01-01

    Since the early 1960s, electrical or neuromuscular electrical stimulation (NMES) has been used to support the rehabilitation of stroke patients. One of the earliest applications of NMES included the use of external muscle stimulation to correct drop-foot after stroke. During the last few decades

  9. Neuromuscular Bandage: Neurophysiological Effects and the Role of Fascias

    Directory of Open Access Journals (Sweden)

    Ximena María Villota Chicaíza

    2014-05-01

    Full Text Available During the last years, neuromuscular bandage, a therapeutic application created in 1979 by doctor Kenzo Kase has been introduced in the management of many disorders of the musculo-skeletal system and even more so in the treatment of neurological disorders; This therapeutic tool which consists of a self adhesive elastic bandage allows recovery of the injured party without diminishing its bodily function. According to the existing literature on the physiological effects of this therapeutic application in the body, you could say that there is consensus. However in this article the author wants to highlight the significant although little highlighted role played by the fas¬cias on the therapeutic effects of neuromuscular bandage, analyzing from a reflective perspective the analgesic, neuromechanical and circulatory effects, as fundamental effects of neuromuscular bandage and fascias in the same function, trying to bring a global understanding on the way they relate to all connective tissues, aspects that are of great importance for the proper evaluation of alterations and prescription of neuromuscular bandage

  10. Diagnostic value of CT scanning in neuromuscular diseases

    International Nuclear Information System (INIS)

    Bulcke, J.A.L.; Leuven Univ.; Herpels, V.

    1983-01-01

    The diagnosis of myopathies has become easier since the CT technique is available. In this article the possibilities of CT for diagnostic procedures of neuromuscular diseases are pointed out. Density measurements increase differentiation of atrophy or hypertrophy of muscles as well as other pathological changes. (orig.)

  11. Deep neuromuscular block improves the surgical conditions for laryngeal microsurgery.

    Science.gov (United States)

    Kim, H J; Lee, K; Park, W K; Lee, B R; Joo, H M; Koh, Y W; Seo, Y W; Kim, W S; Yoo, Y C

    2015-12-01

    Adequate neuromuscular block is required throughout laryngeal microsurgery. We hypothesized that the surgical conditions would improve under a deeper level of rocuronium-induced neuromuscular block. Seventy-two patients undergoing laryngeal microsurgery were randomly allocated to either the 'post-tetanic counts 1-2' (PTC1-2) group or the 'train-of-four counts 1-2' (TOFcount1-2) group according to the level of neuromuscular block used. Two different doses of rocuronium (1.2 or 0.5 mg kg(-1)) were used after anaesthetic induction, and two respective targets of neuromuscular block (post-tetanic counts ≤2 or train-of-four count of 1 or 2) were used. Surgical conditions were assessed by the surgeon using a five-point rating scale (extremely poor/poor/acceptable/good/optimal), and clinically acceptable surgical conditions were defined as those which were rated acceptable, good, or optimal. The occurrence of vocal cord movement and postoperative adverse events was assessed. The surgical conditions were significantly different between the PTC1-2 and TOFcount1-2 groups (extremely poor/poor/acceptable/good/optimal: 0/2/1/7/26 and 3/10/2/14/7, respectively, Pneuromuscular block (post-tetanic count of 1-2) surgical conditions in patients undergoing laryngeal microsurgery improves. NCT01980069. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Neuromuscular function during stair descent in meniscectomized patients and controls

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Roos, Ewa M; Aagaard, Per

    2011-01-01

    The aim of this study was to identify differences in knee range of motion (ROM), movement speed, ground reaction forces (GRF) profile, neuromuscular activity, and muscle coactivation during the transition between stair descent and level walking in meniscectomized patients at high risk of knee...

  13. Drug Development and Challenges for Neuromuscular Clinical Trials.

    Science.gov (United States)

    El Mouelhi, Mohamed

    2016-03-01

    Drug development process faces many challenges, including those encountered in clinical trials for neuromuscular diseases. Drug development is a lengthy and highly costly process. Out of 10 compounds entering first study in man (phase 1), only one compound reaches the market after an average of 14 years with a cost of $2.7 billion. Nevertheless, according to the Centers for Medicare and Medicaid services, prescription drugs constituted only 9 % of each health care dollar spent in USA in 2013. Examples of challenges encountered in neuromuscular clinical trials include lack of validated patient-reported outcome tools, blinding issues, and the use of placebo in addition to lack of health authority guidance for orphan diseases. Patient enrollment challenge is the leading cause of missed clinical trial deadlines observed in about 80 % of clinical trials, resulting in delayed availability of potentially life-saving therapies. Another specific challenge introduced by recent technology is the use of social media and risk of bias. Sharing personal experiences while in the study could easily introduce bias among patients that would interfere with accurate interpretation of collected data. To minimize this risk, recent neuromuscular studies incorporate as an inclusion criterion the patient's agreement not to share any of study experiences through social media with other patients during the study conduct. Consideration of these challenges will allow timely response to the high unmet medical needs for many neuromuscular diseases.

  14. Use of nondepolarizing neuromuscular blocking agents in mechanically ventilated patients.

    Science.gov (United States)

    Buck, M L; Reed, M D

    1991-01-01

    The pharmacology and history of development of nondepolarizing neuromuscular blocking agents are presented, and the pharmacokinetics and pharmacodynamics of these agents, administration guidelines for mechanically ventilated patients, adverse effects, factors affecting paralysis, and methods for blockade reversal are reviewed. Nondepolarizing neuromuscular blocking agents (tubocurarine, metocurine, pancuronium, vecuronium, and atracurium) are frequently used to induce prolonged pharmacologic paralysis in patients in the intensive-care unit (ICU). These agents are poorly absorbed after oral administration and must be administered by injection, preferably by the i.v. route. Individualized adjustment of the dose is necessary to maintain the desired degree of paralysis. Dosing modifications may be necessary in patients with underlying renal or hepatic diseases and in pediatric and geriatric patients. Patients with thermal burns require larger doses of these drugs than other patients. These agents can cause several important adverse effects, including histamine release, cardiovascular changes, and muscle atrophy. Pathophysiologic variables and drug interactions can affect the degree of paralysis. Generally, patients no longer requiring paralysis in the ICU will be allowed to spontaneously regain muscle function after drug therapy has been discontinued. If the effects of the nondepolarizing neuromuscular blocking agents must be reversed more rapidly, acetylcholinesterase-inhibiting agents such as physostigmine, neostigmine, pyridostigmine, and edrophonium can be used. Nondepolarizing neuromuscular blocking agents can be used to paralyze mechanically ventilated patients, facilitating optimal oxygenation and ventilation.

  15. Imaging of respiratory muscles in neuromuscular disease: A review.

    Science.gov (United States)

    Harlaar, L; Ciet, P; van der Ploeg, A T; Brusse, E; van der Beek, N A M E; Wielopolski, P A; de Bruijne, M; Tiddens, H A W M; van Doorn, P A

    2018-03-01

    Respiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease. Copyright © 2017. Published by Elsevier B.V.

  16. Comparison of the Effect of Neuromuscular Electrical Stimulation ...

    African Journals Online (AJOL)

    Children with cerebral palsy (CP) often demonstrate poor hand function due to spasticity. Thus spasticity in the wrist and finger flexors poses a great deal of functional limitations. This study was therefore designed to compare the effectiveness of Cryotherapy and Neuromuscular Electrical Stimulation (NMES) on spasticity ...

  17. Neuromuscular and mitochondrial disorders: what is relevant to the anaesthesiologist?

    NARCIS (Netherlands)

    Driessen, J.J.

    2008-01-01

    PURPOSE OF REVIEW: The review provides an up-to-date information to the anaesthesiologist about the more frequent and important neuromuscular disorders for which new basic insights or clinical implications have been reported. RECENT FINDINGS: The findings include the mechanisms of the hyperkalemia

  18. neuromuscular disease mimicking myasthenia gravis in a nigerian

    African Journals Online (AJOL)

    neuromuscular diseases characterized by abnormal neurotransmission at the motor endplate resulting .... Gait was normal. An assessment of background Myasthenia Gravis in remission with Cor Pulmonale to rule out. Cardiomyopathy and Chronic renal failure was made. She was commenced on intravenous frusemide ...

  19. Biochemistry of Neuromuscular Diseases: A Course for Undergraduate Students

    Science.gov (United States)

    Ohlendieck, Kay

    2002-01-01

    This article outlines an undergraduate course focusing on supramolecular membrane protein complexes involved in the molecular pathogenesis of neuromuscular disorders. The emphasis of this course is to introduce students to the key elements involved in the ion regulation and membrane stabilization during muscle contraction and the role of these…

  20. Selective activation of neuromuscular compartments within the human trapezius muscle

    DEFF Research Database (Denmark)

    Holtermann, A; Roeleveld, K; Mork, P J

    2009-01-01

    to >12% and selective activation of at least one of the four anatomical subdivisions of the trapezius...... of the human trapezius muscle can be independently activated by voluntary command, indicating neuromuscular compartmentalization of the trapezius muscle. The independent activation of the upper and lower subdivisions of the trapezius is in accordance with the selective innervation by the fine cranial and main...

  1. Organizing Multidisciplinary Care for Children with Neuromuscular Diseases

    NARCIS (Netherlands)

    van der Velde, M.F.; Kortbeek, Nikky; Litvak, Nelli

    The Academic Medical Center (AMC) in Amsterdam, The Netherlands, recently opened the `Children's Muscle Center Amsterdam' (CMCA). The CMCA diagnoses and treats children with neuromuscular diseases. These patients require care from a variety of clinicians. Through the establishment of the CMCA,

  2. Quantum synchronization effects in intrinsic Josephson junctions

    International Nuclear Information System (INIS)

    Machida, M.; Kano, T.; Yamada, S.; Okumura, M.; Imamura, T.; Koyama, T.

    2008-01-01

    We investigate quantum dynamics of the superconducting phase in intrinsic Josephson junctions of layered high-T c superconductors motivated by a recent experimental observation for the switching rate enhancement in the low temperature quantum regime. We pay attention to only the capacitive coupling between neighboring junctions and perform large-scale simulations for the Schroedinger equation derived from the Hamiltonian considering the capacitive coupling alone. The simulation focuses on an issue whether the switching of a junction induces those of the other junctions or not. The results reveal that the superconducting phase dynamics show synchronous behavior with increasing the quantum character, e.g., decreasing the junction plane area and effectively the temperature. This is qualitatively consistent with the experimental result

  3. Overlap junctions for high coherence superconducting qubits

    Science.gov (United States)

    Wu, X.; Long, J. L.; Ku, H. S.; Lake, R. E.; Bal, M.; Pappas, D. P.

    2017-07-01

    Fabrication of sub-micron Josephson junctions is demonstrated using standard processing techniques for high-coherence, superconducting qubits. These junctions are made in two separate lithography steps with normal-angle evaporation. Most significantly, this work demonstrates that it is possible to achieve high coherence with junctions formed on aluminum surfaces cleaned in situ by Ar plasma before junction oxidation. This method eliminates the angle-dependent shadow masks typically used for small junctions. Therefore, this is conducive to the implementation of typical methods for improving margins and yield using conventional CMOS processing. The current method uses electron-beam lithography and an additive process to define the top and bottom electrodes. Extension of this work to optical lithography and subtractive processes is discussed.

  4. Cranio-vertebral junction tuberculosis

    Directory of Open Access Journals (Sweden)

    Rajkumar

    2012-01-01

    Full Text Available There are variety of diseases which affect the region of craniovertebral junction, including congenital, malignant lesions, traumatic and infective/inflammatory lesions. CVJ tuberculosis is an extremely rare condition, accounting for 0.3 to 1% of all cases of spinal TB. Few case series have been reported in the literature about this rare condition, but there appears to be lack of consensus even on basic issues like whether to undertake surgical intervention or prefer a conservative approach in cases of CVJ TB. These cases can present with a myriad of symptoms and one needs to have a high index of suspicion for early diagnosis. Early diagnosis and treatment is very important for a favorable outcome. In this article, we have tried to review the available literature and also share our experience about this condition so as to have a better understanding of the disease process and have a more rational treatment protocol.

  5. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.

    1993-01-01

    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc biased...... at different points in the current-voltage characteristic. Both numerical calculations based on the Tien-Gordon theory and 70-GHz microwave experiments have confirmed the wide dynamic range (more than 15-dB attenuation for one stage) and the low insertion loss in the ''open'' state. The performance of a fully...... integrated submillimeter receiver circuit which comprises a flux-flow oscillator (FFO) as local oscillator, a superconducting variable attenuator, and a microwave SIS detector with tuned-out capacitance is also reported....

  6. Does a mental training session induce neuromuscular fatigue?

    Science.gov (United States)

    Rozand, Vianney; Lebon, Florent; Papaxanthis, Charalambos; Lepers, Romuald

    2014-10-01

    Mental training, as physical training, enhances muscle strength. Whereas the repetition of maximal voluntary contractions (MVC) induces neuromuscular fatigue, the effect of maximal imagined contractions (MIC) on neuromuscular fatigue remains unknown. Here, we investigated neuromuscular alterations after a mental training session including MIC, a physical training session including MVC, and a combined training session including both MIC and MVC of the elbow flexor muscles. Ten participants performed 80 MIC (duty cycle, 5-s MIC and 10-s rest), 80 MVC (identical duty cycle), or 80 MVC and 80 MIC (5-s MVC, 2-s rest, 5-s MIC, and 3-s rest) in three separate sessions. MVC torque was assessed five times over the course of the training and 10 min after the end of the training in the three protocols. Central activation ratio (CARc), reflecting central fatigue, and corticospinal excitability, at rest and during MIC, were estimated using transcranial magnetic stimulation. Both the physical training and the combined training induced an approximately 40% drop of MVC torque, accompanied with an approximately 10% decrease of CARc without significant difference between the two sessions. On the contrary, the repetition of MIC did not reduce maximal force production capacity and did not alter CARc. Corticospinal excitability was always facilitated during MIC compared with that during rest, ensuring that the participants imagined the desired movement. These results suggested that one session of mental training alone or combined with physical training do not induce (additional) neuromuscular fatigue despite the repetitive activation of the corticospinal track. Motor imagery may be added to physical practice to increase the total workload without exacerbating neuromuscular fatigue.

  7. Resonance Transport of Graphene Nanoribbon T-Shaped Junctions

    International Nuclear Information System (INIS)

    Xiao-Lan, Kong; Yong-Jian, Xiong

    2010-01-01

    We investigate the transport properties of T-shaped junctions composed of armchair graphene nanoribbons of different widths. Three types of junction geometries are considered. The junction conductance strongly depends on the atomic features of the junction geometry. When the shoulders of the junction have zigzag type edges, sharp conductance resonances usually appear in the low energy region around the Dirac point, and a conductance gap emerges. When the shoulders of the junction have armchair type edges, the conductance resonance behavior is weakened significantly, and the metal-metal-metal junction structures show semimetallic behaviors. The contact resistance also changes notably due to the various interface geometries of the junction

  8. Valley dependent transport in graphene L junction

    Science.gov (United States)

    Chan, K. S.

    2018-05-01

    We studied the valley dependent transport in graphene L junctions connecting an armchair lead and a zigzag lead. The junction can be used in valleytronic devices and circuits. Electrons injected from the armchair lead into the junction is not valley polarized, but they can become valley polarized in the zigzag lead. There are Fermi energies, where the current in the zigzag lead is highly valley polarized and the junction is an efficient generator of valley polarized current. The features of the valley polarized current depend sensitively on the widths of the two leads, as well as the number of dimers in the armchair lead, because this number has a sensitive effect on the band structure of the armchair lead. When an external potential is applied to the junction, the energy range with high valley polarization is enlarged enhancing its function as a generator of highly valley polarized current. The scaling behavior found in other graphene devices is also found in L junctions, which means that the results presented here can be extended to junctions with larger dimensions after appropriate scaling of the energy.

  9. Prolonged static stretching does not influence running economy despite changes in neuromuscular function.

    Science.gov (United States)

    Allison, Sarah J; Bailey, David M; Folland, Jonathan P

    2008-12-01

    The aim of this study was to examine the acute effects of prolonged static stretching (SS) on running economy. Ten male runners (VO2(peak) 60.1 +/- 7.3 ml x kg(-1) x min(-1)) performed 10 min of treadmill running at 70% VO2(peak) before and after SS and no stretching interventions. For the stretching intervention, each leg was stretched unilaterally for 40 s with each of eight different exercises and this was repeated three times. Respiratory gas exchange was measured throughout the running exercise with an automated gas analysis system. On a separate day, participants were tested for sit and reach range of motion, isometric strength and countermovement jump height before and after SS. The oxygen uptake, minute ventilation, energy expenditure, respiratory exchange ratio and heart rate responses to running were unaffected by the stretching intervention. This was despite a significant effect of SS on neuromuscular function (sit and reach range of motion, +2.7 +/- 0.6 cm; isometric strength, -5.6% +/- 3.4%; countermovement jump height -5.5% +/- 3.4%; all P economy despite changes in neuromuscular function.

  10. Neuromuscular responses to mild-muscle damaging eccentric exercise in a low glycogen state.

    Science.gov (United States)

    Gavin, James P; Myers, Stephen D; Willems, Mark E T

    2015-02-01

    The aim of this study was to examine the effect of low muscle glycogen on the neuromuscular responses to maximal eccentric contractions. Fourteen healthy men (22 ± 3 years) performed single-leg cycling (20 min at ~75% maximal oxygen uptake (V̇O2 max); eight 90 s sprints at a 1:1 work-to-rest ratio (5% decrements from 90% to 55% V̇O2 max until exhaustion) the evening before 100 eccentric (1.57 rads(-1)) with reduced (RED) and normal glycogen (NORM). Neuromuscular responses were measured during and up to 48 h after with maximal voluntary and involuntary (twitch, 20 Hz and 50 Hz) isometric contractions. During eccentric contractions, peak torque decreased (RED: -16.1 ± 2.5%; NORM: -6.2 ± 5.1%) and EMG frequency increased according to muscle length. EMG activity decreased for RED only. After eccentric contractions, maximal isometric force was reduced up to 24h for NORM (-13.5 ± 5.8%) and 48 h for RED (-7.4 ± 10.9%). Twelve hours after eccentric contractions, twitch force and the 20:50 Hz ratio were decreased for RED but not for NORM. Immediate involuntary with prolonged voluntary force loss suggests that reduced glycogen is associated with increased susceptibility to mild muscle-damaging eccentric exercise with contributions of peripheral and central mechanisms to be different during recovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. The assessment of neuromuscular fatigue during 120 min of simulated soccer exercise.

    Science.gov (United States)

    Goodall, Stuart; Thomas, Kevin; Harper, Liam David; Hunter, Robert; Parker, Paul; Stevenson, Emma; West, Daniel; Russell, Mark; Howatson, Glyn

    2017-04-01

    This investigation examined the development of neuromuscular fatigue during a simulated soccer match incorporating a period of extra time (ET) and the reliability of these responses on repeated test occasions. Ten male amateur football players completed a 120 min soccer match simulation (SMS). Before, at half time (HT), full time (FT), and following a period of ET, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation (TMS) were obtained from the knee-extensors to measure neuromuscular fatigue. Within 7 days of the first SMS, a second 120 min SMS was performed by eight of the original ten participants to assess the reliability of the fatigue response. At HT, FT, and ET, reductions in maximal voluntary force (MVC; -11, -20 and -27%, respectively, P ≤ 0.01), potentiated twitch force (-15, -23 and -23%, respectively, P Simulated soccer exercise induces a significant level of fatigue, which is consistent on repeat tests, and involves both central and peripheral mechanisms.

  12. Effects of fatigue and surface instability on neuromuscular performance during jumping.

    Science.gov (United States)

    Lesinski, M; Prieske, O; Demps, M; Granacher, U

    2016-10-01

    It has previously been shown that fatigue and unstable surfaces affect jump performance. However, the combination thereof is unresolved. Thus, the purpose of this study was to examine the effects of fatigue and surface instability on jump performance and leg muscle activity. Twenty elite volleyball players (18 ± 2 years) performed repetitive vertical double-leg box jumps until failure. Before and after a fatigue protocol, jump performance (i.e., jump height) and electromyographic activity of selected lower limb muscles were recorded during drop jumps (DJs) and countermovement jumps (CMJs) on a force plate on stable and unstable surfaces (i.e., balance pad on top of force plate). Jump performance (3-7%; P muscle activity (2-27%; P fatigue during DJs and CMJs, and on unstable compared with stable surfaces during DJs only (jump performance: 8%; P muscle activity: 9-25%; P fatigue by surface condition were observed. Our findings revealed that fatigue impairs neuromuscular performance during DJs and CMJs in elite volleyball players, whereas surface instability affects neuromuscular DJ performance only. Absent fatigue × surface interactions indicate that fatigue-induced changes in jump performance are similar on stable and unstable surfaces in jump-trained athletes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Corticosteroids and neuromuscular blockers in development of critical illness neuromuscular abnormalities: A historical review.

    Science.gov (United States)

    Wilcox, Susan R

    2017-02-01

    Weakness is common in critically ill patients, associated with prolonged mechanical ventilation and increased mortality. Corticosteroids and neuromuscular blockade (NMB) administration have been implicated as etiologies of acquired weakness in the intensive care unit. Medical literature since the 1970s is replete with case reports and small case series of patients with weakness after receiving high-dose corticosteroids, prolonged NMB, or both. Several risk factors for weakness appear in the early literature, including large doses of steroids, the dose and duration of NMB, hyperglycemia, and the duration of mechanical ventilation. With improved quality of data, however, the association between weakness and steroids or NMB wanes. This may reflect changes in clinical practice, such as a reduction in steroid dosing, use of cisatracurium besylate instead of aminosteroid NMBs, improved glycemic control, or trends in minimizing mechanical ventilatory support. Thus, based on the most recent and high-quality literature, neither corticosteroids in commonly used doses nor NMB is associated with increased duration of mechanical ventilation, the greatest morbidity of weakness. Minimizing ventilator support as soon as the patient's condition allows may be associated with a reduction in weakness-related morbidity. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report.

    Science.gov (United States)

    Francio, Vinicius T; Boesch, Ron; Tunning, Michael

    2015-03-01

    Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient's perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option.

  15. Channels Active in the Excitability of Nerves and Skeletal Muscles across the Neuromuscular Junction: Basic Function and Pathophysiology

    Science.gov (United States)

    Goodman, Barbara E.

    2008-01-01

    Ion channels are essential for the basic physiological function of excitable cells such as nerve, skeletal, cardiac, and smooth muscle cells. Mutations in genes that encode ion channels have been identified to cause various diseases and disorders known as channelopathies. An understanding of how individual ion channels are involved in the…

  16. Effect of Pyridostigmine on the Physiologic and Morphologic Changes Induced by Soman at the Human Neuromuscular Junction

    National Research Council Canada - National Science Library

    Maselli, Ricardo

    2004-01-01

    Pre-treatment of American troops with pyridostigmine bromide (PB) has been advocated as an effective way to counteract the potential lethal effect of nerve-agent exposure during military operations...

  17. Reduced muscle strength in ether lipid-deficient mice is accompanied by altered development and function of the neuromuscular junction

    NARCIS (Netherlands)

    Dorninger, Fabian; Herbst, Ruth; Kravic, Bojana; Camurdanoglu, Bahar Z.; Macinkovic, Igor; Zeitler, Gerhard; Forss-Petter, Sonja; Strack, Siegfried; Khan, Muzamil Majid; Waterham, Hans R.; Rudolf, Rüdiger; Hashemolhosseini, Said; Berger, Johannes

    2017-01-01

    Inherited deficiency in ether lipids, a subgroup of phospholipids whose biosynthesis needs peroxisomes, causes the fatal human disorder rhizomelic chondrodysplasia punctata. The exact roles of ether lipids in the mammalian organism and, therefore, the molecular mechanisms underlying the disease are

  18. Stimulation Induced Changes in Frog Neuromuscular Junctions: A Quantitative Ultrastructural Comparison of Rapid-Frozen and Chemically Fixed Nerve Terminals

    Science.gov (United States)

    1984-03-06

    superior cervical ganglion, retrieval of uncoated membrane (" macropinocytosis ") occurs within 1-5 seconds following transmitter release, while...organ of Torpedo mamorata. Cell Tiss. Res. 224:685-688. Kadota, T. and Kadota, K. 1982. Membrane retrieval by macropinocytosis in presynaptic

  19. Palladium electrodes for molecular tunnel junctions

    International Nuclear Information System (INIS)

    Chang Shuai; Sen Suman; Zhang Peiming; Gyarfas, Brett; Ashcroft, Brian; Lindsay, Stuart; Lefkowitz, Steven; Peng Hongbo

    2012-01-01

    Gold has been the metal of choice for research on molecular tunneling junctions, but it is incompatible with complementary metal–oxide–semiconductor fabrication because it forms deep level traps in silicon. Palladium electrodes do not contaminate silicon, and also give higher tunnel current signals in the molecular tunnel junctions that we have studied. The result is cleaner signals in a recognition-tunneling junction that recognizes the four natural DNA bases as well as 5-methyl cytosine, with no spurious background signals. More than 75% of all the recorded signal peaks indicate the base correctly. (paper)

  20. Shot noise in YBCO bicrystal Josephson junctions

    DEFF Research Database (Denmark)

    Constantinian, K.Y.; Ovsyannikov, G.A.; Borisenko, I.V.

    2003-01-01

    We measured spectral noise density in YBCO symmetric bicrystal Josephson junctions on sapphire substrates at bias voltages up to 100 mV and T 4.2 K. Normal state resistance of the Josephson junctions, R-N = 20-90 Omega and ICRN up to 2.2 mV have been observed in the experimental samples. Noise...... may explain the experimentally measured linewidth broadening of Josephson oscillations at mm and submm wave frequencies in high-Tc superconducting junctions. Experimental results are discussed in terms of bound states existing at surfaces of d-wave superconducting electrodes....

  1. Soliton excitations in Josephson tunnel junctions

    DEFF Research Database (Denmark)

    Lomdahl, P. S.; Sørensen, O. H.; Christiansen, Peter Leth

    1982-01-01

    A detailed numerical study of a sine-Gordon model of the Josephson tunnel junction is compared with experimental measurements on junctions with different L / λJ ratios. The soliton picture is found to apply well on both relatively long (L / λJ=6) and intermediate (L / λJ=2) junctions. We find good...... agreement for the current-voltage characteristics, power output, and for the shape and height of the zero-field steps (ZFS). Two distinct modes of soliton oscillations are observed: (i) a bunched or congealed mode giving rise to the fundamental frequency f1 on all ZFS's and (ii) a "symmetric" mode which...

  2. Parametric frequency conversion in long Josephson junctions

    International Nuclear Information System (INIS)

    Irie, F.; Ashihara, S.; Yoshida, K.

    1976-01-01

    Current steps at voltages corresponding to the parametric coupling between an applied r.f. field and junction resonant modes have been observed in long Josephson tunnel junctions in the flux-flow state. The observed periodic variations of the step height due to the applied magnetic field are explained quantitatively by a perturbational analysis using Josephson phase equations. The present study demonstrates that the moving vortex array can serve as a coherent pump wave for signal waves propagating in the barrier region, which indicates, as a result, the possibility of traveling-wave parametric devices with long Josephson tunnel junctions. (author)

  3. Microscopic tunneling theory of long Josephson junctions

    DEFF Research Database (Denmark)

    Grønbech-Jensen, N.; Hattel, Søren A.; Samuelsen, Mogens Rugholm

    1992-01-01

    We present a numerical scheme for solving a nonlinear partial integro-differential equation with nonlocal time dependence. The equation describes the dynamics in a long Josephson junction modeled by use of the microscopic theory for tunneling between superconductors. We demonstrate that the detai......We present a numerical scheme for solving a nonlinear partial integro-differential equation with nonlocal time dependence. The equation describes the dynamics in a long Josephson junction modeled by use of the microscopic theory for tunneling between superconductors. We demonstrate...... that the detailed behavior of a solitonic mode (fluxon dynamics) in the junction is different from the results of the conventional perturbed sine-Gordon model....

  4. delta-biased Josephson tunnel junctions

    DEFF Research Database (Denmark)

    Monaco, R.; Mygind, Jesper; Koshelet, V.

    2010-01-01

    Abstract: The behavior of a long Josephson tunnel junction drastically depends on the distribution of the dc bias current. We investigate the case in which the bias current is fed in the central point of a one-dimensional junction. Such junction configuration has been recently used to detect...... the persistent currents circulating in a superconducting loop. Analytical and numerical results indicate that the presence of fractional vortices leads to remarkable differences from the conventional case of uniformly distributed dc bias current. The theoretical findings are supported by detailed measurements...

  5. Aging and its circumvention in rf-plasma oxidized Pb-alloy Josephson junctions

    International Nuclear Information System (INIS)

    Wada, M.; Nakano, J.

    1987-01-01

    The aging phenomenon of Pb-alloy Josephson junctions is investigated and an effective method of circumventing it is presented. Junctions consist of Pb-alloy electrodes and a tunneling barrier formed by rf-plasma oxidation of the Pb-alloy. First, aging and annealing-driven change in normal tunneling resistance are compared to verify the usage of annealing as an experimental method for simulation and acceleration of aging. Next, process variables affecting the annealing change in junction characteristics are examined and their influence is described. The importance of the oxide-base electrode interface is confirmed and that of the counterelectrode-oxide interface is experimentally shown. Furthermore, possible changes in the oxide itself are discussed. Finally, on the basis of these studies, rf-plasma oxidation in a CO 2 atmosphere is employed and proven to be an effective method for circumventing the annealing change in the junction characteristics

  6. Single-molecule detection of dihydroazulene photo-thermal reaction using break junction technique

    DEFF Research Database (Denmark)

    Huang, Cancan; Jevric, Martyn; Borges, Anders Christian

    2017-01-01

    a quantitative approach for probing the reaction kinetics and reversibility, including the occurrence of isomerization during the reaction. The product ratios observed when switching the system in the junction does not follow those observed in solution studies (both experiment and theory), suggesting......Charge transport by tunnelling is one of the most ubiquitous elementary processes in nature. Small structural changes in a molecular junction can lead to significant difference in the single-molecule electronic properties, offering a tremendous opportunity to examine a reaction on the single......-molecule scale by monitoring the conductance changes. Here, we explore the potential of the single-molecule break junction technique in the detection of photo-thermal reaction processes of a photochromic dihydroazulene/vinylheptafulvene system. Statistical analysis of the break junction experiments provides...

  7. DOSE-RESPONSE RELATION, NEUROMUSCULAR BLOCKING ACTION, INTUBATION CONDITIONS, AND CARDIOVASCULAR EFFECTS OF ORG-9273, A NEW NEUROMUSCULAR BLOCKING-AGENT

    NARCIS (Netherlands)

    VANDENBROEK, L; LAMBALK, LM; RICHARDSON, FJ; WIERDA, JMKH

    The ED50 and the ED90, the time-course of the neuromuscular block, the intubation conditions, and the cardiovascular effects of Org 9273, a new steroidal nondepolarizing neuromuscular blocking agent, have been evaluated in 41 anesthetized patients. From cumulative dose-response curves the ED50 and

  8. The role of patient advocacy organisations in neuromuscular disease R&D - The case of the Dutch neuromuscular disease association VSN

    NARCIS (Netherlands)

    Boon, W.P.C.; Broekgaarden, R.

    2010-01-01

    This article investigates to what extent patient advocacy organisations play a role in influencing R&D and policymaking for rare neuromuscular diseases. The Dutch neuromuscular disease organisation VSN is studied in depth. A brief history of the VSN is sketched along with the international

  9. Muscle size, neuromuscular activation, and rapid force characteristics in elderly men and women

    DEFF Research Database (Denmark)

    Suetta, C; Aagaard, P; Magnusson, S P

    2007-01-01

    Substantial evidence exists for the age-related decline in muscle strength and neural function, but the effect of long-term disuse in the elderly is largely unexplored. The present study examined the effect of unilateral long-term limb disuse on maximal voluntary quadriceps contraction (MVC), lean...... (M: 60-86 yr; n = 19) and women (W: 60-86 yr; n = 20) with unilateral chronic hip-osteoarthritis. Both sides were examined to compare the effect of long-term decreased activity on the affected (AF) leg with the unaffected (UN) side. AF had a significant lower MVC (W: 20%; M: 20%), LCSA (W: 8%; M: 10...... data demonstrate that disuse leads to a marked loss of muscle strength and muscle mass in elderly individuals. Furthermore, the data indicate that neuromuscular activation and contractile RFD are more affected by long-term disuse than maximal muscle strength, which may increase the future risk...

  10. Junction size effect on switching current and thermal stability in CoFeB/MgO perpendicular magnetic tunnel junctions

    Science.gov (United States)

    Sato, H.; Yamanouchi, M.; Miura, K.; Ikeda, S.; Gan, H. D.; Mizunuma, K.; Koizumi, R.; Matsukura, F.; Ohno, H.

    2011-07-01

    Junction size dependence of critical current (IC0) for spin transfer torque switching and thermal stability factor (E/kBT) was examined in CoFeB/MgO perpendicular magnetic tunnel junctions (p-MTJs). The IC0 increased with increasing recording layer area (Srec). On the other hand, the E/kBT showed almost constant values even though the Srec was increased from ˜1500 nm2 (44 nmφ) to ˜5000 nm2 (76 nmφ). Both IC0 and E/kBT behavior can be explained with assuming that the nucleation type magnetization reversal takes place in CoFeB/MgO p-MTJs.

  11. Proteomic and bioinformatic analysis of epithelial tight junction reveals an unexpected cluster of synaptic molecules

    Directory of Open Access Journals (Sweden)

    Tang Vivian W

    2006-12-01

    Full Text Available Abstract Background Zonula occludens, also known as the tight junction, is a specialized cell-cell interaction characterized by membrane "kisses" between epithelial cells. A cytoplasmic plaque of ~100 nm corresponding to a meshwork of densely packed proteins underlies the tight junction membrane domain. Due to its enormous size and difficulties in obtaining a biochemically pure fraction, the molecular composition of the tight junction remains largely unknown. Results A novel biochemical purification protocol has been developed to isolate tight junction protein complexes from cultured human epithelial cells. After identification of proteins by mass spectroscopy and fingerprint analysis, candidate proteins are scored and assessed individually. A simple algorithm has been devised to incorporate transmembrane domains and protein modification sites for scoring membrane proteins. Using this new scoring system, a total of 912 proteins have been identified. These 912 hits are analyzed using a bioinformatics approach to bin the hits in 4 categories: configuration, molecular function, cellular function, and specialized process. Prominent clusters of proteins related to the cytoskeleton, cell adhesion, and vesicular traffic have been identified. Weaker clusters of proteins associated with cell growth, cell migration, translation, and transcription are also found. However, the strongest clusters belong to synaptic proteins and signaling molecules. Localization studies of key components of synaptic transmission have confirmed the presence of both presynaptic and postsynaptic proteins at the tight junction domain. To correlate proteomics data with structure, the tight junction has been examined using electron microscopy. This has revealed many novel structures including end-on cytoskeletal attachments, vesicles fusing/budding at the tight junction membrane domain, secreted substances encased between the tight junction kisses, endocytosis of tight junction

  12. Transparency of atom-sized superconducting junctions

    International Nuclear Information System (INIS)

    Van-der-Post, N.; Peters, E.T.; Van Ruitenbeek, J.M.; Yanson, I.K.

    1995-01-01

    We discuss the transparency of atom-size superconducting tunnel junctions by comparing experimental values of the normal resistance and Subgap Structure with the theoretical predictions for these phenomena by Landauer's formula and Multiple Andreev Reflection, respectively

  13. Josephson tunnel junctions in niobium films

    International Nuclear Information System (INIS)

    Wiik, Tapio.

    1976-12-01

    A method of fabricating stable Josephson tunnel junctions with reproducible characteristics is described. The junctions have a sandwich structure consisting of a vacuum evaporated niobium film, a niobium oxide layer produced by the glow discharge method and a lead film deposited by vacuum evaporation. Difficulties in producing thin-film Josephson junctions are discussed. Experimental results suggest that the lower critical field of the niobium film is the most essential parameter when evaluating the quality of these junctions. The dependence of the lower critical field on the film thickness and on the Ginzburg-Landau parameter of the film is studied analytically. Comparison with the properties of the evaporated films and with the previous calculations for bulk specimens shows that the presented model is applicable for most of the prepared samples. (author)

  14. Chirality effect in disordered graphene ribbon junctions

    International Nuclear Information System (INIS)

    Long Wen

    2012-01-01

    We investigate the influence of edge chirality on the electronic transport in clean or disordered graphene ribbon junctions. By using the tight-binding model and the Landauer-Büttiker formalism, the junction conductance is obtained. In the clean sample, the zero-magnetic-field junction conductance is strongly chirality-dependent in both unipolar and bipolar ribbons, whereas the high-magnetic-field conductance is either chirality-independent in the unipolar or chirality-dependent in the bipolar ribbon. Furthermore, we study the disordered sample in the presence of magnetic field and find that the junction conductance is always chirality-insensitive for both unipolar and bipolar ribbons with adequate disorders. In addition, the disorder-induced conductance plateaus can exist in all chiral bipolar ribbons provided the disorder strength is moderate. These results suggest that we can neglect the effect of edge chirality in fabricating electronic devices based on the magnetotransport in a disordered graphene ribbon. (paper)

  15. Persistent junctional reciprocating tachycardia in the fetus

    NARCIS (Netherlands)

    Oudijk, M. A.; Stoutenbeek, P.; Sreeram, N.; Visser, G. H. A.; Meijboom, E. J.

    2003-01-01

    Persistent junctional reciprocating tachycardia (PJRT) tends to be a persistent arrhythmia and requires aggressive therapeutic management. Diagnosis and management of this infrequently occurring tachycardia in the fetus at an early stage is of importance for the prevention of congestive heart

  16. Josephson junction arrays and superconducting wire networks

    International Nuclear Information System (INIS)

    Lobb, C.J.

    1992-01-01

    Techniques used to fabricate integrated circuits make it possible to construct superconducting networks containing as many as 10 6 wires or Josephson junctions. Such networks undergo phase transitions from resistive high-temperature states to ordered low-resistance low-temperature states. The nature of the phase transition depends strongly on controllable parameters such as the strength of the superconductivity in each wire or junction and the external magnetic field. This paper will review the physics of these phase transitions, starting with the simplest zero-magnetic field case. This leads to a Kosterlitz-Thouless transition when the junctions or wires are weak, and a simple mean-field fransition when the junctions or wires are strong. Rich behavior, resulting from frustration, occurs in the presence of a magnetic field. (orig.)

  17. Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis

    Directory of Open Access Journals (Sweden)

    Huang Chi-Ren

    2011-05-01

    Full Text Available Abstract Background Cerebrotendinous xanthomatosis (CTX is a rare lipid-storage disease. Neuromuscular abnormality and autonomic system (ANS dysfuction in CTX are rarely examined in large-scale studies in the literature. We studied the peripheral nervous system, myopathology, and autonomic system of four CTX patients and performed a literature review of the reported CTX patients with peripheral neuropathy. Methods Four biochemically and genetically confirmed CTX patients, belonging to two families, were included for study and all received nerve conduction study (NCS, muscle biopsy for histopathologic and ultrastructural study, skin biopsy for intraepidermal nerve fiber (INEF density measurement, autonomic testings including sympathetic skin response, R-R interval variation and head-up tilt test using an automated tilt table to record the changes of blood pressure and heart rate in different postures. The Q-Sweat test was also applied for the detection of sweat amount and onset time of response. The clinical characteristics, study methods and results of 13 studies of peripheral neuropathy in CTX patients in the literature were also recorded for analysis. Results The results of NCS study showed axonal sensory-motor polyneuropathy in three CTX cases and mixed axonal and demyelinating sensor-motor polyneuropathy in one. The myopathological and histopathologic studies revealed mild denervation characteristics, but the ultrastructural study revealed changes of mitochondria and the membranous system, and increased amounts of glycogen, lipofuscin and lipid deposition. The ANS study revealed different degrees of abnormalities in the applied tests and the INEF density measurement showed small fiber neuropathy in three of the four CTX patients. The literature review of peripheral neuropathy in CTX revealed different types of peripheral neuropathy, of which axonal peripheral neuropathy was the most common. Conclusions Peripheral neuropathy, especially the

  18. Theory of multichannel magnetic stimulation: toward functional neuromuscular rehabilitation.

    Science.gov (United States)

    Ruohonen, J; Ravazzani, P; Grandori, F; Ilmoniemi, R J

    1999-06-01

    Human excitable cells can be stimulated noninvasively with externally applied time-varying electromagnetic fields. The stimulation can be achieved either by directly driving current into the tissue (electrical stimulation) or by means of electro-magnetic induction (magnetic stimulation). While the electrical stimulation of the peripheral neuromuscular system has many beneficial applications, peripheral magnetic stimulation has so far only a few. This paper analyzes theoretically the use of multiple magnetic stimulation coils to better control the excitation and also to eventually mimic electrical stimulation. Multiple coils allow electronic spatial adjustment of the shape and location of the stimulus without moving the coils. The new properties may enable unforeseen uses for peripheral magnetic stimulation, e.g., in rehabilitation of patients with neuromuscular impairment.

  19. Early appearance and possible roles of non-neuromuscular cholinesterases.

    Directory of Open Access Journals (Sweden)

    Carla eFalugi

    2012-04-01

    Full Text Available The biological function of the cholinesterase (ChE enzymes is well known and has been studied since the beginning of the XXth century; in particular, acetylcholinesterase (AChE, E.C. 3.1.1.7 is an enzyme playing a key role in the modulation of neuromuscular impulse transmission. However, in the past decades, there has been increasing interest concerning its role in regulating non-neuromuscular cell-to-cell interactions mediated by intracellular ion concentration changes, like the ones occurring during gamete interaction and embryonic development. An understanding of the mechanisms of the cholinergic regulation of these events can help us foresee the possible impact on environmental and human health, including gamete efficiency and possible teratogenic effects on different models, and help elucidate the extent to which exposure to ChE inhibitors may affect human health.

  20. Neuromuscular paralysis for newborn infants receiving mechanical ventilation.

    Science.gov (United States)

    Cools, F; Offringa, M

    2005-04-18

    Ventilated newborn infants breathing in asynchrony with the ventilator are at risk for complications during mechanical ventilation, such as pneumothorax or intraventricular hemorrhage, and are exposed to more severe barotrauma, which consequently could impair their clinical outcome. Neuromuscular paralysis, which eliminates spontaneous breathing efforts of the infant, has potential advantages in this respect. However, a number of complications have been reported with muscle relaxation in infants, so that concerns exist regarding the safety of prolonged neuromuscular paralysis in newborn infants. To determine whether routine neuromuscular paralysis of newborn infants receiving mechanical ventilation compared with no routine paralysis results in clinically important benefits or harms. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004), MEDLINE (from 1966 to April 2004) and EMBASE (from 1988 to April 2004) were searched. References of review articles were hand searched. Language restriction was not imposed. All trials using random or quasi-random patient allocation, in which the routine use of neuromuscular blocking agents during mechanical ventilation was compared to no paralysis or selective paralysis in newborn infants. Methodological quality was assessed blindly and independently by the two authors. Data were abstracted using standard methods of the Cochrane Collaboration and its Neonatal Review Group, with independent evaluation of trial quality, and abstraction and synthesis of data by both authors. Treatment effect was analysed using relative risk, risk difference and weighted mean difference. Ten possibly eligible trials were identified, of which six were included in the review. All the included trials studied preterm infants ventilated for respiratory distress syndrome, and used pancuronium as the neuromuscular blocking agent. In the analysis of the results of all trials, no significant difference was found in

  1. [Neuromuscular disease: respiratory clinical assessment and follow-up].

    Science.gov (United States)

    Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J

    2014-10-01

    Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  2. American Association of Neuromuscular & Electrodiagnostic Medicine

    Science.gov (United States)

    ... Recording Deadline More Calendar Items... About Vision, Mission & Values Board & Committees AANEM Staff Annual Report History Contact Us Education All Education Products Self-Assessment Examinations Education for Technologists Ethics CME/CEU Meeting Your MOC Fellowship Training Program ...

  3. Spinal Gap Junction Channels in Neuropathic Pain

    OpenAIRE

    Jeon, Young Hoon; Youn, Dong Ho

    2015-01-01

    Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced...

  4. Construction of tunable peptide nucleic acid junctions.

    Science.gov (United States)

    Duan, Tanghui; He, Liu; Tokura, Yu; Liu, Xin; Wu, Yuzhou; Shi, Zhengshuang

    2018-03-15

    We report here the construction of 3-way and 4-way peptide nucleic acid (PNA) junctions as basic structural units for PNA nanostructuring. The incorporation of amino acid residues into PNA chains makes PNA nanostructures with more structural complexity and architectural flexibility possible, as exemplified by building 3-way PNA junctions with tunable nanopores. Given that PNA nanostructures have good thermal and enzymatic stabilities, they are expected to have broad potential applications in biosensing, drug delivery and bioengineering.

  5. Neuromuscular stimulation after stroke: from technology to clinical deployment.

    OpenAIRE

    IJzerman, M.J.; Renzenbrink, G.J.; Geurts, A.C.H.

    2009-01-01

    Since the early 1960s, electrical or neuromuscular electrical stimulation (NMES) has been used to support the rehabilitation of stroke patients. One of the earliest applications of NMES included the use of external muscle stimulation to correct drop-foot after stroke. During the last few decades various clinical applications have been used for the upper and lower limb. Despite a growing body of literature on the use of NMES, its application in stroke is still limited to a few clinical groups ...

  6. Vertebral column resection in children with neuromuscular spine deformity.

    Science.gov (United States)

    Sponseller, Paul D; Jain, Amit; Lenke, Lawrence G; Shah, Suken A; Sucato, Daniel J; Emans, John B; Newton, Peter O

    2012-05-15

    Retrospective analysis. To determine, in pediatric patients with neuromuscular deformity undergoing vertebral column resection (VCR), the (1) characteristics of the surgery performed; (2) amount of pelvic obliquity restoration, and coronal and sagittal correction achieved; (3) associated blood loss and complications; and (4) extent to which curve type and VCR approach influenced correction, blood loss, and complications. VCR allows for correction of severe, rigid spinal deformity. This technique has not been previously reported in children with neuromuscular disorders. We retrospectively reviewed the records of 23 children with neuromuscular disorders (mean age, 15 years) and spinal deformities (severe scoliosis, 9; global kyphosis or angular kyphosis, 4; kyphoscoliosis, 10) who underwent VCR. The Student t test was used to compare correction differences (statistical significance, P < 0.05). A mean 1.5 vertebrae (27 thoracic and 6 lumbar) were resected per patient. Significant corrections were achieved in pelvic obliquity (11°, from 19° ± 13° to 8° ± 7°), in major coronal curve (56°, from 94° ± 36° to 38° ± 20°), and in major sagittal curve (46°, from 86° ± 37° to 40° ± 19°). There was no difference in correction between various curve types. VCR was associated with substantial blood loss (mean, 76% [estimated blood loss per total blood volume]), which correlated with patient weight and operating time. Overall, 6 patients experienced major complications: spinal cord injury, pleural effusion requiring chest tube insertion, pneumonia, pancreatitis, deep wound infection, and prominent implant requiring revision surgery. There were no deaths or permanent neurological injuries. VCR achieved significant pelvic obliquity restoration and coronal and sagittal correction in children with neuromuscular disorders and severe, rigid spinal deformity. However, this challenging procedure involves the potential for major complications.

  7. Report on Adaptive Force, a specific neuromuscular function

    Directory of Open Access Journals (Sweden)

    Marko Hoff

    2015-08-01

    Full Text Available In real life motions, as well as in sports, the adaptation of the neuromuscular systems to externally applied forces plays an important role. The term Adaptive Force (AF shall characterize the ability of the nerve-muscle-system to adapt to impacting external forces during isometric and eccentric muscle action. The focus in this paper is on the concept of this neuromuscular action, which is not yet described in this way. A measuring system was constructed and evaluated for this specific neuromuscular function, but only the main information of the evaluation of the measuring system and the preliminary reference values are mentioned here, while an article with detailed description will be published separately. This paper concentrates on the three following points: 1 What is the peculiarity of this neuromuscular function, introduced as AF? 2 Is the measuring system able to capture its specific characteristics and which phases of measurement occur? 3 It seems reasonable to discuss if AF can be distinguished and classified among the known force concepts. The article describes the measuring system and how it is able to capture special features of real life motions like submaximal intensities and the subjects’ option to react adequately on external varying forces. Furthermore, within one measurement the system records three different force qualities: the isometric submaximal Adaptive Force (AFiso, the maximal isometric Adaptive Force (AFisomax and the maximal eccentric Adaptive Force (AFeccmax. Each of these phases provide different and unique information on the nerve-muscle-system that are discussed in detail. Important, in terms of the Adaptive Force, seems to be the combination of conditional and coordinative abilities.

  8. Treatment of neuromuscular channelopathies: Current concepts and future prospects

    OpenAIRE

    Cleland, James C.; Griggs, Robert C.

    2008-01-01

    Our understanding of the molecular pathogenesis of the neuromuscular ion channelopathies has increased rapidly over the past two decades due to the identification of many of the genes whose mutation causes these diseases. These molecular discoveries have facilitated identification and classification of the hereditary periodic paralyses and the myotonias, and are likely to shed light on acquired ion channelopathies as well. Despite our better understanding of the pathogenesis of these disorder...

  9. Computed tomography of skeletal muscles in neuromuscular disease

    Energy Technology Data Exchange (ETDEWEB)

    Rodiek, S.O.; Kuether, G.

    1985-06-01

    CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions.

  10. Computed tomography of skeletal muscles in neuromuscular disease

    International Nuclear Information System (INIS)

    Rodiek, S.O.; Kuether, G.; Muenchen Univ.

    1985-01-01

    CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions. (orig.) [de

  11. Chronic Resistance Training Does Not Ameliorate Unloading-Induced Decrements in Neuromuscular Function.

    Science.gov (United States)

    Deschenes, Michael R; McCoy, Raymond W; Mangis, Katherine A

    2017-08-01

    The aim of this study was to assess the efficacy of long-term resistance training in preventing the detrimental effects of muscle unloading on neuromuscular function. Eleven untrained men and 11 men with extensive backgrounds in resistance training were tested for several parameters of neuromuscular function at various isokinetic contractile velocities before and after 7 days of muscle unloading. Measurements included muscle mass, strength, power, total work, electromyography, and neuromuscular transmission efficiency using superimposed electrical stimulation of maximally contracting muscles. Muscle performance was superior in resistance-trained subjects before and after unloading. In both groups of participants, unloading resulted in significantly (P neuromuscular transmission efficiency was significantly altered by unloading in trained or untrained participants. Chronic resistance training was found to be ineffective in neutralizing the deleterious effects of unloading on neuromuscular function. It appears that positive adaptations associated with long-term resistance training provide no prophylactic effect when neuromuscular systems are subjected to unloading.

  12. Determination of the dissipation in superconducting Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Mugnai, D., E-mail: d.mugnai@ifac.cnr.it; Ranfagni, A.; Cacciari, I. [“Nello Carrara” Institute of Applied Physics, CNR Florence Research Area, Via Madonna del Piano 10, 50019 Sesto Fiorentino, Florence (Italy)

    2015-02-07

    The results relative to macroscopic quantum tunneling rate, out of the metastable state of Josephson junctions, are examined in view of determining the effect of dissipation. We adopt a simple criterion in accordance to which the effect of dissipation can be evaluated by analyzing the shortening of the semiclassical traversal time of the barrier. In almost all the considered cases, especially those with relatively large capacitance values, the relative time shortening turns out to be about 20% and with a corresponding quality factor Q ≃ 5.5. However, beyond the specific cases here considered, still in the regime of moderate dissipation, the method is applicable also to different situations with different values of the quality factor. The method allows, within the error limits, for a reliable determination of the load resistance R{sub L}, the less accessible quantity in the framework of the resistively and capacitively shunted junction model, provided that the characteristics of the junction (intrinsic capacitance, critical current, and the ratio of the bias current to the critical one) are known with sufficient accuracy.

  13. On the role of string-junction in hadron reactions

    International Nuclear Information System (INIS)

    Imachi, Masahiro; Otsuki, Shoichiro; Toyoda, Fumihiko.

    1977-01-01

    By taking a model that hadrons are confined composite systems of the urbaryon q linked by the string, possible roles of a three-string junction J in hadron reactions are examined. The junction brings about new patterns to the conventional urbaryon rearrangement diagram. The leading behaviour of anti BB annihilation cross section is naturally explained by the exchange of one junction pair (J anti J). The Regge intercept is related to the number of the exchanged q and J, satisfying the sum rule α sub(P) (0) + α sub(B) (0) = 2α sub(M) (0). The rearrangement diagram of q and J divides exotic exchange amplitude into two classes, one with rather slow s dependence and the other with rapid one, in agreement with experiment. In addition to the pole-pole type duality, a new type of duality (pole-cut) is expected for some components of anti BB amplitude. Both of q and J carrying four momentum lead to a successful counting rule at large momentum transfers. (auth.)

  14. Junction depth measurement using carrier illumination

    International Nuclear Information System (INIS)

    Borden, Peter

    2001-01-01

    Carrier Illumination [trade mark] (CI) is a new method recently developed to meet the need for a non-destructive, high throughput junction depth measurement on patterned wafers. A laser beam creates a quasi-static excess carrier profile in the semiconductor underlying the activated junction. The excess carrier profile is fairly constant below the junction, and drops rapidly in the junction, creating a steep index of refraction gradient at the junction edge. Interference with light reflected from this index gradient provides a signal that is analyzed to determine the junction depth. The paper summarizes evaluation of performance in full NMOS and PMOS process flows, on both bare and patterned wafers. The aims have been to validate (1) performance in the presence of underlying layers typically found at the source/drain (S/D) process steps and (2) measurement on patterned wafers. Correlation of CI measurements to SIMS and transistor drive current are shown. The data were obtained from NMOS structures using As S/D and LDD implants. Correlations to SRP, SIMS and sheet resistance are shown for PMOS structures using B 11 LDD implants. Gage capability measurements are also presented

  15. Ballistic Josephson junctions based on CVD graphene

    Science.gov (United States)

    Li, Tianyi; Gallop, John; Hao, Ling; Romans, Edward

    2018-04-01

    Josephson junctions with graphene as the weak link between superconductors have been intensely studied in recent years, with respect to both fundamental physics and potential applications. However, most of the previous work was based on mechanically exfoliated graphene, which is not compatible with wafer-scale production. To overcome this limitation, we have used graphene grown by chemical vapour deposition (CVD) as the weak link of Josephson junctions. We demonstrate that very short, wide CVD-graphene-based Josephson junctions with Nb electrodes can work without any undesirable hysteresis in their electrical characteristics from 1.5 K down to a base temperature of 320 mK, and their gate-tuneable critical current shows an ideal Fraunhofer-like interference pattern in a perpendicular magnetic field. Furthermore, for our shortest junctions (50 nm in length), we find that the normal state resistance oscillates with the gate voltage, consistent with the junctions being in the ballistic regime, a feature not previously observed in CVD-graphene-based Josephson junctions.

  16. Neutralization of the neuromuscular activity of bothropstoxin-i, a myotoxin from Bothrops jararacussu snake venom, by a hydroalcoholic extract of Casearia sylvestris Sw. (guaçatonga

    Directory of Open Access Journals (Sweden)

    Y. Oshima-Franco

    2005-12-01

    Full Text Available Numerous plants are used as snakebite antidotes in Brazilian folk medicine, including Casearia sylvestris Swartz, popularly known as guaçatonga. In this study, we examined the action of a hydroalcoholic extract from C. sylvestris on the neuromuscular blockade caused by bothropstoxin-I (BthTX-I, a myotoxin from Bothrops jararacussu venom, in mouse isolated phrenic nerve-diaphragm (PND preparations. Aqueous (8 and 12 mg/ml, n=4 and 5, respectively and hydroalcoholic (12 mg/ml, n=12 extracts of the leaves of C. sylvestris caused facilitation in PND preparations followed by partial neuromuscular blockade. BthTX-I (20 µg/ml, n=4 caused 50% paralysis after 65±15 min (mean ± S.E.M. Preincubation (30 min at 37° C of BthTX-I (20 µg/ml, n=4 with a concentration of the hydroalcoholic extract (4 mg/ml that had no neuromuscular activity, such as the control (n=5, prevented the neuromuscular blockade caused by the toxin. This protection may be mediated by compounds such as flavonoids and phenols identified by thin-layer chromatography and colorimetric assays.

  17. Neuromuscular interactions around the knee in children, adults and elderly

    Science.gov (United States)

    Kellis, Eleftherios; Mademli, Lida; Patikas, Dimitrios; Kofotolis, Nikolaos

    2014-01-01

    Although injury and neuromuscular activation patterns may be common for all individuals, there are certain factors which differentiate neuromuscular activity responses between children, adults and elderly. The purpose of this study is to review recent evidence on age differences in neural activation and muscle balances around the knee when performing single joint movements. Particularly, current evidence indicates that there are some interesting similarities in the neuromuscular mechanisms by which children or the elderly differ compared with adults. Both children and elderly display a lower absolute muscle strength capacity than adults which cannot fully be explained by differences in muscle mass. Quadriceps activation failure is a common symptom of all knee injuries, irrespective of age but it is likely that its effect is more evident in children or adults. While one might expect that antagonist co-activation would differ between age categories, it appears that this is not the case. Although hamstring: quadriceps ratio levels are altered after knee injury, it is not clear whether this is an age specific response. Finally, evidence suggests that both children and the elderly display less stiffness of the quadriceps muscle-tendon unit than adults which affects their knee joint function. PMID:25232523

  18. Neuromuscular signs associated with acute hypophosphatemia in a dog.

    Science.gov (United States)

    Claus, Kimberly N; Day, Thomas K; Wolf, Christina

    2015-01-01

    The purpose of this report was to describe the successful recognition and management of neuromuscular dysfunction secondary to severe, acute hypophosphatemia in an adult dog with a 2 day history of vomiting, anorexia, and abdominal pain. Radiographs were suggestive of a foreign body obstruction, and surgery was recommended. Resection and anastomosis of the distal duodenum and proximal jejunum was performed. The dog recovered uneventfully, but approximately 36 hr postoperatively, he was found to have significant weakness and muscle tremors that were accompanied by hyperthermia. The only significant abnormality on a serum biochemical profile was a phosphorous level of 0.26 mmol/L. Within 6 hr of initiating phosphorous supplementation, the patient fully recovered and had no residual signs of neuromuscular dysfunction. Signs of neurologic dysfunction secondary to hypophosphatemia are commonly recognized in human patients. Reports of patients with severe muscle weakness, some of which necessitate ventilation due to weakening of muscles of respiration, are common throughout the literature. Less commonly, tremors are noted. This is the first known report of neuromuscular signs recognized and rapidly corrected in a dog. Although it is likely to be uncommon, hypophosphatemia should be recognized as a differential diagnosis in patients with tremors and/or muscle weakness.

  19. Altered neuromuscular control mechanisms of the trapezius muscle in fibromyalgia

    Directory of Open Access Journals (Sweden)

    Karlsson Stefan J

    2010-03-01

    Full Text Available Abstract Background fibromyalgia is a relatively common condition with widespread pain and pressure allodynia, but unknown aetiology. For decades, the association between motor control strategies and chronic pain has been a topic for debate. One long held functional neuromuscular control mechanism is differential activation between regions within a single muscle. The aim of this study was to investigate differences in neuromuscular control, i.e. differential activation, between myalgic trapezius in fibromyalgia patients and healthy controls. Methods 27 fibromyalgia patients and 30 healthy controls performed 3 minutes bilateral shoulder elevations with different loads (0-4 Kg with a high-density surface electromyographical (EMG grid placed above the upper trapezius. Differential activation was quantified by the power spectral median frequency of the difference in EMG amplitude between the cranial and caudal parts of the upper trapezius. The average duration of the differential activation was described by the inverse of the median frequency of the differential activations. Results the median frequency of the differential activations was significantly lower, and the average duration of the differential activations significantly longer in fibromyalgia compared with controls at the two lowest load levels (0-1 Kg (p Conclusion these findings illustrate a different neuromuscular control between fibromyalgia patients and healthy controls during a low load functional task, either sustaining or resulting from the chronic painful condition. The findings may have clinical relevance for rehabilitation strategies for fibromyalgia.

  20. Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

    International Nuclear Information System (INIS)

    Hader, H.; Gadoth, N.; Heifetz, H.

    1983-01-01

    The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen

  1. Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Hader, H.; Gadoth, N.; Heifetz, H.

    1983-11-01

    The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen.

  2. Defective membrane remodeling in neuromuscular diseases: insights from animal models.

    Directory of Open Access Journals (Sweden)

    Belinda S Cowling

    Full Text Available Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1, and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1 a common molecular pathway underlying these different neuromuscular diseases, and (2 tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches.

  3. Ask-Upmark kidney with bilateral pelvi-ureteric junction obstruction ...

    African Journals Online (AJOL)

    A.K. Sokhal

    2016-07-26

    Jul 26, 2016 ... Ask-Upmark kidney with pelvi-ureteric junction obstruction. 191. Fig. 3. Specimen left kidney: gross examination shows left kidney smooth, grossly dilated with thinned out parenchyma. Fig. 4. (Hematoxylin and Eosin, 40×): histopathological examination of resected left kidney shows thyroidisation of tubules, ...

  4. Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission

    Science.gov (United States)

    Naranjo, David; Wen, Hua; Brehm, Paul

    2015-01-01

    The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions. PMID:25650925

  5. Nicotinic acetylcholine receptor and the structural basis of neuromuscular transmission: insights from Torpedo postsynaptic membranes.

    Science.gov (United States)

    Unwin, Nigel

    2013-11-01

    The nicotinic acetylcholine (ACh) receptor, at the neuromuscular junction, is a neurotransmitter-gated ion channel that has been fine-tuned through evolution to transduce a chemical signal into an electrical signal with maximum efficiency and speed. It is composed from three similar and two identical polypeptide chains, arranged in a ring around a narrow membrane pore. Central to the design of this assembly is a hydrophobic gate in the pore, more than 50 Å away from sites in the extracellular domain where ACh binds. Although the molecular properties of the receptor have been explored intensively over the last few decades, only recently have structures emerged revealing its complex architecture and illuminating how ACh entering the binding sites opens the distant gate. Postsynaptic membranes isolated from the (muscle-derived) electric organ of the Torpedo ray have underpinned most of the structural studies: the membranes form tubular vesicles having receptors arranged on a regular surface lattice, which can be imaged directly in frozen physiological solutions. Advances in electron crystallographic techniques have also been important, enabling analysis of the closed- and open-channel forms of the receptor in unreacted tubes or tubes reacted briefly with ACh. The structural differences between these two forms show that all five subunits participate in a concerted conformational change communicating the effect of ACh binding to the gate, but that three of them (αγ, β and δ) play a dominant role. Flexing of oppositely facing pore-lining α-helices is the principal motion determining the closed/open state of the gate. These results together with the findings of biochemical, biophysical and other structural studies allow an integrated description of the receptor and of its mode of action at the synapse.

  6. Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.

    Science.gov (United States)

    Tomàs, Josep; Santafé, Manel M; Garcia, Neus; Lanuza, Maria A; Tomàs, Marta; Besalduch, Núria; Obis, Teresa; Priego, Mercedes; Hurtado, Erica

    2014-05-01

    Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. Copyright © 2014 Wiley Periodicals, Inc.

  7. Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency

    DEFF Research Database (Denmark)

    Thomsen, J L; Nielsen, C V; Palmqvist, D F

    2015-01-01

    if neuromuscular monitoring was not applied before awakening. METHODS: We retrospectively included patients referred to the Danish Cholinesterase Research Unit between 2004 and 2012 on suspicion of BChE deficiency. We collected data on genotype, BChE activity, neuromuscular blocking agents administered......, neuromuscular monitoring, and postoperative respiratory complications, defined as arterial oxygen desaturation ... paralysed. RESULTS: We included 123 patients. Neuromuscular monitoring was applied before awakening in 48 (39%) patients. A nerve stimulator was never used or only after attempted awakening in the remaining 75 (61%) patients. Premature awakening occurred in 75 (100%) and 14 (29%) of the unmonitored...

  8. Tunneling junctions of the heavy-fermion superconductor UPd 2Al 3

    Science.gov (United States)

    Jourdan, M.; Huth, M.; Mouloud, S.; Adrian, H.

    1998-01-01

    Tunneling spectroscopy on planar Giaever-type junctions is a powerful tool for the investigation of the superconducting state of metals. Since it is possible to prepare high-quality epitaxial thin films of the heavy-fermion compound UPd 2Al 3, this method can be used to examine the energy gap of this presumably unconventional superconductor. We prepared cross-junctions consisting of a UPd 2Al 3 base electrode and a metal counter electrode (Au, Al or Ag). These small area contacts without artificial barriers have only low junction resistances and suffer from irreproducibility. On the other hand, on some of those junctions we observed BCS-like tunneling conductivity. In order to increase the junction resistances AlO x or UO x were used as a artificial barrier with Al as a counter-electrode. As an alternative to quasi-particle tunneling, the preparation of Josephson-junctions could be an easier approach. A supercurrent between a small In-dot and an UPd 2Al 3 film was observed.

  9. Posterior spinal fusion to sacrum in non-ambulatory hypotonic neuromuscular patients: sacral rod/bone graft onlay method.

    Science.gov (United States)

    Bui, Theresa; Shapiro, Frederic

    2014-05-01

    A retrospective study involving 65 non-ambulatory patients with hypotonic neuromuscular scoliosis has assessed the effectiveness of a sacral rod/bone onlay technique for extending spinal fusion to the sacrum. To extend posterior spinal fusion to the sacrum, we used either 1 Harrington rod and 1 Luque L rod with sublaminar wires in 14 patients (Group 1) or two rods with sublaminar wires in 51 patients (Group 2) along with abundant autograft and allograft bone covering the ends of the rods. Diagnoses were Duchenne muscular dystrophy 53, spinal muscular atrophy 4, myopathy 3, limb girdle muscular dystrophy 2, infantile FSH muscular dystrophy 1, cerebral palsy 1, and Friedreich ataxia 1. Mean age at surgery was 14.3 years (±2.2, range 10.9-25.2). Radiographic follow-up (2 years post-surgery or greater) was 6.4 years (±4.4, range 2-25.3). Using the onlay technique, all patients fused with no rod breakage or pseudarthrosis. For the entire series, the mean pre-operative scoliosis was 54.7° (±31.1, range 0°-120°) with post-operative correction to 21.8° (±21.7, range 0°-91°) and long-term follow-up 24° (±22.9, range 0°-94°). For pelvic obliquity, pre-operative deformity was 17.3° (±11.3, range 0°-51°) with post-operative correction to 8.9° (±7.8, range 0°-35°) and long-term follow-up 10.1° (±8.1, range 0°-27°). Five required revision at a mean of 3.3 years post-original surgery involving rod shortening at the distal end. One of these had associated infection. Lumbosacral stability and long-term sitting comfort have been achieved in all patients. Problems can be minimized by positioning the rods firmly against the sacrum at the time of surgery with a relatively short extension beyond the L5-S1 junction. The procedure is valuable in hypotonic non-ambulatory neuromuscular patients whose immobility enhances the success rate for fusion due to diminished stress at the lumbosacral junction. It is particularly warranted for those with osteoporosis and

  10. Specialized neuromuscular training to improve neuromuscular function and biomechanics in a patient with quiescent juvenile rheumatoid arthritis.

    Science.gov (United States)

    Myer, Gregory D; Brunner, Hermine I; Melson, Paula G; Paterno, Mark V; Ford, Kevin R; Hewett, Timothy E

    2005-08-01

    The purpose of this case report is to describe a novel multidisciplinary approach for evaluating and preparing a patient with quiescent juvenile rheumatoid arthritis (JRA) for safe sports participation. The patient was a 10-year-old girl with a history of bilateral knee arthritis who desired to participate in soccer and basketball. Range of motion and manual muscle testing of the lower extremity were within normal limits. Neuromuscular testing included kinematic and kinetic testing, isokinetic assessment, and postural stability testing. The patient's gait was near normal; however, she had narrowed step width and increased knee flexion at heel-strike. Landing analysis during a box drop vertical jump task showed increased and imbalanced (right versus left lower extremity) peak impact forces. The testing was followed by specialized neuromuscular training (SNT). Following SNT, heel-strike and step width were within normal limits, peak impact forces on the box drop test decreased by 31%, imbalance decreased by 46%, and vertical jump increased 15%. The isokinetic strength ratio between knee flexors and extensors and the overall balance measures were within normal limits and equal bilaterally. Patients with quiescent JRA may have abnormal biomechanics, which could place them at increased risk for injury or future articular cartilage damage. Specialized neuromuscular training may have helped to decrease the patient's risk for future injury or disease progression.

  11. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  12. Dose-Response Relationship of Neuromuscular Training for Injury Prevention in Youth Athletes: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Simon Steib

    2017-11-01

    Full Text Available Background: Youth athletes with intensive sports participation are at an increased risk of sustaining injuries. Neuromuscular training programs reduce sports-related injury risk in this population, however, the dose-response relationship is largely unknown. Thus, the aim of this meta-analysis was to identify the optimal frequency, volume, duration, and period of neuromuscular training to prevent injuries in youth athletes.Methods: Computerized database searches (PubMed, Scopus, SPORTDiscus, The Cochrane Library, PEDro were conducted in January 2017, with search terms related to youth sports, neuromuscular training, and injury prevention. Eligible trials (i evaluated a neuromuscular training program; (ii included youth athletes of 21 years or younger; (iii had an analytical design (RCTs, quasi-experimental, cohort studies; (iv contained original data; (v and provided injury data. Two reviewers independently extracted data and assessed quality of eligible studies. Injury rate ratios (IRRs for lower extremity injuries were pooled meta-analytically, and moderator analyses examined the effect of training frequency, duration, volume, and period.Results: Data from 16 trials yielded an overall risk reduction of 42% with neuromuscular training (IRR = 0.58, 95%CI 0.47–0.72. Training frequencies of two (IRR = 0.50; 95%CI 0.29–0.86 or three times (IRR = 0.40; 95%CI 0.31–0.53 per week revealed the largest risk reduction, and a weekly training volume of more than 30 min tended to be more effective compared to lower volumes. Programs with 10–15 min (IRR = 0.55; 95%CI 0.42–0.72 session duration produced effects comparable to those with longer session duration (IRR = 0.60; 95%CI 0.46–0.76. Interventions lasting more than 6 months were not superior to shorter programs.Conclusion: This meta-analysis revealed that NMT performed in short bouts of 10–15 min, two to three times per week, with a weekly training volume of 30–60 min had the largest

  13. Neuromuscular partitioning, architectural design, and myosin fiber types of the M. vastus lateralis of the llama (Lama glama).

    Science.gov (United States)

    Graziotti, Guillermo H; Palencia, Pablo; Delhon, Gustavo; Rivero, José-Luis L

    2004-11-01

    The llama (Lama glama) is one of the few mammals of relatively large body size in which three fast myosin heavy chain isoforms (i.e., IIA, IIX, IIB) are extensively expressed in their locomotory muscles. This study was designed to gain insight into the morphological and functional organization of skeletal musculature in this peculiar animal model. The neuromuscular partitioning, architectural design, and myosin fiber types were systematically studied in the M. vastus lateralis of adult llamas (n = 15). Four nonoverlapping neuromuscular partitions or compartments were identified macroscopically (using a modified Sihler's technique for muscle depigmentation), although they did not conform strictly to the definitions of "neuromuscular compartments." Each neuromuscular partition was innervated by primary branches of the femoral nerve and was arranged within the muscle as paired partitions, two in parallel (deep-superficial compartmentalization) and the other two in-series (proximo-distal compartmentalization). These neuromuscular partitions of the muscle varied in their respective architectural designs (studied after partial digestion with diluted nitric acid) and myosin fiber type characteristics (identified immunohistochemically with specific anti-myosin monoclonal antibodies, then examined by quantitative histochemistry and image analysis). The deep partitions of the muscle had longer fibers, with lower angles of pinnation, and higher percentages of fast-glycolytic fibers than the superficial partitions of the muscle. These differences clearly suggest a division of labor in the whole M. vastus lateralis of llamas, with deep partitions exhibiting features well adapted for dynamic activities in the extension of stifle, whereas superficial portions seem to be related to the antigravitational role of the muscle in preserving the extension of the stifle during standing and stance phase of the stride. This peculiar structural and functional organization of the llama M

  14. Josephson tunnel junctions with ferromagnetic interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Weides, M.P.

    2006-07-01

    Superconductivity and ferromagnetism are well-known physical properties of solid states that have been widely studied and long thought about as antagonistic phenomena due to difference in spin ordering. It turns out that the combination of both superconductor and ferromagnet leads to a very rich and interesting physics. One particular example, the phase oscillations of the superconducting order parameter inside the ferromagnet, will play a major role for the devices discussed in this work. In this thesis, I present Josephson junctions with a thin Al{sub 2}O{sub 3} tunnel barrier and a ferromagnetic interlayer, i.e. superconductor-insulator-ferromagnet-superconductor (SIFS) stacks. The fabrication of junctions was optimized regarding the insulation of electrodes and the homogeneity of the current transport. The junctions were either in the 0 or {pi} coupled ground state, depending on the thickness of the ferromagnetic layer and on temperature. The influence of ferromagnetic layer thickness on the transport properties and the coupling (0, {pi}) of SIFS tunnel junctions was studied. Furthermore, using a stepped ferromagnetic layer with well-chosen thicknesses, I obtained the so-called 0-{pi} Josephson junction. At a certain temperature this 0-{pi} junction can be made perfectly symmetric. In this case the ground state corresponds to a vortex of supercurrent creating a magnetic flux which is a fraction of the magnetic flux quantum {phi}{sub 0}. Such structures allow to study the physics of fractional vortices and to build various electronic circuits based on them. The SIFS junctions presented here have an exponentially vanishing damping at T {yields} 0. The SIFS technology developed within the framework of this work may be used to construct classical and quantum devices such as oscillators, memory cells and qubits. (orig.)

  15. Neuromuscular Risk Factors for Knee and Ankle Ligament Injuries in Male Youth Soccer Players.

    Science.gov (United States)

    Read, Paul J; Oliver, Jon L; De Ste Croix, Mark B A; Myer, Gregory D; Lloyd, Rhodri S

    2016-08-01

    Injuries reported in male youth soccer players most commonly occur in the lower extremities, and include a high proportion of ligament sprains at the ankle and knee with a lower proportion of overuse injuries. There is currently a paucity of available literature that examines age- and sex-specific injury risk factors for such injuries within youth soccer players. Epidemiological data have reported movements that lead to non-contact ligament injury include running, twisting and turning, over-reaching and landing. Altered neuromuscular control during these actions has been suggested as a key mechanism in females and adult populations; however, data available in male soccer players is sparse. The focus of this article is to review the available literature and elucidate prevalent risk factors pertaining to male youth soccer players which may contribute to their relative risk of injury.

  16. The effects of band exercise using proprioceptive neuromuscular facilitation on muscular strength in lower extremity.

    Science.gov (United States)

    Rhyu, Hyun-Seung; Kim, Su-Hyun; Park, Hye-Sang

    2015-02-01

    The purpose of this study was to examine whether a six-week elastic band exercise program using proprioceptive neuromuscular facilitation (PNF) can increase isotonic strength of abductor muscles in the lower extremity. Twenty-eight healthy students from S university were divided into an experimental group and control group. Each group was participated in pre and post-measurement in isotonic strength using an isotonic analyzer, En-treeM. Experimental group performed elastic band exercise using PNF pattern for a six-weeks, in contrast, control group did not take any exercise. In the results of this study, isotonic strength measurements of abductor muscles in lower extremity in experimental group were significantly different after exercise, but control group did not show any significant changes. Therefore, we hope that resistive exercise would be very valuable for healthy people as well as the old people with weakened muscle strength.

  17. Neuromuscular function in patients with Subacromial Impingement Syndrome and clinical assessment of scapular kinematics

    DEFF Research Database (Denmark)

    Larsen, Camilla Marie; Lund, Hans; Juul-Kristensen, Birgit

    Neuromuscular function in patients with Subacromial Impingement Syndrome and clinical assessment of scapular kinematics Larsen CM1, Juul-Kristensen B1,2 Holtermann A3, Lund H1,2, Søgaard K1 1University of Southern Denmark, Institute of Sports Science and Clinical Biomechanics, DK 2Institute...... patient sample with SIS, and to assess the clinimetric properties of clinical assessment methods of scapular kinematics as important aspects for optimising effect measures of treatment in order to improve clinical guidelines in this area. METHODS: Scapular muscle activity was examined, 1) during...... a voluntary arm movement task and 2) selective activation tasks during sessions with and without on-line biofeedback, in a general population consisting of 16 SIS patients and 15 controls (No-SIS). Furthermore, 3) a systematic review was conducted of all available clinical scapular assessment methods...

  18. Specific adaptations of neuromuscular control and knee joint stiffness following sensorimotor training.

    Science.gov (United States)

    Gruber, M; Bruhn, S; Gollhofer, A

    2006-08-01

    The aim of this study was to examine how fixations of the ankle joint during sensorimotor training (SMT) influence adaptations in mechanical stiffness and neuromuscular control of the knee joint. Sixty-three healthy subjects were randomly assigned to three training groups that differed in their degree of ankle joint fixation, which was either barefooted, with an ankle brace or with a ski boot. Mechanical knee joint stiffness and reflex control of m. vastus medialis, m. vastus lateralis, m. biceps femoris, and m. semitendinosus were tested during force controlled anterior tibial displacements. This force was applied as both a fast and a slow stimulus. After the training period the group that trained barefooted showed an increase in mechanical stiffness of the knee joint from 79 +/- 21 (Mean +/- SD) N/mm to 110 +/- 38 N/mm (p boots was able to improve knee joint stiffness from 67 +/- 26 N/mm to 96 +/- 47 N/mm (p knee joint injuries.

  19. Modeling single molecule junction mechanics as a probe of interface bonding

    Science.gov (United States)

    Hybertsen, Mark S.

    2017-03-01

    Using the atomic force microscope based break junction approach, applicable to metal point contacts and single molecule junctions, measurements can be repeated thousands of times resulting in rich data sets characterizing the properties of an ensemble of nanoscale junction structures. This paper focuses on the relationship between the measured force extension characteristics including bond rupture and the properties of the interface bonds in the junction. A set of exemplary model junction structures has been analyzed using density functional theory based calculations to simulate the adiabatic potential surface that governs the junction elongation. The junction structures include representative molecules that bond to the electrodes through amine, methylsulfide, and pyridine links. The force extension characteristics are shown to be most effectively analyzed in a scaled form with maximum sustainable force and the distance between the force zero and force maximum as scale factors. Widely used, two parameter models for chemical bond potential energy versus bond length are found to be nearly identical in scaled form. Furthermore, they fit well to the present calculations of N-Au and S-Au donor-acceptor bonds, provided no other degrees of freedom are allowed to relax. Examination of the reduced problem of a single interface, but including relaxation of atoms proximal to the interface bond, shows that a single-bond potential form renormalized by an effective harmonic potential in series fits well to the calculated results. This allows relatively accurate extraction of the interface bond energy. Analysis of full junction models shows cooperative effects that go beyond the mechanical series inclusion of the second bond in the junction, the spectator bond that does not rupture. Calculations for a series of diaminoalkanes as a function of molecule length indicate that the most important cooperative effect is due to the interactions between the dipoles induced by the donor

  20. Model Building to Facilitate Understanding of Holliday Junction and Heteroduplex Formation, and Holliday Junction Resolution

    Science.gov (United States)

    Selvarajah, Geeta; Selvarajah, Susila

    2016-01-01

    Students frequently expressed difficulty in understanding the molecular mechanisms involved in chromosomal recombination. Therefore, we explored alternative methods for presenting the two concepts of the double-strand break model: Holliday junction and heteroduplex formation, and Holliday junction resolution. In addition to a lecture and…

  1. Quantitative description of hysteresis loops induced by rf radiation in long Josephson junctions

    DEFF Research Database (Denmark)

    Olsen, Ole H.; Samuelsen, Mogens Rugholm

    1991-01-01

    The effect of an applied rf signal on the radiation emitted from a long Josephson junction is examined by means of a model based on the sine-Gordon equation. This system exhibits a variety of interesting phenomena, e.g., chaos and hysteresis. The hysteresis loop is examined in detail. These simple...... analyses show that for rf frequencies larger than a certain threshold value no hysteresis is expected. This is verified in numerical simulations where the frequency and length of the junction have been varied....

  2. Increasing gap junctional coupling: a tool for dissecting the role of gap junctions

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Haugan, Ketil; Stahlhut, Martin

    2007-01-01

    . In a number of cases, gap junctions have been implicated in the initiation and progress of disease, and experimental uncoupling has been used to investigate the exact role of coupling. The inverse approach, i.e., to increase coupling, has become possible in recent years and represents a new way of testing......Much of our current knowledge about the physiological and pathophysiological role of gap junctions is based on experiments where coupling has been reduced by either chemical agents or genetic modification. This has brought evidence that gap junctions are important in many physiological processes...... the role of gap junctions. The aim of this review is to summarize the current knowledge obtained with agents that selectively increase gap junctional intercellular coupling. Two approaches will be reviewed: increasing coupling by the use of antiarrhythmic peptide and its synthetic analogs...

  3. Regulation of gap junctions by protein phosphorylation

    Directory of Open Access Journals (Sweden)

    J.C. Sáez

    1998-05-01

    Full Text Available Gap junctions are constituted by intercellular channels and provide a pathway for transfer of ions and small molecules between adjacent cells of most tissues. The degree of intercellular coupling mediated by gap junctions depends on the number of gap junction channels and their activity may be a function of the state of phosphorylation of connexins, the structural subunit of gap junction channels. Protein phosphorylation has been proposed to control intercellular gap junctional communication at several steps from gene expression to protein degradation, including translational and post-translational modification of connexins (i.e., phosphorylation of the assembled channel acting as a gating mechanism and assembly into and removal from the plasma membrane. Several connexins contain sites for phosphorylation for more than one protein kinase. These consensus sites vary between connexins and have been preferentially identified in the C-terminus. Changes in intercellular communication mediated by protein phosphorylation are believed to control various physiological tissue and cell functions as well as to be altered under pathological conditions.

  4. Etiology and Recovery of Neuromuscular Fatigue following Competitive Soccer Match-Play

    Directory of Open Access Journals (Sweden)

    Callum G. Brownstein

    2017-10-01

    Full Text Available Aim: Previous research into the etiology of neuromuscular fatigue following competitive soccer match-play has primarily focused on peripheral perturbations, with limited research assessing central nervous system function in the days post-match. The aim of the present study was to examine the contribution and time-course of recovery of central and peripheral factors toward neuromuscular fatigue following competitive soccer match-play.Methods: Sixteen male semi-professional soccer players completed a 90-min soccer match. Pre-, post- and at 24, 48, and 72 h participants completed a battery of neuromuscular, physical, and perceptual tests. Maximal voluntary contraction force (MVC and twitch responses to electrical (femoral nerve and transcranial magnetic stimulation (TMS of the motor cortex during isometric knee-extension and at rest were measured to assess central nervous system (voluntary activation, VA and muscle contractile (potentiated twitch force, Qtw, pot function. Electromyography responses of the rectus femoris to single- and paired-pulse TMS were used to assess corticospinal excitability and short-interval intracortical inhibition (SICI, respectively. Fatigue and perceptions of muscle soreness were assessed via visual analog scales, and physical function was assessed through measures of jump (countermovement jump height and reactive strength index and sprint performance.Results: Competitive match-play elicited significant post-match declines in MVC force (−14%, P < 0.001 that persisted for 48 h (−4%, P = 0.01, before recovering by 72 h post-exercise. VA (motor point stimulation was reduced immediately post-match (−8%, P < 0.001, and remained depressed at 24 h (−5%, P = 0.01 before recovering by 48 h post-exercise. Qtw,pot was reduced post-match (−14%, P < 0.001, remained depressed at 24 h (−6%, P = 0.01, before recovering by 48 h post-exercise. No changes were evident in corticospinal excitability or SICI. Jump performance

  5. Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults.

    Science.gov (United States)

    Hristovska, Ana-Marija; Duch, Patricia; Allingstrup, Mikkel; Afshari, Arash

    2017-08-14

    Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs have significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety, reduced incidence of residual block on recovery, and more efficient use of healthcare resources. The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents in adults. We searched the following databases on 2 May 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (WebSPIRS Ovid SP), Embase (WebSPIRS Ovid SP), and the clinical trials registries www.controlled-trials.com, clinicaltrials.gov, and www.centerwatch.com. We re-ran the search on 10 May 2017. We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We included adults, classified as American Society of Anesthesiologists (ASA) I to IV, who received non-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration. Two review authors independently screened titles and abstracts to identify trials for eligibility, examined articles for eligibility, abstracted data, assessed the articles, and excluded obviously irrelevant reports. We resolved

  6. Tunnel magnetoresistance in double spin filter junctions

    International Nuclear Information System (INIS)

    Saffarzadeh, Alireza

    2003-01-01

    We consider a new type of magnetic tunnel junction, which consists of two ferromagnetic tunnel barriers acting as spin filters (SFs), separated by a nonmagnetic metal (NM) layer. Using the transfer matrix method and the free-electron approximation, the dependence of the tunnel magnetoresistance (TMR) on the thickness of the central NM layer, bias voltage and temperature in the double SF junction are studied theoretically. It is shown that the TMR and electron-spin polarization in this structure can reach very large values under suitable conditions. The highest value of the TMR can reach 99%. By an appropriate choice of the thickness of the central NM layer, the degree of spin polarization in this structure will be higher than that of the single SF junctions. These results may be useful in designing future spin-polarized tunnelling devices

  7. Josephson junctions with ferromagnetic alloy interlayer

    International Nuclear Information System (INIS)

    Himmel, Nico

    2015-01-01

    Josephson junctions are used as active devices in superconducting electronics and quantum information technology. Outstanding properties are their distinct non-linear electrical characteristics and a usually sinusoidal relation between the current and the superconducting phase difference across the junction. In general the insertion of ferromagnetic material in the barrier of a Josephson junction is associated with a suppression of superconducting correlations. But also new phenomena can arise which may allow new circuit layouts and enhance the performance of applications. This thesis presents a systematic investigation for two concepts to fabricate Josephson junctions with a rather uncommon negative critical current. Such devices exhibit an intrinsic phase slip of π between the electrodes, so they are also known as π junctions. Both studies go well beyond existing experiments and in one system a π junction is shown for the first time. All the thin film junctions are based on superconducting Nb electrodes. In a first approach, barriers made from Si and Fe were investigated with respect to the realisation of π junctions by spin-flip processes. The distribution of Fe in the Si matrix was varied from pure layers to disperse compounds. The systematic fabrication of alloy barriers was facilitated by the development of a novel timing-based combinatorial sputtering technique for planetary deposition systems. An orthogonal gradient approach allowed to create binary layer libraries with independent variations of thickness and composition. Second, Nb vertical stroke AlO x vertical stroke Nb vertical stroke Ni 60 Cu 40 vertical stroke Nb (SIsFS) double barrier junctions were experimentally studied for the occurrence of proximity effect induced order parameter oscillations. Detailed dependencies of the critical current density on the thickness of s-layer and F-layer were acquired and show a remarkable agreement to existing theoretical predictions. Especially a variation of

  8. Silicon fiber with p-n junction

    Energy Technology Data Exchange (ETDEWEB)

    Homa, D.; Cito, A.; Pickrell, G.; Hill, C.; Scott, B. [Department of Materials Science and Engineering, Virginia Polytechnic Institute and State University, 312 Holden Hall, Blacksburg, Virginia 24060 (United States)

    2014-09-22

    In this study, we fabricated a p-n junction in a fiber with a phosphorous doped silicon core and fused silica cladding. The fibers were fabricated via a hybrid process of the core-suction and melt-draw techniques and maintained overall diameters ranging from 200 to 900 μm and core diameters of 20–800 μm. The p-n junction was formed by doping the fiber with boron and confirmed via the current-voltage characteristic. The demonstration of a p-n junction in a melt-drawn silicon core fiber paves the way for the seamless integration of optical and electronic devices in fibers.

  9. Silicon fiber with p-n junction

    International Nuclear Information System (INIS)

    Homa, D.; Cito, A.; Pickrell, G.; Hill, C.; Scott, B.

    2014-01-01

    In this study, we fabricated a p-n junction in a fiber with a phosphorous doped silicon core and fused silica cladding. The fibers were fabricated via a hybrid process of the core-suction and melt-draw techniques and maintained overall diameters ranging from 200 to 900 μm and core diameters of 20–800 μm. The p-n junction was formed by doping the fiber with boron and confirmed via the current-voltage characteristic. The demonstration of a p-n junction in a melt-drawn silicon core fiber paves the way for the seamless integration of optical and electronic devices in fibers.

  10. Nanomembrane-based mesoscopic superconducting hybrid junctions.

    Science.gov (United States)

    Thurmer, Dominic J; Bof Bufon, Carlos Cesar; Deneke, Christoph; Schmidt, Oliver G

    2010-09-08

    A new method for combining top-down and bottom-up approaches to create superconductor-normal metal-superconductor niobium-based Josephson junctions is presented. Using a rolled-up semiconductor nanomembrane as scaffolding, we are able to create mesoscopic gold filament proximity junctions. These are created by electromigration of gold filaments after inducing an electric field mediated breakdown in the semiconductor nanomembrane, which can generate nanometer sized structures merely using conventional optical lithography techniques. We find that the created point contact junctions exhibit large critical currents of a few milliamps at 4.2 K and an I(c)R(n) product placing their characteristic frequency in the terahertz region. These nanometer-sized filament devices can be further optimized and integrated on a chip for their use in superconductor hybrid electronics circuits.

  11. Ferromagnetic resonance with long Josephson junction

    Science.gov (United States)

    Golovchanskiy, I. A.; Abramov, N. N.; Stolyarov, V. S.; Emelyanova, O. V.; Golubov, A. A.; Ustinov, A. V.; Ryazanov, V. V.

    2017-05-01

    In this work we propose a hybrid device based on a long Josephson junction (JJ) coupled inductively to an external ferromagnetic (FM) layer. The long JJ in a zero-field operation mode induces a localized AC magnetic field in the FM layer and enables a synchronized magnetostatic standing wave. The magnetostatic wave induces additional dissipation for soliton propagation in the junction and also enables a phase locking (resonant soliton synchronization) at a frequency of natural ferromagnetic resonance. The later manifests itself as an additional constant voltage step on the current-voltage characteristics at the corresponding voltage. The proposed device allows to study magnetization dynamics of individual micro-scaled FM samples using just DC technique, and also it provides additional phase locking frequency in the junction, determined exclusively by characteristics of the ferromagnet.

  12. Josephson junctions with ferromagnetic alloy interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Himmel, Nico

    2015-07-23

    Josephson junctions are used as active devices in superconducting electronics and quantum information technology. Outstanding properties are their distinct non-linear electrical characteristics and a usually sinusoidal relation between the current and the superconducting phase difference across the junction. In general the insertion of ferromagnetic material in the barrier of a Josephson junction is associated with a suppression of superconducting correlations. But also new phenomena can arise which may allow new circuit layouts and enhance the performance of applications. This thesis presents a systematic investigation for two concepts to fabricate Josephson junctions with a rather uncommon negative critical current. Such devices exhibit an intrinsic phase slip of π between the electrodes, so they are also known as π junctions. Both studies go well beyond existing experiments and in one system a π junction is shown for the first time. All the thin film junctions are based on superconducting Nb electrodes. In a first approach, barriers made from Si and Fe were investigated with respect to the realisation of π junctions by spin-flip processes. The distribution of Fe in the Si matrix was varied from pure layers to disperse compounds. The systematic fabrication of alloy barriers was facilitated by the development of a novel timing-based combinatorial sputtering technique for planetary deposition systems. An orthogonal gradient approach allowed to create binary layer libraries with independent variations of thickness and composition. Second, Nb vertical stroke AlO{sub x} vertical stroke Nb vertical stroke Ni{sub 60}Cu{sub 40} vertical stroke Nb (SIsFS) double barrier junctions were experimentally studied for the occurrence of proximity effect induced order parameter oscillations. Detailed dependencies of the critical current density on the thickness of s-layer and F-layer were acquired and show a remarkable agreement to existing theoretical predictions. Especially

  13. Strong Josephson Coupling in Planar Graphene Junctions

    Science.gov (United States)

    Park, Jinho; Lee, Gil-Ho; Lee, Jae Hyeong; Takane, Yositake; Imura, Ken-Ichiro; Taniguchi, Takashi; Watanabe, Kenji; Lee, Hu-Jong

    A recent breakthrough of processing graphene, employing encapsulation by hexagonal boron nitride layers (BGB structure), allows realizing the ballistic carrier transport in graphene. Thereafter, ballistic Josephson coupling has been studied by closely edge-contacted BGB structure with two superconducting electrodes. Here, we report on the strong Josephson coupling with planar graphene junction in truly short and ballistic regime. Our device showed high transmission probability and the junction critical current (IC) oscillating for sweeping the gate voltage along with the normal conductance oscillation (Fabry-Perot oscillations), providing a direct evidence for the ballistic nature of the junction pair current. We also observed the convex-upward shape of decreasing critical currents with increasing temperature, canonical properties of the short Josephson coupling. By fitting these curves into theoretical models, we demonstrate the strong Josephson coupling in our devices, which is also supported by the exceptionally large value of ICRN ( 2 Δ / e RNis the normal resistance).

  14. A congenital form of junctional ectopic tachycardia.

    Science.gov (United States)

    Tulino, Domenico; Dattilo, Giuseppe; Tulino, Viviana; Marte, Filippo; Patanè, Salvatore

    2010-11-19

    Accessory pathways have been described as well as their Ecg identification criteria also in pediatric population. Radiofrequency ablation is a curative treatment but its application has been more limited in the paediatric population. The congenital form of junctional ectopic tachycardia was firstly described by Coumel et al. in 1976. It usually occurs in the first six months of life presenting as a persistent sustained form, lasting up to 90% of the time and it is hampered by high mortality. Its clinical presentation may be dramatic, being associated in up to 60% of cases with cardiomegaly and/or heart failure. Secondary dilated cardiomyopathy, ventricular fibrillation and sudden cardiac death have also been reported. We present a case of congenital form of junctional ectopic tachycardia in a 12-day-old newborn infant. Also this case is illustrative of the congenital form of junctional ectopic tachycardia. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

  15. Terahertz Responses of Intrinsic Josephson Junctions in High TC Superconductors

    International Nuclear Information System (INIS)

    Wang, H. B.; Wu, P. H.; Yamashita, T.

    2001-01-01

    High frequency responses of intrinsic Josephson junctions up to 2.5THz, including the observation of Shapiro steps under various conditions, are reported and discussed in this Letter. The sample was an array of intrinsic Josephson junctions singled out from inside a high T C superconducting Bi 2 Sr 2 CaCu 2 O 8+x single crystal, with a bow-tie antenna integrated to it. The number of junctions in the array was controllable, the junctions were homogeneous, the distribution of applied irradiation among the junctions was even, and the junctions could synchronously respond to high frequency irradiation

  16. Systematic study of shallow junction formation on germanium substrates

    DEFF Research Database (Denmark)

    Hellings, Geert; Rosseel, Erik; Clarysse, Trudo

    2011-01-01

    Published results on Ge junctions are benchmarked systematically using RS–XJ plots. The electrical activation level required to meet the ITRS targets is calculated. Additionally, new results are presented on shallow furnace-annealed B junctions and shallow laser-annealed As junctions. Co-implanti......Published results on Ge junctions are benchmarked systematically using RS–XJ plots. The electrical activation level required to meet the ITRS targets is calculated. Additionally, new results are presented on shallow furnace-annealed B junctions and shallow laser-annealed As junctions. Co...

  17. Electronic Properties of Carbon Nanotubes and Junctions

    Science.gov (United States)

    Anantram, M. P.; Han, Jie; Yang, Liu; Govindan, T. R.; Jaffe, R.; Saini, Subhash (Technical Monitor)

    1998-01-01

    Metallic and semiconducting Single Wall Carbon Nanotubes (CNT) have recently been characterized using scanning tunneling microscopy (STM) and the manipulation of individual CNT has been demonstrated. These developments make the prospect of using CNT as molecular wires and possibly as electronic devices an even more interesting one. We have been modeling various electronic properties such as the density of states and the transmission coefficient of CNT wires and junctions. These studies involve first calculating the stability of junctions using molecular dynamics simulations and then calculating the electronic properties using a pi-electron tight binding Hamiltonian. We have developed the expertise to calculate the electronic properties of both finite-sized CNT and CNT systems with semi-infinite boundary conditions. In this poster, we will present an overview of some of our results. The electronic application of CNT that is most promising at this time is their use as molecular wires. The conductance can however be greatly reduced because of reflection due to defects and contacts. We have modeled the transmission through CNT in the presence of two types of defects: weak uniform disorder and strong isolated scatterers. We find that the conductance is affected in significantly different manners due to these defects Junctions of CNT have also been imaged using STM. This makes it essential to derive rules for the formation of junctions between tubes of different chirality, study their relative energies and electronic properties. We have generalized the rules for connecting two different CNT and have calculated the transmission and density of states through CNT junctions. Metallic and semiconducting CNT can be joined to form a stable junction and their current versus voltage characteristics are asymmetric. CNT are deformed by the application of external forces including interactions with a substrate or other CNT. In many experiments, these deformation are expected to

  18. Fatigue in neuromuscular disorders: Focus on Guillain-Barré syndrome and Pompe disease

    NARCIS (Netherlands)

    J.M. de Vries (Juna); M.L.C. Hagemans (Marloes); J.B.J. Bussmann (Hans); A.T. van der Ploeg (Ans); P.A. van Doorn (Pieter)

    2010-01-01

    textabstractFatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain-Barré syndrome and Pompe disease. Fatigue can be subdivided

  19. A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Driessen, J.J.; Booij, L.H.D.J.

    2010-01-01

    A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs

  20. The development of a model of fatigue in neuromuscular disorders: a longitudinal study.

    NARCIS (Netherlands)

    Kalkman, J.S.; Schillings, M.L.; Zwarts, M.J.; Engelen, B.G.M. van; Bleijenberg, G.

    2007-01-01

    BACKGROUND: Severe fatigue is reported by the majority of patients with three relatively common types of neuromuscular disorders. OBJECTIVE: This study aimed to identify predictors of fatigue in a longitudinal study and to develop a model of fatigue in patients with three neuromuscular disorders.