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Sample records for mammalian neuromuscular systems

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

    Energy Technology Data Exchange (ETDEWEB)

    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 (/sup 125/I)..cap alpha..-BGT binding to tissue membranes. Scatchard analysis of (/sup 175/I)..cap alpha..-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 (/sup 125/I)-..cap alpha..-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.

  2. 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.

  3. Maximum likelihood q-estimator reveals nonextensivity regulated by extracellular potassium in the mammalian neuromuscular junction

    CERN Document Server

    da Silva, A J; Santos, D O C; Lima, R F

    2013-01-01

    Recently, we demonstrated the existence of nonextensivity in neuromuscular transmission [Phys. Rev. E 84, 041925 (2011)]. In the present letter, we propose a general criterion based on the q-calculus foundations and nonextensive statistics to estimate the values for both scale factor and q-index using the maximum likelihood q-estimation method (MLqE). We next applied our theoretical findings to electrophysiological recordings from neuromuscular junction (NMJ) where spontaneous miniature end plate potentials (MEPP) were analyzed. These calculations were performed in both normal and high extracellular potassium concentration, [K+]o. This protocol was assumed to test the validity of the q-index in electrophysiological conditions closely resembling physiological stimuli. Surprisingly, the analysis showed a significant difference between the q-index in high and normal [K+]o, where the magnitude of nonextensivity was increased. Our letter provides a general way to obtain the best q-index from the q-Gaussian distrib...

  4. 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.

  5. Functional characterization of mammalian Wntless homolog in mammalian system.

    Science.gov (United States)

    Wang, Li-Ting; Wang, Shih-Jong; Hsu, Shih-Hsien

    2012-07-01

    Wntless (GPR177) protein is a newly identified regulator of Wnt signals in Drosophila, but its cellular function in mammals is still unclear. In this study, we explored the expression pattern and potential cellular function of Wntless in mammalian cells. Wntless mRNA was expressed in many mouse tissues, including the spleen, lung, kidney, thymus, and stomach, and lower levels of expression were detected in the mouse brain and testis. Expression of Wntless protein analyzed by Western blot and immunohistochemical staining was only detected in the submucosa, muscle, ganglia, and nerve cells of murine large intestines. Both immunofluorescence staining and subcellular fraction extraction analysis revealed that endogenous Wntless protein was expressed predominantly in the cytoplasmic organelles with a morphologically dot-shaped distribution. Furthermore, overexpression of Wntless could be corrected by and may activate the nuclear factor-κB (NF-κB) signaling pathway in cancer (HeLa) cells. These results suggest that Wntless plays a role in signaling regulation during the formation of cancer in addition to its role as a retromer protein in mammalian systems.

  6. Fuzzy Control Method with Application for Functional Neuromuscular Stimulation System

    Institute of Scientific and Technical Information of China (English)

    吴怀宇; 周兆英; 熊沈蜀

    2001-01-01

    A fuzzy control technique is applied to a functional neuromuscular stimulation (FNS) physicalmultiarticular muscle control system. The FNS multiarticular muscle control system based on the fuzzy controllerwas developed with the fuzzy control rule base. Simulation experiments were then conducted for the joint angletrajectories of both the elbow flexion and the wrist flexion using the proposed fuzzy control algorithm and aconventional PID control algorithm with the FNS physical multiarticular muscle control system. The simulationresults demonstrated that the proposed fuzzy control method is more suitable for the physiologicalcharacteristics than conventional PID control. In particular, both the trajectory-following and the stability of theFNS multiarticular muscle control system were greatly improved. Furthermore, the stimulating pulse trainsgenerated by the fuzzy controller were stable and smooth.``

  7. Mammalian Cell-Based Sensor System

    Science.gov (United States)

    Banerjee, Pratik; Franz, Briana; Bhunia, Arun K.

    Use of living cells or cellular components in biosensors is receiving increased attention and opens a whole new area of functional diagnostics. The term "mammalian cell-based biosensor" is designated to biosensors utilizing mammalian cells as the biorecognition element. Cell-based assays, such as high-throughput screening (HTS) or cytotoxicity testing, have already emerged as dependable and promising approaches to measure the functionality or toxicity of a compound (in case of HTS); or to probe the presence of pathogenic or toxigenic entities in clinical, environmental, or food samples. External stimuli or changes in cellular microenvironment sometimes perturb the "normal" physiological activities of mammalian cells, thus allowing CBBs to screen, monitor, and measure the analyte-induced changes. The advantage of CBBs is that they can report the presence or absence of active components, such as live pathogens or active toxins. In some cases, mammalian cells or plasma membranes are used as electrical capacitors and cell-cell and cell-substrate contact is measured via conductivity or electrical impedance. In addition, cytopathogenicity or cytotoxicity induced by pathogens or toxins resulting in apoptosis or necrosis could be measured via optical devices using fluorescence or luminescence. This chapter focuses mainly on the type and applications of different mammalian cell-based sensor systems.

  8. Some principles of regeneration in mammalian systems.

    Science.gov (United States)

    Carlson, Bruce M

    2005-11-01

    This article presents some general principles underlying regenerative phenomena in vertebrates, starting with the epimorphic regeneration of the amphibian limb and continuing with tissue and organ regeneration in mammals. Epimorphic regeneration following limb amputation involves wound healing, followed shortly by a phase of dedifferentiation that leads to the formation of a regeneration blastema. Up to the point of blastema formation, dedifferentiation is guided by unique regenerative pathways, but the overall developmental controls underlying limb formation from the blastema generally recapitulate those of embryonic limb development. Damaged mammalian tissues do not form a blastema. At the cellular level, differentiation follows a pattern close to that seen in the embryo, but at the level of the tissue and organ, regeneration is strongly influenced by conditions inherent in the local environment. In some mammalian systems, such as the liver, parenchymal cells contribute progeny to the regenerate. In others, e.g., skeletal muscle and bone, tissue-specific progenitor cells constitute the main source of regenerating cells. The substrate on which regeneration occurs plays a very important role in determining the course of regeneration. Epimorphic regeneration usually produces an exact replica of the structure that was lost, but in mammalian tissue regeneration the form of the regenerate is largely determined by the mechanical environment acting on the regenerating tissue, and it is normally an imperfect replica of the original. In organ hypertophy, such as that occurring after hepatic resection, the remaining liver mass enlarges, but there is no attempt to restore the original form.

  9. Some aspects of the neuromuscular system of Ascaris.

    Science.gov (United States)

    del Castillo, J; Rivera, A; Solórzano, S; Serrato, J

    1989-12-01

    1. The structure and physiological properties of the somatic neuromuscular system of the nematode Ascaris lumbricoides var. suum are discussed taking into account early work from this laboratory, the results of other workers, and experiments in progress. 2. Anatomically, the central feature of the somatic musculature is the presence of a specialized muscular, but not contractile, structure: the syncytium or sarcopile, formed by the terminal processes of the muscle cell arms that contact the nerve cord. In this region, they are electrically coupled to one another and form chemical synapses with the nerve fibres. 3. The syncytium serves, primarily, as a nerve-muscle manifold, or device which allows the neural control of the muscle fields with great economy in the amount of nervous tissue, numbers of chemical junctions and quantities of synaptic transmitters. 4. The structure of the syncytium is being studied with the scanning electron microscope. The results reveal the convergence of the arms on discrete sites as they approach the cords, as well as a longitudinal arrangement of the terminal processes as they course over the cords, at least in the posterior region of the animal. 5. The characteristics of the electrical coupling between the muscle cells are being investigated. A pattern has been observed that is dependent on the position of the cell pairs with respect to the longitudinal axis of the animal. 6. A study of signal propagation in the arms has revealed that the morphology of the muscle cells contributes to the extent and preferential direction of propagation.

  10. Movement Symmetries and the Mammalian Vestibular System

    Science.gov (United States)

    McCollum, Gin; Boyle, Richard

    2000-03-01

    Unity of movement requires vertebrates to have an ability to symmetrize along the midline. For example, human erect stance involves symmetry with respect to gravity. The mammalian vestibular system provides a mechanism for maintaining symmetries, which is also open to influence and adaptation by the rest of the organism. The vestibular system includes the inner ear endorgans and central nuclei, along with projections to oculomotor, cerebellar, thalamic, and spinal motor centers. The vestibular endorgans - the semicircular canals and the otoliths - use sensory hairs to register inertia. The vestibular endorgans are right-left symmetric and the semicircular canals form an approximately orthogonal coordinate system for angular motion. Primary afferent axons project from the endorgans to the vestibular nuclei (and a few other places). The vestibular nuclei integrate vestibular, visual, and somatosensory signals, along with a proposed copy of the voluntary motor command and signals from other central structures. The relationship between the canals and the otoliths gives rise to symmetries among neurons, in the organization among the several vestibular nuclei, and in the projections from the vestibular nuclei. These symmetries organize the space of body movements so that functional relationships are maintained in spite of the many free variables of body movement. They also provide a foundation for adaptive reinterpretation of the relationship between canal and otolith signals, for example in freefall.

  11. An electrophysiological analysis of the effects of noradrenaline and alpha-receptor antagonists on neuromuscular transmission in mammalian muscular arteries.

    Science.gov (United States)

    Holman, M E; Surprenant, A

    1980-01-01

    1 The effects of exogenously applied noradrenaline (NA) and alpha-adrenoceptor antagonists on the mechanical and intracellularly recorded responses to perivascular nerve stimulation were examined in the rabbit ear artery, rabbit saphenous artery and rat tail artery. 2 Excitatory junction potentials (e.j.ps) and action potentials recorded from these smooth muscles were not blocked or depressed by phentolamine, phenoxybenzamine, prazosin, or labetolol in concentrations as high as 10 microgram/ml. Phentolamine (1 to 10 microgram/ml) depressed neurally-evoked contractions of the ear and saphenous, but not the tail artery, and also depressed the contractions produced by direct muscle stimulation in the ear and saphenous arteries. Prazosin and labetolol (0.1 to 10 microgram/ml) had no effect on the neurally evoked contractile response in any of the arteries examined. 3 The amplitude of the steady-state e.j.p. during repetitive stimulation at 0.45 to 2 Hz was increased by phentolamine or phenoxybenzamine but not by prazosin or labetolol. Phentolamine and phenoxybenzamine also increased the amplitude of the e.j.p. evoked by a single stimulus in the majority of the preparations. 4 Concentrations of NA greater than or equal to 1 microgram/ml depolarized the smooth muscle while concentrations greater than or equal to 0.5 microgram/ml depressed the amplitude of the e.j.ps recorded from these arteries. alpha-Antagonists did not suppress either the NA-induced membrane depolarization or depression of e.j.ps. 5 These observations call into question the physiological relevance of both pre- and postsynaptic alpha-receptors in regard to adrenergic neuromuscular transmission in muscular arteries.

  12. Man-machine interface system for neuromuscular training and evaluation based on EMG and MMG signals.

    Science.gov (United States)

    de la Rosa, Ramon; Alonso, Alonso; Carrera, Albano; Durán, Ramon; Fernández, Patricia

    2010-01-01

    This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals.

  13. Man-Machine Interface System for Neuromuscular Training and Evaluation Based on EMG and MMG Signals

    Directory of Open Access Journals (Sweden)

    Patricia Fernández

    2010-12-01

    Full Text Available This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System, a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES and, as a novelty, the myomechanic signals (MMS. In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals.

  14. Non-invasive neuromuscular electrical stimulation in patients with central nervous system lesions: an educational review.

    Science.gov (United States)

    Schuhfried, Othmar; Crevenna, Richard; Fialka-Moser, Veronika; Paternostro-Sluga, Tatjana

    2012-02-01

    The aim of this educational review is to provide an overview of the clinical application of transcutaneous electrical stimulation of the extremities in patients with upper motor neurone lesions. In general two methods of electrical stimulation can be distinguished: (i) therapeutic electrical stimulation, and (ii) functional electrical stimulation. Therapeutic electrical stimulation improves neuromuscular functional condition by strengthening muscles, increasing motor control, reducing spasticity, decreasing pain and increasing range of motion. Transcutaneous electrical stimulation may be used for neuromuscular electrical stimulation inducing repetitive muscle contraction, electromyography-triggered neuromuscular electrical stimulation, position-triggered electrical stimulation and subsensory or sensory transcutaneous electric stimulation. Functional electrical stimulation provokes muscle contraction and thereby produces a functionally useful movement during stimulation. In patients with spinal cord injuries or stroke, electrical upper limb neuroprostheses are applied to enhance upper limb and hand function, and electrical lower limb neuroprostheses are applied for restoration of standing and walking. For example, a dropped foot stimulator is used to trigger ankle dorsiflexion to restore gait function. A review of the literature and clinical experience of the use of therapeutic electrical stimulation as well as of functional electrical stimulation in combination with botulinum toxin, exercise therapy and/or splinting are presented. Although the evidence is limited we conclude that neuromuscular electrical stimulation in patients with central nervous system lesions can be an effective modality to improve function, and that combination with other treatments has an additive therapeutic effect.

  15. Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis.

    Science.gov (United States)

    Tuk, Bert

    2016-01-01

    Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity.

  16. Fate and Metabolism of PBDEs in Mammalian Systems

    Science.gov (United States)

    Polybrominated diphenyl ethers (PBDEs) belong to an emerging class of persistent organic pollutants (POPs). Although the toxicology of PBDEs is not well developed, they are persistent and bioaccumulative, and therefore, of growing environmental concern. The metabolism of PBDEs in mammalian systems h...

  17. Evolution and Structure of Neuromuscular Systems in Spiralian Meiofauna

    DEFF Research Database (Denmark)

    Bekkouche, Nicolas Tarik

    into their evolution: Lobatocerebrum is an aberrant annelid showing only few common traits with Annelida, yet, our detailed studies unravel putative resemblances of muscular, nervous and glandular system to previous findings in annelids. Micrognathozoa shows more resemblances with Rotifera than Gnathostomulida (these...... on the evolution of this group. Diuronotus aspetos shows a unique combination of muscular traits not easily traceable, but in contrast the nervous system traits can be compared in high details, hereby bridging to other Chaetonotida (Gastrotricha). Moreover, we describe new gastrotrich characters...... such as the ciliary pattern or a system of pharyngeal canals of possible importance for future comparative approaches. These different studies show that information on rare and phylogenetically isolated animals with their unique combination of neural and muscular characters are necessary to understand the evolution...

  18. Upper limb functions regained in quadriplegia: a hybrid computerized neuromuscular stimulation system.

    Science.gov (United States)

    Nathan, R H; Ohry, A

    1990-05-01

    A new, computerized neuromuscular stimulation system was applied to the upper limbs of two patients with complete quadriplegia below the C4 level. The stimulation-generated movements were integrated and augmented by residual, voluntary shoulder girdle movements and mechanical splinting. Up to 12 muscles were stimulated individually with high-resolution surface electrodes; coordination and control of the stimulation was effected by microcomputer. Simple vocal commands to the computer triggered preprogrammed hand prehensions, arm motion, and other functions, giving the patient complete control over the system. In pilot clinical trials of six weeks, writing, eating, and drinking, including picking up and replacing the pen or cup, were achieved.

  19. Phytoestrogen Biological Actions on Mammalian Reproductive System and Cancer Growth

    OpenAIRE

    Zhao, E; Mu, Qing

    2010-01-01

    Phytoestrogens are a family of diverse polyphenolic compounds derived from nature plant that structurally or functionally mimic circulating estrogen in the mammalian reproductive system. They induce estrogenic and anti-estrogenic effects in the brain-pituitary-gonad axis (a principal endocrine system involving in reproductive regulation) and peripheral reproductive organs. The dichotomy of phytoestrogen-mediated actions elucidates that they play the biological activities via complex mechanism...

  20. Functional connectivity in the neuromuscular system underlying bimanual coordination.

    Science.gov (United States)

    de Vries, Ingmar E J; Daffertshofer, Andreas; Stegeman, Dick F; Boonstra, Tjeerd W

    2016-12-01

    Neural synchrony has been suggested as a mechanism for integrating distributed sensorimotor systems involved in coordinated movement. To test the role of corticomuscular and intermuscular coherence in bimanual coordination, we experimentally manipulated the degree of coordination between hand muscles by varying the sensitivity of the visual feedback to differences in bilateral force. In 16 healthy participants, cortical activity was measured using EEG and muscle activity of the flexor pollicis brevis of both hands using high-density electromyography (HDsEMG). Using the uncontrolled manifold framework, coordination between bilateral forces was quantified by the synergy index RV in the time and frequency domain. Functional connectivity was assessed using corticomuscular coherence between muscle activity and cortical source activity and intermuscular coherence between bilateral EMG activity. The synergy index increased in the high coordination condition. RV was higher in the high coordination condition in frequencies between 0 and 0.5 Hz; for the 0.5- to 2-Hz frequency band, this pattern was inverted. Corticomuscular coherence in the beta band (16-30 Hz) was maximal in the contralateral motor cortex and was reduced in the high coordination condition. In contrast, intermuscular coherence was observed at 5-12 Hz and increased with bimanual coordination. Within-subject comparisons revealed a negative correlation between RV and corticomuscular coherence and a positive correlation between RV and intermuscular coherence. Our findings suggest two distinct neural pathways: 1) corticomuscular coherence reflects direct corticospinal projections involved in controlling individual muscles; and 2) intermuscular coherence reflects diverging pathways involved in the coordination of multiple muscles. Copyright © 2016 the American Physiological Society.

  1. Neuromuscular and muscle-tendon system adaptations to isotonic and isokinetic eccentric exercise.

    Science.gov (United States)

    Guilhem, G; Cornu, C; Guével, A

    2010-06-01

    To present the properties of an eccentric contraction and compare neuromuscular and muscle-tendon system adaptations induced by isotonic and isokinetic eccentric trainings. An eccentric muscle contraction is characterized by the production of muscle force associated to a lengthening of the muscle-tendon system. This muscle solicitation can cause micro lesions followed by a regeneration process of the muscle-tendon system. Eccentric exercise is commonly used in functional rehabilitation for its positive effect on collagen synthesis but also for resistance training to increase muscle strength and muscle mass in athletes. Indeed, eccentric training stimulates muscle hypertrophy, increases the fascicle pennation angle, fascicles length and neural activation, thus inducing greater strength gains than concentric or isometric training programs. Eccentric exercise is commonly performed either against a constant external load (isotonic) or at constant velocity (isokinetic), inducing different mechanical constraints. These different mechanical constraints could induce structural and neural adaptive strategies specific to each type of exercise. The literature tends to show that isotonic mode leads to a greater strength gain than isokinetic mode. This observation could be explained by a greater neuromuscular activation after IT training. However, the specific muscle adaptations induced by each mode remain difficult to determine due to the lack of standardized, comparative studies. 2010 Elsevier Masson SAS. All rights reserved.

  2. Adult neural stem cells in the mammalian central nervous system

    Institute of Scientific and Technical Information of China (English)

    Dengke K Ma; Michael A Bonaguidi; Guo-li Ming; Hongjun Song

    2009-01-01

    Neural stem cells (NSCs) are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, in-cluding topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.

  3. Therapeutic effects of anti-spastic medication on neuromuscular abnormalities in SCI: a system identification approach.

    Science.gov (United States)

    Mirbagheri, M M; Kindig, M; Niu, X; Varoqui, D

    2013-01-01

    Previous attempts to investigate the effects of antispastic medications are limited to clinical studies using that use clinical evaluations to assess. Since these measures are neither objective nor quantitative, the therapeutic effects of such medications on neuromuscular properties have not been fully evaluated. In this study, as a first attempt, we examined the effect of tizanidine, an anti-spastic medication, on modification of the neuromuscular properties of patients with chronic incomplete spinal cord injury (SCI). Each patient was administered 2 mg of tizanidine four times per day for four weeks. The spastic ankle of each patient was evaluated at baseline (prior to any medication, and then 1, 2, and 4 weeks after the start of medication. The ankle was perturbed with a small-amplitude Pseudo-Random Binary Sequence (PRBS) perturbation at various positions over the ankle range-of-motion. A parallel-cascade system identification technique, which provides an objective and quantitative measure of neuromuscular properties, was used to calculate the intrinsic and reflex stiffness. The stiffness vs. joint angle trends were then calculated for each evaluation; these curves were compared across the intervention time to determine the recovery pattern (i.e. change over time) due to the tizanidine intervention. All patients exhibited decreases in reflex stiffness (which abnormally increase after SCI) due to the medication; however, patients were observed to exhibit multiple recovery patterns. For some patients, the reflex stiffness continuously reduced over the four-week intervention period, while for other patients, the decrease during the first week (i.e. between the baseline and 1-Week evaluations) was most pronounced. Also, some patients presented a significant decrease with time, while others presented no improvement in the intrinsic stiffness. These findings suggest that tizanidine may be effective in reducing not only reflex stiffness, but also the subject

  4. Development of network-based multichannel neuromuscular electrical stimulation system for stroke rehabilitation.

    Science.gov (United States)

    Qu, Hongen; Xie, Yongji; Liu, Xiaoxuan; He, Xin; Hao, Manzhao; Bao, Yong; Xie, Qing; Lan, Ning

    2016-01-01

    Neuromuscular electrical stimulation (NMES) is a promising assistive technology for stroke rehabilitation. Here we present the design and development of a multimuscle stimulation system as an emerging therapy for people with paretic stroke. A network-based multichannel NMES system was integrated based on dual bus architecture of communication and an H-bridge current regulator with a power booster. The structure of the system was a body area network embedded with multiple stimulators and a communication protocol of controlled area network to transmit muscle stimulation parameter information to individual stimulators. A graphical user interface was designed to allow clinicians to specify temporal patterns and muscle stimulation parameters. We completed and tested a prototype of the hardware and communication software modules of the multichannel NMES system. The prototype system was first verified in nondisabled subjects for safety, and then tested in subjects with stroke for feasibility with assisting multijoint movements. Results showed that synergistic stimulation of multiple muscles in subjects with stroke improved performance of multijoint movements with more natural velocity profiles at elbow and shoulder and reduced acromion excursion due to compensatory trunk rotation. The network-based NMES system may provide an innovative solution that allows more physiological activation of multiple muscles in multijoint task training for patients with stroke.

  5. Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bert Tuk

    2016-08-01

    Full Text Available Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity.

  6. Video game-based neuromuscular electrical stimulation system for calf muscle training: a case study.

    Science.gov (United States)

    Sayenko, D G; Masani, K; Milosevic, M; Robinson, M F; Vette, A H; McConville, K M V; Popovic, M R

    2011-03-01

    A video game-based training system was designed to integrate neuromuscular electrical stimulation (NMES) and visual feedback as a means to improve strength and endurance of the lower leg muscles, and to increase the range of motion (ROM) of the ankle joints. The system allowed the participants to perform isotonic concentric and isometric contractions in both the plantarflexors and dorsiflexors using NMES. In the proposed system, the contractions were performed against exterior resistance, and the angle of the ankle joints was used as the control input to the video game. To test the practicality of the proposed system, an individual with chronic complete spinal cord injury (SCI) participated in the study. The system provided a progressive overload for the trained muscles, which is a prerequisite for successful muscle training. The participant indicated that he enjoyed the video game-based training and that he would like to continue the treatment. The results show that the training resulted in a significant improvement of the strength and endurance of the paralyzed lower leg muscles, and in an increased ROM of the ankle joints. Video game-based training programs might be effective in motivating participants to train more frequently and adhere to otherwise tedious training protocols. It is expected that such training will not only improve the properties of their muscles but also decrease the severity and frequency of secondary complications that result from SCI. Copyright © 2010 IPEM. All rights reserved.

  7. The effects of electromechanical wrist robot assistive system with neuromuscular electrical stimulation for stroke rehabilitation.

    Science.gov (United States)

    Hu, X L; Tong, K Y; Li, R; Xue, J J; Ho, S K; Chen, P

    2012-06-01

    An electromyography (EMG)-driven electromechanical robot system integrated with neuromuscular electrical stimulation (NMES) was developed for wrist training after stroke. The performance of the system in assisting wrist flexion/extension tracking was evaluated on five chronic stroke subjects, when the system provided five different schemes with or without NMES and robot assistance. The tracking performances were measured by range of motion (ROM) of the wrist and root mean squared error (RMSE). The performance is better when both NMES and robot assisted in the tracking than those with either NMES or robot only (Pmotor functions in the hand, wrist and elbow functions after the training, as indicated by the clinical scores of Fugl-Meyer Assessment, Action Research Arm Test, Wolf Motor Function Test; and also showed reduced spasticity in the wrist and the elbow as measured by the Modified Ashworth Score of each subject. After the training, the co-contractions were reduced between the flexor carpi radialis and extensor carpi radialis, and between the biceps brachii and triceps brachii. Assistance from the robot helped improve the movement accuracy; and the NMES helped increase the muscle activation for the wrist joint and suppress the excessive muscular activities from the elbow joint. The NMES-robot assisted wrist training could improve the hand, wrist, and elbow functions.

  8. A versatile expression vector system for mammalian cell factories

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Kildegaard, Helene Faustrup; Hansen, Bjarne Gram

    The development of the field of mammalian cell factories requests fast and high-throughput methods which means high need for simpler and more efficient cloning techniques. This project applies the ligation-free USERTM (uracil-specific excision reagent) cloning technique to construct mammalian...

  9. INVESTIGATION OF THE NEURO-MUSCULAR SYSTEM IN PATIENTS WITH UNCOMPLICATED FRACTURES OF THE SPINE

    Directory of Open Access Journals (Sweden)

    A. B. Tomilov

    2011-01-01

    Full Text Available The results of electroneuromyography of the neuromuscular system of the lower extremities in patients with uncomplicated fractures of the lower thoracic spine showed that during the rehabilitation period after surgery (1 year the function of foot flexors remain fully intact. In 12-22% of cases in the early stages there are signs of motor deficit of foot extensor muscles, which disappears for half a year after surgery and again detected in 17% at 1 year after injury. In the early postoperative period electroneuromyography of peripheral nerves of the lower extremities revealed a mild subclinical neuropathy of n. tibialis in 24% of cases, n. peroneus - in 38%. A year after the operation a complete normalization of the tibial nerves functions occurred as the signs of «hidden» neuropathy of peroneal nerves were found in every third patient. In 2 weeks after the surgery at the level of the lumbosacral plexus the signs of hyperexcitability of motoneurons pool were reported in 50% of patients, which grew to half a year after surgery In a year at plexus level signs of deficiency of efferent fibers excitability, more expressed on L4-L5 level have been revealed. In the study of reflex activity of the lower extremities in 70-80% of patients with uncomplicated spine fractures bilateral suprasegmental violations by type of increased excitability of afferent fibers at the level L5-S1 were registered.

  10. 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.

  11. A novel gene delivery system for mammalian cells.

    Science.gov (United States)

    Gibson, Brian; Duffy, Angela M; Gould Fogerite, Susan; Krause-Elsmore, Sara; Lu, Ruying; Shang, Gaofeng; Chen, Zi-Wei; Mannino, Raphael J; Bouchier-Hayes, David J; Harmey, Judith H

    2004-01-01

    Although gene therapy holds great promise for the treatment of both acquired and genetic diseases, its development has been limited by practical considerations. Non-viral efficacy of delivery remains quite poor. We are investigating the feasibility of a novel lipid-based delivery system, cochleates, to deliver transgenes to mammalian cells. Rhodamine-labelled empty cochleates were incubated with two cell-lines (4T1 adenocarcinoma and H36.12 macrophage hybridoma) and primary macrophages in vitro and in vivo. Cochleates containing green fluorescent protein (GFP) expression plasmid were incubated with 4T1 adenocarcinoma cells. Cellular uptake of labelled cochleates or transgene GFP expression were visualised with fluorescence microscopy. 4T1 and H36.12 lines showed 39% and 23.1% uptake of rhodamine-cochleates, respectively. Human monocyte-derived macrophages and mouse peritoneal macrophages had 48+/-5.38% and 51.46+/-15.6% uptake of rhodamine-cochleates in vitro. In vivo 25.69+/-0.127% of peritoneal macrophages were rhodamine-positive after intra-peritoneal injection of rhodamine-cochleates. 19.49+/-10.12% of 4T1 cells expressed GFP. Cochleates may therefore be an effective, non-toxic and non-immunogenic method to introduce transgenes in vitro and in vivo.

  12. A Versatile System for USER Cloning-Based Assembly of Expression Vectors for Mammalian Cell Engineering

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Kildegaard, Helene Faustrup; Petersen, Maja Borup Kjær

    2014-01-01

    A new versatile mammalian vector system for protein production, cell biology analyses, and cell factory engineering was developed. The vector system applies the ligation-free uracil-excision based technique – USER cloning – to rapidly construct mammalian expression vectors of multiple DNA fragments...... efficiency above 90%. The functionality of basic vectors for FAST assembly was tested and validated by transient expression of fluorescent model proteins in CHO, U-2-OS and HEK293 cell lines. In this test, we included many of the most common vector elements for heterologous gene expression in mammalian cells......, in addition the system is fully extendable by other users. The vector system is designed to facilitate high-throughput genome-scale studies of mammalian cells, such as the newly sequenced CHO cell lines, through the ability to rapidly generate high-fidelity assembly of customizable gene expression vectors....

  13. The mathematical basis of population rhythms in nervous and neuromuscular systems.

    Science.gov (United States)

    Christakos, C N

    1986-03-01

    The mechanism underlying rhythmical aggregate activity of a population of neural or neuromuscular elements is examined in this report. By making use of the spectral properties of stochastic processes (Papoulis, 1965), it is shown that such population rhythms are the inevitable effect of the rhythmical activities of the individual elements, irrespective of the phase relations of the latter. This result applies to both "discrete" signals, such as spike trains, and "continuous" ones, such as membrane potential fluctuations. It has implications regarding the generation of common physiological rhythms and the preservation of rhythms when converging activity of one of the above two types is transformed into activity of the other type.

  14. [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.

  15. THE RELAXOMETER - A COMPLETE AND COMPREHENSIVE COMPUTER-CONTROLLED NEUROMUSCULAR-TRANSMISSION MEASUREMENT SYSTEM DEVELOPED FOR CLINICAL RESEARCH ON MUSCLE-RELAXANTS

    NARCIS (Netherlands)

    ROWAAN, CJ; VANDENBROM, RHG; WIERDA, JMKH

    The Relaxometer is a computer-controlled system developed for reliable clinical experimental measurements on neuromuscular block. This system is based on an adapted personal computer (Atari 1040 ST) with a monochrome monitor (Atari SM 124), and a microcomputer-driven slave unit (stimulator). There

  16. THE RELAXOMETER - A COMPLETE AND COMPREHENSIVE COMPUTER-CONTROLLED NEUROMUSCULAR-TRANSMISSION MEASUREMENT SYSTEM DEVELOPED FOR CLINICAL RESEARCH ON MUSCLE-RELAXANTS

    NARCIS (Netherlands)

    ROWAAN, CJ; VANDENBROM, RHG; WIERDA, JMKH

    1993-01-01

    The Relaxometer is a computer-controlled system developed for reliable clinical experimental measurements on neuromuscular block. This system is based on an adapted personal computer (Atari 1040 ST) with a monochrome monitor (Atari SM 124), and a microcomputer-driven slave unit (stimulator). There a

  17. Manufacture of biopharmaceutical proteins by mammalian cell culture systems.

    Science.gov (United States)

    Tolbert, W R

    1990-01-01

    In the last several years, dramatic advances have been in the development of new biopharmaceuticals including monoclonal antibodies for diagnosis and treatment and such genetically engineered proteins as tPA, Factor VIIIc, erythropoietin and soluble CD4, an anti-AIDS protein. Currently, there are several hundred such candidate drugs in human clinical trials. In most cases, these protein-based drugs will require manufacture by mammalian cell culture due to the inability of lower organisms to properly glycosylate, fold, make correct disulfide bonds and secrete active biomolecular forms. The need for large scale production from cell culture will greatly increase as more of the products in clinical trials are approved for commercial production. This will require significant reduction in manufacturing costs per gram, concomitant with increased capacity to hundreds or perhaps even thousands of kilograms annually. As an example, Invitron's multi-reactor manufacturing facility has operated at greater than one-half million liters per year and has experience with more than 250 mammalian cell lines for producing protein drug products.

  18. Virtual reality and gaming systems to improve walking and mobility for people with musculoskeletal and neuromuscular conditions.

    Science.gov (United States)

    Deutsch, Judith E

    2009-01-01

    Improving walking for individuals with musculoskeletal and neuromuscular conditions is an important aspect of rehabilitation. The capabilities of clinicians who address these rehabilitation issues could be augmented with innovations such as virtual reality gaming based technologies. The chapter provides an overview of virtual reality gaming based technologies currently being developed and tested to improve motor and cognitive elements required for ambulation and mobility in different patient populations. Included as well is a detailed description of a single VR system, consisting of the rationale for development and iterative refinement of the system based on clinical science. These concepts include: neural plasticity, part-task training, whole task training, task specific training, principles of exercise and motor learning, sensorimotor integration, and visual spatial processing.

  19. Activity-sensitive signaling by muscle-derived insulin-like growth factors in the developing and regenerating neuromuscular system.

    Science.gov (United States)

    Caroni, P

    1993-08-27

    In the nervous system, activity-sensitive retrograde signaling pathways couple the status of postsynaptic activation to elimination of collaterals during development and collateral sprouting in the adult. This article presents evidence supporting the hypothesis that in the neuromuscular system, skeletal muscle fiber derived insulin-like growth factors play a central role in such signaling. This evidence includes (1) timing and activity-sensitive expression of IGFs in skeletal muscle fibers, (2) identification of an IGF- and activity-sensitive retrograde signaling pathway from developing muscle to motoneurons in the spinal cord, (3) demonstration that IGFs in the muscle are both sufficient and necessary to induce interstitial cell proliferation and intramuscular nerve sprouting in adult muscle.

  20. Naringenin-type flavonoids show different estrogenic effects in mammalian and teleost test systems.

    Science.gov (United States)

    Zierau, Oliver; Hamann, Juliane; Tischer, Sandra; Schwab, Pia; Metz, Peter; Vollmer, Günter; Gutzeit, Herwig O; Scholz, Stefan

    2005-01-28

    The estrogenic activity of several intermediary plant compounds has raised concern about possible risks of unwanted interference with endocrine regulation, but on the other hand there are potential medical benefits, in particular in treatment of menopausal symptoms or cancer. In the present study, we compare the estrogenic effects of phytoestrogens naringenin, 8-prenylnaringenin, 6-(1,1-dimethylallyl)naringenin, and the synthetic 4'-acetyl-7-prenyloxynaringenin. Two mammalian in vitro systems and a fish in vivo system were used to study the estrogenic properties with reference to genistein, 17-beta-estradiol or ethynylestradiol. Strong differences were observed between the mammalian in vitro and the fish in vivo test system. In the medaka sex reversal/vtg gene expression assay no estrogenic effects of the naringenin-type flavonoids were observed, while mammalian in vitro systems showed a similar and graded response to the test compounds.

  1. Stable Isotope Tracer Analysis in Isolated Mitochondria from Mammalian Systems

    Directory of Open Access Journals (Sweden)

    Simon-Pierre Gravel

    2014-04-01

    Full Text Available Mitochondria are a focal point in metabolism, given that they play fundamental roles in catabolic, as well as anabolic reactions. Alterations in mitochondrial functions are often studied in whole cells, and metabolomics experiments using 13C-labeled substrates, coupled with mass isotopomer distribution analyses, represent a powerful approach to study global changes in cellular metabolic activities. However, little is known regarding the assessment of metabolic activities in isolated mitochondria using this technology. Studies on isolated mitochondria permit the evaluation of whether changes in cellular metabolic activities are due to modifications in the intrinsic properties of the mitochondria. Here, we present a streamlined approach to accurately determine 13C, as well as 12C enrichments in isolated mitochondria from mammalian tissues or cultured cells by GC/MS. We demonstrate the relevance of this experimental approach by assessing the effects of drugs perturbing mitochondrial functions on the mass isotopomer enrichment of metabolic intermediates. Furthermore, we investigate 13C and 12C enrichments in mitochondria isolated from cancer cells given the emerging role of metabolic alterations in supporting tumor growth. This original method will provide a very sensitive tool to perform metabolomics studies on isolated mitochondria.

  2. Oxidative stress in toxicology: established mammalian and emerging piscine model systems.

    Science.gov (United States)

    Kelly, K A; Havrilla, C M; Brady, T C; Abramo, K H; Levin, E D

    1998-07-01

    Interest in the toxicological aspects of oxidative stress has grown in recent years, and research has become increasingly focused on the mechanistic aspects of oxidative damage and cellular responses in biological systems. Toxic consequences of oxidative stress at the subcellular level include lipid peroxidation and oxidative damage to DNA and proteins. These effects are often used as end points in the study of oxidative stress. Typically, mammalian species have been used as models to study oxidative stress and to elucidate the mechanisms underlying cellular damage and response, largely because of the interest in human health issues surrounding oxidative stress. However, it is becoming apparent that oxidative stress also affects aquatic organisms exposed to environmental pollutants. Research in fish has demonstrated that mammalian and piscine systems exhibit similar toxicological and adaptive responses to oxidative stress. This suggests that piscine models, in addition to traditional mammalian models, may be useful for further understanding the mechanisms underlying the oxidative stress response.

  3. Genome engineering of mammalian haploid embryonic stem cells using the Cas9/RNA system

    Directory of Open Access Journals (Sweden)

    Takuro Horii

    2013-12-01

    Full Text Available Haploid embryonic stem cells (ESCs are useful for studying mammalian genes because disruption of only one allele can cause loss-of-function phenotypes. Here, we report the use of haploid ESCs and the CRISPR RNA-guided Cas9 nuclease gene-targeting system to manipulate mammalian genes. Co-transfection of haploid ESCs with vectors expressing Cas9 nuclease and single-guide RNAs (sgRNAs targeting Tet1, Tet2, and Tet3 resulted in the complete disruption of all three genes and caused a loss-of-function phenotype with high efficiency (50%. Co-transfection of cells with vectors expressing Cas9 and sgRNAs targeting two loci on the same chromosome resulted in the creation of a large chromosomal deletion and a large inversion. Thus, the use of the CRISPR system in combination with haploid ESCs provides a powerful platform to manipulate the mammalian genome.

  4. Strength training prior to endurance exercise: impact on the neuromuscular system, endurance performance and cardiorespiratory responses.

    Science.gov (United States)

    Conceição, Matheus; Cadore, Eduardo Lusa; González-Izal, Miriam; Izquierdo, Mikel; Liedtke, Giane Veiga; Wilhelm, Eurico Nestor; Pinto, Ronei Silveira; Goltz, Fernanda Reistenbach; Schneider, Cláudia Dornelles; Ferrari, Rodrigo; Bottaro, Martim; Kruel, Luiz Fernando Martins

    2014-12-09

    This study aimed to investigate the acute effects of two strength-training protocols on the neuromuscular and cardiorespiratory responses during endurance exercise. Thirteen young males (23.2 ± 1.6 years old) participated in this study. The hypertrophic strength-training protocol was composed of 6 sets of 8 squats at 75% of maximal dynamic strength. The plyometric strength-training protocol was composed of 6 sets of 8 jumps performed with the body weight as the workload. Endurance exercise was performed on a cycle ergometer at a power corresponding to the second ventilatory threshold until exhaustion. Before and after each protocol, a maximal voluntary contraction was performed, and the rate of force development and electromyographic parameters were assessed. After the hypertrophic strength-training and plyometric strength-training protocol, significant decreases were observed in the maximal voluntary contraction and rate of force development, whereas no changes were observed in the electromyographic parameters. Oxygen uptake and a heart rate during endurance exercise were not significantly different among the protocols. However, the time-to-exhaustion was significantly higher during endurance exercise alone than when performed after hypertrophic strength-training or plyometric strength-training (p strength-training, with no oxygen uptake or heart rate changes during the exercise.

  5. Strength Training Prior to Endurance Exercise: Impact on the Neuromuscular System, Endurance Performance and Cardiorespiratory Responses

    Directory of Open Access Journals (Sweden)

    Conceição Matheus

    2014-12-01

    Full Text Available This study aimed to investigate the acute effects of two strength-training protocols on the neuromuscular and cardiorespiratory responses during endurance exercise. Thirteen young males (23.2 ± 1.6 years old participated in this study. The hypertrophic strength-training protocol was composed of 6 sets of 8 squats at 75% of maximal dynamic strength. The plyometric strength-training protocol was composed of 6 sets of 8 jumps performed with the body weight as the workload. Endurance exercise was performed on a cycle ergometer at a power corresponding to the second ventilatory threshold until exhaustion. Before and after each protocol, a maximal voluntary contraction was performed, and the rate of force development and electromyographic parameters were assessed. After the hypertrophic strengthtraining and plyometric strength-training protocol, significant decreases were observed in the maximal voluntary contraction and rate of force development, whereas no changes were observed in the electromyographic parameters. Oxygen uptake and a heart rate during endurance exercise were not significantly different among the protocols. However, the time-to-exhaustion was significantly higher during endurance exercise alone than when performed after hypertrophic strength-training or plyometric strength-training (p <0.05. These results suggest that endurance performance may be impaired when preceded by strength-training, with no oxygen uptake or heart rate changes during the exercise.

  6. Neuromuscular control: introduction and overview.

    Science.gov (United States)

    van Leeuwen, J L

    1999-05-29

    This paper introduces some basic concepts of the interdisciplinary field of neuromuscular control, without the intention to be complete. The complexity and multifaceted nature of neuromuscular control systems is briefly addressed. Principles of stability and planning of motion trajectories are discussed. Closed-loop and open-loop control are considered, together with the inherent stability properties of muscles and the geometrical design of animal bodies. Various modelling approaches, as used by several authors in the Philosophical Transactions of the Royal Society of London, Series B, May 1999 issue, such as inverse and forward dynamics are outlined. An introductory overview is presented of the other contributions in that issue.

  7. [THE VIBRATION TRAINING AS SARCOPENIA INTERVENTION: IMPACT ON THE NEUROMUSCULAR SYSTEM OF THE ELDERLY].

    Science.gov (United States)

    Palop Montoro, María Victoria; Párraga Montilla, Juan Antonio; Lozano Aguilera, Emilio; Arteaga Checa, Milagros

    2015-10-01

    Introducción: el envejecimiento se acompaña de una reducción progresiva de la masa muscular que contribuye al desarrollo de limitaciones funcionales, donde el entrenamiento vibratorio puede ser una opción de intervención óptima en la prevención y tratamiento de la sarcopenia. Objetivo: comprobar la efectividad del entrenamiento de vibraciones de cuerpo completo en el sistema neuromuscular de los adultos mayores. Métodos: revisión sistemática en las bases de datos Medline, CINAHL, WOS y PEDro, mediante la combinación de los descriptores del Medical Subjects Headings (MeSH) referentes a entrenamiento vibratorio, fuerza muscular, masa muscular y personas mayores. Resultados: fueron encontrados un total de 214 estudios sobre el entrenamiento vibratorio en personas mayores, bien como única intervención o en combinación con otros ejercicios, de los cuales 45 cumplían los criterios de selección. De ellos, 30 artículos fueron eliminados por no superar los 5 puntos según la escala de PEDro. Se incluyeron para el análisis final 15 ensayos clínicos. Conclusión: el entrenamiento con plataformas vibratorias demuestra ser un método de entrenamiento de la fuerza seguro, adecuado y eficaz para la población de mayor edad, pero con resultados similares al ejercicio de resistencia convencional, en la prevención y tratamiento de la sarcopenia.

  8. Accuracy of a Custom Physical Activity and Knee Angle Measurement Sensor System for Patients with Neuromuscular Disorders and Gait Abnormalities

    Directory of Open Access Journals (Sweden)

    Frank Feldhege

    2015-05-01

    Full Text Available Long-term assessment of ambulatory behavior and joint motion are valuable tools for the evaluation of therapy effectiveness in patients with neuromuscular disorders and gait abnormalities. Even though there are several tools available to quantify ambulatory behavior in a home environment, reliable measurement of joint motion is still limited to laboratory tests. The aim of this study was to develop and evaluate a novel inertial sensor system for ambulatory behavior and joint motion measurement in the everyday environment. An algorithm for behavior classification, step detection, and knee angle calculation was developed. The validation protocol consisted of simulated daily activities in a laboratory environment. The tests were performed with ten healthy subjects and eleven patients with multiple sclerosis. Activity classification showed comparable performance to commercially available activPAL sensors. Step detection with our sensor system was more accurate. The calculated flexion-extension angle of the knee joint showed a root mean square error of less than 5° compared with results obtained using an electro-mechanical goniometer. This new system combines ambulatory behavior assessment and knee angle measurement for long-term measurement periods in a home environment. The wearable sensor system demonstrated high validity for behavior classification and knee joint angle measurement in a laboratory setting.

  9. Accuracy of a custom physical activity and knee angle measurement sensor system for patients with neuromuscular disorders and gait abnormalities.

    Science.gov (United States)

    Feldhege, Frank; Mau-Moeller, Anett; Lindner, Tobias; Hein, Albert; Markschies, Andreas; Zettl, Uwe Klaus; Bader, Rainer

    2015-05-06

    Long-term assessment of ambulatory behavior and joint motion are valuable tools for the evaluation of therapy effectiveness in patients with neuromuscular disorders and gait abnormalities. Even though there are several tools available to quantify ambulatory behavior in a home environment, reliable measurement of joint motion is still limited to laboratory tests. The aim of this study was to develop and evaluate a novel inertial sensor system for ambulatory behavior and joint motion measurement in the everyday environment. An algorithm for behavior classification, step detection, and knee angle calculation was developed. The validation protocol consisted of simulated daily activities in a laboratory environment. The tests were performed with ten healthy subjects and eleven patients with multiple sclerosis. Activity classification showed comparable performance to commercially available activPAL sensors. Step detection with our sensor system was more accurate. The calculated flexion-extension angle of the knee joint showed a root mean square error of less than 5° compared with results obtained using an electro-mechanical goniometer. This new system combines ambulatory behavior assessment and knee angle measurement for long-term measurement periods in a home environment. The wearable sensor system demonstrated high validity for behavior classification and knee joint angle measurement in a laboratory setting.

  10. A versatile system for USER cloning-based assembly of expression vectors for mammalian cell engineering.

    Directory of Open Access Journals (Sweden)

    Anne Mathilde Lund

    Full Text Available A new versatile mammalian vector system for protein production, cell biology analyses, and cell factory engineering was developed. The vector system applies the ligation-free uracil-excision based technique--USER cloning--to rapidly construct mammalian expression vectors of multiple DNA fragments and with maximum flexibility, both for choice of vector backbone and cargo. The vector system includes a set of basic vectors and a toolbox containing a multitude of DNA building blocks including promoters, terminators, selectable marker- and reporter genes, and sequences encoding an internal ribosome entry site, cellular localization signals and epitope- and purification tags. Building blocks in the toolbox can be easily combined as they contain defined and tested Flexible Assembly Sequence Tags, FASTs. USER cloning with FASTs allows rapid swaps of gene, promoter or selection marker in existing plasmids and simple construction of vectors encoding proteins, which are fused to fluorescence-, purification-, localization-, or epitope tags. The mammalian expression vector assembly platform currently allows for the assembly of up to seven fragments in a single cloning step with correct directionality and with a cloning efficiency above 90%. The functionality of basic vectors for FAST assembly was tested and validated by transient expression of fluorescent model proteins in CHO, U-2-OS and HEK293 cell lines. In this test, we included many of the most common vector elements for heterologous gene expression in mammalian cells, in addition the system is fully extendable by other users. The vector system is designed to facilitate high-throughput genome-scale studies of mammalian cells, such as the newly sequenced CHO cell lines, through the ability to rapidly generate high-fidelity assembly of customizable gene expression vectors.

  11. Cultivation of mammalian cells using a single-use pneumatic bioreactor system.

    Science.gov (United States)

    Obom, Kristina M; Cummings, Patrick J; Ciafardoni, Janelle A; Hashimura, Yasunori; Giroux, Daniel

    2014-10-10

    Recent advances in mammalian, insect, and stem cell cultivation and scale-up have created tremendous opportunities for new therapeutics and personalized medicine innovations. However, translating these advances into therapeutic applications will require in vitro systems that allow for robust, flexible, and cost effective bioreactor systems. There are several bioreactor systems currently utilized in research and commercial settings; however, many of these systems are not optimal for establishing, expanding, and monitoring the growth of different cell types. The culture parameters most challenging to control in these systems include, minimizing hydrodynamic shear, preventing nutrient gradient formation, establishing uniform culture medium aeration, preventing microbial contamination, and monitoring and adjusting culture conditions in real-time. Using a pneumatic single-use bioreactor system, we demonstrate the assembly and operation of this novel bioreactor for mammalian cells grown on micro-carriers. This bioreactor system eliminates many of the challenges associated with currently available systems by minimizing hydrodynamic shear and nutrient gradient formation, and allowing for uniform culture medium aeration. Moreover, the bioreactor's software allows for remote real-time monitoring and adjusting of the bioreactor run parameters. This bioreactor system also has tremendous potential for scale-up of adherent and suspension mammalian cells for production of a variety therapeutic proteins, monoclonal antibodies, stem cells, biosimilars, and vaccines.

  12. Development-inspired reprogramming of the mammalian central nervous system.

    Science.gov (United States)

    Amamoto, Ryoji; Arlotta, Paola

    2014-01-31

    In 2012, John Gurdon and Shinya Yamanaka shared the Nobel Prize for the demonstration that the identity of differentiated cells is not irreversibly determined but can be changed back to a pluripotent state under appropriate instructive signals. The principle that differentiated cells can revert to an embryonic state and even be converted directly from one cell type into another not only turns fundamental principles of development on their heads but also has profound implications for regenerative medicine. Replacement of diseased tissue with newly reprogrammed cells and modeling of human disease are concrete opportunities. Here, we focus on the central nervous system to consider whether and how reprogramming of cell identity may affect regeneration and modeling of a system historically considered immutable and hardwired.

  13. Aging of the mammalian gastrointestinal tract: a complex organ system.

    Science.gov (United States)

    Saffrey, M Jill

    2014-06-01

    Gastrointestinal disorders are a major cause of morbidity in the elderly population. The gastrointestinal tract is the most complex organ system; its diverse cells perform a range of functions essential to life, not only secretion, digestion, absorption and excretion, but also, very importantly, defence. The gastrointestinal tract acts not only as a barrier to harmful materials and pathogens but also contains the vast number of beneficial bacterial populations that make up the microbiota. Communication between the cells of the gastrointestinal tract and the central nervous and endocrine systems modifies behaviour; the organisms of the microbiota also contribute to this brain-gut-enteric microbiota axis. Age-related physiological changes in the gut are not only common, but also variable, and likely to be influenced by external factors as well as intrinsic aging of the cells involved. The cellular and molecular changes exhibited by the aging gut cells also vary. Aging intestinal smooth muscle cells exhibit a number of changes in the signalling pathways that regulate contraction. There is some evidence for age-associated degeneration of neurons and glia of the enteric nervous system, although enteric neuronal losses are likely not to be nearly as extensive as previously believed. Aging enteric neurons have been shown to exhibit a senescence-associated phenotype. Epithelial stem cells exhibit increased mitochondrial mutation in aging that affects their progeny in the mucosal epithelium. Changes to the microbiota and intestinal immune system during aging are likely to contribute to wider aging of the organism and are increasingly important areas of analysis. How changes of the different cell types of the gut during aging affect the numerous cellular interactions that are essential for normal gut functions will be important areas for future aging research.

  14. A robust TALENs system for highly efficient mammalian genome editing.

    Science.gov (United States)

    Feng, Yuanxi; Zhang, Siliang; Huang, Xin

    2014-01-10

    Recently, transcription activator-like effector nucleases (TALENs) have emerged as a highly effective tool for genomic editing. A pair of TALENs binds to two DNA recognition sites separated by a spacer sequence, and the dimerized FokI nucleases at the C terminal then cleave DNA in the spacer. Because of its modular design and capacity to precisely target almost any desired genomic locus, TALEN is a technology that can revolutionize the entire biomedical research field. Currently, for genomic editing in cultured cells, two plasmids encoding a pair of TALENs are co-transfected, followed by limited dilution to isolate cell colonies with the intended genomic manipulation. However, uncertain transfection efficiency becomes a bottleneck, especially in hard-to-transfect cells, reducing the overall efficiency of genome editing. We have developed a robust TALENs system in which each TALEN plasmid also encodes a fluorescence protein. Thus, cells transfected with both TALEN plasmids, a prerequisite for genomic editing, can be isolated by fluorescence-activated cell sorting. Our improved TALENs system can be applied to all cultured cells to achieve highly efficient genomic editing. Furthermore, an optimized procedure for genomic editing using TALENs is also presented. We expect our system to be widely adopted by the scientific community.

  15. Systems analysis of N-glycan processing in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Patrick Hossler

    Full Text Available N-glycosylation plays a key role in the quality of many therapeutic glycoprotein biologics. The biosynthesis reactions of these oligosaccharides are a type of network in which a relatively small number of enzymes give rise to a large number of N-glycans as the reaction intermediates and terminal products. Multiple glycans appear on the glycoprotein molecules and give rise to a heterogeneous product. Controlling the glycan distribution is critical to the quality control of the product. Understanding N-glycan biosynthesis and the etiology of microheterogeneity would provide physiological insights, and facilitate cellular engineering to enhance glycoprotein quality. We developed a mathematical model of glycan biosynthesis in the Golgi and analyzed the various reaction variables on the resulting glycan distribution. The Golgi model was modeled as four compartments in series. The mechanism of protein transport across the Golgi is still controversial. From the viewpoint of their holding time distribution characteristics, the two main hypothesized mechanisms, vesicular transport and Golgi maturation models, resemble four continuous mixing-tanks (4CSTR and four plug-flow reactors (4PFR in series, respectively. The two hypotheses were modeled accordingly and compared. The intrinsic reaction kinetics were first evaluated using a batch (or single PFR reactor. A sufficient holding time is needed to produce terminally-processed glycans. Altering enzyme concentrations has a complex effect on the final glycan distribution, as the changes often affect many reaction steps in the network. Comparison of the glycan profiles predicted by the 4CSTR and 4PFR models points to the 4PFR system as more likely to be the true mechanism. To assess whether glycan heterogeneity can be eliminated in the biosynthesis of biotherapeutics the 4PFR model was further used to assess whether a homogeneous glycan profile can be created through metabolic engineering. We demonstrate by

  16. Elabela-apelin receptor signaling pathway is functional in mammalian systems.

    Science.gov (United States)

    Wang, Zhi; Yu, Daozhan; Wang, Mengqiao; Wang, Qilong; Kouznetsova, Jennifer; Yang, Rongze; Qian, Kun; Wu, Wenjun; Shuldiner, Alan; Sztalryd, Carole; Zou, Minghui; Zheng, Wei; Gong, Da-Wei

    2015-02-02

    Elabela (ELA) or Toddler is a recently discovered hormone which is required for normal development of heart and vasculature through activation of apelin receptor (APJ), a G protein-coupled receptor (GPCR), in zebrafish. The present study explores whether the ELA-APJ signaling pathway is functional in the mammalian system. Using reverse-transcription PCR, we found that ELA is restrictedly expressed in human pluripotent stem cells and adult kidney whereas APJ is more widely expressed. We next studied ELA-APJ signaling pathway in reconstituted mammalian cell systems. Addition of ELA to HEK293 cells over-expressing GFP-AJP fusion protein resulted in rapid internalization of the fusion receptor. In Chinese hamster ovarian (CHO) cells over-expressing human APJ, ELA suppresses cAMP production with EC50 of 11.1 nM, stimulates ERK1/2 phosphorylation with EC50 of 14.3 nM and weakly induces intracellular calcium mobilization. Finally, we tested ELA biological function in human umbilical vascular endothelial cells and showed that ELA induces angiogenesis and relaxes mouse aortic blood vessel in a dose-dependent manner through a mechanism different from apelin. Collectively, we demonstrate that the ELA-AJP signaling pathways are functional in mammalian systems, indicating that ELA likely serves as a hormone regulating the circulation system in adulthood as well as in embryonic development.

  17. Oxidative stress in toxicology: established mammalian and emerging piscine model systems.

    OpenAIRE

    Kelly, K.A.; Havrilla, C M; Brady, T C; Abramo, K H; Levin, E.D.

    1998-01-01

    Interest in the toxicological aspects of oxidative stress has grown in recent years, and research has become increasingly focused on the mechanistic aspects of oxidative damage and cellular responses in biological systems. Toxic consequences of oxidative stress at the subcellular level include lipid peroxidation and oxidative damage to DNA and proteins. These effects are often used as end points in the study of oxidative stress. Typically, mammalian species have been used as models to study o...

  18. Yeast as a model system for mammalian seven-transmembrane segment receptors

    Energy Technology Data Exchange (ETDEWEB)

    Jeansonne, N.E. [East Carolina Univ. Medical School, Greenville, NC (United States)

    1994-05-01

    Investigators have used the budding yeast Saccharomyces cerevisiae as a model system in which to study the {beta}-adrenergic receptor, the T-cell receptor pathway, initiation of mammalian DNA replication, initiation of mammalian transcription, secretion, the CDC2 kinase system, cell cycle control, and aging, as well as the function of oncogenes. This list continues to growth with the discovery of an immunoglobulin heavy-chain binding homologue in yeast, an Rb binding protein homologue, and a possible yeast arrestin. Yeast is relatively easy to maintain, to grow, and to genetically manipulate. A single gene can be overexpressed, selectively mutated or deleted from its chromosomal location. In this way, the in vivo function of a gene can be studied. It has become reasonable to consider yeast as a model system for studying the seven transmembrane segments (7-TMS) receptor family. Currently, subtypes of the {beta}-adrenergic receptor are being studied in yeast. The receptor and its G{sub {alpha}}-G-protein, trigger the mating pheromone receptor pathway. This provides a powerful assay for determining receptor function. Studies expressing the muscarinic cholinergic receptor in yeast are underway. The yeast pheromone receptor belongs to this receptor family, sharing sequences and secondary structure homology. An effective strategy has been to identify a yeast pathway or process which is homologous to a mammalian system. The pathway is delineated in yeast, identifying other genetic components. Then yeast genes are used to screen for human homologues of these components. The putative human homologues are then expressed in yeast and in mammalian cells to determine function. When this type of {open_quotes}mixing and matching{close_quotes} works, yeast genetics can be a powerful tool. 115 refs.

  19. Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system.

    Science.gov (United States)

    Xue, Mingshan; Stradomska, Alicja; Chen, Hongmei; Brose, Nils; Zhang, Weiqi; Rosenmund, Christian; Reim, Kerstin

    2008-06-03

    Complexins (Cplxs) are key regulators of synaptic exocytosis, but whether they act as facilitators or inhibitors is currently being disputed controversially. We show that genetic deletion of all Cplxs expressed in the mouse brain causes a reduction in Ca(2+)-triggered and spontaneous neurotransmitter release at both excitatory and inhibitory synapses. Our results demonstrate that at mammalian central nervous system synapses, Cplxs facilitate neurotransmitter release and do not simply act as inhibitory clamps of the synaptic vesicle fusion machinery.

  20. The risk of extrapolation in neuroanatomy: the case of the mammalian vomeronasal system

    Directory of Open Access Journals (Sweden)

    Ignacio Salazar

    2009-10-01

    Full Text Available The sense of smell plays a crucial role in mammalian social and sexual behaviour, identification of food, and detection of predators. Nevertheless, mammals vary in their olfactory ability. One reason for this concerns the degree of development of their pars basalis rhinencephali, an anatomical feature that has has been considered in classifying this group of animals as macrosmatic, microsmatic or anosmatic. In mammals, different structures are involved in detecting odours: the main olfactory system, the vomeronasal system (VNS, and two subsystems, namely the ganglion of Grüneberg and the septal organ. Here, we review and summarise some aspects of the comparative anatomy of the VNS and its putative relationship to other olfactory structures. Even in the macrosmatic group, morphological diversity is an important characteristic of the VNS, specifically of the vomeronasal organ and the accessory olfactory bulb. We conclude that it is a big mistake to extrapolate anatomical data of the VNS from species to species, even in the case of relatively close evolutionary proximity between them. We propose to study other mammalian VNS than those of rodents in depth as a way to clarify its exact role in olfaction. Our experience in this field leads us to hypothesise that the VNS, considered for all mammalian species, could be a system undergoing involution or regression, and could serve as one more integrated olfactory subsystem.

  1. Doenças neuromusculares Neuromuscular disorders

    OpenAIRE

    Umbertina C. Reed

    2002-01-01

    Objetivo: apresentar os dados essenciais para o diagnóstico diferencial entre as principais doenças neuromusculares, denominação genérica sob a qual agrupam-se diferentes afecções, decorrentes do acometimento primário da unidade motora (motoneurônio medular, raiz nervosa, nervo periférico, junção mioneural e músculo). Fontes dos dados: os aspectos clínicos fundamentais para estabelecer o diagnóstico diferencial entre as diferentes doenças neuromusculares, bem como entre estas e as causas de h...

  2. Evolution of the archaeal and mammalian information processing systems: towards an archaeal model for human disease.

    Science.gov (United States)

    Lyu, Zhe; Whitman, William B

    2017-01-01

    Current evolutionary models suggest that Eukaryotes originated from within Archaea instead of being a sister lineage. To test this model of ancient evolution, we review recent studies and compare the three major information processing subsystems of replication, transcription and translation in the Archaea and Eukaryotes. Our hypothesis is that if the Eukaryotes arose within the archaeal radiation, their information processing systems will appear to be one of kind and not wholly original. Within the Eukaryotes, the mammalian or human systems are emphasized because of their importance in understanding health. Biochemical as well as genetic studies provide strong evidence for the functional similarity of archaeal homologs to the mammalian information processing system and their dissimilarity to the bacterial systems. In many independent instances, a simple archaeal system is functionally equivalent to more elaborate eukaryotic homologs, suggesting that evolution of complexity is likely an central feature of the eukaryotic information processing system. Because fewer components are often involved, biochemical characterizations of the archaeal systems are often easier to interpret. Similarly, the archaeal cell provides a genetically and metabolically simpler background, enabling convenient studies on the complex information processing system. Therefore, Archaea could serve as a parsimonious and tractable host for studying human diseases that arise in the information processing systems.

  3. Some assembly required: evolutionary and systems perspectives on the mammalian reproductive system.

    Science.gov (United States)

    Mordhorst, Bethany R; Wilson, Miranda L; Conant, Gavin C

    2016-01-01

    In this review, we discuss the way that insights from evolutionary theory and systems biology shed light on form and function in mammalian reproductive systems. In the first part of the review, we contrast the rapid evolution seen in some reproductive genes with the generally conservative nature of development. We discuss directional selection and coevolution as potential drivers of rapid evolution in sperm and egg proteins. Such rapid change is very different from the highly conservative nature of later embryo development. However, it is not unique, as some regions of the sex chromosomes also show elevated rates of evolutionary change. To explain these contradictory trends, we argue that it is not reproductive functions per se that induce rapid evolution. Rather, it is the fact that biotic interactions, such as speciation events and sexual conflict, have no evolutionary endpoint and hence can drive continuous evolutionary changes. Returning to the question of sex chromosome evolution, we discuss the way that recent advances in evolutionary genomics and systems biology and, in particular, the development of a theory of gene balance provide a better understanding of the evolutionary patterns seen on these chromosomes. We end the review with a discussion of a surprising and incompletely understood phenomenon observed in early embryos: namely the Warburg effect, whereby glucose is fermented to lactate and alanine rather than respired to carbon dioxide. We argue that evolutionary insights, from both yeasts and tumor cells, help to explain the Warburg effect, and that new metabolic modeling approaches are useful in assessing the potential sources of the effect.

  4. Neuromuscular disorders in pregnancy.

    Science.gov (United States)

    Guidon, Amanda C; Massey, E Wayne

    2012-08-01

    Preexisting and coincident neuromuscular disorders in pregnancy are challenging for clinicians because of the heterogeneity of disease and the limited data in the literature. Many questions arise regarding the effect of disease on the pregnancy, delivery, and newborn in addition to the effect of pregnancy on the course of disease. Each disorder has particular considerations and possible complications. An interdisciplinary team of physicians is essential. This article discusses the most recent literature on neuromuscular disorders in pregnancy including acquired root, plexus, and peripheral nerve lesions; acquired and inherited neuropathies and myopathies; disorders of the neuromuscular junction; and motor neuron diseases.

  5. Processing by the main olfactory system of chemosignals that facilitate mammalian reproduction.

    Science.gov (United States)

    Baum, Michael J; Cherry, James A

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction". Most mammalian species possess two parallel circuits that process olfactory information. One of these circuits, the accessory system, originates with sensory neurons in the vomeronasal organ (VNO). This system has long been known to detect non-volatile pheromonal odorants from conspecifics that influence numerous aspects of social communication, including sexual attraction and mating as well as the release of luteinizing hormone from the pituitary gland. A second circuit, the main olfactory system, originates with sensory neurons in the main olfactory epithelium (MOE). This system detects a wide range of non-pheromonal odors relevant to survival (e.g., food and predator odors). Over the past decade evidence has accrued showing that the main olfactory system also detects a range of volatile odorants that function as pheromones to facilitate mate recognition and activate the hypothalamic-pituitary-gonadal neuroendocrine axis. We review early studies as well as the new literature supporting the view that the main olfactory system processes a variety of different pheromonal cues that facilitate mammalian reproduction.

  6. The neuromuscular system of Pycnophyes kielensis (Kinorhyncha: Allomalorhagida investigated by confocal laser scanning microscopy

    Directory of Open Access Journals (Sweden)

    Andreas Altenburger

    2016-11-01

    Full Text Available Abstract Background Kinorhynchs are ecdysozoan animals with a phylogenetic position close to priapulids and loriciferans. To understand the nature of segmentation within Kinorhyncha and to infer a probable ancestry of segmentation within the last common ancestor of Ecdysozoa, the musculature and the nervous system of the allomalorhagid kinorhynch Pycnophyes kielensis were investigated by use of immunohistochemistry, confocal laser scanning microscopy, and 3D reconstruction software. Results The kinorhynch body plan comprises 11 trunk segments. Trunk musculature consists of paired ventral and dorsal longitudinal muscles in segments 1–10 as well as dorsoventral muscles in segments 1–11. Dorsal and ventral longitudinal muscles insert on apodemes of the cuticle inside the animal within each segment. Strands of longitudinal musculature extend over segment borders in segments 1–6. In segments 7–10, the trunk musculature is confined to the segments. Musculature of the digestive system comprises a strong pharyngeal bulb with attached mouth cone muscles as well as pharyngeal bulb protractors and retractors. The musculature of the digestive system shows no sign of segmentation. Judged by the size of the pharyngeal bulb protractors and retractors, the pharyngeal bulb, as well as the introvert, is moved passively by internal pressure caused by concerted action of the dorsoventral muscles. The nervous system comprises a neuropil ring anterior to the pharyngeal bulb. Associated with the neuropil ring are flask-shaped serotonergic somata extending anteriorly and posteriorly. A ventral nerve cord is connected to the neuropil ring and runs toward the anterior until an attachment point in segment 1, and from there toward the posterior with one ganglion in segment 6. Conclusions Segmentation within Kinorhyncha likely evolved from an unsegmented ancestor. This conclusion is supported by continuous trunk musculature in the anterior segments 1–6, continuous

  7. Steroidal neuromuscular blocking agents

    NARCIS (Netherlands)

    Wierda, JMKH; Mori, K; Ohmura, A; Toyooka, H; Hatano, Y; Shingu, K; Fukuda, K

    1998-01-01

    Since 1964 approximately 20 steroidal neuromuscular blocking agents have been evaluated clinically. Pancuronium, a bisquaternary compound designed on the drawingboard, was the first steroidal relaxant introduced into clinical practice worldwide in the 1970's. Although a major improvement, pancuroniu

  8. Robotic-locomotor training as a tool to reduce neuromuscular abnormality in spinal cord injury: the application of system identification and advanced longitudinal modeling.

    Science.gov (United States)

    Mirbagheri, Mehdi M; Kindig, Matthew; Niu, Xun; Varoqui, Deborah; Conaway, Petra

    2013-06-01

    In this study, the effect of the LOKOMAT, a robotic-assisted locomotor training system, on the reduction of neuromuscular abnormalities associated with spasticity was examined, for the first time in the spinal cord injury (SCI) population. Twenty-three individuals with chronic incomplete SCI received 1-hour training sessions in the LOKOMAT three times per week, with up to 45 minutes of training per session; matched control group received no intervention. The neuromuscular properties of the spastic ankle were then evaluated prior to training and after 1, 2, and 4 weeks of training. A parallel-cascade system identification technique was used to determine the reflex and intrinsic stiffness of the ankle joint as a function of ankle position at each time point. The slope of the stiffness vs. joint angle curve, i.e. the modulation of stiffness with joint position, was then calculated and tracked over the four-week period. Growth Mixture Modeling (GMM), an advanced statistical method, was then used to classify subjects into subgroups based on similar trends in recovery pattern of slope over time, and Random Coefficient Regression (RCR) was used to model the recovery patterns within each subgroup. All groups showed significant reductions in both reflex and intrinsic slope over time, but subjects in classes with higher baseline values of the slope showed larger improvements over the four weeks of training. These findings suggest that LOKOMAT training may also be useful for reducing the abnormal modulation of neuromuscular properties that arises as secondary effects after SCI. This can advise clinicians as to which patients can benefit the most from LOKOMAT training prior to beginning the training. Further, this study shows that system identification and GMM/RCR can serve as powerful tools to quantify and track spasticity over time in the SCI population.

  9. A cost-effective approach to microporate mammalian cells with the Neon Transfection System.

    Science.gov (United States)

    Brees, Chantal; Fransen, Marc

    2014-12-01

    Electroporation is one of the most efficient nonviral methods for transferring exogenous DNA into mammalian cells. However, the relatively high costs of electroporation kits and reagents temper the routine use of this fast and easy to perform technique in many laboratories. Several years ago, a new flexible and easy to operate electroporation device was launched under the name Neon Transfection System. This device uses specialized pipette tips containing gold-plated electrodes as electroporation chamber. Here we report a protocol to regenerate these expensive tips as well as some other Neon kit accessories, thereby reducing the cost of electroporation at least 10-fold.

  10. The role of habitat patches on mammalian diversity in cork oak agroforestry systems

    Science.gov (United States)

    Rosalino, Luis M.; Rosário, João do; Santos-Reis, Margarida

    2009-07-01

    Habitat patches, depending on the degree of differentiation from the matrix, can add few or many elements to the species pool of a particular landscape. Their importance to biodiversity is particularly relevant in areas with complex landscapes, where natural, naturalized, or managed habitats are interspersed by small patches of habitat types with very different biophysical characteristics; e.g., fruit orchards and riparian areas. This is the case of the montado landscape, a cork oak agroforestry system that largely covers south-western Portugal. We evaluated whether the high mammalian biodiversity found in this system is, in part, the cumulative result of the species found in the non-matrix habitats. Our results indicate that in areas where there are inclusions of orchards/olive yards and riparian vegetation in the cork oak woodland, a significantly higher number of mammalian species are present. We further detected a positive effect of low human disturbance on mammal diversity. Ultimately, our results can be used by managers to augment their management options, since we show that the inclusion and maintenance of non-matrix habitat patches in cork oak agro-silvo-forestry systems can help to maximize mammal biodiversity without compromising services associated with agriculture and forestry.

  11. The Drosophila larval neuromuscular junction as a model for scaffold complexes at glutamatergic synapses: benefits and limitations.

    Science.gov (United States)

    Thomas, Ulrich; Kobler, Oliver; Gundelfinger, Eckart D

    2010-09-01

    Based on unbeatable genetic accessibility and relative simplicity, the Drosophila larval neuromuscular junction has become a widely used model system for studying functional and structural aspects of excitatory glutamatergic synapses. Membrane-associated guanylate kinase-like proteins (MAGUKs) are first-order scaffolding molecules enriched at many cellular junctions, including synapses, where they coordinate multiple binding partners, including cell adhesion molecules and ion channels. The enrichment of the prototypic MAGUK Discs-Large at larval NMJs apparently parallels the high abundance of its homologs at excitatory synapses in the mammalian central nervous system. Here, the authors review selected aspects of the long-standing work on Dlg at fly neuromuscular junctions, thereby scrutinizing its subcellular localization, function, and regulation with regard to corresponding aspects of MAGUKs in vertebrate neurons.

  12. The Neuromuscular System

    NARCIS (Netherlands)

    Hosman, R.J.A.W.; Abbink, D.A.; Cardullo, F.M.

    2010-01-01

    The aim of flight simulation is to create an environment for the pilot wherein he or she can perform the piloting task in such a way that the objective of the simulation, training or research, is reached. To simulate the flight environment in a simulator models describing the aircraft dynamic behavi

  13. Inf luence of Spirulina platensis exudates on the endocrine and nervous systems of a mammalian model

    Institute of Scientific and Technical Information of China (English)

    Samah; Mamdouh; Mohamed; Fathy; Ashraf; Mohamed; Mohamed; Essa

    2015-01-01

    Objective: To investigate the ef ect of intra-peritoneal injection of purii ed exudates of axenic Spirulina platensis on the mammalian endocrine and nervous systems. Methods: The intra-peritoneal injection of the cyanobacterial exudates in mice was applied. Sex hormonal levels of testosterone and progesterone were measured using radioimmunoassay while the follicular stimulating hormone and luteinizing hormone were evaluated by direct chemiluminescence. In addition, superoxide dismutase, catalase and glutathione peroxidase were monitored in the hippocampus region using spectrophotometric method. The levels of the hippocampal monoamines, dopamine, noradrenaline and serotonin were analyzed by high performance liquid chromatography while the acetyl choline neurotransmitter was measured by colorimetric method using choline/acetylcholine assay kit. Results: A sharp disruption in the sex hormones levels of testosterone, progesterone, follicular stimulating hormone and luteinizing hormone was demonstrated in the serum of the treated mice. At the same time, a signii cant reduction in the endogenous antioxidant defense enzymes, superoxide dismutase, catalase and glutathione peroxidase was observed in the hippocampus region of the injected mice. Moreover, levels of dopamine, noradrenaline, serotonin and acetyl choline neurotransmitter in the same region were signii cantly af ected as a result of the treatment with Spirulina i ltrate. The gas chromatography-mass spectrometer and liquid chromatography mass spectrometry/mass spectrometry analysis showed the presence of some sterol-like compounds in the cyanobacterial i ltrate. Conclusions: This study demonstrated the capability of Spirulina to release detrimental bioactive metabolites into their surrounding that can disrupt the mammalian endocrine and nervous systems.

  14. Purification of replication factors using insect and mammalian cell expression systems.

    Science.gov (United States)

    Uno, Shuji; You, Zhiying; Masai, Hisao

    2012-06-01

    Purification of factors for DNA replication in an amount sufficient for detailed biochemical characterization is essential to elucidating its mechanisms. Insect cell expression systems are commonly used for purification of the factors proven to be difficult to deal with in bacteria. We describe first the detailed protocols for purification of mammalian Mcm complexes including the Mcm2/3/4/5/6/7 heterohexamer expressed in insect cells. We then describe a convenient and economical system in which large-sized proteins and multi-factor complexes can be transiently overexpressed in human 293T cells and be rapidly purified in a large quantity. We describe various expression vectors and detailed methods for transfection and purification of various replication factors which have been difficult to obtain in a sufficient amount in other systems. Availability of efficient methods to overproduce and purify the proteins that have been challenging would facilitate the enzymatic analyses of the processes of DNA replication.

  15. Nanovesicle-Carbon Nanotube Hybrid Structures Mimicking Mammalian Pain Sensory System

    Science.gov (United States)

    Cho, Youngtac; Jin, Hye Jun; An, Jeong Mi; Park, Juhun; Moon, Seok Jun; Hong, Seunghun

    2015-03-01

    We developed a ``chemical-pain sensor'' based on a single-walled carbon nanotube-based field effect transistor (SWNT-FET) functionalized with rat pain sensory receptor, rat transient receptor potential vanilloid 1 (rTRPV1) mimicking a mammalian pain sensory system. The sensor can selectively detect chemical pain stimuli such as capsaicin and resiniferatoxin with a sensitivity of a 1 pM detection limit. Since this sensor allows one to quantitatively measure the concentration of chemical pain stimuli just like animal sensory systems, it can be used for various practical applications such as food screening. In addition, TRP families including rTRPV1 protein used for the sensor are now suggested as potential drug targets related to nerve and circulation disorders. Thus, the capability of measuring TRP responses using our sensor platform should open up other applications such as drug screening and basic research related with nerve and circulation systems.

  16. Identification of mammalian noggin and its expression in the adult nervous system.

    Science.gov (United States)

    Valenzuela, D M; Economides, A N; Rojas, E; Lamb, T M; Nuñez, L; Jones, P; Lp, N Y; Espinosa, R; Brannan, C I; Gilbert, D J

    1995-09-01

    The multiple roles of noggin during dorsal fate specification in Xenopus embryos, together with noggin's ability to directly induce neural tissue, inspired an effort to determine whether a similar molecule exists in mammals. Here we describe the identification of human and rat noggin and explore their expression patterns; we also localize the human NOGGIN gene to chromosome 17q22, and the mouse gene to a syntenic region of chromosome 11. Mammalian noggin is remarkably similar in its sequence to Xenopus noggin, and is similarly active in induction assays performed on Xenopus embryo tissues. In the adult mammal, noggin is most notably expressed in particular regions of the nervous system, such as the tufted cells of the olfactory bulb, the piriform cortex of the brain, and the Purkinje cells of the cerebellum, suggesting that one of the earliest acting neural inducers also has important roles in the adult nervous system.

  17. Rescue the failed half-ZFN by a sensitive mammalian cell-based luciferase reporter system.

    Directory of Open Access Journals (Sweden)

    Weifeng Zhang

    Full Text Available ZFN technology is a powerful research tool and has been used for genome editing in cells lines, animals and plants. The generation of functional ZFNs for particular targets in mammalian genome is still challenging for an average research group. The modular-assembly method is relatively fast, easy-to-practice but has a high failure rate. Some recent studies suggested that a ZFP with low binding activity might be able to form a working ZFN pair with another binding active half-ZFP. In order to unveil the potential ZFP candidates among those with low binding activities, this paper established a highly sensitive mammalian cell-based transcriptional reporter system to assess the DNA binding activities of ZFPs by inserting multiple copies of ZFN target sequence fragment (TSF of an interested gene (e. g., hPGRN or hVEGF. Our results showed that this system increased the screening sensitivity up to 50-fold and markedly amplified the differences in the binding activities between different ZFPs. We also found that the targeted chromosomal gene repair efficiency of each hPGRN or hVEGF ZFN pair was in proportion with the combination of the binding activities of the ZFL (Left zinc finger and ZFR (Right zinc finger. A hPGRN ZFR with low binding ability was able to form a biological active ZFN if combined with a hPGRN ZFL with relatively high binding ability. Lastly, site-specific genome editing by hPGRN ZFNs generated by this system was confirmed by sequencing, and the PGRN knock-out cell line showed significantly decreased cell growth compared with the control. Our system will provide a valuable tool for further optimizing the nucleases with regard to specificity and cytotoxicity.

  18. 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.

  19. Electrodiagnosis in neuromuscular disease.

    Science.gov (United States)

    Lipa, Bethany M; Han, Jay J

    2012-08-01

    Electromyography (EMG) is an important diagnostic tool for the assessment of individuals with various neuromuscular diseases. It should be an extension of a thorough history and physical examination. Some prototypical characteristics and findings of EMG and nerve conduction studies are discussed; however, a more thorough discussion can be found in the textbooks and resources sited in the article. With an increase in molecular genetic diagnostics, EMG continues to play an important role in the diagnosis and management of patients with neuromuscular diseases and also provides a cost-effective diagnostic workup before ordering a battery of costly genetic tests.

  20. Mechanisms of Long Non-coding RNAs in Mammalian Nervous System Development, Plasticity, Disease, and Evolution.

    Science.gov (United States)

    Briggs, James A; Wolvetang, Ernst J; Mattick, John S; Rinn, John L; Barry, Guy

    2015-12-02

    Only relatively recently has it become clear that mammalian genomes encode tens of thousands of long non-coding RNAs (lncRNAs). A striking 40% of these are expressed specifically in the brain, where they show precisely regulated temporal and spatial expression patterns. This begs the question, what is the functional role of these many lncRNA transcripts in the brain? Here we canvass a growing number of mechanistic studies that have elucidated central roles for lncRNAs in the regulation of nervous system development and function. We also survey studies indicating that neurological and psychiatric disorders may ensue when these mechanisms break down. Finally, we synthesize these insights with evidence from comparative genomics to argue that lncRNAs may have played important roles in brain evolution, by virtue of their abundant sequence innovation in mammals and plausible mechanistic connections to the adaptive processes that occurred recently in the primate and human lineages.

  1. A compact light-sheet microscope for the study of the mammalian central nervous system

    Science.gov (United States)

    Yang, Zhengyi; Haslehurst, Peter; Scott, Suzanne; Emptage, Nigel; Dholakia, Kishan

    2016-05-01

    Investigation of the transient processes integral to neuronal function demands rapid and high-resolution imaging techniques over a large field of view, which cannot be achieved with conventional scanning microscopes. Here we describe a compact light sheet fluorescence microscope, featuring a 45° inverted geometry and an integrated photolysis laser, that is optimized for applications in neuroscience, in particular fast imaging of sub-neuronal structures in mammalian brain slices. We demonstrate the utility of this design for three-dimensional morphological reconstruction, activation of a single synapse with localized photolysis, and fast imaging of neuronal Ca2+ signalling across a large field of view. The developed system opens up a host of novel applications for the neuroscience community.

  2. Understanding mammalian genetic systems: the challenge of phenotyping in the mouse.

    Directory of Open Access Journals (Sweden)

    Steve D M Brown

    2006-08-01

    Full Text Available Understanding mammalian genetic systems is predicated on the determination of the relationship between genetic variation and phenotype. Several international programmes are under way to deliver mutations in every gene in the mouse genome. The challenge for mouse geneticists is to develop approaches that will provide comprehensive phenotype datasets for these mouse mutant libraries. Several factors are critical to success in this endeavour. It will be important to catalogue assay and environment and where possible to adopt standardised procedures for phenotyping tests along with common environmental conditions to ensure comparable datasets of phenotypes. Moreover, the scale of the task underlines the need to invest in technological development improving both the speed and cost of phenotyping platforms. In addition, it will be necessary to develop new informatics standards that capture the phenotype assay as well as other factors, genetic and environmental, that impinge upon phenotype outcome.

  3. Towards quantitative mass spectrometry-based metabolomics in microbial and mammalian systems.

    Science.gov (United States)

    Kapoore, Rahul Vijay; Vaidyanathan, Seetharaman

    2016-10-28

    Metabolome analyses are a suite of analytical approaches that enable us to capture changes in the metabolome (small molecular weight components, typically less than 1500 Da) in biological systems. Mass spectrometry (MS) has been widely used for this purpose. The key challenge here is to be able to capture changes in a reproducible and reliant manner that is representative of the events that take place in vivo Typically, the analysis is carried out in vitro, by isolating the system and extracting the metabolome. MS-based approaches enable us to capture metabolomic changes with high sensitivity and resolution. When developing the technique for different biological systems, there are similarities in challenges and differences that are specific to the system under investigation. Here, we review some of the challenges in capturing quantitative changes in the metabolome with MS based approaches, primarily in microbial and mammalian systems.This article is part of the themed issue 'Quantitative mass spectrometry'. © 2016 The Author(s).

  4. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    Science.gov (United States)

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  5. Scoliosis and the impact in neuromuscular disease.

    Science.gov (United States)

    Mayer, Oscar Henry

    2015-01-01

    Scoliosis can alter respiratory mechanics by changing the orientation of the muscles and joints of the respiratory system and in severe forms can put a patient at risk of severe respiratory morbidity or respiratory failure. However, perhaps the most important factor in determining the pulmonary morbidity in scoliosis is the balance between the "load" or altered respiratory mechanics and the "pump" or the respiratory muscle strength. Therefore, scoliosis in patients with neuromuscular disease will both lead to increased "load" and a weakened "pump", an exceptionally unfortunate combination. While progressive neuromuscular disease by its nature does not respond favorably to attempts to improve respiratory muscle strength, the natural approach of early proactive management of the "load" and in the case of scoliosis a variety of different strategies have been tried with variable short term and long term results. Figuring this out requires both an understanding of the underlying pathophysiology of a particular neuromuscular condition and the available options for and timing of surgical intervention.

  6. 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

  7. High-throughput screens in mammalian cells using the CRISPR-Cas9 system.

    Science.gov (United States)

    Peng, Jingyu; Zhou, Yuexin; Zhu, Shiyou; Wei, Wensheng

    2015-06-01

    As a powerful genome-editing tool, the clustered regularly interspaced short palindromic repeats (CRISPR)-clustered regularly interspaced short palindromic repeats-associated protein 9 (Cas9) system has been quickly developed into a large-scale function-based screening strategy in mammalian cells. This new type of genetic library is constructed through the lentiviral delivery of single-guide RNA collections that direct Cas9 or inactive dead Cas9 fused with effectors to interrogate gene function or regulate gene transcription in targeted cells. Compared with RNA interference screening, the CRISPR-Cas9 system demonstrates much higher levels of effectiveness and reliability with respect to both loss-of-function and gain-of-function screening. Unlike the RNA interference strategy, a CRISPR-Cas9 library can target both protein-coding sequences and regulatory elements, including promoters, enhancers and elements transcribing microRNAs and long noncoding RNAs. This powerful genetic tool will undoubtedly accelerate the mechanistic discovery of various biological processes. In this mini review, we summarize the general procedure of CRISPR-Cas9 library mediated functional screening, system optimization strategies and applications of this new genetic toolkit. © 2015 FEBS.

  8. Two inhibitory systems and CKIs regulate cell cycle exit of mammalian cardiomyocytes after birth

    Energy Technology Data Exchange (ETDEWEB)

    Tane, Shoji; Okayama, Hitomi; Ikenishi, Aiko; Amemiya, Yuki [School of Life Sciences, Faculty of Medicine, Tottori University, Yonago 683-8503 (Japan); Nakayama, Keiichi I. [Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582 (Japan); Takeuchi, Takashi, E-mail: takeuchi@med.tottori-u.ac.jp [School of Life Sciences, Faculty of Medicine, Tottori University, Yonago 683-8503 (Japan)

    2015-10-16

    Mammalian cardiomyocytes actively proliferate during embryonic stages, following which they exit their cell cycle after birth, and the exit is maintained. Previously, we showed that two inhibitory systems (the G1-phase inhibitory system: repression of cyclin D1 expression; the M-phase inhibitory system: inhibition of CDK1 activation) maintain the cell cycle exit of mouse adult cardiomyocytes. We also showed that two CDK inhibitors (CKIs), p21{sup Cip1} and p27{sup Kip1}, regulate the cell cycle exit in a portion of postnatal cardiomyocytes. It remains unknown whether the two inhibitory systems are involved in the cell cycle exit of postnatal cardiomyocytes and whether p21{sup Cip1} and p27{sup Kip1} also inhibit entry to M-phase. Here, we showed that more than 40% of cardiomyocytes entered an additional cell cycle by induction of cyclin D1 expression at postnatal stages, but M-phase entry was inhibited in the majority of cardiomyocytes. Marked cell cycle progression and endoreplication were observed in cardiomyocytes of p21{sup Cip1} knockout mice at 4 weeks of age. In addition, tri- and tetranucleated cardiomyocytes increased significantly in p21{sup Cip1} knockout mice. These data showed that the G1-phase inhibitory system and two CKIs (p21{sup Cip1} and p27{sup Kip1}) inhibit entry to an additional cell cycle in postnatal cardiomyocytes, and that the M-phase inhibitory system and p21{sup Cip1} inhibit M-phase entry of cardiomyocytes which have entered the additional cell cycle. - Highlights: • Many postnatal cardiomyocytes entered an additional cell cycle by cyclin D1 induction. • The majority of cardiomyocytes could not enter M-phase after cyclin D1 induction. • Cell cycle progressed markedly in p21{sup Cip1} knockout mice after postnatal day 14. • Tri- and tetranucleated cardiomyocytes increased in p21{sup Cip1} knockout mice.

  9. Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

    Directory of Open Access Journals (Sweden)

    Dimitrov Mitko

    2009-08-01

    Full Text Available Abstract Background N,N-Diethyl-3-methylbenzamide (deet remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system. Results By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase. Conclusion These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.

  10. Peptidomics and Secretomics of the Mammalian Peripheral Sensory-Motor System

    Science.gov (United States)

    Tillmaand, Emily G.; Yang, Ning; Kindt, Callie A. C.; Romanova, Elena V.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2015-12-01

    The dorsal root ganglion (DRG) and its anatomically and functionally associated spinal nerve and ventral and dorsal roots are important components of the peripheral sensory-motor system in mammals. The cells within these structures use a number of peptides as intercellular signaling molecules. We performed a variety of mass spectrometry (MS)-based characterizations of peptides contained within and secreted from these structures, and from isolated and cultured DRG cells. Liquid chromatography-Fourier transform MS was utilized in DRG and nerve peptidome analysis. In total, 2724 peptides from 296 proteins were identified in tissue extracts. Neuropeptides are among those detected, including calcitonin gene-related peptide I, little SAAS, and known hemoglobin-derived peptides. Solid phase extraction combined with direct matrix-assisted laser desorption/ionization time-of-flight MS was employed to investigate the secretome of these structures. A number of peptides were detected in the releasate from semi-intact preparations of DRGs and associated nerves, including neurofilament- and myelin basic protein-related peptides. A smaller set of analytes was observed in releasates from cultured DRG neurons. The peptide signals observed in the releasates have been mass-matched to those characterized and identified in homogenates of entire DRGs and associated nerves. This data aids our understanding of the chemical composition of the mammalian peripheral sensory-motor system, which is involved in key physiological functions such as nociception, thermoreception, itch sensation, and proprioception.

  11. Dog and mouse: Towards a balanced view of the mammalian olfactory system

    Directory of Open Access Journals (Sweden)

    William Arthur Barrios Santos

    2014-09-01

    Full Text Available Although the most intensively studied mammalian olfactory system is that of the mouse, in which olfactory chemical cues of one kind or another are detected in four different nasal areas (the main olfactory epithelium, the septal organ, Grüneberg’s ganglion, and the sensory epithelium of the vomeronasal organ, the extraordinarily sensitive olfactory system of the dog is also an important model that is increasingly used, for example in genomic studies of species evolution. Here we describe the topography and extent of the main olfactory and vomeronasal sensory epithelia of the dog, and we report finding no structures equivalent to the Grüneberg ganglion and septal organ of the mouse. Since we examined adults, newborns and foetuses we conclude that these latter structures are absent in dogs, possibly as the result of regression or involution.The absence of a vomeronasal component based on VR2 receptors suggests that the vomeronasal organ may be undergoing a similar involutionary process.

  12. A mammalian nervous-system-specific plasma membrane proteasome complex that modulates neuronal function.

    Science.gov (United States)

    Ramachandran, Kapil V; Margolis, Seth S

    2017-04-01

    In the nervous system, rapidly occurring processes such as neuronal transmission and calcium signaling are affected by short-term inhibition of proteasome function. It is unclear how proteasomes are able to acutely regulate such processes, as this action is inconsistent with their canonical role in proteostasis. Here we describe a mammalian nervous-system-specific membrane proteasome complex that directly and rapidly modulates neuronal function by degrading intracellular proteins into extracellular peptides that can stimulate neuronal signaling. This proteasome complex is closely associated with neuronal plasma membranes, exposed to the extracellular space, and catalytically active. Selective inhibition of the membrane proteasome complex by a cell-impermeable proteasome inhibitor blocked the production of extracellular peptides and attenuated neuronal-activity-induced calcium signaling. Moreover, we observed that membrane-proteasome-derived peptides were sufficient to induce neuronal calcium signaling. Our discoveries challenge the prevailing notion that proteasomes function primarily to maintain proteostasis, and highlight a form of neuronal communication that takes place through a membrane proteasome complex.

  13. Maltose-Binding Protein (MBP, a Secretion-Enhancing Tag for Mammalian Protein Expression Systems.

    Directory of Open Access Journals (Sweden)

    Raphael Reuten

    Full Text Available Recombinant proteins are commonly expressed in eukaryotic expression systems to ensure the formation of disulfide bridges and proper glycosylation. Although many proteins can be expressed easily, some proteins, sub-domains, and mutant protein versions can cause problems. Here, we investigated expression levels of recombinant extracellular, intracellular as well as transmembrane proteins tethered to different polypeptides in mammalian cell lines. Strikingly, fusion of proteins to the prokaryotic maltose-binding protein (MBP generally enhanced protein production. MBP fusion proteins consistently exhibited the most robust increase in protein production in comparison to commonly used tags, e.g., the Fc, Glutathione S-transferase (GST, SlyD, and serum albumin (ser alb tag. Moreover, proteins tethered to MBP revealed reduced numbers of dying cells upon transient transfection. In contrast to the Fc tag, MBP is a stable monomer and does not promote protein aggregation. Therefore, the MBP tag does not induce artificial dimerization of tethered proteins and provides a beneficial fusion tag for binding as well as cell adhesion studies. Using MBP we were able to secret a disease causing laminin β2 mutant protein (congenital nephrotic syndrome, which is normally retained in the endoplasmic reticulum. In summary, this study establishes MBP as a versatile expression tag for protein production in eukaryotic expression systems.

  14. Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

    Directory of Open Access Journals (Sweden)

    Bodo C. Melnik

    2015-07-01

    Full Text Available Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1, the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1 essential branched-chain amino acids (BCAAs; (2 glutamine; (3 palmitic acid; and (4 bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER stress and drives an aimless quasi-program, which promotes aging and age-related diseases.

  15. Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems.

    OpenAIRE

    Nestor, Colm E; Ottaviano, Raffaele; Reinhardt, Diana; Cruickshanks, Hazel A; Mjoseng, Heidi K.; McPherson, Rhoanne C; Lentini, Antonio; Thomson, John P; Dunican, Donncha S; Pennings, Sari; Anderton, Stephen M.; Benson, Mikael; Meehan, Richard R

    2015-01-01

    BackgroundThe DNA methylation profile of mammalian cell lines differs from the primary tissue from which they were derived, exhibiting increasing divergence from the in vivo methylation profile with extended time in culture. Few studies have directly examined the initial epigenetic and transcriptional consequences of adaptation of primary mammalian cells to culture, and the potential mechanisms through which this epigenetic dysregulation occurs is unknown.ResultsWe demonstrate that adaptation...

  16. A role for Id2 in regulating photic entrainment of the mammalian circadian system.

    Science.gov (United States)

    Duffield, Giles E; Watson, Nathan P; Mantani, Akio; Peirson, Stuart N; Robles-Murguia, Maricela; Loros, Jennifer J; Israel, Mark A; Dunlap, Jay C

    2009-02-24

    Inhibitor of DNA binding genes (Id1-Id4) encode helix-loop-helix (HLH) transcriptional repressors associated with development and tumorigenesis [1, 2], but little is known concerning the function(s) of these genes in normal adult animals. Id2 was identified in DNA microarray screens for rhythmically expressed genes [3-5], and further analysis revealed a circadian pattern of expression of all four Id genes in multiple tissues including the suprachiasmatic nucleus. To explore an in vivo function, we generated and characterized deletion mutations of Id2 and of Id4. Id2(-/-) mice exhibit abnormally rapid entrainment and an increase in the magnitude of the phase shift of the pacemaker. A significant proportion of mice also exhibit disrupted rhythms when maintained under constant darkness. Conversely, Id4(-/-) mice did not exhibit a noticeable circadian phenotype. In vitro studies using an mPer1 and an AVP promoter reporter revealed the potential for ID1, ID2, and ID3 proteins to interact with the canonical basic HLH clock proteins BMAL1 and CLOCK. These data suggest that the Id genes may be important for entrainment and operation of the mammalian circadian system, potentially acting through BMAL1 and CLOCK targets.

  17. Optimisations and evolution of the mammalian respiratory system : A suggestion of possible gene sharing in evolution.

    Science.gov (United States)

    Sapoval, Bernard; Filoche, Marcel

    2013-09-01

    The respiratory system of mammalians is made of two successive branched structures with different physiological functions. The upper structure, or bronchial tree, is a fluid transportation system made of approximately 15 generations of bifurcations leading to the order of about 2(15) = 30, 000 terminal bronchioles with a diameter of approximately 0.5mm in the human lung. The branching pattern continues up to generation 23 but the structure and function of each of the subsequent structures, called acini, is different. Each acinus consists in a branched system of ducts surrounded by alveoli and plays the role of a diffusion cell where oxygen and carbon dioxide are exchanged with blood across the alveolar membrane. We show here that the bronchial tree simultaneously presents several different optimal properties. It is first energy efficient, second, it is space filling and third it is also "rapid". This physically based multi-optimality suggests that, in the course of evolution, an organ selected against one criterion could have been used later for a totally different purpose. For example, once selected for its energetic efficiency for the transport of a viscous fluid like blood, the same genetic material could have been used for its optimized rapidity. This would have allowed the emergence of atmospheric respiration made of inspiration-expiration cycles. For this phenomenon to exist, rapidity is essential as fresh air has to reach the gas exchange organs, the pulmonary acini, before the beginning of expiration. We finally show that the pulmonary acinus is optimized in the sense that the acinus morphology is directly related to the notion of a "best possible" extraction of entropic energy by a diffusion exchanger that has to feed oxygen efficiently from air to blood across a membrane of finite permeability.

  18. Paraplegic standing controlled by functional neuromuscular stimulation: Part I--computer model and control-system design.

    Science.gov (United States)

    Khang, G; Zajac, F E

    1989-09-01

    We have developed a planar computer model to investigate paraplegic standing induced by functional neuromuscular stimulation. The model consists of nonlinear musculotendon dynamics (pulse train activation dynamics and musculotendon actuator dynamics), nonlinear body-segmental dynamics, and a linear output-feedback control law. The model of activation dynamics is an analytic expression that characterizes the relation between the stimulus parameters (pulse width and interpulse interval) and the muscle activation. Hill's classic two-element muscle model was modified into a musculotendon actuator model in order to account for the effects of submaximal activation and tendon elasticity on development of force by the actuator. The three body-segmental, multijoint model accounts for the anterior-posterior movements of the head and trunk, the thigh, and the shank. We modeled arm movement as an external disturbance and imposed the disturbance to the body-segmental dynamics by means of a quasistatic analysis. Linearization, and at times linear approximation of the computer model, enabled us to compute a constant, linear feedback-gain matrix, whose output is the net activation needed by a dynamical joint-torque actuator. Motivated by an assumption that minimization of energy expenditure lessens muscle fatigue, we developed an algorithm that then computes how to distribute the net activation among all the muscles crossing the joint. In part II, the combined feedback control strategy is applied to the nonlinear model of musculotendon and body-segmental dynamics to study how well the body ought to maintain balance should the feedback control strategy be employed.

  19. Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Walden, T.L.; Holahan, E.V.; Catravas, G.N.

    1986-01-01

    Leukotrienes (LT) are an important class of biological mediators, for which no information exists concerning their synthesis following a radiation insult, or on their ability to modify cellular response to a subsequent radiation exposure. LT are derived from arachidonic acid, as are prostaglandins, although by a separate enzyme system. Prostaglandins are able to modify radiosensitivity of mammalian cells in vivo and in vitro. In addition, the cytoprotective effect induced by prostaglandins may have significance in cancer therapy since certain breast cancers which secrete elevated levels of prostaglandins are more resistant to therapy than similar tumors without the prostaglandin elevation. The objective of this study was to define a model system in which the metabolic fate of the LT could be monitored, and the effort of LT on the ionizing radiation sensitivity of mammalian cells in vitro could also be characterized.

  20. Preliminary evidence for a postsynaptic action of beta-bungarotoxin in mammalian skeletal muscle

    Science.gov (United States)

    Storella, R. J.; Schouchoff, A. L.; Fujii, M.; Hill, J.; Fletcher, J. E.; Jiang, M. S.; Smith, L. A.

    1992-01-01

    Two hours after treatment with beta-bungarotoxin (0.34-0.4 microM), when there was complete neuromuscular block, the peak contracture response to 50 microM succinylcholine was significantly reduced by about 35% in the mouse phrenic nerve-diaphragm preparation. Additionally, significant phospholipase A2 activity was detected on primary cell cultures from skeletal muscle which were incubated for 2 hr with concentrations of beta-bungarotoxin greater than or equal to 0.1 microM. Thus, beta-bungarotoxin appears to have pharmacologically and biochemically detectable postsynaptic actions in mammalian muscle systems.

  1. Preliminary evidence for a postsynaptic action of beta-bungarotoxin in mammalian skeletal muscle

    Science.gov (United States)

    Storella, R. J.; Schouchoff, A. L.; Fujii, M.; Hill, J.; Fletcher, J. E.; Jiang, M. S.; Smith, L. A.

    1992-01-01

    Two hours after treatment with beta-bungarotoxin (0.34-0.4 microM), when there was complete neuromuscular block, the peak contracture response to 50 microM succinylcholine was significantly reduced by about 35% in the mouse phrenic nerve-diaphragm preparation. Additionally, significant phospholipase A2 activity was detected on primary cell cultures from skeletal muscle which were incubated for 2 hr with concentrations of beta-bungarotoxin greater than or equal to 0.1 microM. Thus, beta-bungarotoxin appears to have pharmacologically and biochemically detectable postsynaptic actions in mammalian muscle systems.

  2. Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Walden, T.L. Jr.; Holahan, E.V. Jr.; Catravas, G.N.

    1986-01-01

    Leukotrienes (LT) are an important class of biological mediators for which no information exists concerning their synthesis following a radiation insult or on their ability to modify cellular response to a subsequent radiation exposure. Results are presented which illustrate that the Chinese hamster lung fibroblast cell line, V79A03, is useful as a model system to study the metabolic fate of leukotrienes and the effect of LT on radiation sensitivity of mammalian cells in vitro. (U.K.).

  3. Tooth and scale morphogenesis in shark: an alternative process to the mammalian enamel knot system.

    Science.gov (United States)

    Debiais-Thibaud, Mélanie; Chiori, Roxane; Enault, Sébastien; Oulion, Silvan; Germon, Isabelle; Martinand-Mari, Camille; Casane, Didier; Borday-Birraux, Véronique

    2015-12-24

    The gene regulatory network involved in tooth morphogenesis has been extremely well described in mammals and its modeling has allowed predictions of variations in regulatory pathway that may have led to evolution of tooth shapes. However, very little is known outside of mammals to understand how this regulatory framework may also account for tooth shape evolution at the level of gnathostomes. In this work, we describe expression patterns and proliferation/apoptosis assays to uncover homologous regulatory pathways in the catshark Scyliorhinus canicula. Because of their similar structural and developmental features, gene expression patterns were described over the four developmental stages of both tooth and scale buds in the catshark. These gene expression patterns differ from mouse tooth development, and discrepancies are also observed between tooth and scale development within the catshark. However, a similar nested expression of Shh and Fgf suggests similar signaling involved in morphogenesis of all structures, although apoptosis assays do not support a strictly equivalent enamel knot system in sharks. Similarities in the topology of gene expression pattern, including Bmp signaling pathway, suggest that mouse molar development is more similar to scale bud development in the catshark. These results support the fact that no enamel knot, as described in mammalian teeth, can be described in the morphogenesis of shark teeth or scales. However, homologous signaling pathways are involved in growth and morphogenesis with variations in their respective expression patterns. We speculate that variations in this topology of expression are also a substrate for tooth shape evolution, notably in regulating the growth axis and symmetry of the developing structure.

  4. A versatile viral system for expression and depletion of proteins in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Eric Campeau

    Full Text Available The ability to express or deplete proteins in living cells is crucial for the study of biological processes. Viral vectors are often useful to deliver DNA constructs to cells that are difficult to transfect by other methods. Lentiviruses have the additional advantage of being able to integrate into the genomes of non-dividing mammalian cells. However, existing viral expression systems generally require different vector backbones for expression of cDNA, small hairpin RNA (shRNA or microRNA (miRNA and provide limited drug selection markers. Furthermore, viral backbones are often recombinogenic in bacteria, complicating the generation and maintenance of desired clones. Here, we describe a collection of 59 vectors that comprise an integrated system for constitutive or inducible expression of cDNAs, shRNAs or miRNAs, and use a wide variety of drug selection markers. These vectors are based on the Gateway technology (Invitrogen whereby the cDNA, shRNA or miRNA of interest is cloned into an Entry vector and then recombined into a Destination vector that carries the chosen viral backbone and drug selection marker. This recombination reaction generates the desired product with >95% efficiency and greatly reduces the frequency of unwanted recombination in bacteria. We generated Destination vectors for the production of both retroviruses and lentiviruses. Further, we characterized each vector for its viral titer production as well as its efficiency in expressing or depleting proteins of interest. We also generated multiple types of vectors for the production of fusion proteins and confirmed expression of each. We demonstrated the utility of these vectors in a variety of functional studies. First, we show that the FKBP12 Destabilization Domain system can be used to either express or deplete the protein of interest in mitotically-arrested cells. Also, we generate primary fibroblasts that can be induced to senesce in the presence or absence of DNA damage

  5. Regulation of taurine transport systems by protein kinase CK2 in mammalian cells

    DEFF Research Database (Denmark)

    Lambert, Ian Henry; Hansen, Daniel Bloch

    2011-01-01

    Maintaining cell volume is critical for cellular function yet shift in cell volume is a prerequisite for mitosis and apoptosis. The ubiquitously and evolutionary conserved serine/threonine kinase CK2 promotes cell survival and suppresses apoptosis. The present review describes how mammalian cells...

  6. Excretion of fluorescent substrates of mammalian multidrug resistance-associated protein (MRP) in the Schistosoma mansoni excretory system.

    Science.gov (United States)

    Sato, H; Kusel, J R; Thornhill, J

    2004-01-01

    The protonephridium of platyhelminths including Schistosoma mansoni plays a pivotal role in their survival by excretion of metabolic wastes as well as xenobiotics, and can be revealed in the living adult parasite by certain fluorescent compounds which are concentrated in excretory tubules and collecting ducts. To determine the presence of the multidrug resistance-associated protein (MRP) as a possible transporter in protonephridial epithelium, adult schistosomes were exposed to a fluorescent Ca2+ indicator, fluo-3 acetyloxymethyl ester, which is a potential substrate of mammalian MRP. Specific fluorescence related to fluo-3/Ca2+ chelate delineated the whole length of the protonephridial system. Simultaneously, a fluorescent substance was accumulated in the posterior part of collecting ducts and the excretory bladder. Similarly, when other fluorogenic substrates for mammalian MRP such as monoclorobimane, fluorescein diacetate, and 5(6)-carboxyfluorescein diacetate were applied to adult schistosomes, these fluorescent markers were observed in the excretory tubules through to the excretory bladder. The excretory system of mechanically-transformed schistosomula was not labelled with any of these 4 fluorescent markers. These findings suggest that the protonephridial epithelium of adult schistosomes, but not schistosomula, might express the homologue of the mammalian MRP transporting organic anionic conjugates with glutathione, glucuronate or sulphate as well as unconjugated amphiphilic organic anions.

  7. Using PBPK guided “Body-on-a-Chip” Systems to Predict Mammalian Response to Drug and Chemical Exposure

    Science.gov (United States)

    Sung, Jong Hwan; Srinivasan, Balaji; Esch, Mandy Brigitte; McLamb, William T.; Bernabini, Catia; Shuler, Michael L.; Hickman, James J.

    2014-01-01

    The continued development of in vitro systems that accurately emulate human response to drugs or chemical agents will impact drug development, our understanding of chemical toxicity, and enhance our ability to respond to threats from chemical or biological agents. A promising technology is to build microscale replicas of humans that capture essential elements of physiology, pharmacology and/or toxicology (microphysiological systems). Here, we review progress on systems for microscale models of mammalian systems that include two or more integrated cellular components. These systems are described as a “Body-on-a-Chip.”, and utilize the concept of physiologically-based pharmacokinetic (PBPK) modeling in the design. These microscale systems can also be used as model systems to predict whole-body responses to drugs as well as study the mechanism of action of drugs using PBPK analysis. In this review, we provide examples of various approaches to construct such systems with a focus on their physiological usefulness and various approaches to measure responses (e.g. chemical, electrical, or mechanical force and cellular viability and morphology). While the goal is to predict human response, other mammalian cell types can be utilized with the same principle to predict animal response. These systems will be evaluated on their potential to be physiologically accurate, to provide effective and efficient platform for analytics with accessibility to a wide range of users, for ease of incorporation of analytics, functional for weeks to months, and the ability to replicate previously observed human responses. PMID:24951471

  8. Functional state of blood circulation and neuromuscular system of the lower limb of patients with congenital pseudarthrosis of the tibia after consolidation of the nonunion

    Directory of Open Access Journals (Sweden)

    Александр Павлович Поздеев

    2015-12-01

    Full Text Available The aim of this study was to evaluate the clinical and functional state of the neuromuscular system and the blood supply to the lower limbs of children with congenital pseudarthrosis of the tibia (CPT after consolidation. Material and Methods. A total of 100 patients with CPT were analyzed. We performed a clinical examination of patients, panoramic X-ray of the lower extremities, electroneuromyogram, and reovasography. Results and Conclusions. The primary complaints of patients with CPT after the consolidation of the non-union were lameness, deformations of lower extremities, and pain in the local joints. The electromyoneuromyogram data of the lower limbs of patients with CPT exhibited a decrease of the contractility of the muscles of the lower limbs, and neuropathy of the peroneal nerves of both lower limbs. The reovasography data of the lower limbs of patients with CPT displayed improvement in blood circulation in the lower extremities after the consolidation of the tibia. These data promote the current methods of treatment of patients with CPT; however, the temperature, degree of limb lengthening, and deformity correction should be considered in the future.

  9. Generation of an Avian-Mammalian Rotavirus Reassortant by Using a Helper Virus-Dependent Reverse Genetics System.

    Science.gov (United States)

    Johne, Reimar; Reetz, Jochen; Kaufer, Benedikt B; Trojnar, Eva

    2015-11-18

    The genetic diversity of rotavirus A (RVA) strains is facilitated in part by genetic reassortment. Although this process of genome segment exchange has been reported frequently among mammalian RVAs, it remained unknown if mammalian RVAs also could package genome segments from avian RVA strains. We generated a simian RVA strain SA11 reassortant containing the VP4 gene of chicken RVA strain 02V0002G3. To achieve this, we transfected BSR5/T7 cells with a T7 polymerase-driven VP4-encoding plasmid, infected the cells with a temperature-sensitive SA11 VP4 mutant, and selected the recombinant virus by increasing the temperature. The reassortant virus could be stably passaged and exhibited cytopathic effects in MA-104 cells, but it replicated less efficiently than both parental viruses. Our results show that avian and mammalian rotaviruses can exchange genome segments, resulting in replication-competent reassortants with new genomic and antigenic features. This study shows that rotaviruses of mammals can package genome segments from rotaviruses of birds. The genetic diversity of rotaviruses could be broadened by this process, which might be important for their antigenic variability. The reverse genetics system applied in the study could be useful for targeted generation and subsequent characterization of distinct rotavirus reassortant strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Neuromuscular complications of acromegaly.

    Science.gov (United States)

    Pickett, J B; Layzer, R B; Levin, S R; Scheider, V; Campbell, M J; Sumner, A J

    1975-07-01

    Seventeen consecutive acromegalic patients were evaluated for evidence of neuromuscular dysfunction and followed for 1 year after hypophysectomy. Before treatment, four patients had both a myopathy and the carpal tunnel syndrome, five had myopathy alone, four had carpal tunnel syndrome alone, and four had neither. The myopathy was caracterized by mild, strictly promixal weakness and flabbiness of muscles; electromyography revealed typical myopathic abnormalities, but serum enzymes and muscle biopsy usually were normal. The presence of myopathy or the carpal tunnel syndrrome could not be correlated with the magnitude of growth hormone elevation or any secondary endocrine derangement, but myopathy was associated with a longer duration of acromegaly. Carpal tunnel symptoms usually improved in the first 6 weeks after hypophysectomy, while myopathy improved more slowly and sometimes was detectable 1 year later.

  11. Two emerging concepts for elite athletes: the short-term effects of testosterone and cortisol on the neuromuscular system and the dose-response training role of these endogenous hormones.

    Science.gov (United States)

    Crewther, Blair T; Cook, Christian; Cardinale, Marco; Weatherby, Robert P; Lowe, Tim

    2011-02-01

    The aim of this review is to highlight two emerging concepts for the elite athlete using the resistance-training model: (i) the short-term effects of testosterone (T) and cortisol (C) on the neuromuscular system; and (ii) the dose-response training role of these endogenous hormones. Exogenous evidence confirms that T and C can regulate long-term changes in muscle growth and performance, especially with resistance training. This evidence also confirms that changes in T or C concentrations can moderate or support neuromuscular performance through various short-term mechanisms (e.g. second messengers, lipid/protein pathways, neuronal activity, behaviour, cognition, motor-system function, muscle properties and energy metabolism). The possibility of dual T and C effects on the neuromuscular system offers a new paradigm for understanding resistance-training performance and adaptations. Endogenous evidence supports the short-term T and C effects on human performance. Several factors (e.g. workout design, nutrition, genetics, training status and type) can acutely modify T and/or C concentrations and thereby potentially influence resistance-training performance and the adaptive outcomes. This novel short-term pathway appears to be more prominent in athletes (vs non-athletes), possibly due to the training of the neuromuscular and endocrine systems. However, the exact contribution of these endogenous hormones to the training process is still unclear. Research also confirms a dose-response training role for basal changes in endogenous T and C, again, especially for elite athletes. Although full proof within the physiological range is lacking, this athlete model reconciles a proposed permissive role for endogenous hormones in untrained individuals. It is also clear that the steroid receptors (cell bound) mediate target tissue effects by adapting to exercise and training, but the response patterns of the membrane-bound receptors remain highly speculative. This information

  12. Effects of neuromuscular electrical stimulation, laser therapy and LED therapy on the masticatory system and the impact on sleep variables in cerebral palsy patients: a randomized, five arms clinical trial

    Directory of Open Access Journals (Sweden)

    Giannasi Lilian

    2012-05-01

    Full Text Available Abstract Background Few studies demonstrate effectiveness of therapies for oral rehabilitation of patients with cerebral palsy (CP, given the difficulties in chewing, swallowing and speech, besides the intellectual, sensory and social limitations. Due to upper airway obstruction, they are also vulnerable to sleep disorders. This study aims to assess the sleep variables, through polysomnography, and masticatory dynamics, using electromiography, before and after neuromuscular electrical stimulation, associated or not with low power laser (Gallium Arsenide- Aluminun, =780 nm and LED (= 660 nm irradiation in CP patients. Methods/design 50 patients with CP, both gender, aged between 19 and 60 years will be enrolled in this study. The inclusion criteria are: voluntary participation, patient with hemiparesis, quadriparesis or diparetic CP, with ability to understand and respond to verbal commands. The exclusion criteria are: patients undergoing/underwent orthodontic, functional maxillary orthopedic or botulinum toxin treatment. Polysomnographic and surface electromyographic exams on masseter, temporalis and suprahyoid will be carry out in all sample. Questionnaire assessing oral characteristics will be applied. The sample will be divided into 5 treatment groups: Group 1: neuromuscular electrical stimulation; Group 2: laser therapy; Group 3: LED therapy; Group 4: neuromuscular electrical stimulation and laser therapy and Group 5: neuromuscular electrical stimulation and LED therapy. All patients will be treated during 8 consecutive weeks. After treatment, polysomnographic and electromiographic exams will be collected again. Discussion This paper describes a five arm clinical trial assessing the examination of sleep quality and masticatory function in patients with CP under non-invasive therapies. Trial registration The protocol for this study is registered with the Brazilian Registry of Clinical Trials - ReBEC RBR-994XFS Descriptors Cerebral Palsy

  13. Neuromuscular retraining for facial paralysis.

    Science.gov (United States)

    Diels, H J; Combs, D

    1997-10-01

    Neuromuscular retraining is an effective method for rehabilitating facial musculature in patients with facial paralysis. This nonsurgical therapy has demonstrated improved functional outcomes and is an important adjunct to surgical treatment for restoring facial movement. Treatment begins with an intensive clinical evaluation and incorporates appropriate sensory feedback techniques into a patient-specific, comprehensive, home therapy program. This article discusses appropriate patients, timelines for referral, and basic treatment practices of facial neuromuscular retraining for restoring function and expression to the highest level possible.

  14. Neuromuscular adaptation to actual and simulated weightlessness

    Science.gov (United States)

    Edgerton, V. R.; Roy, R. R.

    1994-01-01

    The chronic "unloading" of the neuromuscular system during spaceflight has detrimental functional and morphological effects. Changes in the metabolic and mechanical properties of the musculature can be attributed largely to the loss of muscle protein and the alteration in the relative proportion of the proteins in skeletal muscle, particularly in the muscles that have an antigravity function under normal loading conditions. These adaptations could result in decrements in the performance of routine or specialized motor tasks, both of which may be critical for survival in an altered gravitational field, i.e., during spaceflight and during return to 1 G. For example, the loss in extensor muscle mass requires a higher percentage of recruitment of the motor pools for any specific motor task. Thus, a faster rate of fatigue will occur in the activated muscles. These consequences emphasize the importance of developing techniques for minimizing muscle loss during spaceflight, at least in preparation for the return to 1 G after spaceflight. New insights into the complexity and the interactive elements that contribute to the neuromuscular adaptations to space have been gained from studies of the role of exercise and/or growth factors as countermeasures of atrophy. The present chapter illustrates the inevitable interactive effects of neural and muscular systems in adapting to space. It also describes the considerable progress that has been made toward the goal of minimizing the functional impact of the stimuli that induce the neuromuscular adaptations to space.

  15. Mammalian pheromones.

    Science.gov (United States)

    Liberles, Stephen D

    2014-01-01

    Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors.

  16. Fatigue Modeling via Mammalian Auditory System for Prediction of Noise Induced Hearing Loss.

    Science.gov (United States)

    Sun, Pengfei; Qin, Jun; Campbell, Kathleen

    2015-01-01

    Noise induced hearing loss (NIHL) remains as a severe health problem worldwide. Existing noise metrics and modeling for evaluation of NIHL are limited on prediction of gradually developing NIHL (GDHL) caused by high-level occupational noise. In this study, we proposed two auditory fatigue based models, including equal velocity level (EVL) and complex velocity level (CVL), which combine the high-cycle fatigue theory with the mammalian auditory model, to predict GDHL. The mammalian auditory model is introduced by combining the transfer function of the external-middle ear and the triple-path nonlinear (TRNL) filter to obtain velocities of basilar membrane (BM) in cochlea. The high-cycle fatigue theory is based on the assumption that GDHL can be considered as a process of long-cycle mechanical fatigue failure of organ of Corti. Furthermore, a series of chinchilla experimental data are used to validate the effectiveness of the proposed fatigue models. The regression analysis results show that both proposed fatigue models have high corrections with four hearing loss indices. It indicates that the proposed models can accurately predict hearing loss in chinchilla. Results suggest that the CVL model is more accurate compared to the EVL model on prediction of the auditory risk of exposure to hazardous occupational noise.

  17. Fatigue Modeling via Mammalian Auditory System for Prediction of Noise Induced Hearing Loss

    Directory of Open Access Journals (Sweden)

    Pengfei Sun

    2015-01-01

    Full Text Available Noise induced hearing loss (NIHL remains as a severe health problem worldwide. Existing noise metrics and modeling for evaluation of NIHL are limited on prediction of gradually developing NIHL (GDHL caused by high-level occupational noise. In this study, we proposed two auditory fatigue based models, including equal velocity level (EVL and complex velocity level (CVL, which combine the high-cycle fatigue theory with the mammalian auditory model, to predict GDHL. The mammalian auditory model is introduced by combining the transfer function of the external-middle ear and the triple-path nonlinear (TRNL filter to obtain velocities of basilar membrane (BM in cochlea. The high-cycle fatigue theory is based on the assumption that GDHL can be considered as a process of long-cycle mechanical fatigue failure of organ of Corti. Furthermore, a series of chinchilla experimental data are used to validate the effectiveness of the proposed fatigue models. The regression analysis results show that both proposed fatigue models have high corrections with four hearing loss indices. It indicates that the proposed models can accurately predict hearing loss in chinchilla. Results suggest that the CVL model is more accurate compared to the EVL model on prediction of the auditory risk of exposure to hazardous occupational noise.

  18. Assembly of alphavirus replication complexes from RNA and protein components in a novel trans-replication system in mammalian cells.

    Science.gov (United States)

    Spuul, Pirjo; Balistreri, Giuseppe; Hellström, Kirsi; Golubtsov, Andrey V; Jokitalo, Eija; Ahola, Tero

    2011-05-01

    For positive-strand RNA viruses, the viral genomic RNA also acts as an mRNA directing the translation of the replicase proteins of the virus. Replication takes place in association with cytoplasmic membranes, which are heavily modified to create specific replication compartments. Here we have expressed by plasmid DNA transfection the large replicase polyprotein of Semliki Forest virus (SFV) in mammalian cells from a nonreplicating mRNA and provided a separate RNA containing the replication signals. The replicase proteins were able to efficiently and specifically replicate the template in trans, leading to accumulation of RNA and marker gene products expressed from the template RNA. The replicase proteins and double-stranded RNA replication intermediates localized to structures similar to those seen in SFV-infected cells. Using correlative light electron microscopy (CLEM) with fluorescent marker proteins to relocate those transfected cells, in which active replication was ongoing, abundant membrane modifications, representing the replication complex spherules, were observed both at the plasma membrane and in intracellular endolysosomes. Thus, replication complexes are faithfully assembled and localized in the trans-replication system. We demonstrated, using CLEM, that the replication proteins alone or a polymerase-negative polyprotein mutant together with the template did not give rise to spherule formation. Thus, the trans-replication system is suitable for cell biological dissection and examination in a mammalian cell environment, and similar systems may be possible for other positive-strand RNA viruses.

  19. A Human-machine-interface Integrating Low-cost Sensors with a Neuromuscular Electrical Stimulation System for Post-stroke Balance Rehabilitation.

    Science.gov (United States)

    Kumar, Deepesh; Das, Abhijit; Lahiri, Uttama; Dutta, Anirban

    2016-04-12

    A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to reorganize its structure, function and connections as a response to intrinsic or extrinsic stimuli is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. Beneficial neuroplastic changes may be facilitated with non-invasive electrotherapy, such as neuromuscular electrical stimulation (NMES) and sensory electrical stimulation (SES). NMES involves coordinated electrical stimulation of motor nerves and muscles to activate them with continuous short pulses of electrical current while SES involves stimulation of sensory nerves with electrical current resulting in sensations that vary from barely perceivable to highly unpleasant. Here, active cortical participation in rehabilitation procedures may be facilitated by driving the non-invasive electrotherapy with biosignals (electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG)) that represent simultaneous active perception and volitional effort. To achieve this in a resource-poor setting, e.g., in low- and middle-income countries, we present a low-cost human-machine-interface (HMI) by leveraging recent advances in off-the-shelf video game sensor technology. In this paper, we discuss the open-source software interface that integrates low-cost off-the-shelf sensors for visual-auditory biofeedback with non-invasive electrotherapy to assist postural control during balance rehabilitation. We demonstrate the proof-of-concept on healthy volunteers.

  20. Effects of coal combustion and gasification process contaminants on the neuromuscular system. Sub-task on peripheral nervous system effects. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Franz, G.N.

    1979-01-01

    This study is a preliminary investigation of the possible toxic effects of flyash particles from an experimental fluidized-bed combustion process at the Morgantown Energy Research Center. Emphasis has been placed on the action of trace metals present on the surface and in the matrix of the particulates emissions, since these elements may be toxic in low dosages. It is well established that external calcium (Ca/sup 2 +/) is essential for neuromuscular transmission. In the absence of Ca/sup 2 +/ from the external medium, nerve impulses continue to invade the terminal but do not evoke transmitter release. Many of the di- and trivalent metal ions have been tested for their ability to substitute for Ca/sup 2 +/ and have been shown to affect evoked and spontaneous transmitter release. Many of these ions cause a decrease in amplitude of the evoked end-plate potential (e.p.p.), but raise the frequency of spontaneously occurring miniature end-plate potentials (m.e.p.p.s). Several investigators have found that the effective concentration necessary to cause an increase in m.e.p.p. frequency is far greater than that which decreases the e.p.p. amplitude. The neuromuscular junction of the frog was selected to test the effects of flyash particles and pure metal ions, since its general characteristics are well documented and its sensitivity to metal ions is well known. Cadmium (Cd/sup 2 +/) was chosen for our investigation because it had previously been reported to be a highly potent inhibitor of evoked release, yet having no significant effect on spontaneous release even at high concentrations. In this report it was shown that the effective concentrations necessary to increase m.e.p.p. frequency are in the same range as those which decrease e.p.p. amplitude.

  1. Neuromuscular disease and hypoventilation.

    Science.gov (United States)

    Sivak, E D; Shefner, J M; Sexton, J

    1999-11-01

    Alveolar hypoventilation associated with neuromuscular disease can occur in acute and chronic forms. In the acute form, progressive weakness of respiratory muscles leads to rapid reduction in vital capacity followed by respiratory failure with hypoxemia and hypercarbia. Symptoms are those of acute respiratory failure, including dyspnea, tachypnea, and tachycardia. In the chronic form, impairment of the respiratory muscles affects mechanical properties of the lungs and chest wall, decreases the ability to clear secretions, and eventually may alter the function of the central respiratory centers. Symptoms include orthopnea, fatigue, disturbed sleep, and hypersomnolence. Treatment and outcome of the disease's chronic form are dependent on the underlying clinical cause of the alveolar hypoventilation. For chronic but stable diseases such as old polio, quadriplegia, or kyposcoliosis, mechanical support of minute ventilation can reverse symptoms. For chronic and progressive disease such as muscular dystrophy and amyotrophic lateral sclerosis, mechanical support of minute ventilation provides only symptomatic relief and is usually associated with deterioration to the point of complete ventilator dependency for survival. For the chronic progressive forms of alveolar hypoventilation, there is currently a need for quality randomized controlled clinical trials to define physiologic indicators and appropriate timing for mechanical support of minute ventilation.

  2. Neuromuscular control of trunk stability: clinical implications for sports injury prevention.

    Science.gov (United States)

    Zazulak, Bohdanna; Cholewicki, Jacek; Reeves, N Peter

    2008-09-01

    Recent prospective evidence supports the hypothesis that impaired trunk control is a contributing factor to sports injuries of the spine as well as to segments of the kinetic chain. The current concepts regarding neuromuscular control of trunk stability are best described from a systems engineering perspective. In the analysis of current neuromuscular training protocols for sports injury prevention, these principles are applied to identify components that optimize neuromuscular control of trunk stability. Current perspectives of neuromuscular learning can be applied clinically to aid in the formulation of injury prevention strategies.

  3. From 20th century metabolic wall charts to 21st century systems biology: database of mammalian metabolic enzymes.

    Science.gov (United States)

    Corcoran, Callan C; Grady, Cameron R; Pisitkun, Trairak; Parulekar, Jaya; Knepper, Mark A

    2017-03-01

    The organization of the mammalian genome into gene subsets corresponding to specific functional classes has provided key tools for systems biology research. Here, we have created a web-accessible resource called the Mammalian Metabolic Enzyme Database (https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/MetabolicEnzymeDatabase.html) keyed to the biochemical reactions represented on iconic metabolic pathway wall charts created in the previous century. Overall, we have mapped 1,647 genes to these pathways, representing ~7 percent of the protein-coding genome. To illustrate the use of the database, we apply it to the area of kidney physiology. In so doing, we have created an additional database (Database of Metabolic Enzymes in Kidney Tubule Segments: https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/), mapping mRNA abundance measurements (mined from RNA-Seq studies) for all metabolic enzymes to each of 14 renal tubule segments. We carry out bioinformatics analysis of the enzyme expression pattern among renal tubule segments and mine various data sources to identify vasopressin-regulated metabolic enzymes in the renal collecting duct.

  4. Mammalian ribosomal and chaperone protein RPS3A counteracts α-synuclein aggregation and toxicity in a yeast model system.

    Science.gov (United States)

    De Graeve, Stijn; Marinelli, Sarah; Stolz, Frank; Hendrix, Jelle; Vandamme, Jurgen; Engelborghs, Yves; Van Dijck, Patrick; Thevelein, Johan M

    2013-11-01

    Accumulation of aggregated forms of αSyn (α-synuclein) into Lewy bodies is a known hallmark associated with neuronal cell death in Parkinson's disease. When expressed in the yeast Saccharomyces cerevisiae, αSyn interacts with the plasma membrane, forms inclusions and causes a concentration-dependent growth defect. We have used a yeast mutant, cog6Δ, which is particularly sensitive to moderate αSyn expression, for screening a mouse brain-specific cDNA library in order to identify mammalian proteins that counteract αSyn toxicity. The mouse ribosomal and chaperone protein RPS3A was identified as a suppressor of αSyn [WT (wild-type) and A53T] toxicity in yeast. We demonstrated that the 50 N-terminal amino acids are essential for this function. The yeast homologues of RPS3A were not effective in suppressing the αSyn-induced growth defect, illustrating the potential of our screening system to identify modifiers that would be missed using yeast gene overexpression as the first screening step. Co-expression of mouse RPS3A delayed the formation of αSyn-GFP inclusions in the yeast cells. The results of the present study suggest that the recently identified extraribosomal chaperonin function of RPS3A also acts on the neurodegeneration-related protein αSyn and reveal a new avenue for identifying promising candidate mammalian proteins involved in αSyn functioning.

  5. Characterization of L1 ORF1p self-interaction and cellular localization using a mammalian two-hybrid system.

    Directory of Open Access Journals (Sweden)

    Mark Sokolowski

    Full Text Available Long INterspersed Element-1 (LINE-1, L1 is an active retrotransposon that mobilizes using a ribonucleoprotein particle (RNP intermediate composed of the full-length bicistronic L1 mRNA and the two proteins (ORF1p and ORF2p encoded by that mRNA. ORF1p and ORF2p demonstrate cis-preference for their encoding mRNA. Previous studies of ORF1p, purified from bacterial and insect cells demonstrated that this protein forms trimers in vitro. While valuable for understanding ORF1p function, these in vitro approaches do not provide any information on ORF1p self-interaction in the context of mammalian cells. We used a mammalian two-hybrid (M2H system in order to study L1 ORF1p self-interaction in human and mouse cells. We demonstrate that the M2H system successfully detects human and mouse ORF1p self-interactions in transiently transfected mammalian cells. We also generated mouse and human ORF1p-specific antibodies to characterize the expression of ORF1p fusion proteins used in the M2H system. Using these antibodies, we demonstrate that ORF1p interaction in trans leads to the formation of heterodimers that are expected to produce a positive signal in the M2H system. Although the role for L1 ORF1p cis-preference in L1 mobilization is established, the impact of ability of ORF1pto interact in trans on the L1 replication cycle is not known. Furthermore, western blot analysis of ORF1p generated by a full-length L1, wild type ORF1, or a codon-optimized ORF1 expression vector is detected in the nucleus. In contrast, the addition of a tag to the N-terminus of the mouse and human ORF1 proteins can significantly alter the subcellular localization in a tag-specific manner. These data support that nuclear localization of ORF1p may contribute to L1 (and potentially the SINE Alu RNP nuclear access in the host cell.

  6. Effective Targeted Gene Knockdown in Mammalian Cells Using the piggyBac Transposase-based Delivery System

    Directory of Open Access Journals (Sweden)

    Jesse B Owens

    2013-01-01

    Full Text Available Nonviral gene delivery systems are rapidly becoming a desirable and applicable method to overexpress genes in various types of cells. We have recently developed a piggyBac transposase-based, helper-independent and self-inactivating delivery system (pmGENIE-3 capable of high-efficiency transfection of mammalian cells including human cells. In the following study, we have assessed the potential of this delivery system to drive the expression of short hairpin RNAs to knock down genes in human cells. Two independent pmGENIE-3 vectors were developed to specifically target knockdown of an endogenous gene, telomerase reverse transcriptase (TERT, in telomerase-positive human immortalized cell lines. As compared with a transposase-deficient vector, pmGENIE-3 showed significantly improved short-term transfection efficiency (~4-fold enhancement, 48 hours posttransfection and long-term integration efficiency (~5-fold enhancement following antibiotic selection. We detected a significant reduction of both TERT expression and telomerase activity in both HEK293 and MCF-7 breast carcinoma cells transfected with two pmGENIE-3 construct targeting distinct regions of TERT. Importantly, this knockdown of expression was sufficient to abrogate telomerase function since telomeres were significantly shortened (3–4 Kb, P < 0.001 in both TERT-targeted cell lines following antibiotic selection of stable integrants. Together, these data show the capacity of the piggyBac nonviral delivery system to stably knockdown gene expression in mammalian cells and indicate the potential to develop novel tumor-targeting therapies.

  7. The mammalian target of rapamycin modulates the immunoproteasome system in the heart.

    Science.gov (United States)

    Zhang, Hong-Mei; Fu, Jianliang; Hamilton, Ryan; Diaz, Vivian; Zhang, Yiqiang

    2015-09-01

    The mammalian target of rapamycin (mTOR) plays an important role in cardiac development and function. Inhibition of mTOR by rapamycin has been shown to attenuate pathological cardiac hypertrophy and improve the function of aging heart, accompanied by an inhibition of the cardiac proteasome activity. The current study aimed to determine the potential mechanism(s) by which mTOR inhibition modulates cardiac proteasome. Inhibition of mTOR by rapamycin was found to reduce primarily the immunoproteasome in both H9c2 cells in vitro and mouse heart in vivo, without significant effect on the constitutive proteasome and protein ubiquitination. Concurrent with the reduction of the immunoproteasome, rapamycin reduced two important inflammatory response pathways, the NF-κB and Stat3 signaling. In addition, rapamycin attenuated the induction of the immunoproteasome in H9c2 cells by inflammatory cytokines, including INFγ and TNFα, by suppressing NF-κB signaling. These data indicate that rapamycin indirectly modulated immunoproteasome through the suppression of inflammatory response pathways. Lastly, the role of the immunoproteasome during the development of cardiac hypertrophy was investigated. Administration of a specific inhibitor of the immunoproteasome ONX 0914 attenuated isoproterenol-induced cardiac hypertrophy, suggesting that the immunoproteasome may be involved in the development of cardiac hypertrophy and therefore could be a therapeutic target. In conclusion, rapamycin inhibits the immunoproteasome through its effect on the inflammatory signaling pathways and the immunoproteasome could be a potential therapeutic target for pathological cardiac hypertrophy.

  8. Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system.

    Science.gov (United States)

    Gudmundsson, G H; Agerberth, B

    1999-12-17

    The bactericidal machinery of mammalian neutrophils is built up of many components with different chemical properties, involving proteins, peptides and oxygen-dependent radicals. All these components work in synergy, leading to destruction and elimination of ingested microbes. During the eighties, it gradually became clear, that cationic peptides are a part of the oxygen-independent bactericidal effectors in phagocytic cells. In mammals, these antimicrobial peptides are represented by two families, the defensins and the cathelicidins. These potent broad spectra peptides are included as immediate effector molecules in innate immunity. The detailed killing mechanism for these effectors is partly known, but nearly all of them have membrane affinity, and permeate bacterial membranes, resulting in lysis of the bacteria. This peptide-membrane interaction includes also eukaryotic membranes, that implicates cytotoxic effects on host cells. Studies in vitro have established that the microenvironment is critical for their activities. In connection to cystic fibrosis, the effects of microenvironment changes are apparent, causing inactivation of peptide defences and leading to repeated serious bacterial infections. Thus, the importance of the microenvironment is also supported in vivo. Additional functions of these peptides such as chemotactic, mitogenic and stimulatory in the wound healing process suggest further important roles for these peptides.

  9. Neuromuscular ultrasound of cranial nerves.

    Science.gov (United States)

    Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

    2015-04-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

  10. Doenças neuromusculares

    OpenAIRE

    Umbertina C. Reed

    2002-01-01

    Objetivo: apresentar os dados essenciais para o diagnóstico diferencial entre as principais doenças neuromusculares, denominação genérica sob a qual agrupam-se diferentes afecções, decorrentes do acometimento primário da unidade motora (motoneurônio medular, raiz nervosa, nervo periférico, junção mioneural e músculo). Fontes dos dados: os aspectos clínicos fundamentais para estabelecer o diagnóstico diferencial entre as diferentes doenças neuromusculares, bem como entre estas e as causas de h...

  11. Doenças neuromusculares

    OpenAIRE

    Umbertina C. Reed

    2002-01-01

    Objetivo: apresentar os dados essenciais para o diagnóstico diferencial entre as principais doenças neuromusculares, denominação genérica sob a qual agrupam-se diferentes afecções, decorrentes do acometimento primário da unidade motora (motoneurônio medular, raiz nervosa, nervo periférico, junção mioneural e músculo). Fontes dos dados: os aspectos clínicos fundamentais para estabelecer o diagnóstico diferencial entre as diferentes doenças neuromusculares, bem como entre estas e as causas de h...

  12. Genetic regulation of bone metabolism in the chicken: similarities and differences to Mammalian systems.

    Directory of Open Access Journals (Sweden)

    Martin Johnsson

    2015-05-01

    Full Text Available Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL and expression QTL (eQTL mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone.

  13. 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

    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

  14. 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

  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 th

  16. 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 th

  17. A validated system for ligation-free USER™ -based assembly of expression vectors for mammalian cell engineering

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Kildegaard, Helene Faustrup; Hansen, Bjarne Gram

    The development in the field of mammalian cell factories require fast and high-throughput methods, this means a high need for simpler and more efficient cloning techniques. For optimization of protein expression by genetic engineering and for allowing metabolic engineering in mammalian cells, a new...

  18. Mammalian sleep

    Science.gov (United States)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  19. 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

  20. Orthotic management of instability of the knee related to neuromuscular and central nervous system disorders: systematic review, qualitative study, survey and costing analysis.

    Science.gov (United States)

    O'Connor, Joanne; McCaughan, Dorothy; McDaid, Catriona; Booth, Alison; Fayter, Debra; Rodriguez-Lopez, Roccio; Bowers, Roy; Dyson, Lisa; Iglesias, Cynthia P; Lalor, Simon; O'Connor, Rory J; Phillips, Margaret; Ramdharry, Gita

    2016-07-01

    Patients who have knee instability that is associated with neuromuscular disease (NMD) and central nervous system (CNS) conditions can be treated using orthoses, such as knee-ankle-foot orthoses (KAFOs). To assess existing evidence on the effectiveness of orthoses; patient perspectives; types of orthotic devices prescribed in the UK NHS; and associated costs. Qualitative study of views of orthoses users - a qualitative in-depth interview study was undertaken. Data were analysed for thematic content. A coding scheme was developed and an inductive approach was used to identify themes. Systematic review - 18 databases were searched up to November 2014: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health, EMBASE, PASCAL, Scopus, Science Citation Index, BIOSIS Previews, Physiotherapy Evidence Database, Recal Legacy, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, Cochrane Central Register of Controlled Trials, Conference Proceedings Citation Index: Science, Health Management Consortium, ClinicalTrials.gov, International Clinical Trials Registry Platform and National Technical Information Service. Studies of adults using an orthosis for instability of the knee related to NMD or a CNS disorder were included. Data were extracted and quality was assessed by two researchers. Narrative synthesis was undertaken. Survey and costing analysis - a web survey of orthotists, physiotherapists and rehabilitation medicine physicians was undertaken. Telephone interviews with orthotists informed a costing analysis. Qualitative study - a total of 24 people participated. Potential for engagement in daily activities was of vital importance to patients; the extent to which their device enabled this was the yardstick by which it was measured. Patients' prime desired outcome was a reduction in pain, falls or trips, with improved balance and stability. Effectiveness

  1. Orthotic management of instability of the knee related to neuromuscular and central nervous system disorders: systematic review, qualitative study, survey and costing analysis.

    Science.gov (United States)

    O'Connor, Joanne; McCaughan, Dorothy; McDaid, Catriona; Booth, Alison; Fayter, Debra; Rodriguez-Lopez, Roccio; Bowers, Roy; Dyson, Lisa; Iglesias, Cynthia P; Lalor, Simon; O'Connor, Rory J; Phillips, Margaret; Ramdharry, Gita

    2016-01-01

    BACKGROUND Patients who have knee instability that is associated with neuromuscular disease (NMD) and central nervous system (CNS) conditions can be treated using orthoses, such as knee-ankle-foot orthoses (KAFOs). OBJECTIVES To assess existing evidence on the effectiveness of orthoses; patient perspectives; types of orthotic devices prescribed in the UK NHS; and associated costs. METHODS Qualitative study of views of orthoses users - a qualitative in-depth interview study was undertaken. Data were analysed for thematic content. A coding scheme was developed and an inductive approach was used to identify themes. Systematic review - 18 databases were searched up to November 2014: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health, EMBASE, PASCAL, Scopus, Science Citation Index, BIOSIS Previews, Physiotherapy Evidence Database, Recal Legacy, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, Cochrane Central Register of Controlled Trials, Conference Proceedings Citation Index: Science, Health Management Consortium, ClinicalTrials.gov, International Clinical Trials Registry Platform and National Technical Information Service. Studies of adults using an orthosis for instability of the knee related to NMD or a CNS disorder were included. Data were extracted and quality was assessed by two researchers. Narrative synthesis was undertaken. Survey and costing analysis - a web survey of orthotists, physiotherapists and rehabilitation medicine physicians was undertaken. Telephone interviews with orthotists informed a costing analysis. RESULTS Qualitative study - a total of 24 people participated. Potential for engagement in daily activities was of vital importance to patients; the extent to which their device enabled this was the yardstick by which it was measured. Patients' prime desired outcome was a reduction in pain, falls or trips, with improved

  2. The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells.

    Science.gov (United States)

    Lee, Ciaran M; Cradick, Thomas J; Bao, Gang

    2016-03-01

    The clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system from Streptococcus pyogenes (Spy) has been successfully adapted for RNA-guided genome editing in a wide range of organisms. However, numerous reports have indicated that Spy CRISPR-Cas9 systems may have significant off-target cleavage of genomic DNA sequences differing from the intended on-target site. Here, we report the performance of the Neisseria meningitidis (Nme) CRISPR-Cas9 system that requires a longer protospacer-adjacent motif for site-specific cleavage, and present a comparison between the Spy and Nme CRISPR-Cas9 systems targeting the same protospacer sequence. The results with the native crRNA and tracrRNA as well as a chimeric single guide RNA for the Nme CRISPR-Cas9 system were also compared. Our results suggest that, compared with the Spy system, the Nme CRISPR-Cas9 system has similar or lower on-target cleavage activity but a reduced overall off-target effect on a genomic level when sites containing three or fewer mismatches are considered. Thus, the Nme CRISPR-Cas9 system may represent a safer alternative for precision genome engineering applications.

  3. A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells.

    Science.gov (United States)

    Zhang, Haiwei; Zhang, Xixi; Fan, Cunxian; Xie, Qun; Xu, Chengxian; Zhao, Qun; Liu, Yongbo; Wu, Xiaoxia; Zhang, Haibing

    2016-03-18

    CRISPR-Cas9 mediated genome editing system has been developed as a powerful tool for elucidating the function of genes through genetic engineering in multiple cells and organisms. This system takes advantage of a single guide RNA (sgRNA) to direct the Cas9 endonuclease to a specific DNA site to generate mutant alleles. Since the targeting efficiency of sgRNAs to distinct DNA loci can vary widely, there remains a need for a rapid, simple and efficient sgRNA selection method to overcome this limitation of the CRISPR-Cas9 system. Here we report a novel system to select sgRNA with high efficacy for DNA sequence modification by a luciferase assay. Using this sgRNAs selection system, we further demonstrated successful examples of one sgRNA for generating one gene knockout cell lines where the targeted genes are shown to be functionally defective. This system provides a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs.

  4. [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.

  5. Immunomodulation of Host as a Predictive Bio-Indicator of Toxicity in the Mammalian System

    Directory of Open Access Journals (Sweden)

    P. K. Ray

    1987-04-01

    Full Text Available Immune system is complex in nature, consisting of multi organ involvement in its activity. It is one of the most sensitive systems in the body. Any foreign material i.e. chemicals, drugs and micro-organisms, if enters in the body, may produce alteration in the function of the immune system. Only recently information has been generated that many environmental chemicals and drugs can produce modulation of the immune system in even low doses of exposure and for a short period. Some chemicals in low doses produce severe immunotoxicity well before producing any sign of overt toxicity to the other system. This can be only predicted by using immunotoxicological tests. The chemicals that enhance the immune response may predispose the host to auto-immune disease or lymphoreticular disorders resulting in allergic or hypersensitivity reactions. On the other hand, the chemicals that suppress immunity may sufficiently disrupt the immunoregulatory network, resulting in increased susceptibility to infection or to develop cancer.In the recent past toxicological assessments were done by using lethal dose (50% evaluation, use of biochemical and pathological examination of different organs, which gives information only about the cell number or degree of cellularity. The early effect of chemicals on the cell function may be missing in that type of study. Currently, the inclusion of immunological assessment parameters in toxicity evaluation of chemicals have made it possible to test the toxicity at the cellular level.It has been well known that many of the environmental chemicals at very low doses can modulate immune system without producing any clinical sign or symptoms of the disease or disorders. It is of importance that assessment of  immunomodulation can be used as a sensitive bio-indicator for predicting the toxicity caused by environmental chemicals, since immunotoxicitv can be determined with much smaller dosages of chemicals than is needed for toxicity

  6. Enhanced genome editing in mammalian cells with a modified dual-fluorescent surrogate system.

    Science.gov (United States)

    Zhou, Yan; Liu, Yong; Hussmann, Dianna; Brøgger, Peter; Al-Saaidi, Rasha Abdelkadhem; Tan, Shuang; Lin, Lin; Petersen, Trine Skov; Zhou, Guang Qian; Bross, Peter; Aagaard, Lars; Klein, Tino; Rønn, Sif Groth; Pedersen, Henrik Duelund; Bolund, Lars; Nielsen, Anders Lade; Sørensen, Charlotte Brandt; Luo, Yonglun

    2016-07-01

    Programmable DNA nucleases such as TALENs and CRISPR/Cas9 are emerging as powerful tools for genome editing. Dual-fluorescent surrogate systems have been demonstrated by several studies to recapitulate DNA nuclease activity and enrich for genetically edited cells. In this study, we created a single-strand annealing-directed, dual-fluorescent surrogate reporter system, referred to as C-Check. We opted for the Golden Gate Cloning strategy to simplify C-Check construction. To demonstrate the utility of the C-Check system, we used the C-Check in combination with TALENs or CRISPR/Cas9 in different scenarios of gene editing experiments. First, we disrupted the endogenous pIAPP gene (3.0 % efficiency) by C-Check-validated TALENs in primary porcine fibroblasts (PPFs). Next, we achieved gene-editing efficiencies of 9.0-20.3 and 4.9 % when performing single- and double-gene targeting (MAPT and SORL1), respectively, in PPFs using C-Check-validated CRISPR/Cas9 vectors. Third, fluorescent tagging of endogenous genes (MYH6 and COL2A1, up to 10.0 % frequency) was achieved in human fibroblasts with C-Check-validated CRISPR/Cas9 vectors. We further demonstrated that the C-Check system could be applied to enrich for IGF1R null HEK293T cells and CBX5 null MCF-7 cells with frequencies of nearly 100.0 and 86.9 %, respectively. Most importantly, we further showed that the C-Check system is compatible with multiplexing and for studying CRISPR/Cas9 sgRNA specificity. The C-Check system may serve as an alternative dual-fluorescent surrogate tool for measuring DNA nuclease activity and enrichment of gene-edited cells, and may thereby aid in streamlining programmable DNA nuclease-mediated genome editing and biological research.

  7. [The organizational characteristics of the APUD system in mammalian lungs at different stages of ontogeny].

    Science.gov (United States)

    Blinova, S A

    1991-02-01

    The organization peculiarities of APUD-system in the lungs of rabbits, rats and guinea pigs has been studied. The endocrine system in the lungs of rabbits in pre- and postnatal ontogenesis is presented by the adipocytes and neuroepithelial bodies (NEB) containing a considerable number of monoamines. The number of argyrophil adipocytes and NEBs in the lungs of 21 and more day-old adult rats seem to be less than in fetuses and newborns. Monoamines are not revealed in the endocrine rat lung structures by means of the glyoxylic acid. In the lungs of guinea pigs the single argyrophil adipocytes and NEBs are determined in the gestation period.

  8. Neuromuscular disruption with ultrashort electrical pulses

    Science.gov (United States)

    Pakhomov, Andrei; Kolb, Juergen F.; Joshi, Ravindra P.; Schoenbach, Karl H.; Dayton, Thomas; Comeaux, James; Ashmore, John; Beason, Charles

    2006-05-01

    Experimental studies on single cells have shown that application of pulsed voltages, with submicrosecond pulse duration and an electric field on the order of 10 kV/cm, causes sudden alterations in the intracellular free calcium concentration, followed by immobilization of the cell. In order to examine electrical stimulation and incapacitation with such ultrashort pulses, experiments on anesthetized rats have been performed. The effect of single, 450 nanosecond monopolar pulses have been compared with that of single pulses with multi-microsecond duration (TASER pulses). Two conditions were explored: 1. the ability to elicit a muscle twitch, and, 2. the ability to suppress voluntary movement by using nanosecond pulses. The second condition is relevant for neuromuscular incapacitation. The preliminary results indicate that for stimulation microsecond pulses are advantageous over nanosecond pulses, whereas for incapacitation, the opposite seems to apply. The stimulation effects seem to scale with electrical charge, whereas the disruption effects don't follow a simple scaling law. The increase in intensity (time of incapacitation) for a given pulse duration, is increasing with electrical energy, but is more efficient for nanosecond than for microsecond pulses. This indicates different cellular mechanisms for incapacitation, most likely subcellular processes, which have been shown to become increasingly important when the pulse duration is shortened into the nanosecond range. If further studies can confirm these initial results, consequences of reduced pulse duration are a reduction in weight and volume of the pulse delivery system, and likely, because of the lower required energy for neuromuscular incapacitation, reduced safety risks.

  9. Neuromuscular dressing effects: a literature review

    Directory of Open Access Journals (Sweden)

    Calero PA

    2012-05-01

    Full Text Available The kinesio taping is a technique that was created in 1979 by Doctor Kenzo Kase I’m looking through it that could generate a new therapeutic option to control pain, improve athletic performance and reduce the impact of musculoskeletal disorders. From the Sydney 2000 Olympic Games, this technique as a therapeutic alternative PTO and is composed of health professionals in the field of sport and physical rehabilitation.Objetive: This article aims to identify theoretical approaches on the bandage neuromuscular. Material and methods: held today, for which conducted a literature search of databases such as como Proquest, Ovid, Cochraine, PEDro, Journal of Orthopedic and Sports Physical, Sciencedirect, Pubmed y Literatura Latinoamericana y del Caribe en Ciencias de la Salud (Lilacs.The paper proposes a scheme of contextualization of the current landscape of the use and effects of kinesio taping in the management of different pathologies of the musculo-skeletal system in sports. Conclusion: it is concluded that currently many health professionals, and take the neuromuscular bandage a good therapeutic option in the management of diseases affecting the human body is investigated and every day more about the subject, which makes these new therapeutic methods to acquire a scientific value and transcends knowledge.

  10. Expression System Based on an MTIIa Promoter to Produce hPSA in Mammalian Cell Cultures

    Science.gov (United States)

    Santos, Anderson K.; Parreira, Ricardo C.; Resende, Rodrigo R.

    2016-01-01

    Because of the limitations of standard culture techniques, the development of new recombinant protein expression systems with biotechnological potential is a key challenge. Ideally, such systems should be able to effectively and accurately synthesize a protein of interest with intrinsic metabolic capacity. Here, we describe such a system that was designed based on a plasmid vector containing promoter elements derived from the metallothionein MTIIa promoter, as well as processing and purification elements. This promoter can be induced by heavy metals in a culture medium to induce the synthesis of human prostate-specific antigen (hPSA), which has been modified to insert elements for purification, proteolysis, and secretion. We optimized hPSA production in this system by comparing the effects and contributions of ZnCl2, CdCl2, and CuSO4 in HEK293FT, HeLa, BHK-21, and CHO-K1 cells. We also compared the effectiveness of three different transfection agents: multi-walled carbon nanotubes, Lipofectamine 2000, and X-tremeGENE HP Reagent. hPSA production was confirmed via the detection of enhanced green fluorescent protein fluorescence, and cell viability was determined. The expression of hPSA was compared with that of the native protein produced by LNCaP cells, using enzyme-linked immunosorbent assay and sodium dodecyl sulfate polyacrylamide gel electrophoresis. X-tremeGENE reagent, the BHK-21 cell line, and CuSO4 showed the highest hPSA production rates. Furthermore, BHK-21 cells were more resistant to the oxidative stress caused by 100 μM CuSO4. These results suggest that the proposed optimized inducible expression system can effectively produce recombinant proteins with desired characteristics for a wide range of applications in molecular biology. PMID:27582737

  11. Expression system based on an MTIIa promoter to produce hPSA in mammalian cell cultures

    Directory of Open Access Journals (Sweden)

    Anderson K Santos

    2016-08-01

    Full Text Available Because of the limitations of standard culture techniques, the development of new recombinant protein expression systems with biotechnological potential is a key challenge. Ideally, such systems should be able to effectively and accurately synthesize a protein of interest with intrinsic metabolic capacity. Here, we describe such a system that was designed based on a plasmid vector containing promoter elements derived from the metallothionein MTIIa promoter, as well as processing and purification elements. This promoter can be induced by heavy metals in a culture medium to induce the synthesis of human prostate-specific antigen (hPSA, which has been modified to insert elements for purification, proteolysis, and secretion. We optimized hPSA production in this system by comparing the effects and contributions of ZnCl2, CdCl2, and CuSO4 in HEK293FT, HeLa, BHK-21, and CHO-K1 cells. We also compared the effectiveness of three different transfection agents: multi-walled carbon nanotubes, Lipofectamine 2000, and X-tremeGENE HP Reagent. hPSA production was confirmed via the detection of enhanced green fluorescent protein fluorescence, and cell viability was determined. The expression of hPSA was compared with that of the native protein produced by LNCaP cells, using enzyme-linked immunosorbent assay and sodium dodecyl sulphate polyacrylamide gel electrophoresis. X-tremeGENE reagent, the BHK-21 cell line, and CuSO4 showed the highest hPSA production rates. Furthermore, BHK-21 cells were more resistant to the oxidative stress caused by 100 μM CuSO4. These results suggest that the proposed optimized inducible expression system can effectively produce recombinant proteins with desired characteristics for a wide range of applications in molecular biology.

  12. 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...

  13. The mammalian complement system as an epitome of host-pathogen genetic conflicts.

    Science.gov (United States)

    Cagliani, Rachele; Forni, Diego; Filippi, Giulia; Mozzi, Alessandra; De Gioia, Luca; Pontremoli, Chiara; Pozzoli, Uberto; Bresolin, Nereo; Clerici, Mario; Sironi, Manuela

    2016-03-01

    The complement system is an innate immunity effector mechanism; its action is antagonized by a wide array of pathogens and complement evasion determines the virulence of several infections. We investigated the evolutionary history of the complement system and of bacterial-encoded complement-interacting proteins. Complement components targeted by several pathogens evolved under strong selective pressure in primates, with selection acting on residues at the contact interface with microbial/viral proteins. Positively selected sites in CFH and C4BPA account for the human specificity of gonococcal infection. Bacterial interactors, evolved adaptively as well, with selected sites located at interaction surfaces with primate complement proteins. These results epitomize the expectation under a genetic conflict scenario whereby the host's and the pathogen's genes evolve within binding avoidance-binding seeking dynamics. In silico mutagenesis and protein-protein docking analyses supported this by showing that positively selected sites, both in the host's and in the pathogen's interacting partner, modulate binding.

  14. Sensitivity Measures for Oscillating Systems: Application to Mammalian Circadian Gene Network.

    Science.gov (United States)

    Taylor, Stephanie R; Gunawan, Rudiyanto; Petzold, Linda R; Doyle, Francis J

    2008-01-01

    Vital physiological behaviors exhibited daily by bacteria, plants, and animals are governed by endogenous oscillators called circadian clocks. The most salient feature of the circadian clock is its ability to change its internal time (phase) to match that of the external environment. The circadian clock, like many oscillators in nature, is regulated at the cellular level by a complex network of interacting components. As a complementary approach to traditional biological investigation, we utilize mathematical models and systems theoretic tools to elucidate these mechanisms. The models are systems of ordinary differential equations exhibiting stable limit cycle behavior. To study the robustness of circadian phase behavior, we use sensitivity analysis. As the standard set of sensitivity tools are not suitable for the study of phase behavior, we introduce a novel tool, the parametric impulse phase response curve (pIPRC).

  15. Analysis of benzo[a]pyrene diolepoxide mutagenesis in a mammalian in vitro DNA replication system

    Energy Technology Data Exchange (ETDEWEB)

    Vasunia, K.; Cheng, L.; Carty, M. [Univ. of Cincinnati, OH (United States)] [and others

    1995-11-01

    Chemicals that interact with DNA and cause mutations, thereby activating protooncogenes or inactivating tumor suppressor genes, are thought to initiate the process of carcinogenesis. To elucidate the molecular mechanisms involved in mutagenesis of bulky adducts, we used an in vitro DNA replication system. An SV40-based shuttle vector, PZ189, was treated with anti-benzo[a]pyrene-7,8- dihydrodiol-9,10-epoxide (BPDE) and then replicated in vitro using hypotonic extracts of human HeLa cells. The replication efficiency was monitored by the incorporation of a radiolabelled nucleotide into DNA. The products of the replication reaction were then digested with Dpn-1 to inactivate the unreplicated plasmid and the mutation frequency was evaluated by transfection into E. coli MBM7070. Our results show that BPDE-damaged plasmids undergo replication in the in vitro system. The efficiency of replication and the mutant frequency is dose-dependent, such that the replication efficiency decreases and mutation frequency increases with increasing BPDE dose to the plasmid. This study further validates the in vitro DNA replication system by demonstrating the mutagenicity of bulky adducts of BPDE.

  16. Drosophila CLIP-190 and mammalian CLIP-170 display reduced microtubule plus end association in the nervous system.

    Science.gov (United States)

    Beaven, Robin; Dzhindzhev, Nikola S; Qu, Yue; Hahn, Ines; Dajas-Bailador, Federico; Ohkura, Hiroyuki; Prokop, Andreas

    2015-04-15

    Axons act like cables, electrically wiring the nervous system. Polar bundles of microtubules (MTs) form their backbones and drive their growth. Plus end-tracking proteins (+TIPs) regulate MT growth dynamics and directionality at their plus ends. However, current knowledge about +TIP functions, mostly derived from work in vitro and in nonneuronal cells, may not necessarily apply to the very different context of axonal MTs. For example, the CLIP family of +TIPs are known MT polymerization promoters in nonneuronal cells. However, we show here that neither Drosophila CLIP-190 nor mammalian CLIP-170 is a prominent MT plus end tracker in neurons, which we propose is due to low plus end affinity of the CAP-Gly domain-containing N-terminus and intramolecular inhibition through the C-terminus. Instead, both CLIP-190 and CLIP-170 form F-actin-dependent patches in growth cones, mediated by binding of the coiled-coil domain to myosin-VI. Because our loss-of-function analyses in vivo and in culture failed to reveal axonal roles for CLIP-190, even in double-mutant combinations with four other +TIPs, we propose that CLIP-190 and -170 are not essential axon extension regulators. Our findings demonstrate that +TIP functions known from nonneuronal cells do not necessarily apply to the regulation of the very distinct MT networks in axons.

  17. An Overview of Stress Response and Hypometabolic Strategies in Caenorhabditis elegans: Conserved and Contrasting Signals with the Mammalian System

    Directory of Open Access Journals (Sweden)

    Benjamin Lant, Kenneth B. Storey

    2010-01-01

    Full Text Available Studies of the molecular mechanisms that are involved in stress responses (environmental or physiological have long been used to make links to disease states in humans. The nematode model organism, Caenorhabditis elegans, undergoes a state of hypometabolism called the 'dauer' stage. This period of developmental arrest is characterized by a significant reduction in metabolic rate, triggered by ambient temperature increase and restricted oxygen/ nutrients. C. elegans employs a number of signal transduction cascades in order to adapt to these unfavourable conditions and survive for long times with severely reduced energy production. The suppression of cellular metabolism, providing energetic homeostasis, is critical to the survival of nematodes through the dauer period. This transition displays molecular mechanisms that are fundamental to control of hypometabolism across the animal kingdom. In general, mammalian systems are highly inelastic to environmental stresses (such as extreme temperatures and low oxygen, however, there is a great deal of conservation between the signal transduction pathways of nematodes and mammals. Along with conserving many of the protein targets in the stress response, many of the critical regulatory mechanisms are maintained, and often differ only in their level of expression. Hence, the C. elegans model outlines a framework of critical molecular mechanisms that may be employed in the future as therapeutic targets for addressing disease states.

  18. Use of neuromuscular blockers in Brazil.

    Science.gov (United States)

    Locks, Giovani de Figueiredo; Cavalcanti, Ismar Lima; Duarte, Nadia Maria Conceição; da Cunha, Rafael Martins; de Almeida, Maria Cristina Simões

    2015-01-01

    The objective of this study was to evaluate how Brazilian anesthesiologists are using neuromuscular blockers, focusing on how they establish the diagnosis of postoperative residual curarization and the incidence of complications associated with the use of neuromuscular blockers. A questionnaire was sent to anesthesiologists inviting them to participate in the study. The online data collection remained open from March 2012 to June 2013. During the study period, 1296 responses were collected. Rocuronium, atracurium, and cisatracurium were the main neuromuscular blockers used in cases of elective surgery. Succinylcholine and rocuronium were the main neuromuscular blockers used in cases of emergency surgery. Less than 15% of anesthesiologists reported the frequent use of neuromuscular function monitors. Only 18% of those involved in the study reported that all workplaces have such a monitor. Most respondents reported using only the clinical criteria to assess whether the patient is recovered from the muscle relaxant. Most respondents also reported always using some form of neuromuscular blockade reversal. The major complications attributed to neuromuscular blockers were residual curarization and prolonged blockade. Eighteen anesthesiologists reported death attributed to neuromuscular blockers. Residual or prolonged blockade is possibly recorded as a result of the high rate of using clinical criteria to diagnose whether the patient has recovered or not from motor block and, as a corollary, the poor use of neuromuscular transmission monitors in daily practice. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  19. NMR imaging and spectroscopy of the mammalian central nervous system after heavy ion radiation

    Energy Technology Data Exchange (ETDEWEB)

    Richards, T.

    1984-09-01

    NMR imaging, NMR spectroscopic, and histopathologic techniques were used to study the proton relaxation time and related biochemical changes in the central nervous system after helium beam in vivo irradiation of the rodent brain. The spectroscopic observations reported in this dissertation were made possible by development of methods for measuring the NMR parameters of the rodent brain in vivo and in vitro. The methods include (1) depth selective spectroscopy using an optimization of rf pulse energy based on a priori knowledge of N-acetyl aspartate and lipid spectra of the normal brain, (2) phase-encoded proton spectroscopy of the living rodent using a surface coil, and (3) dual aqueous and organic tissue extraction technique for spectroscopy. Radiation induced increases were observed in lipid and p-choline peaks of the proton spectrum, in vivo. Proton NMR spectroscopy measurements on brain extracts (aqueous and organic solvents) were made to observe chemical changes that could not be seen in vivo. Radiation-induced changes were observed in lactate, GABA, glutamate, and p-choline peak areas of the aqueous fraction spectra. In the organic fraction, decreases were observed in peak area ratios of the terminal-methyl peaks, the N-methyl groups of choline, and at a peak at 2.84 ppM (phosphatidyl ethanolamine and phosphatidyl serine resonances) relative to TMS. With histology and Evans blue injections, blood-brain barrier alternations were seen as early as 4 days after irradiation. 83 references, 53 figures.

  20. Potassium ion recycling pathway via gap junction systems in the mammalian cochlea and its interruption in hereditary nonsyndromic deafness.

    Science.gov (United States)

    Kikuchi, T; Adams, J C; Miyabe, Y; So, E; Kobayashi, T

    2000-01-01

    In the mammalian cochlea, there are two independent gap junction systems, the epithelial cell gap junction system and the connective tissue cell gap junction system. Thus far, four different connexin molecules, including connexin 26, 30, 31, and 43, have been reported in the cochlea. The two networks of gap junctions form the route by which K+ ions that pass through the sensory cells during mechanosensory transduction can be recycled back to the endolymphatic space, from which they reenter the sensory cells. Activation of hair cells by acoustic stimuli induces influx of K+ ions from the endolymph to sensory hair cells. These K+ ions are released basolaterally to the extracellular space of the organ of Corti, from which they enter the cochlear supporting cells. Once inside the supporting cells they move via the epithelial cell gap junction system laterally to the lower part of the spiral ligament. The K+ ions are released into the extracellular space of the spiral ligament by root cells and taken up by type II fibrocytes. This uptake incorporates K+ into the connective tissue gap junction system. Within this system, the K+ ions pass through the tight junctional barrier of the stria vascularis and are released within the intrastrial extracellular space. The marginal cells of the stria vascularis then take up K+ and return it to the endolymphatic space, where it can be used again in sensory transduction. It is highly probable that mutations of connexin genes that result in human nonsyndromic deafness cause dysfunction of cochlear gap junctions and thereby interrupt K+ ion recirculation pathways. In addition to connexin mutations, other conditions may disrupt gap junctions within the ear. For example, mice with a functionally significant mutation of Brain-4, which is expressed in the connective tissue cells within the cochlea, show marked depression of the endolymphatic potential and profound sensorineural hearing loss. It seems likely that disruption of connective

  1. Radiation induced nuclear factor kappa-B signaling cascade study in mammalian cells by improved detection systems

    Science.gov (United States)

    Chishti, Arif Ali; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther

    To enable long-term human space flight cellular radiation response to densely ionizing radiation needs to be better understood for developing appropriate countermeasures to mitigate acute effects and late radiation risks for the astronaut. The biological effectiveness of accelerated heavy ions with high linear energy transfer (LET) for effecting DNA damage response pathways as a gateway to cell death or survival is of major concern, not only for tumor radiotherapy but also for new regimes of space missions. Ionizing radiation modulates several signaling pathways resulting in transcription factor activation. NF-kappaB is one of the important transcription factors that respond to changes in the environment of a mammalian cell and plays a key role in many biological processes relevant to radiation response, such as apoptosis, inflammation and carcinogenesis. From medical and biological point of view it is important to understand radiation induced NF-kappaB signaling cascade. For studying NF-kappaB signaling, green fluorescent proteins EGFP and d2EGFP were used previously (Advances in Space Research, 36: 1673-1679, 2005). The current study aims to improve reporter assays by the use of a destabilized variant of red fluorescent protein tdTomato (DD-tdTomato) which gives high fluorescence signals and a better signal/noise ratio for NF-kappaB activation. The reporter system HEK-pNFkappaB-DD-tdTomato-C8 is a dual reporter system which can provide both discrete and cumulative signals after exposure to ionizing radiation (X-rays, heavy ions). In the presence of Shield-1, the fluorescent protein DD-tdTomato is not degraded but accumulated inside the cell which helps to quantify the fold induction of NF-kappaB-dependent gene expression. The minimum dose required to activate NF-kappaB is 6 Gy but accumulated signals data shows that NF-kappaB is activated after 3 Gy in the presence of Shield-1. Average dose and number of heavy ions’ hits per nucleus necessary to double the NF

  2. Tortuosity and anomalous diffusion in the neuromuscular junction

    Science.gov (United States)

    Lacks, Daniel J.

    2008-04-01

    The signal transfer from nerve to muscle occurs by diffusion across the neuromuscular junction. The continuum level analysis of diffusion processes is based on the diffusion equation, which in one dimension is ∂c/∂t=D(∂2c/∂x2) , where c is the molecular concentration and D is the diffusivity. However, in confined systems such as the neuromuscular junction, the diffusion equation may not be valid, and even if valid the value of D may be altered by the confinement. In this paper, Monte Carlo simulations are used to probe diffusion at the molecular level in a realistic model of a neuromuscular junction. The results show that diffusion is anomalous (i.e., not described by the diffusion equation) for time scales less than ˜0.01s , which is the time scale relevant for signaling processes in the synapse. At longer time scales, the diffusion is normal (i.e., described by the diffusion equation), but with a value of D that is reduced by a factor of ˜5 times compared to the value for diffusion in open space. As the width of the synaptic cleft decreases, these effects become even more pronounced. The physical basis of these results is described in terms of the structure of the neuromuscular junction.

  3. 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

  4. Facial rehabilitation: a neuromuscular reeducation, patient-centered approach.

    Science.gov (United States)

    Vanswearingen, Jessie

    2008-05-01

    Individuals with facial paralysis and distorted facial expressions and movements secondary to a facial neuromotor disorder experience substantial physical, psychological, and social disability. Previously, facial rehabilitation has not been widely available or considered to be of much benefit. An emerging rehabilitation science of neuromuscular reeducation and evidence for the efficacy of facial neuromuscular reeducation, a process of facilitating the return of intended facial movement patterns and eliminating unwanted patterns of facial movement and expression, may provide patients with disorders of facial paralysis or facial movement control opportunity for the recovery of facial movement and function. We provide a brief overview of the scientific rationale for facial neuromuscular reeducation in the structure and function of the facial neuromotor system, the neuropsychology of facial expression, and relations among expressions, movement, and emotion. The primary purpose is to describe principles of neuromuscular reeducation, assessment and outcome measures, approach to treatment, the process, including surface-electromyographic biofeedback as an adjunct to reeducation, and the goal of enhancing the recovery of facial expression and function in a patient-centered approach to facial rehabilitation.

  5. A comprehensive complex systems approach to the study and analysis of mammalian cell cycle control system in the presence of DNA damage stress.

    Science.gov (United States)

    Abroudi, Ali; Samarasinghe, Sandhya; Kulasiri, Don

    2017-09-21

    Not many models of mammalian cell cycle system exist due to its complexity. Some models are too complex and hard to understand, while some others are too simple and not comprehensive enough. Moreover, some essential aspects, such as the response of G1-S and G2-M checkpoints to DNA damage as well as the growth factor signalling, have not been investigated from a systems point of view in current mammalian cell cycle models. To address these issues, we bring a holistic perspective to cell cycle by mathematically modelling it as a complex system consisting of important sub-systems that interact with each other. This retains the functionality of the system and provides a clearer interpretation to the processes within it while reducing the complexity in comprehending these processes. To achieve this, we first update a published ODE mathematical model of cell cycle with current knowledge. Then the part of the mathematical model relevant to each sub-system is shown separately in conjunction with a diagram of the sub-system as part of this representation. The model sub-systems are Growth Factor, DNA damage, G1-S, and G2-M checkpoint signalling. To further simplify the model and better explore the function of sub-systems, they are further divided into modules. Here we also add important new modules of: chk-related rapid cell cycle arrest, p53 modules expanded to seamlessly integrate with the rapid arrest module, Tyrosine phosphatase modules that activate Cyc_Cdk complexes and play a crucial role in rapid and delay arrest at both G1-S and G2-M, Tyrosine Kinase module that is important for inactivating nuclear transport of CycB_cdk1 through Wee1 to resist M phase entry, Plk1-Related module that is crucial in activating Tyrosine phosphatases and inactivating Tyrosine kinase, and APC-Related module to show steps in CycB degradation. This multi-level systems approach incorporating all known aspects of cell cycle allowed us to (i) study, through dynamic simulation of an ODE model

  6. BIOLOGY OF SOME NEUROMUSCULAR DISORDERS

    Directory of Open Access Journals (Sweden)

    Gerta Vrbova

    2004-12-01

    Full Text Available In order to understand and possibly interfere/ treat neuromuscular disorders it is important to analyze the biological events that may be causing the disability. We illustrate such attempts on two examples of genetically determined neuromuscular diseases: 1 Duchenne muscular dystrophy (DMD, and 2 Spinal muscular atrophy (SMA.DMD is an x-linked hereditary muscle disease that leads to progressive muscle weakness. The altered gene in DMD affects dystrophin, a muscle membrane associated proteine. Attempts were made to replace the deficient or missing gene/ protein into muscles of Duchenne children. Two main strategies were explored: 1 Myoblast and stem cell transfer and 2 Gene delivery. The possible use of methods other than the introduction of the missing gene for dystrophin into muscle fibres are based on the knowledge about the adaptive potential of muscle to different functional demands and the ability of the muscle to express a new set of genes in response to such stimuli. Stretch or overload is now known to lead to changes of gene expression in normal muscle, and the success of muscle stretch in the management of Duchenne boys is most likely to be due to such adaptive changes. Electrical stimulation of muscles is also a powerful stimulus for inducing the expression of new genes and this method too has produced beneficial effects on the progress of the disease in mice and men.SMA is a heterogeneous group of hereditary neuromuscular disorders where the loss of lower motoneurones leads to progressive weakness and muscle atrophy. The disease subdivides into 3 forms according to the severity of the symptoms and age of onset. All three forms of SMA have been mapped to chromosome 5q11.2-13.2. Clinical features of all these forms of SMA include hypotonia shortly after birth, symmetrical muscle weakness and atrophy, finger tremor, areflexia or hyporeflexia and later contractures. In patients with SMA 1 and 2 the development of all parts of the motor

  7. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

    Science.gov (United States)

    Baer, Matthew L.; Henderson, Scott C.; Colello, Raymond J.

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID:26562295

  8. Elucidating the Role of Injury-Induced Electric Fields (EFs in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

    Directory of Open Access Journals (Sweden)

    Matthew L Baer

    Full Text Available Injury to the vertebrate central nervous system (CNS induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

  9. Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

    Science.gov (United States)

    Baer, Matthew L; Henderson, Scott C; Colello, Raymond J

    2015-01-01

    Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

  10. Neuromuscular Control and Coordination during Cycling

    Science.gov (United States)

    Li, Li

    2004-01-01

    The neuromuscular control aspect of cycling has been investigated through the effects of modifying posture and cadence. These studies show that changing posture has a more profound influence on neuromuscular coordination than does changing slope. Most of the changes with standing posture occur late in the downstroke: increased ankle and knee joint…

  11. Aggravated neuromuscular symptoms of mercury exposure from dental amalgam fillings.

    Science.gov (United States)

    Akbal, Ayla; Yılmaz, Hınç; Tutkun, Engin; Köş, Durdu Mehmet

    2014-01-01

    Dental amalgam fillings are widely used all over the world. However, their mercury content can lead to various side effects and clinical problems. Acute or chronic mercury exposure can cause several side effects on the central nerve system, renal and hepatic functions, immune system, fetal development and it can play a role on exacerbation of neuromuscular diseases. In this case, we will present a patient with vacuolar myopathy whose symptoms were started and aggravated with her dental amalgam fillings.

  12. 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.

  13. Mitochondrial dysfunction in neuromuscular disorders.

    Science.gov (United States)

    Katsetos, Christos D; Koutzaki, Sirma; Melvin, Joseph J

    2013-09-01

    This review deciphers aspects of mitochondrial (mt) dysfunction among nosologically, pathologically, and genetically diverse diseases of the skeletal muscle, lower motor neuron, and peripheral nerve, which fall outside the traditional realm of mt cytopathies. Special emphasis is given to well-characterized mt abnormalities in collagen VI myopathies (Ullrich congenital muscular dystrophy and Bethlem myopathy), megaconial congenital muscular dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy, Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies. Among inflammatory myopathies, mt abnormalities are more prominent in inclusion body myositis and a subset of polymyositis with mt pathology, both of which are refractory to corticosteroid treatment. Awareness is raised about instances of phenotypic mimicry between cases harboring primary mtDNA depletion, in the context of mtDNA depletion syndrome, and established neuromuscular disorders such as spinal muscular atrophy. A substantial body of experimental work, derived from animal models, attests to a major role of mitochondria (mt) in the early process of muscle degeneration. Common mechanisms of mt-related cell injury include dysregulation of the mt permeability transition pore opening and defective autophagy. The therapeutic use of mt permeability transition pore modifiers holds promise in various neuromuscular disorders, including muscular dystrophies.

  14. Identification of minimal sequences of the Rhopalosiphum padi virus 5' untranslated region required for internal initiation of protein synthesis in mammalian, plant and insect translation systems

    DEFF Research Database (Denmark)

    Groppelli, Elisabetta; Belsham, Graham; Roberts, Lisa O.

    2007-01-01

    Rhopalosiphum padi virus (RhPV) is a member of the family Dicistroviridae. The genomes of viruses in this family contain two open reading frames, each preceded by distinct internal ribosome entry site (IRES) elements. The RhPV 5' IRES is functional in mammalian, insect and plant translation systems...... (rabbit reticulocyte lysate), plant (wheatgerm extract) and insect (Sf21 cells) translation systems have now been defined. A fragment (nt 426–579) from the 3' portion of the 5' UTR can direct translation in each of these translation systems. In addition, a distinct region (nt 300–429) is also active. Thus...

  15. Electroporation into Cultured Mammalian Embryos

    Science.gov (United States)

    Nomura, Tadashi; Takahashi, Masanori; Osumi, Noriko

    Over the last century, mammalian embryos have been used extensively as a common animal model to investigate fundamental questions in the field of developmental biology. More recently, the establishment of transgenic and gene-targeting systems in laboratory mice has enabled researchers to unveil the genetic mechanisms under lying complex developmental processes (Mak, 2007). However, our understanding of cell—cell interactions and their molecular basis in the early stages of mammalian embryogenesis is still very fragmentary. One of the major problems is the difficulty of precise manipulation and limited accessibility to mammalian embryos via uterus wall. Unfortunately, existing tissue and organotypic culture systems per se do not fully recapitulate three-dimensional, dynamic processes of organogenesis observed in vivo. Although transgenic animal technology and virus-mediated gene delivery are useful to manipulate gene expression, these techniques take much time and financial costs, which limit their use.

  16. An overview of neurological and neuromuscular signs in mitochondrial diseases.

    Science.gov (United States)

    Chaussenot, A; Paquis-Flucklinger, V

    2014-05-01

    Mitochondrial disorders have a broad clinical spectrum and are genetically heterogeneous, involving two genomes. These disorders may be develop at any age, with isolated or multiple system involvement, and any pattern of inheritance. Neurological involvement is the most frequent, and concerns muscular, peripheral and central nervous system. Among these diverse signs, some are suggestive of mitochondrial disease, such as progressive external ophthalmoplegia, exercise intolerance, psychomotor regression, stroke-like episodes, refractory epilepsy and Epilepsia Partialis Continua. Others are less specific and mitochondrial hypothesis may be evocated because of either association of different neuromuscular signs or a multisystemic involvement. This review describes the wealth of this neurological and neuromuscular symptomatology through different syndromes reported in the literature, according to preponderant signs and to modes of inheritance, as key elements to guide genetics testing.

  17. The effects of roxatidine on neuromuscular transmission.

    Science.gov (United States)

    Bossa, R; Chiericozzi, M; Galatulas, I; Salvatore, G; Teli, M; Baggio, G; Castelli, M

    1995-01-01

    We have investigated the effects of the H2 receptor antagonist roxatidine on the neuromuscular transmission by using the sciatic nerve-gastrocnemius muscle preparation of the rat in vivo. Roxatidine, administered by i.v. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and aminoglycoside antibiotic, kanamycin. Moreover, the drug alone is capable of producing a blockade on the preparation stimulated at high frequency. The neuromuscular blockade induced by roxatidine is partially reversed by 4-aminopyridine but not by dimaprit.

  18. Histochemical and immunohistological approach to comparative neuromuscular diseases.

    Directory of Open Access Journals (Sweden)

    Serenella Papparella

    2009-12-01

    Full Text Available The broad category of neuromuscular diseases covers conditions that involve the weakness or wasting of the body muscles. These problems may occur in the spinal cord, the peripheral nerves or the muscle fibers. Some may be hereditary, while others are acquired. Commonly recognized conditions fall into the categories of myopathies, which are diseases of the muscle like muscular dystrophy, disorders of the junction where the nerve impulses are transmitted to the muscle like myasthenia gravis, and neuropathies, which are diseases of the peripheral nervous system. The diagnosis of most neuromuscular diseases rest on careful clinical evaluation of the patient, electromyography, the muscle biopsy, and in some instances, molecular genetic studies. Muscle biopsy, associated to histochemical and immunohistological techniques, plays a key role in diagnosis of many neuromuscular disorders. A number of morphological abnormalities of muscle can be recognized on histological stains such as haematoxylin and eosin and Engel trichrome. Histochemical techniques are essential for the study of muscle biopsies for four main reasons. First, they demonstrate the non-uniform nature of the muscle highlighting the different biochemical properties of specific fibre type and their selective involvement in certain disease processes. Second, they may show an absences of a particular enzyme. Third, an excess of a particular substrate can be demonstrated. Fourth, they may show structural changes in the muscle which would not be apparent with routine histological stains, such as the enzyme-deficient cores in central core disease "mouth-eaten" fibers, and abnormalities in the distribution of mitochondria. In some neuromuscular disorders there could be only non-specific myopathological features. However, a number of proteins, including sarcolemmal, sarcomeric, and nuclear proteins as well as enzymes with defects responsible for neuromuscular disorders, have been identified during

  19. Metabolic-flux analysis of mammalian-cell culture.

    NARCIS (Netherlands)

    Bonarius, H.P.J.

    1998-01-01

    In the biopharmaceutical industry mammalian cells are cultivated for the production of recombinant glycoproteins, vaccines, and monoclonal antibodies. In contrast to other expression systems, such as prokaryotes or yeasts, mammalian cells are able to glycosylate and fold therapeutic proteins correct

  20. Metabolic-flux analysis of mammalian-cell culture

    NARCIS (Netherlands)

    Bonarius, H.P.J.

    1998-01-01

    In the biopharmaceutical industry mammalian cells are cultivated for the production of recombinant glycoproteins, vaccines, and monoclonal antibodies. In contrast to other expression systems, such as prokaryotes or yeasts, mammalian cells are able to glycosylate and fold therapeutic

  1. Acute neuromuscular weakness associated with dengue infection

    OpenAIRE

    Harmanjit Singh Hira; Amandeep Kaur; Anuj Shukla

    2012-01-01

    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 ...

  2. Sugammadex: A revolutionary drug in neuromuscular pharmacology

    Science.gov (United States)

    Nag, Kusha; Singh, Dewan Roshan; Shetti, Akshaya N.; Kumar, Hemanth; Sivashanmugam, T.; Parthasarathy, S.

    2013-01-01

    Sugammadex (ORG 25969) is a unique neuromuscular reversal drug; a novel cyclodextrin, the first in a new class of selective relaxant binding agents, which reverse neuromuscular blockade (NMB) with the aminosteroid non-depolarizing muscle relaxants rocuronium and vecuronium. Sugammadex can reverse moderate or deep NMB. The clinical use of sugammadex promises to eliminate many of the shortcomings in current anesthetic practice with regard to antagonism of rocuronium and other aminosteroid muscle relaxants. PMID:25885973

  3. 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.

  4. Neuromuscular blockade in the elderly patient

    Directory of Open Access Journals (Sweden)

    Lee LA

    2016-06-01

    Full Text Available Luis A Lee, Vassilis Athanassoglou, Jaideep J Pandit Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Abstract: Neuromuscular blockade is a desirable or even essential component of general anesthesia for major surgical operations. As the population continues to age, and more operations are conducted in the elderly, due consideration must be given to neuromuscular blockade in these patients to avoid possible complications. This review considers the pharmacokinetics and pharmacodynamics of neuromuscular blockade that may be altered in the elderly. Compartment distribution, metabolism, and excretion of drugs may vary due to age-related changes in physiology, altering the duration of action with a need for reduced dosage (eg, aminosteroids. Other drugs (atracurium, cisatracurium have more reliable duration of action and should perhaps be considered for use in the elderly. The range of interpatient variability that neuromuscular blocking drugs may exhibit is then considered and drugs with a narrower range, such as cisatracurium, may produce more predictable, and inherently safer, outcomes. Ultimately, appropriate neuromuscular monitoring should be used to guide the administration of muscle relaxants so that the risk of residual neuromuscular blockade postoperatively can be minimized. The reliability of various monitoring is considered. This paper concludes with a review of the various reversal agents, namely, anticholinesterase drugs and sugammadex, and the alterations in dosing of these that should be considered for the elderly patient. Keywords: anesthesia, elderly, drugs, pharmacokinetics, pharmacodynamics 

  5. Sugammadex: A Review of Neuromuscular Blockade Reversal.

    Science.gov (United States)

    Keating, Gillian M

    2016-07-01

    Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade.

  6. From heterochromatin islands to the NAD World: a hierarchical view of aging through the functions of mammalian Sirt1 and systemic NAD biosynthesis.

    Science.gov (United States)

    Imai, Shin-ichiro

    2009-10-01

    For the past couple of decades, aging science has been rapidly evolving, and powerful genetic tools have identified a variety of evolutionarily conserved regulators and signaling pathways for the control of aging and longevity in model organisms. Nonetheless, a big challenge still remains to construct a comprehensive concept that could integrate many distinct layers of biological events into a systemic, hierarchical view of aging. The "heterochromatin island" hypothesis was originally proposed 10 years ago to explain deterministic and stochastic aspects of cellular and organismal aging, which drove the author to the study of evolutionarily conserved Sir2 proteins. Since a surprising discovery of their NAD-dependent deacetylase activity, Sir2 proteins, now called "sirtuins," have been emerging as a critical epigenetic regulator for aging. In this review, I will follow the process of conceptual development from the heterochromatin island hypothesis to a novel, comprehensive concept of a systemic regulatory network for mammalian aging, named "NAD World," summarizing recent studies on the mammalian NAD-dependent deacetylase Sirt1 and nicotinamide phosphoribosyltransferase (Nampt)-mediated systemic NAD biosynthesis. This new concept of the NAD World provides critical insights into a systemic regulatory mechanism that fundamentally connects metabolism and aging and also conveys the ideas of functional hierarchy and frailty for the regulation of aging in mammals.

  7. Using physiologically-based pharmacokinetic-guided "body-on-a-chip" systems to predict mammalian response to drug and chemical exposure.

    Science.gov (United States)

    Sung, Jong Hwan; Srinivasan, Balaji; Esch, Mandy Brigitte; McLamb, William T; Bernabini, Catia; Shuler, Michael L; Hickman, James J

    2014-09-01

    The continued development of in vitro systems that accurately emulate human response to drugs or chemical agents will impact drug development, our understanding of chemical toxicity, and enhance our ability to respond to threats from chemical or biological agents. A promising technology is to build microscale replicas of humans that capture essential elements of physiology, pharmacology, and/or toxicology (microphysiological systems). Here, we review progress on systems for microscale models of mammalian systems that include two or more integrated cellular components. These systems are described as a "body-on-a-chip", and utilize the concept of physiologically-based pharmacokinetic (PBPK) modeling in the design. These microscale systems can also be used as model systems to predict whole-body responses to drugs as well as study the mechanism of action of drugs using PBPK analysis. In this review, we provide examples of various approaches to construct such systems with a focus on their physiological usefulness and various approaches to measure responses (e.g. chemical, electrical, or mechanical force and cellular viability and morphology). While the goal is to predict human response, other mammalian cell types can be utilized with the same principle to predict animal response. These systems will be evaluated on their potential to be physiologically accurate, to provide effective and efficient platform for analytics with accessibility to a wide range of users, for ease of incorporation of analytics, functional for weeks to months, and the ability to replicate previously observed human responses. © 2014 by the Society for Experimental Biology and Medicine.

  8. 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.

  9. Neuromuscular dentistry: Occlusal diseases and posture.

    Science.gov (United States)

    Khan, Mohd Toseef; Verma, Sanjeev Kumar; Maheshwari, Sandhya; Zahid, Syed Naved; Chaudhary, Prabhat K

    2013-01-01

    Neuromuscular dentistry has been a controversial topic in the field of dentistry and still remains debatable. The issue of good occlusion and sound health has been repeatedly discussed. Sometimes we get complains of sensitive teeth and sometimes of tired facial muscles on getting up in the morning. Owing to the intimate relation of masticatory apparatus with the cranium and cervico-scapular muscular system, the disorders in any system, draw attention from concerned clinicians involved in management, to develop an integrated treatment protocol for the suffering patients. There may be patients reporting to the dental clinics after an occlusal restoration or extraction, having pain in or around the temporomandibular joint, headache or neck pain. Although their esthetic demands must not be undermined during the course of treatment plan, whenever dental treatment of any sort is planned, occlusion/bite should be given prime importance. Very few dentist are able to diagnose the occlusal disease and of those who diagnose many people resort to aggressive treatment modalities. This paper aims to report the signs of occlusal disease, and discuss their association with TMDs and posture.

  10. 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.

  11. A model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by Leptospira interrogans serovar Copenhageni.

    Directory of Open Access Journals (Sweden)

    Melissa J Caimano

    2014-03-01

    Full Text Available Leptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus Leptospira. More than 500,000 cases of severe leptospirosis are reported annually, with >10% of these being fatal. Leptospires can survive for weeks in suitably moist conditions before encountering a new host. Reservoir hosts, typically rodents, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. In humans, leptospires can cause a variety of clinical manifestations, ranging from asymptomatic or mild fever to severe icteric (Weil's disease and pulmonary haemorrhage. Currently, little is known about how Leptospira persist within a reservoir host. Prior in vitro studies have suggested that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. However, no study has examined gene expression by leptospires within a mammalian host-adapted state. To obtain a more faithful representation of how leptospires respond to host-derived signals, we used RNA-Seq to compare the transcriptome of L. interrogans cultivated within dialysis membrane chambers (DMCs implanted into the peritoneal cavities of rats with that of organisms grown in vitro. In addition to determining the relative expression levels of "core" housekeeping genes under both growth conditions, we identified 166 genes that are differentially-expressed by L. interrogans in vivo. Our analyses highlight physiological aspects of host adaptation by leptospires relating to heme uptake and utilization. We also identified 11 novel non-coding transcripts that are candidate small regulatory RNAs. The DMC model provides a facile system for studying the transcriptional and antigenic changes associated with mammalian host

  12. Baculoviruses as Vectors in Mammalian Cells

    Institute of Scientific and Technical Information of China (English)

    Chang-yong LIANG; Xin-wen CHEN

    2007-01-01

    The Baculoviridae are a large family of enveloped DNA viruses exclusively pathogenic to arthropods. Baculoviruses have been extensively used in insect cell-based recombinant protein expression system and as biological pesticides. They have been deomostrated to be safe to mammals, birds and fish. Recently, baculoviruses has been shown to transduce different mammalian cells in spite of the fact that they cannot replicate in mammalian cells (11, 73, 76). This has resulted in the development of baculoviruses as mammalian expression systems and even as vestors for gene therapy.

  13. Electrophysiology of autonomic neuromuscular transmission involving ATP.

    Science.gov (United States)

    Sneddon, P

    2000-07-01

    Electrophysiological investigations of autonomic neuromuscular transmission have provided great insights into the role of ATP as a neurotransmitter. Burnstock and Holman made the first recordings of excitatory junction potentials (e.j.p.s) produced by sympathetic nerves innervating the smooth muscle of the guinea-pig vas deferens. This led to the identification of ATP as the mediator of e.j.p.s in this tissue, where ATP acts as a cotransmitter with noradrenaline. The e.j.p.s are mediated solely by ATP acting on P2X(1) receptors leading to action potentials and a rapid phasic contraction, whilst noradrenaline mediates a slower, tonic contraction which is not dependent on membrane depolarisation. Subsequent electrophysiological studies of the autonomic innervation of smooth muscles of the urogenital, gastrointestinal and cardiovascular systems have revealed a similar pattern of response, where ATP mediates a fast electrical and mechanical response, whilst another transmitter such as noradrenaline, acetylcholine, nitric oxide or a peptide mediates a slower response. The modulation of junction potentials by a variety of pre-junctional receptors and the mechanism of inactivation of ATP as a neurotransmitter will also be described.

  14. 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

  15. [Use of neuromuscular blockers in Brazil].

    Science.gov (United States)

    Locks, Giovani de Figueiredo; Cavalcanti, Ismar Lima; Duarte, Nadia Maria Conceição; Cunha, Rafael Martins da; Almeida, Maria Cristina Simões de

    2015-01-01

    The objective of this study was to evaluate how Brazilian anesthesiologists are using neuromuscular blockers (NMB), focusing on how they establish the diagnosis of postoperative residual curarization and the incidence of complications associated with the use of NMB. A questionnaire was sent to anesthesiologists inviting them to participate in the study. The online data collection remained open from March 2012 to June 2013. During the study period, 1296 responses were collected. Rocuronium, atracurium, and cisatracurium were the main neuromuscular blockers used in cases of elective surgery. Succinylcholine and rocuronium were the main NMB used in cases of emergency surgery. Less than 15% of anesthesiologists reported the frequent use of neuromuscular function monitors. Only 18% of those involved in the study reported that all workplaces have such a monitor. Most respondents reported using only the clinical criteria to assess whether the patient is recovered from the muscle relaxant. Most respondents also reported always using some form of neuromuscular blockade reversal. The major complications attributed to NMB were residual curarization and prolonged blockade. Eighteen anesthesiologists reported death attributed to NMB. Residual or prolonged blockade is possibly recorded as a result of the high rate of using clinical criteria to diagnose whether the patient has recovered or not from motor block and, as a corollary, the poor use of neuromuscular transmission monitors in daily practice. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  16. Employment profiles in neuromuscular diseases.

    Science.gov (United States)

    Fowler, W M; Abresch, R T; Koch, T R; Brewer, M L; Bowden, R K; Wanlass, R L

    1997-01-01

    Consumer and rehabilitation provider factors that might limit employment opportunities for 154 individuals with six slowly progressive neuromuscular diseases (NMD) were investigated. The NMDs were spinal muscular atrophy (SMA), hereditary motor sensory neuropathy (HMSN), Becker's muscular dystrophy (BMD), facioscapulohumeral muscular dystrophy (FSHD), myotonic muscular dystrophy (MMD), and limb-girdle syndrome (LGS). Forty percent were employed in the competitive labor market at the time of the study, 50% had been employed in the past, and 10% had never been employed. The major consumer barrier to employment was education. Other important factors were type of occupation, intellectual capacity, psychosocial adjustment, and the belief by most individuals that their physical disability was the only or major barrier to obtaining a job. Psychological characteristics were associated with level of unemployment. However, physical impairment and disability were not associated with level of unemployment. There also were differences among the types of NMDs. Compared with the SMA, HMSN, BMD, and FSHD groups, the MMD and LGS groups had significantly higher levels of unemployment, lower educational levels, and fewer employed professional, management, and technical workers. Nonphysical impairment factors such as a low percentage of college graduates, impaired intellectual function in some individuals, and poor psychological adjustment were correlated with higher unemployment levels in the MMD group. Unemployment in the LGS group was correlated with a failure to complete high school. Major provider barriers to employment were the low level of referrals to Department of Rehabilitation by physicians and the low percentage of acceptance into the State Department of Rehabilitation. The low rate of acceptance was primarily attributable to the low number of referrals compounded by a lack of counselor experience with individuals with NMD. Both consumer and provider barriers may

  17. 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.

  18. The effect of timing electrical stimulation to robotic-assisted stepping on neuromuscular activity and associated kinematics

    OpenAIRE

    Sina Askari, MS; TeKang Chao; Ray D. de Leon, PhD; Deborah S. Won, PhD

    2013-01-01

    Results of previous studies raise the question of how timing neuromuscular functional electrical stimulation (FES) to limb movements during stepping might alter neuromuscular control differently than patterned stimulation alone. We have developed a prototype FES system for a rodent model of spinal cord injury (SCI) that times FES to robotic treadmill training (RTT). In this study, one group of rats (n = 6) was trained with our FES+RTT system and received stimulation of the ankle flexor (tibia...

  19. Biomonitoring of non-dioxin-like polychlorinated biphenyls in transgenic Arabidopsis using the mammalian pregnane X receptor system: a role of pectin in pollutant uptake.

    Directory of Open Access Journals (Sweden)

    Lieming Bao

    Full Text Available Polychlorinated biphenyls (PCBs are persistent organic pollutants damaging to human health and the environment. Techniques to indicate PCB contamination in planta are of great interest to phytoremediation. Monitoring of dioxin-like PCBs in transgenic plants carrying the mammalian aryl hydrocarbon receptor (AHR has been reported previously. Herein, we report the biomonitoring of non-dioxin-like PCBs (NDL-PCBs using the mammalian pregnane X receptor (PXR. In the transgenic Arabidopsis designated NDL-PCB Reporter, the EGFP-GUS reporter gene was driven by a promoter containing 18 repeats of the xenobiotic response elements, while PXR and its binding partner retinoid X receptor (RXR were coexpressed. Results showed that, in live cells, the expression of reporter gene was insensitive to endogenous lignans, carotenoids and flavonoids, but responded to all tested NDL-PCBs in a dose- and time- dependent manner. Two types of putative PCB metabolites, hydroxy- PCBs and methoxy- PCBs, displayed different activation properties. The vascular tissues seemed unable to transport NDL-PCBs, whereas mutation in QUASIMODO1 encoding a 1,4-galacturonosyltransferase led to reduced PCB accumulation in Arabidopsis, revealing a role for pectin in the control of PCB translocation. Taken together, the reporter system may serve as a useful tool to biomonitor the uptake and metabolism of NDL-PCBs in plants.

  20. Amplitude and phase measurement circuit design used on neuromuscular disease assessment system%一种用于神经肌肉疾病评估系统的幅相测量电路的设计

    Institute of Scientific and Technical Information of China (English)

    李丽丽; 田学隆; 李一言

    2011-01-01

    神经肌肉疾病评估系统的关键是能同时准确提取幅值和相位信息.利用AD8302的高度集成特性设计了一种幅相测量电路.给出了电路原理图,详细论述了测量频率为50 kHz时,幅相测量电路设计的具体方法.性能分析结果表明,幅值和相位的测量性能与额定值比较接近.在±20dB范围内,幅值测量精度在±0.5db以内;在±90°范围内,相位测量精度在±0.9°以内.%Accurately picking up amplitude and phase at the same time is essential for neuromuscular disease assessment system. Based on the feature of highly integration of AD8302, a circuit to measure amplitude and phase was designed in this research, and the schematic diagram was provided. The method of circuit design was provied in detail with the frequency of 50 kHz. As a result of performance analysis of this system, the measured value of amplitude and phase is approach to rated value: (L5 Db accuracy was achieved over a 20 Db range when measuring gain. Phase accuracy was 0.9° for a 90° range.

  1. Development and aging of the Kisspeptin-GPR54 system in the mammalian brain: what are the impacts on female reproductive function?

    Directory of Open Access Journals (Sweden)

    Isabelle eFranceschini

    2013-03-01

    Full Text Available The prominent role of the G protein coupled receptor GPR54 and its peptide ligand kisspeptin in the progression of puberty has been extensively documented in many mammalian species including humans. Kisspeptins are very potent GnRH secretagogues produced by two main populations of neurons located in two ventral forebrain regions, the preoptic area and the arcuate nucleus (ARC. Within the last two years a substantial amount of data has accumulated concerning the development of these neuronal populations and their timely regulation by central and peripheral factors during fetal, neonatal and peripubertal stages of development. This review focuses on the development of the Kisspeptin-GPR54 system in the brain of female mouse, rat, sheep, monkey and humans. The notion that this system represents a major target through which signals from the environment early in life can re-program reproductive function will also be discussed.

  2. Mammalian gut immunity

    Directory of Open Access Journals (Sweden)

    Benoit Chassaing

    2014-10-01

    Full Text Available The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells and hemopoietic (macrophages, dendritic cells, T-cells origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a "love-hate relationship." Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases.

  3. Neuromuscular action of crotalid venom: preliminar data

    OpenAIRE

    Maria Dorvalina Silva; Luiz Antônio L. Resende; Anete Kimuni Ueda; Benedito Barraviera; Mendes, R P; Montenegro, Mário Rubens G. [UNESP

    1996-01-01

    Estudamos 6 pacientes, 2 cães e um coelho com intoxicação crotálica. Avaliamos a condução nervosa periférica sensitiva e motora, a transmissão neuromuscular e eletromiografias. As biópsias de músculo foram processadas por histoquímica. Os 6 pacientes apresentaram mononeuropatia sensitiva no nervo periférico adjacente ao local da inoculação do veneno e encontramos evidências histoquímicas de miopatia mitocondrial. Os defeitos da transmissão neuromuscular foram mínimos. A maioria dos autores ad...

  4. Atividade neuromuscular no swing do golfe

    OpenAIRE

    Marta, Sérgio Miguel Álvaro

    2014-01-01

    Doutoramento em Motricidade Humana na especialidade de Comportamento Motor O objetivo desta tese foi estudar da atividade neuromuscular da técnica de swing da modalidade de golfe. Para concretizar o objetivo foram realizados cinco estudos: um estudo em que se efetuou uma revisão de literatura sobre a atividade neuromuscular do swing de golfe e quatro estudos laboratoriais que analisaram o swing de golfe nos músculos do membro superior, tronco e do membro inferior. A revisão de ...

  5. 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... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5860 Implanted neuromuscular stimulator. (a) Identification. An implanted neuromuscular stimulator is a device that...

  6. 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.

  7. Tissue engineering for neuromuscular disorders of the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Kenneth L Koch; Khalil N Bitar; John E Fortunato

    2012-01-01

    The digestive tract is designed for the optimal processing of food that nourishes all organ systems.The esophagus,stomach,small bowel,and colon are sophisticated neuromuscular tubes with specialized sphincters that transport ingested food-stuffs from one region to another.Peristaltic contractions move ingested solids and liquids from the esophagus into the stomach; the stomach mixes the ingested nutrients into chyme and empties chyme from the stomach into the duodenum.The to-and-fro movement of the small bowel maximizes absorption of fat,protein,and carbohydrates.Peristaltic contractions are necessary for colon function and defecation.

  8. The autonomic nervous system and chromaffin tissue: neuroendocrine regulation of catecholamine secretion in non-mammalian vertebrates.

    Science.gov (United States)

    Perry, Steve F; Capaldo, Anna

    2011-11-16

    If severe enough, periods of acute stress in animals may be associated with the release of catecholamine hormones (noradrenaline and adrenaline) into the circulation; a response termed the acute humoral adrenergic stress response. The release of catecholamines from the sites of storage, the chromaffin cells, is under neuroendocrine control, the complexity of which appears to increase through phylogeny. In the agnathans, the earliest branching vertebrates, the chromaffin cells which are localized predominantly within the heart, lack neuronal innervation and thus catecholamine secretion in these animals is initiated solely by humoral mechanisms. In the more advanced teleost fish, the chromaffin cells are largely confined to the walls of the posterior cardinal vein at the level of the head kidney where they are intermingled with the steroidogenic interrenal cells. Catecholamine secretion from teleost chromaffin cells is regulated by a host of cholinergic and non-cholinergic pathways that ensure sufficient redundancy and flexibility in the secretion process to permit synchronized responses to a myriad of stressors. The complexity of catecholamine secretion control mechanisms continues through the amphibians, reptiles and birds although neural (cholinergic) regulation may become increasingly important in birds. Discrete adrenal glands are present in the non-mammalian tetrapods but unlike in mammals, there is no clear division of a steroidogenic cortex and a chromaffin cell enriched medulla. However, in all groups, there is an obvious intermingling of chromaffin and steroiodogenic cells. The association of the two cell types may be particularly important in the amphibians and birds because like in mammals, the enzyme catalysing the methylation of noradrenaline to adrenaline, PNMT, is under the control of the steroid cortisol.

  9. Structural characterization and anti-aging activity of a novel extracellular polysaccharide from fungus Phellinus sp. in a mammalian system.

    Science.gov (United States)

    Ma, Xiao-Kui; Guo, Dan Dan; Peterson, Eric Charles; Dun, Ying; Li, Dan Yang

    2016-08-10

    Little is known about the chemical structure of purified extracellular polysaccharides from Phellinus sp., a fungal species with known medicinal properties. A combination of IR spectroscopy, methylation analysis and NMR were performed for the structural analysis of a purified extracellular polysaccharide derived from Phellinus sp. culture, denoted as SHP-1, along with an evaluation of the anti-aging effect in vivo of the polysaccharide supplementation. The structure of SHP-1 was established, with a backbone composed of →2,4)-α-d-glucopyranose-(1→ and →2)-β-d-mannopyranose-(1→ and two terminal glucopyranose branches. Biochemical analysis from mammalian animal experiments demonstrated that SHP-1 possesses the ability to enhance antioxidant enzyme activities, such as catalase (CAT) and superoxide dismutase (SOD) activities, Trolox equivalent antioxidant capacity (TEAC) in serum of d-galactose-aged mice, while reducing lipofuscin levels, another indicator of cell aging, indicating a potential association with anti-aging activities in a dose dependent manner. This compound had a favourable influence on immune organ indices, and a marked amelioration ability of histopathological hepatic lesions such as necrosis, karyolysis and reduced inflammation and apoptosis in mouse hepatocytes. These results suggest that SHP-1 has strong antioxidant activities and a significant protective effect against oxidative stress or hepatotoxicity induced by d-galactose in mice and it could be developed as a food ingredient or a pharmaceutical to prevent many age-associated diseases such as major depressive disorder and hepatotoxicity. To our knowledge, this is the first report on the antioxidant effects of a novel purified exopolysaccharide derived from Phellinus sp.

  10. Reconstruction of the neuromuscular system of the swimming-type larva of Loxosomella atkinsae (Entoprocta) as inferred by fluorescence labelling and confocal microscopy

    DEFF Research Database (Denmark)

    Fuchs, Judith; Wanninger, Andreas Wilhelm Georg

    2008-01-01

    Entoprocta is one of the most enigmatic phyla of the Animal Kingdom. The morphology of their larvae has been little investigated, with details on the larval musculature lacking entirely and immunocytochemical data on the larval nervous system available for only 2 species. Here, we provide the first...

  11. CLINICAL PHARMACOKINETICS OF NEUROMUSCULAR BLOCKING-DRUGS

    NARCIS (Netherlands)

    AGOSTON, S; VANDENBROM, RHG; WIERDA, JMKH

    1992-01-01

    Neuromuscular blocking agents provide muscle relaxation for a great variety of surgical procedures with light planes of general anaesthesia. Besides having a significant impact in the development of anaesthesia and surgery, these agents continue to play an important role as pharmacological tools in

  12. Neuromuscular transmission: new concepts and agents.

    NARCIS (Netherlands)

    Boer, H.D. de

    2009-01-01

    Sugammadex is the first selective relaxant binding agent which was originally designed to reverse the steroidal NMB drug rocuronium. The results of recent studies demonstrate that sugammadex is effective for reversal of rocuronium and vecuronium-induced neuromuscular block without apparent

  13. 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...

  14. Neuromuscular Effects of Acute Organophosphate Poisoning

    Directory of Open Access Journals (Sweden)

    Taylan Pekoz

    2014-08-01

    Conclusion: There is no evoked potential studies performed in organophosphate poisoning althoung electroneurography repetitive and P300 studies exist in literature. More further studies are needed to evaluate the cardiac and neuromuscular effects of organophosphate poisoning. [Cukurova Med J 2014; 39(4.000: 795-800

  15. Experienced and physiological fatigue in neuromuscular disorders.

    NARCIS (Netherlands)

    Schillings, M.L.; Kalkman, J.S.; Janssen, H.M.; Engelen, B.G.M. van; Bleijenberg, G.; Zwarts, M.J.

    2007-01-01

    OBJECTIVE: Fatigue has been described as a typical symptom of neurological diseases. It might be caused both by changes at the peripheral and at the central level. This study measured the level of experienced fatigue and physiological correlates of fatigue in three genetically defined neuromuscular

  16. Electrodiagnosis of disorders of neuromuscular transmission.

    Science.gov (United States)

    Howard, James F

    2013-02-01

    This article reviews the use of electrodiagnostic testing in disorders of neuromuscular transmission and discusses the differences between various presynaptic and postsynaptic disorders. Attention is paid to quality control issues that influence the sensitivity of repetitive nerve stimulation and single fiber electromyography. Electrodiagnostic testing, when used as an extension of the clinician's history and physical examination, will provide appropriate direction in establishing the diagnosis.

  17. Protein and genome evolution in Mammalian cells for biotechnology applications.

    Science.gov (United States)

    Majors, Brian S; Chiang, Gisela G; Betenbaugh, Michael J

    2009-06-01

    Mutation and selection are the essential steps of evolution. Researchers have long used in vitro mutagenesis, expression, and selection techniques in laboratory bacteria and yeast cultures to evolve proteins with new properties, termed directed evolution. Unfortunately, the nature of mammalian cells makes applying these mutagenesis and whole-organism evolution techniques to mammalian protein expression systems laborious and time consuming. Mammalian evolution systems would be useful to test unique mammalian cell proteins and protein characteristics, such as complex glycosylation. Protein evolution in mammalian cells would allow for generation of novel diagnostic tools and designer polypeptides that can only be tested in a mammalian expression system. Recent advances have shown that mammalian cells of the immune system can be utilized to evolve transgenes during their natural mutagenesis processes, thus creating proteins with unique properties, such as fluorescence. On a more global level, researchers have shown that mutation systems that affect the entire genome of a mammalian cell can give rise to cells with unique phenotypes suitable for commercial processes. This review examines the advances in mammalian cell and protein evolution and the application of this work toward advances in commercial mammalian cell biotechnology.

  18. Interpretation of electroneuromyographic studies in diseases of neuromuscular junction and myopathies

    Directory of Open Access Journals (Sweden)

    Mansukhani Khushnuma

    2008-01-01

    Full Text Available Electroneuromyography (ENMG also called electrodiagnosis or at times simply (and erroneously electromyography (EMG, has been used for the diagnosis of neuromuscular and muscle diseases. It consists of tests done serially and assessed collectively, to arrive at a diagnosis of neuromuscular weakness. The test should be treated as an extension of the clinical examination and not a replacement. When done adequately ENMG is the only test which gives information about the function of the peripheral nervous system and hence co-relates well with the clinical signs. This article reviews the role of ENMG in the evaluation of neuromuscular and muscle disease. We hope this will meet the requirements of both practicing neurologists and dedicated electromyographers.

  19. Neuromuscular contributions to the age-related reduction in muscle power: Mechanisms and potential role of high velocity power training.

    Science.gov (United States)

    McKinnon, Neal B; Connelly, Denise M; Rice, Charles L; Hunter, Susan W; Doherty, Timothy J

    2017-05-01

    Although much of the literature on neuromuscular changes with aging has focused on loss of muscle mass and isometric strength, deficits in muscle power are more pronounced with aging and may be a more sensitive measure of neuromuscular degeneration. This review aims to identify the adaptations to the neuromuscular system with aging, with specific emphasis on changes that result in decreased muscle power. We discuss how these changes in neuromuscular performance can affect mobility, and ultimately contribute to an increased risk for falls in older adults. Finally, we evaluate the literature regarding high-velocity muscle power training (PT), and its potential advantages over conventional strength training for improving functional performance and mitigating fall risk in older adults. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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    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

  1. A rapid Flp-In system for expression of secreted H5N1 influenza hemagglutinin vaccine immunogen in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Hanxin Lu

    Full Text Available BACKGROUND: Continuing transmissions of highly pathogenic H5N1 viruses in poultry and humans underscores the need for a rapid response to potential pandemic in the form of vaccine. Recombinant technologies for production of immunogenic hemagglutinin (HA could provide an advantage over the traditional inactivated vaccine manufacturing process. Generation of stably transfected mammalian cells secreting properly folded HA proteins is important for scalable controlled manufacturing. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a Flp-In based 293 stable cell lines through targeted site-specific recombination for expression of secreted hemagglutinin (HA proteins and evaluated their immunogenicity. H5N1 globular domain HA1(1-330 and HA0(1-500 proteins were purified from the supernatants of 293 Flp-In stable cell lines. Both proteins were properly folded as confirmed by binding to H5N1-neutralizing conformation-dependent human monoclonal antibodies. The HA0 (with unmodified cleavage site was monomeric, while the HA1 contained oligomeric forms. Upon rabbit immunization, both HA proteins elicited neutralizing antibodies against the homologous virus (A/Vietnam/1203/2004, clade 1 as well as cross-neutralizing antibodies against heterologous H5N1 clade 2 strains, including A/Indonesia/5/2005. These results exceeded the human antibody responses against the inactivated sub-virion H5N1 vaccine. CONCLUSIONS/SIGNIFICANCE: Our data suggest that the 293 Flp-In system could serve as a platform for rapid expression of HA immunogens in mammalian cells from emerging influenza strains.

  2. Clinical applications of immunoglobulin in neuromuscular diseases: focus on inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Paulo Victor Sgobbi de Souza

    2014-12-01

    Full Text Available During recent years, an increasing number of neuromuscular diseases have been recognized either to be caused primarily by autoimmune mechanisms, or to have important autoimmune components. The involved pathophysiological mechanisms and clinical manifestations have been better recognized and many of these disorders are potentially treatable by immunosuppression or by immunomodulation with intravenous immunoglobulin (IVIg. IVIg has been tried in a variety of immune-mediated neurological diseases, being target of widespread use in central and peripheral nervous systems diseases. Objective To give an overview of the main topics regarding the mechanism of action and different therapeutic uses of IVIg in neurological practice, mainly in neuromuscular diseases.

  3. Neuromuscular study of early branching Diuronotus aspetos (Paucitubulatina) yields insights into the evolution of organs systems in Gastrotricha

    DEFF Research Database (Denmark)

    Bekkouche, Nicolas Tarik; Worsaae, Katrine

    2016-01-01

    within Muselliferidae, and find this family to be the sister group to Xenotrichulidae. The muscular system, revealed by F-actin staining, shows a simple, but unique organization of the trunk musculature with a reduction to three pairs of longitudinal muscles and addition of up to five pairs of dorso...... by immunohistochemistry, shows the general pattern of Gastrotricha having a bilobed brain and a pair of ventro-longitudinal nerve cords. However, in addition are found an anterior nerve ring, several anterior longitudinal nerves, and four ventral commissures (pharyngeal, trunk, pre-anal, and terminal). Two pairs...... of protonephridia are documented, while other Paucitubulatina have one. Moreover, the precise arrangement of multiciliated cells is unraveled, yielding a pattern of possibly systematic importance. CONCLUSION: Several neural structures of Diuronotus resemble those found in Xenotrichula (Xenotrichulidae) and may...

  4. Immunocytochemistry of the Neuromuscular Systems of Loxosomella vivipara and L. parguerensis (Entoprocta: Loxosomatidae)

    DEFF Research Database (Denmark)

    Fuchs, Judith; Bright, Monika; Funch, Peter

    2006-01-01

    Little detailed information exists on the anatomy of the nervous system and the musculature of Entoprocta. Herein we describe the distribution of the neurotransmitters RFamide and serotonin as well as the myo-anatomy of adults and asexually produced budding stages of the solitary entoproct species...... of oral nerves that innervate two pairs of nerve cell clusters in the heel of the foot, a pair of aboral nerves, the paired lateral nerves, the calyx nerves, the atrial ring nerve, the tentacle nerves, the stomach nerves, and the rectal nerves. Serotonin is only found in the cerebral ganglion, the oral....... We found several circular muscles in the calyx. The stalk and parts of the foot and the calyx are surrounded by a fine outer layer of ring muscles. In addition to the congruent details regarding the myo-anatomy of both species, species-specific muscle structures could be revealed. The comparison...

  5. Neuromuscular blockade in children Bloqueadores neuromusculares em crianças

    Directory of Open Access Journals (Sweden)

    João Fernando Lourenço de Almeida

    2000-06-01

    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.Os bloqueadores neuromusculares têm sido amplamente utilizados para controlar pacientes que necessitem imobilidade para algum tipo de intervenção médica, desde a realização de procedimentos invasivos até a obtenção de sincronismo com a ventilação mecânica. O objetivo básico desta monografia é revisar a farmacologia dos principais bloqueadores neuromusculares, analisar as diferenças existentes na junção neuromuscular de neonatos, lactentes, pré-escolares e adultos, além de discutir suas indicações em pacientes criticamente enfermos internados em unidade de terapia intensiva pediátrica. Revisão computadorizada da literatura (Medline 1990-2000 associado a busca ativa de artigos compuseram o mecanismo de busca dos dados desta revisão.

  6. Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease.

    Science.gov (United States)

    Sardone, Valentina; Zhou, Haiyan; Muntoni, Francesco; Ferlini, Alessandra; Falzarano, Maria Sofia

    2017-04-05

    Neuromuscular disorders such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy are neurodegenerative genetic diseases characterized primarily by muscle weakness and wasting. Until recently there were no effective therapies for these conditions, but antisense oligonucleotides, a new class of synthetic single stranded molecules of nucleic acids, have demonstrated promising experimental results and are at different stages of regulatory approval. The antisense oligonucleotides can modulate the protein expression via targeting hnRNAs or mRNAs and inducing interference with splicing, mRNA degradation, or arrest of translation, finally, resulting in rescue or reduction of the target protein expression. Different classes of antisense oligonucleotides are being tested in several clinical trials, and limitations of their clinical efficacy and toxicity have been reported for some of these compounds, while more encouraging results have supported the development of others. New generation antisense oligonucleotides are also being tested in preclinical models together with specific delivery systems that could allow some of the limitations of current antisense oligonucleotides to be overcome, to improve the cell penetration, to achieve more robust target engagement, and hopefully also be associated with acceptable toxicity. This review article describes the chemical properties and molecular mechanisms of action of the antisense oligonucleotides and the therapeutic implications these compounds have in neuromuscular diseases. Current strategies and carrier systems available for the oligonucleotides delivery will be also described to provide an overview on the past, present and future of these appealing molecules.

  7. Neuromuscular disorders in zebrafish: state of the art and future perspectives.

    Science.gov (United States)

    Pappalardo, Andrea; Pitto, Letizia; Fiorillo, Chiara; Alice Donati, M; Bruno, Claudio; Santorelli, Filippo M

    2013-06-01

    Neuromuscular disorders are a broad group of inherited conditions affecting the structure and function of the motor system with polymorphic clinical presentation and disease severity. Although individually rare, collectively neuromuscular diseases have an incidence of 1 in 3,000 and represent a significant cause of disability of the motor system. The past decade has witnessed the identification of a large number of human genes causing muscular disorders, yet the underlying pathogenetic mechanisms remain largely unclear, limiting the developing of targeted therapeutic strategies. To overcome this barrier, model systems that replicate the different steps of human disorders are increasingly being developed. Among these, the zebrafish (Danio rerio) has emerged as an excellent organism for studying genetic disorders of the central and peripheral motor systems. In this review, we will encounter most of the available zebrafish models for childhood neuromuscular disorders, providing a brief overview of results and the techniques, mainly transgenesis and chemical biology, used for genetic manipulation. The amount of data collected in the past few years will lead zebrafish to became a common functional tool for assessing rapidly drug efficacy and off-target effects in neuromuscular diseases and, furthermore, to shed light on new etiologies emerging from large-scale massive sequencing studies.

  8. 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...... would provide a better surgical workspace. METHODS: This was an investigator-initiated, assessor- and patient-blinded randomised cross-over study. A total of 34 patients with planned laparoscopic umbilical, incisional and linea alba herniotomy were studied. Patients would be randomised to receive deep......'s rating of surgical conditions during suturing, duration of surgery and duration of the suturing of the hernia. CONCLUSION: This randomised cross-over study investigated a potential effect on the surgical workspace in laparoscopic ventral herniotomy using deep NMB compared with no NMB. The study may...

  9. Neuromuscular monitoring: old issues, new controversies.

    Science.gov (United States)

    Kopman, Aaron F

    2009-03-01

    "Expert" editorial opinion suggests that objective or quantitative neuromuscular monitors should be used whenever nondepolarizing blocking agents are administered. It is clear that this advice has by and large fallen on deaf ears. A sizeable number of clinicians here (North America) and abroad (Europe) fail to use even conventional peripheral nerve stimulators routinely. This chapter will explore potential reasons for and consequences of this disconnect between academia and "the real world." Along the way, we will examine such questions as how do we define and measure adequate recovery from nondepolarizing block. What are the limitations of clinical tests of recovery such as the "head-lift test?" What is the incidence of undetected postoperative residual curarization (PORC)? Does neuromuscular monitoring reduce the frequency of PORC? How will the availability of sugammadex alter the above discussion?

  10. Neuromuscular electrical stimulation for skeletal muscle function.

    Science.gov (United States)

    Doucet, Barbara M; Lam, Amy; Griffin, Lisa

    2012-06-01

    Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle.

  11. Autoregulation of Neuromuscular Transmission by Nerve Terminals.

    Science.gov (United States)

    1985-09-01

    strengthen muscular FC because of the so- called "margin of safety." However, select prejunctional cholinoceptor antagonism may have the potential...receptor. Br. J. Anaesth. 54: 115- 130, 1982. 17. Peper , K., Bradley, R.J. and Dreyer, F. The acetylcholine 28 receptor at the neuromuscular junction...and Peper , K., Prejunctional effects of anticholinesterase drugs at the endplate mediated by presynaptic acetylcholine receptors or by postsynaptic

  12. Application of three-dimensional culture systems to study mammalian spermatogenesis, with an emphasis on the rhesus monkey (Macaca mulatta).

    Science.gov (United States)

    Huleihel, Mahmoud; Nourashrafeddin, Seyedmehdi; Plant, Tony M

    2015-01-01

    In vitro culture of spermatogonial stem cells (SSCs) has generally been performed using two-dimensional (2D) culture systems; however, such cultures have not led to the development of complete spermatogenesis. It seems that 2D systems do not replicate optimal conditions of the seminiferous tubules (including those generated by the SSC niche) and necessary for spermatogenesis. Recently, one of our laboratories has been able to induce proliferation and differentiation of mouse testicular germ cells to meiotic and postmeiotic stages including generation of sperm in a 3D soft agar culture system (SACS) and a 3D methylcellulose culture system (MCS). It was suggested that SACS and MCS form a special 3D microenvironment that mimics germ cell niche formation in the seminiferous tubules, and thus permits mouse spermatogenesis in vitro. In this review, we (1) provide a brief overview of the differences in spermatogenesis in rodents and primates, (2) summarize data related to attempts to generate sperm in vitro, (3) report for the first time formation of colonies/clusters of cells and differentiation of meiotic (expression of CREM-1) and postmeiotic (expression of acrosin) germ cells from undifferentiated spermatogonia isolated from the testis of prepubertal rhesus monkeys and cultured in SACS and MCS, and (4) indicate research needed to optimize 3D systems for in vitro primate spermatogenesis and for possible future application to man.

  13. Stathmin is required for stability of the Drosophila neuromuscular junction.

    Science.gov (United States)

    Graf, Ethan R; Heerssen, Heather M; Wright, Christina M; Davis, Graeme W; DiAntonio, Aaron

    2011-10-19

    Synaptic connections can be stably maintained for prolonged periods, yet can be rapidly disassembled during the developmental refinement of neural circuitry and following cytological insults that lead to neurodegeneration. To date, the molecular mechanisms that determine whether a synapse will persist versus being remodeled or eliminated remain poorly understood. Mutations in Drosophila stathmin were isolated in two independent genetic screens that sought mutations leading to impaired synapse stability at the Drosophila neuromuscular junction (NMJ). Here we demonstrate that Stathmin, a protein that associates with microtubules and can function as a point of signaling integration, is necessary to maintain the stability of the Drosophila NMJ. We show that Stathmin protein is widely distributed within motoneurons and that loss of Stathmin causes impaired NMJ growth and stability. In addition, we show that stathmin mutants display evidence of defective axonal transport, a common feature associated with neuronal degeneration and altered synapse stability. The disassembly of the NMJ in stathmin includes a predictable sequence of cytological events, suggesting that a common program of synapse disassembly is induced following the loss of Stathmin protein. These data define a required function for Stathmin during synapse maintenance in a model system in which there is only a single stathmin gene, enabling future genetic investigation of Stathmin function with potential relevance to the cause and progression of neuromuscular degenerative disease.

  14. Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells.

    Science.gov (United States)

    Flaherty, Rebecca A; Lee, Shaun W

    2016-08-19

    Many bacterial pathogens secrete potent toxins to aid in the destruction of host tissue, to initiate signaling changes in host cells or to manipulate immune system responses during the course of infection. Though methods have been developed to successfully purify and produce many of these important virulence factors, there are still many bacterial toxins whose unique structure or extensive post-translational modifications make them difficult to purify and study in in vitro systems. Furthermore, even when pure toxin can be obtained, there are many challenges associated with studying the specific effects of a toxin under relevant physiological conditions. Most in vitro cell culture models designed to assess the effects of secreted bacterial toxins on host cells involve incubating host cells with a one-time dose of toxin. Such methods poorly approximate what host cells actually experience during an infection, where toxin is continually produced by bacterial cells and allowed to accumulate gradually during the course of infection. This protocol describes the design of a permeable membrane insert-based bacterial infection system to study the effects of Streptolysin S, a potent toxin produced by Group A Streptococcus, on human epithelial keratinocytes. This system more closely mimics the natural physiological environment during an infection than methods where pure toxin or bacterial supernatants are directly applied to host cells. Importantly, this method also eliminates the bias of host responses that are due to direct contact between the bacteria and host cells. This system has been utilized to effectively assess the effects of Streptolysin S (SLS) on host membrane integrity, cellular viability, and cellular signaling responses. This technique can be readily applied to the study of other secreted virulence factors on a variety of mammalian host cell types to investigate the specific role of a secreted bacterial factor during the course of infection.

  15. DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens

    Directory of Open Access Journals (Sweden)

    Dolores L. Guzmán-Herrador

    2017-08-01

    Full Text Available We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human pathogen Bartonella henselae. Moreover, the DNA is delivered covalently attached to the conjugative relaxase TrwC, which promotes its integration into the recipient genome. In this work, we report that this tool can be adapted to other target cells by using different relaxases and secretion systems. The promiscuous relaxase MobA from plasmid RSF1010 can be used to deliver DNA into human cells with higher efficiency than TrwC. MobA also promotes DNA integration, albeit at lower rates than TrwC. Notably, we report that DNA transfer to human cells can also take place through the Type IV secretion system of two intracellular human pathogens, Legionella pneumophila and Coxiella burnetii, which code for a distantly related Dot/Icm Type IV B secretion system. This suggests that DNA transfer could be an intrinsic ability of this family of secretion systems, expanding the range of target human cells. Further analysis of the DNA transfer process showed that recruitment of MobA by Dot/Icm was dependent on the IcmSW chaperone, which may explain the higher DNA transfer rates obtained. Finally, we observed that the presence of MobA negatively affected the intracellular replication of C. burnetii, suggesting an interference with Dot/Icm translocation of virulence factors.

  16. Utilization of a quantitative mammalian cell mutation system, CHO/HGPRT, in experimental mutagenesis and genetic toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Hsie, A. W.; Couch, D. B.; O' Neill, J. P.

    1977-01-01

    Development of the CHO/HGPRT system is described and a host-mediated CHO/HGPRT assay is discussed. The following topics are discussed: evidence for the genetic origin of mutation induction in the CHO/HGPRT system; dose-response relationship for EMS-mediated mutation induction and cell lethality; apparent dosimetry of EMS-induced mutagenesis; structure-activity relationship of alkylating agents and ICR compounds; mutagenicity and cytotoxicity of congeners of two classes of nitrosi compounds; and preliminary validation of the CHO/HGPRT assay in predicting chemical carcinogenicity. (HLW)

  17. Muscle mechanics and neuromuscular control

    NARCIS (Netherlands)

    Hof, AL

    2003-01-01

    The purpose of this paper is to demonstrate that the properties of the mechanical system, especially muscle elasticity and limb mass, to a large degree determine force output and movement. This makes the control demands of the central nervous system simpler and more robust. In human triceps surae, a

  18. The Neuropeptide Systems and their Potential Role in the Treatment of Mammalian Retinal Ischemia: A Developing Story

    OpenAIRE

    Cervia, D; Casini, G.

    2013-01-01

    The multiplicity of peptidergic receptors and of the transduction pathways they activate offers the possibility of important advances in the development of specific drugs for clinical treatment of central nervous system disorders. Among them, retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Ischemia is a primary cause of neuronal death, and it can be considered as a sort of final common pathwa...

  19. Electrochemical monitoring of intracellular enzyme activity of single living mammalian cells by using a double-mediator system

    Energy Technology Data Exchange (ETDEWEB)

    Matsumae, Yoshiharu [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Takahashi, Yasufumi [Advanced Institute for Materials Research, Tohoku University, Katahira 2-1-1, Aoba, Sendai 980-8577 (Japan); Ino, Kosuke [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Shiku, Hitoshi, E-mail: shiku@bioinfo.che.tohoku.ac.jp [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Matsue, Tomokazu, E-mail: matsue@bioinfo.che.tohoku.ac.jp [Graduate School of Environmental Studies, Tohoku University, Aramaki 6-6-11-605, Aoba, Sendai 980-8579 (Japan); Advanced Institute for Materials Research, Tohoku University, Katahira 2-1-1, Aoba, Sendai 980-8577 (Japan)

    2014-09-09

    Graphical abstract: NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells were evaluated by using the menadione–ferrocyanide double mediator system combined with scanning electrochemical microscopy (SECM). - Highlights: • NAD(P)H:quinone oxidoreductase activity of single cells were evaluated with SECM. • Fe(CN){sub 6}{sup 3−}/menadione concentrations were optimized for long-term SECM monitoring. • Menadione affect the intracellular levels of reactive oxygen species and GSH. • At 100 μM menadione, the Fe(CN){sub 6}{sup 3−} generation rate decreased rapidly within 30 min. - Abstract: We evaluated the intracellular NAD(P)H:quinone oxidoreductase (NQO) activity of single HeLa cells by using the menadione–ferrocyanide double-mediator system combined with scanning electrochemical microscopy (SECM). The double-mediator system was used to amplify the current response from the intracellular NQO activity and to reduce menadione-induced cell damage. The electron shuttle between the electrode and menadione was mediated by the ferrocyanide/ferricyanide redox couple. Generation of ferrocyanide was observed immediately after the addition of a lower concentration (10 μM) of menadione. The ferrocyanide generation rate was constant for 120 min. At a higher menadione concentration (100 μM), the ferrocyanide generation rate decreased within 30 min because of the cytotoxic effect of menadione. We also investigated the relationship between intracellular reactive oxygen species or glutathione levels and exposure to different menadione concentrations to determine the optimal condition for SECM with minimal invasiveness. The present study clearly demonstrates that SECM is useful for the analysis of intracellular enzymatic activities in single cells with a double-mediator system.

  20. Two-dimensional gel electrophoresis for controlling and comparing culture supernatants of mammalian cell culture productions systems.

    Science.gov (United States)

    Wimmer, K; Harant, H; Reiter, M; Blüml, G; Gaida, T; Katinger, H

    1994-01-01

    A recombinant Chinese hamster ovary cell line, producing human erythropoietin, was cultivated in a continuous mode in a stirred tank reactor applying different dilution rates. In order to monitor the stability of this expression system, product and non-product proteins of the cell culture supernatant were analyzed by two-dimensional electrophoresis. The consistency of the isoforms of the recombinant product was determined by western blot combined with specific staining. The same cell line was propagated in a high cell density cultivation system based on macro-cell-aggregates. The patterns of secreted proteins of the cell line cultivated in the different systems were compared in order to detect modifications in protein expression of the product and of non product proteins relevant for cell culture supernatant. Hardly any alterations in two-dimensional pattern were detectable. The isoforms of erythropoietin, as well as the overall pattern of secreted proteins, detectable with the two-dimensional electrophoresis method were remarkably stable under different cultivation conditions.

  1. Progressive adaptation in physical activity and neuromuscular performance during 520d confinement.

    Science.gov (United States)

    Belavý, Daniel L; Gast, Ulf; Daumer, Martin; Fomina, Elena; Rawer, Rainer; Schießl, Hans; Schneider, Stefan; Schubert, Harald; Soaz, Cristina; Felsenberg, Dieter

    2013-01-01

    To understand whether prolonged confinement results in reductions in physical activity and adaptation in the musculoskeletal system, six subjects were measured during 520 d isolation in the Mars500 study. We tested the hypothesis that physical activity reduces in prolonged confinement and that this would be associated with decrements of neuromuscular performance. Physical activity, as measured by average acceleration of the body's center of mass ("activity temperature") using the actibelt® device, decreased progressively over the course of isolation (p<0.00001). Concurrently, countermovement jump power and single-leg hop force decreased during isolation (p<0.001) whilst grip force did not change (p≥0.14). Similar to other models of inactivity, greater decrements of neuromuscular performance occurred in the lower-limb than in the upper-limb. Subject motivational state increased non-significantly (p = 0.20) during isolation, suggesting reductions in lower-limb neuromuscular performance were unrelated to motivation. Overall, we conclude that prolonged confinement is a form of physical inactivity and is associated with adaptation in the neuromuscular system.

  2. Progressive adaptation in physical activity and neuromuscular performance during 520d confinement.

    Directory of Open Access Journals (Sweden)

    Daniel L Belavý

    Full Text Available To understand whether prolonged confinement results in reductions in physical activity and adaptation in the musculoskeletal system, six subjects were measured during 520 d isolation in the Mars500 study. We tested the hypothesis that physical activity reduces in prolonged confinement and that this would be associated with decrements of neuromuscular performance. Physical activity, as measured by average acceleration of the body's center of mass ("activity temperature" using the actibelt® device, decreased progressively over the course of isolation (p<0.00001. Concurrently, countermovement jump power and single-leg hop force decreased during isolation (p<0.001 whilst grip force did not change (p≥0.14. Similar to other models of inactivity, greater decrements of neuromuscular performance occurred in the lower-limb than in the upper-limb. Subject motivational state increased non-significantly (p = 0.20 during isolation, suggesting reductions in lower-limb neuromuscular performance were unrelated to motivation. Overall, we conclude that prolonged confinement is a form of physical inactivity and is associated with adaptation in the neuromuscular system.

  3. Vladimir Karlovich Roth (1848-1916): the founder of neuromuscular diseases studies in Russia.

    Science.gov (United States)

    Kazakov, Valery M; Rudenko, Dmitry I; Stuchevskaya, Tima R

    2014-05-01

    This article shortly examines the biography, scientific activity and scientific work on neuromuscular diseases of the famous Russian neurologist Vladimir Roth who was the founder of neuromuscular disorders study in Russia. In 1876 he was the first in Russia who performed an autopsy and a detailed histological study of a case of progressive muscular atrophy, in which he did not find changes in the nervous system. He called this disease "muscular tabes" i.e. myopathy. In 1884 Vladimir Roth expressed his opinion about the nosological place of the peripheral type of muscular tabes to be considered as a distal myopathy. Dr. Roth became well-known for his monograph of the neuromuscular diseases, published in Moscow in 1895 under the name "Muscular Tabes" in which he described the history of neuromuscular diseases in a very detailed way, analyzing 1014 cases published in the world literature from 1830 to 1893 and 125 personal observations in the period 1874-1894. He performed a thorough analysis of the pattern of muscle involvement using both electrodiagnostic and histological study of muscles and central/peripheral nervous system. We report a short review of this monograph and two cases of peripheral (distal) myopathy.

  4. 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....

  5. Historical Perspectives: plasticity of mammalian skeletal muscle.

    Science.gov (United States)

    Pette, D

    2001-03-01

    More than 40 years ago, the nerve cross-union experiment of Buller, Eccles, and Eccles provided compelling evidence for the essential role of innervation in determining the properties of mammalian skeletal muscle fibers. Moreover, this experiment revealed that terminally differentiated muscle fibers are not inalterable but are highly versatile entities capable of changing their phenotype from fast to slow or slow to fast. With the use of various experimental models, numerous studies have since confirmed and extended the notion of muscle plasticity. Together, these studies demonstrated that motoneuron-specific impulse patterns, neuromuscular activity, and mechanical loading play important roles in both the maintenance and transition of muscle fiber phenotypes. Depending on the type, intensity, and duration of changes in any of these factors, muscle fibers adjust their phenotype to meet the altered functional demands. Fiber-type transitions resulting from multiple qualitative and quantitative changes in gene expression occur sequentially in a regular order within a spectrum of pure and hybrid fiber types.

  6. Evaluation of the genotoxic potential of the alkaloid boldine in mammalian cell systems in vitro and in vivo.

    Science.gov (United States)

    Tavares, D C; Takahashi, C S

    1994-05-01

    Boldine is an alkaloid present in Peumus boldus (popularly called "boldo-do-chile" in Brazil) which has healing properties and is used for the treatment of gastrointestinal disorders. The possible clastogenic effect of the drug was tested in vitro on human peripheral blood lymphocytes by evaluating the induction of chromosome aberrations and sister-chromatid exchanges (SCEs). Cultures from different individuals were treated with boldine at concentrations of 10, 20 and 40 micrograms/ml of culture medium. The effect of the alkaloid was also tested in an in vivo assay using BALB/c mouse bone marrow cells. Boldine was administered to the animals by gavage at the concentrations of 225, 450 and 900 mg/kg body weight. Under the conditions used, boldine did not induce a statistically significant increase in the frequency of chromosome aberrations or SCEs in either test system.

  7. A spiking neural network model of self-organized pattern recognition in the early mammalian olfactory system

    Directory of Open Access Journals (Sweden)

    Bernhard A. Kaplan

    2014-02-01

    Full Text Available Olfactory sensory information passes through several processing stages before an odor percept emerges. The question how the olfactory system learns to create odor representations linking those different levels and how it learns to connect and discriminate between them is largely unresolved. We present a large-scale network model with single and multi-compartmental Hodgkin-Huxley type model neurons representing olfactory receptor neurons (ORNs in the epithelium, periglomerular cells, mitral/tufted cells and granule cells in the olfactory bulb (OB, and three types of cortical cells in the piriform cortex (PC. Odor patterns are calculated based on affinities between ORNs and odor stimuli derived from physico-chemical descriptors of behaviorally relevant real-world odorants. The properties of ORNs were tuned to show saturated response curves with increasing concentration as seen in experiments. On the level of the OB we explored the possibility to use a fuzzy concentration interval code, which was implemented through dendro-dendritic inhibition leading to winner-take-all like dynamics between mitral/tufted cells belonging to the same glomerulus. The connectivity from mitral/tuftedcells to PC neurons was self-organized from a mutual information measure and by using a competitive Hebbian-Bayesian learning algorithm based on the response patterns of mitral/tufted cells to different odors yielding a distributed feed-forward projection to the PC. The PC was implemented as a modular attractor network with a recurrent connectivity that was likewiseorganized through Hebbian-Bayesian learning. We demonstrate the functionality of the model in a one-sniff-learning and recognition task on a set of 50 odorants. Furthermore, we study its robustness against noise on the receptor level and its ability to perform concentration invariant odor recognition. Moreover, we investigate the pattern completion capabilities of the system and rivalry dynamics for odor mixtures.

  8. A spiking neural network model of self-organized pattern recognition in the early mammalian olfactory system.

    Science.gov (United States)

    Kaplan, Bernhard A; Lansner, Anders

    2014-01-01

    Olfactory sensory information passes through several processing stages before an odor percept emerges. The question how the olfactory system learns to create odor representations linking those different levels and how it learns to connect and discriminate between them is largely unresolved. We present a large-scale network model with single and multi-compartmental Hodgkin-Huxley type model neurons representing olfactory receptor neurons (ORNs) in the epithelium, periglomerular cells, mitral/tufted cells and granule cells in the olfactory bulb (OB), and three types of cortical cells in the piriform cortex (PC). Odor patterns are calculated based on affinities between ORNs and odor stimuli derived from physico-chemical descriptors of behaviorally relevant real-world odorants. The properties of ORNs were tuned to show saturated response curves with increasing concentration as seen in experiments. On the level of the OB we explored the possibility of using a fuzzy concentration interval code, which was implemented through dendro-dendritic inhibition leading to winner-take-all like dynamics between mitral/tufted cells belonging to the same glomerulus. The connectivity from mitral/tufted cells to PC neurons was self-organized from a mutual information measure and by using a competitive Hebbian-Bayesian learning algorithm based on the response patterns of mitral/tufted cells to different odors yielding a distributed feed-forward projection to the PC. The PC was implemented as a modular attractor network with a recurrent connectivity that was likewise organized through Hebbian-Bayesian learning. We demonstrate the functionality of the model in a one-sniff-learning and recognition task on a set of 50 odorants. Furthermore, we study its robustness against noise on the receptor level and its ability to perform concentration invariant odor recognition. Moreover, we investigate the pattern completion capabilities of the system and rivalry dynamics for odor mixtures.

  9. Two Novel 30K Proteins Overexpressed in Baculovirus System and Their Antiapoptotic Effect in Insect and Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Wei Yu

    2013-01-01

    Full Text Available The 30K family of proteins is important in energy metabolism and may play a role in inhibiting cellular apoptosis in silkworms (Bombyx mori. Several 30K-family proteins have been identified. In this study, two new silkworm genes, referred to as Slp (NM 001126256 and Lsp-t (NM 001043443, were analyzed by a bioinformatics approach according to the sequences of 30K proteins previously reported in the silkworm. Both Slp and Lsp-t shared more than 41% amino acid sequence homology with the reported 30K proteins and displayed a conserved domain consistent with that of lipoprotein-11. Additionally, the cDNA sequences of both Slp and Lsp-t were obtained from the fat bodies of silkworm larvae by reverse transcription polymerase chain reaction. Both genes were expressed in BmN cells using the Bac-to-Bac system. Purified Slp and Lsp-t were added to cultured BmN and human umbilical vein endothelial cells (HUVEC that were treated with H2O2. Both Slp and Lsp-t significantly enhanced the viability and suppressed DNA fragmentation in H2O2 treated BmN and HUVEC cells. This study suggested that Slp and Lsp-t exhibit similar biological activities as their known 30K-protein counterparts and mediate an inhibitory effect against H2O2-induced apoptosis.

  10. Molecular mechanism of mutagenesis induced by olaquindox using a shuttle vector pSP189/mammalian cell system

    Energy Technology Data Exchange (ETDEWEB)

    Hao Lihua [Division of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100094 (China); Chen Qian [Division of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100094 (China); Xiao Xilong [Division of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100094 (China)]. E-mail: xiaoxl@cau.edu.cn

    2006-07-25

    Olaquindox, a quinoxaline 1,4-dioxide derivative from quindoxin, is widely used as an animal growth promoter in China. We tested olaquindox as a mutagen in a SV40-based shuttle vector pSP189 and African green kidney cell (Vero E6 cell line) system to define the safety of olaquindox as a food-additive for animals. When applied at 6.6 {mu}g/ml, olaquindox caused 12 times higher mutation frequency in comparison to untreated controls. More than 70% of base substitutions happened at G:C base pairs featuring G:C to T:A or G:C to A:T conversions. Frequency of point mutations for in vitro modified plasmids was also dramatically increased from the spontaneous background level. Olaquindox-induced mutations did not occur randomly along the supF shuttle vector, but instead, had a hot spot at base pair no. 155 which accounts for 37% of total mutations. Olaquindox-induced mutations also showed sequence-specificity in which most point mutations occurred at site N in a 5'-NNTTNN-3' sequence while most tandem bases deletion and rearrangement were seen at the 5'-ANGGCCNAAA-3' sequence. We conclude that olaquindox induces DNA mutation, therefore, should not be used as an additive to promote animal growth.

  11. Wnt signalling pathway parameters for mammalian cells.

    Directory of Open Access Journals (Sweden)

    Chin Wee Tan

    Full Text Available Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins β-catenin, Axin, APC, GSK3β and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian cells. There are significant differences in concentrations of key proteins between Xenopus extracts and mammalian whole cell lysates. Higher concentrations of Axin and lower concentrations of APC are present in mammalian cells. Axin concentrations are greater than APC in kidney epithelial cells, whereas in intestinal epithelial cells the APC concentration is higher than Axin. Computational simulations based on Lee's model, with this new data, suggest a need for a recalibration of the model.A quantitative understanding of Wnt signalling in mammalian cells, in particular human colorectal cancers requires a detailed understanding of the concentrations of key protein complexes over time. Simulations of Wnt signalling in mammalian cells can be initiated

  12. Design of low-cost general purpose microcontroller based neuromuscular stimulator.

    Science.gov (United States)

    Koçer, S; Rahmi Canal, M; Güler, I

    2000-04-01

    In this study, a general purpose, low-cost, programmable, portable and high performance stimulator is designed and implemented. For this purpose, a microcontroller is used in the design of the stimulator. The duty cycle and amplitude of the designed system can be controlled using a keyboard. The performance test of the system has shown that the results are reliable. The overall system can be used as the neuromuscular stimulator under safe conditions.

  13. Ultrastructural comparison of the Drosophila larval and adult ventral abdominal neuromuscular junction.

    Science.gov (United States)

    Wagner, Nicole

    2017-07-01

    Drosophila melanogaster has recently emerged as model system for studying synaptic transmission and plasticity during adulthood, aging and neurodegeneration. However, still little is known about the basic neuronal mechanisms of synaptic function in the adult fly. Per se, adult Drosophila neuromuscular junctions should be highly suited for studying these aspects as they allow for genetic manipulations in combination with ultrastructural and electrophysiological analyses. Although different neuromuscular junctions of the adult fly have been described during the last years, a direct ultrastructural comparison with their larval counterpart is lacking. The present study was designed to close this gap by providing a detailed ultrastructural comparison of the larval and the adult neuromuscular junction of the ventrolongitudinal muscle. Assessment of several parameters revealed similarities but also major differences in the ultrastructural organisation of the two model neuromuscular junctions. While basic morphological parameters are retained from the larval into the adult stage, the analysis discovered major differences of potential functional relevance in the adult: The electron-dense membrane apposition of the presynaptic and postsynaptic membrane is shorter, the subsynaptic reticulum is less elaborated and the number of synaptic vesicles at a certain distance of the presynaptic membrane is higher. © 2017 Wiley Periodicals, Inc.

  14. 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

  15. Feedback control of arm movements using Neuro-Muscular Electrical Stimulation (NMES) combined with a lockable, passive exoskeleton for gravity compensation

    OpenAIRE

    Christian eKlauer; Thomas eSchauer; Werner eReichenfelser; Jakob eKarner; Sven eZwicker; Marta eGandolla; Emilia eAmbrosini; Simona eFerrante; Marco eHack; Andreas eJedlitschka; Alexander eDuschau-Wicke; Margit eGfoehler; Alessandra ePedrocchi

    2014-01-01

    Within the European project MUNDUS, an assistive framework was developed for the support of arm and hand functions during daily life activities in severely impaired people. Potential users of this system are patients with high-level spinal cord injury and neurodegenerative neuromuscular diseases, such as amyotrophic lateral sclerosis, Friedreich ataxia, and multiple sclerosis. This contribution aims at designing a feedback control system for Neuro-Muscular Electrical Stimulation (NMES) to ena...

  16. 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.

  17. 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...

  18. [Transition experience of patients with neuromuscular disease].

    Science.gov (United States)

    Greif, Valeria; Ugo, Florencia; de Castro Pérez, M Fernanda; Mozzoni, Julieta; Aguerre, Verónica; Saldías, Milagros; Monges, M Soledad

    2017-02-01

    Neuromuscular diseases are mostly genetic disorders, with chronic and progressive course. Affected people are at high risk of developing physical and emotional disabilities. In the last decades, the advance in technology and science has increased chronic pediatric patients survival rate, thus requiring an ongoing assistance in adult hospitals, making the transition a necessity and a challenge. This article reports the clinical practice designed between Hospital Garrahan and Hospital Ramos Mejía for the transition of 27 adolescents during 2015, setting achievements, findings and challenges resulting from this experience.

  19. Autofluorescence of viable cultured mammalian cells.

    Science.gov (United States)

    Aubin, J E

    1979-01-01

    The autofluorescence other than intrinsic protein emission of viable cultured mammalian cells has been investigated. The fluorescence was found to originate in discrete cytoplasmic vesicle-like regions and to be absent from the nucleus. Excitation and emission spectra of viable cells revealed at least two distinct fluorescent species. Comparison of cell spectra with spectra of known cellular metabolites suggested that most, if not all, of the fluorescence arises from intracellular nicotinamide adenine dinucleotide (NADH) and riboflavin and flavin coenzymes. Various changes in culture conditions did not affect the observed autofluorescence intensity. A multiparameter flow system (MACCS) was used to compare the fluorescence intensities of numerous cultured mammalian cells.

  20. Motoneuron and sensory neuron plasticity to varying neuromuscular activity levels

    Science.gov (United States)

    Ishihara, Akihiko; Roy, Roland R.; Ohira, Yoshinobu; Edgerton, V. Reggie

    2002-01-01

    The size and phenotypic properties of the neural and muscular elements of the neuromuscular unit are matched under normal conditions. When subjected to chronic decreases or increases in neuromuscular activity, however, the adaptations in these properties are much more limited in the neural compared with the muscular elements.

  1. Archetype, adaptation and the mammalian heart.

    Science.gov (United States)

    Meijler, F L; Meijler, T D

    2011-03-01

    Forty years ago, we started our quest for 'The Holy Grail' of understanding ventricular rate control and rhythm in atrial fibrillation (AF). We therefore studied the morphology and function of a wide range of mammalian hearts. From mouse to whale, we found that all hearts show similar structural and functional characteristics. This suggests that the mammalian heart remained well conserved during evolution and in this aspect it differs from other organs and parts of the mammalian body. The archetype of the mammalian heart was apparently so successful that adaptation by natural selection (evolution) caused by varying habitat demands, as occurred in other organs and many other aspects of mammalian anatomy, bypassed the heart. The structure and function of the heart of placental mammals have thus been strikingly conserved throughout evolution. The changes in the mammalian heart that did take place were mostly adjustments (scaling), to compensate for variations in body size and shape. A remarkable scaling effect is, for instance, the difference in atrioventricular (AV) conduction time, which is vital for optimal cardiac function in all mammals, small and large. Scaling of AV conduction takes place in the AV node (AVN), but its substrate is unknown. This sheds new light on the vital role of the AVN in health and disease. The AVN is master and servant of the heart at the same time and is of salient importance for our understanding of supraventricular arrhythmias in humans, especially AF. In Information Technology a software infra-structure called 'enterprise service bus' (ESB) may provide understanding of the mammalian heart's conservation during evolution. The ESB is quite unspecific (and thus general) when compared with the specialised components it has to support. For instance, one of the functions of an ESB is the routing of messages between system nodes. This routing is independent and unaware of the content of the messages. The function of the heart is likewise

  2. 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

  3. Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

    Science.gov (United States)

    Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

    2016-06-01

    Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

  4. 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). Neostigmi

  5. 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.)

  6. Cardiorespiratory and neuromuscular responses to motocross riding.

    Science.gov (United States)

    Konttinen, Tomi; Kyröläinen, Heikki; Häkkinen, Keijo

    2008-01-01

    The aim of the present study was to examine physiological and neuromuscular responses during motocross riding at individual maximal speed together with the riding-induced changes in maximal isometric force production. Seven A-level (group A) and 5 hobby-class (group H) motocross-riders performed a 30-minute riding test on a motocross track and maximal muscle strength and oxygen uptake (VO2max) tests in a laboratory. During the riding the mean (+/-SD) VO2 reduced in group A from 86 +/- 10% to 69 +/- 6% of the maximum (P correlated with riding speed (r = 0.70, P sport that causes great physical stress and demands on both skill and physical capacity of the rider. Physical stress occurs as the result of handling of the bike when receiving continuous impacts in the situation requiring both aerobic and anaerobic metabolism. Our data suggest that both maximal capacity and strain during the ride should be measured to analyze the true physiological and neuromuscular demands of motocross ride. For the practice, this study strongly suggests to train not only aerobic and anaerobic capacity but also to use strength and power training for successful motocross riding.

  7. 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.

  8. Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27308070

  9. Autophagy in mammalian cells

    Institute of Scientific and Technical Information of China (English)

    Kadija; Abounit; Tiziano; M; Scarabelli; Roy; B; McCauley

    2012-01-01

    Autophagy is a regulated process for the degradation of cellular components that has been well conserved in eukaryotic cells. The discovery of autophagy-regulating proteins in yeast has been important in understanding this process. Although many parallels exist between fungi and mammals in the regulation and execution of autophagy, there are some important differences. The preautophagosomal structure found in yeast has not been identified in mammals, and it seems that there may be multiple origins for autophagosomes, including endoplasmic reticulum, plasma membrane and mitochondrial outer membrane. The maturation of the phagophore is largely dependent on 5’-AMP activated protein kinase and other factors that lead to the dephosphorylation of mammalian target of rapamycin. Once the process is initiated, the mammalian phagophore elongates and matures into an autophagosome by processes that are similar to those in yeast. Cargo selection is dependent on the ubiquitin conjugation of protein aggregates and organelles and recognition of these conjugates by autophagosomal receptors. Lysosomal degradation of cargo produces metabolites that can be recycled during stress. Autophagy is an impor-tant cellular safeguard during starvation in all eukaryotes; however, it may have more complicated, tissue specific roles in mammals. With certain exceptions, autophagy seems to be cytoprotective, and defects in the process have been associated with human disease.

  10. EFFECT OF NEUROMUSCULAR TRAINING ON BALANCE AMONG UNIVERSITY ATHLETES

    Directory of Open Access Journals (Sweden)

    Mohansundar Sankaravel

    2016-06-01

    Full Text Available Background: Proprioceptive deficiency followed by lateral ankle sprain leads to poor balance is not uncommon. It has been linked with increased injury risk among young athletes. Introducing neuromuscular training programs for this have been believed as one of the means of injury prevention. Hence, this study was aimed to determine the effects of six weeks progressive neuromuscular training (PNM Training on static balance gains among the young athletes with a previous history of ankle sprains. Methods: This study was an experimental study design, with pre and post test method to determine the effects of PNM Training on static balance gains. All data were collected at university’s sports rehabilitation lab before and after six weeks of intervention period. There were 20 male and female volunteer young athletes (20.9 ± 0.85 years of age with a previous history of ankle sprain involving various sports were recruited from the University community. All the subjects were participated in a six week PNM Training that included stability, strength and power training. Outcome measures were collected by calculating the errors on balance error scoring system made by the athletes on static balance before and after the six weeks of intervention period. Static balance was tested in firm and foam surfaces and recorded accordingly. Results: The researchers found a significant decrease (2.40 ± 0.82 in total errors among the samples at the post test compared with their pre test (P >0.05. Conclusions: The study demonstrates that a PNM Training can improve the static balance on both the firm and foam surfaces among the young athletes with a previous history of ankle sprains.

  11. 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

  12. Electrical stimulation for testing neuromuscular function: from sport to pathology.

    Science.gov (United States)

    Millet, Guillaume Y; Martin, Vincent; Martin, Alain; Vergès, Samuel

    2011-10-01

    The use of electrical stimulation (ES) can contribute to our knowledge of how our neuromuscular system can adapt to physical stress or unloading. Although it has been recently challenged, the standard technique used to explore central modifications is the twitch interpolated method which consists in superimposing single twitches or high-frequency doublets on a maximal voluntary contraction (MVC) and to compare the superimposed response to the potentiated response obtained from the relaxed muscle. Alternative methods consist in (1) superimposing a train of stimuli (central activation ratio), (2) comparing the MVC response to the force evoked by a high-frequency tetanus or (3) examining the change in maximal EMG response during voluntary contractions, if this variable is normalized to the maximal M wave, i.e. EMG response to a single stimulus. ES is less used to examine supraspinal factors but it is useful for investigating changes at the spinal level, either by using H reflexes, F waves or cervicomedullary motor-evoked potentials. Peripheral changes can be examined with ES, usually by stimulating the muscle in the relaxed state. Neuromuscular propagation of action potentials on the sarcolemma (M wave, high-frequency fatigue), excitation-contraction coupling (e.g. low-frequency fatigue) and intrinsic force (high-frequency stimulation at supramaximal intensity) can all be used to non-invasively explore muscular function with ES. As for all indirect methods, there are limitations and these are discussed in this review. Finally, (1) ES as a method to measure respiratory muscle function and (2) the comparison between electrical and magnetic stimulation will also be considered.

  13. Genome regulation in mammalian cells.

    Science.gov (United States)

    Puck, T T; Krystosek, A; Chan, D C

    1990-05-01

    A theory is presented proposing that genetic regulation in mammalian cells is at least a two-tiered effect; that one level of regulation involves the transition between gene exposure and sequestration; that normal differentiation requires a different spectrum of genes to be exposed in each separate state of differentiation; that the fiber systems of the cell cytoskeleton and the nuclear matrix together control the degree of gene exposure; that specific phosphorylation of these elements causes them to assume a different organizational network and to impose a different pattern of sequestration and exposure on the elements of the genome; that the varied gene phosphorylation mechanisms in the cell are integrated in this function; that attachment of this network system to specific parts of the chromosomes brings about sequestration or exposure of the genes in their neighborhood in a fashion similar to that observed when microtubule elements attach through the kinetochore to the centromeric DNA; that one function of repetitive sequences is to serve as elements for the final attachment of this fibrous network to the specific chromosomal loci; and that at least an important part of the calcium manifestation as a metabolic trigger of different differentiation states involves its acting as a binding agent to centers of electronegativity, in particular proteins and especially phosphorylated groups, so as to change the conformation of the fiber network that ultimately controls gene exposure in the mammalian cell. It would appear essential to determine what abnormal gene exposures and sequestrations are characteristic of each type of cancer; which agonists, if any, will bring about reverse transformation; and whether these considerations can be used in therapy.

  14. Neuromuscular blockade in cardiac surgery: An update for clinicians

    Directory of Open Access Journals (Sweden)

    Hemmerling Thomas

    2008-01-01

    Full Text Available There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.

  15. Mammalian cytosolic glutathione transferases.

    Science.gov (United States)

    Dourado, Daniel F A R; Fernandes, Pedro Alexandrino; Ramos, Maria João

    2008-08-01

    Glutathione Transferases (GSTs) are crucial enzymes in the cell detoxification process catalyzing the nucleophilic attack of glutathione (GSH) on toxic electrophilic substrates and producing a less dangerous compound. GSTs studies are of great importance since they have been implicated in the development of drug resistance in tumoral cells and are related to human diseases such as Parkinson's, Alzheimer's, atherosclerois, liver cirrhosis, aging and cataract formation. In this review we start by providing an evolutionary perspective of the mammalian cytosolic GSTs known to date. Later on we focus on the more abundant classes alpha, mu and pi and their structure, catalysis, metabolic associated functions, drug resistance relation and inhibition methods. Finally, we introduce the recent insights on the GST class zeta from a metabolic perspective.

  16. Mammalian phospholipase C.

    Science.gov (United States)

    Kadamur, Ganesh; Ross, Elliott M

    2013-01-01

    Phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP(2)) to inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG). DAG and IP(3) each control diverse cellular processes and are also substrates for synthesis of other important signaling molecules. PLC is thus central to many important interlocking regulatory networks. Mammals express six families of PLCs, each with both unique and overlapping controls over expression and subcellular distribution. Each PLC also responds acutely to its own spectrum of activators that includes heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca(2+), and phospholipids. Mammalian PLCs are autoinhibited by a region in the catalytic TIM barrel domain that is the target of much of their acute regulation. In combination, the PLCs act as a signaling nexus that integrates numerous signaling inputs, critically governs PIP(2) levels, and regulates production of important second messengers to determine cell behavior over the millisecond to hour timescale.

  17. Cell-penetrating peptides: From mammalian to plant cells

    OpenAIRE

    Eudes, François; Chugh, Archana

    2008-01-01

    Internalization of cell-penetrating peptides, well described in mammalian cell system, has recently been reported in a range of plant cells by three independent groups. Despite fundamental differences between animal cell and plant cell composition, the CPP uptake pattern between the mammalian system and the plant system is very similar. Tat, Tat-2 pVEC and transportan internalisation is concentration dependent and non saturable, enhanced at low temperature (4°C), and receptor independent. The...

  18. Neuromuscular ultrasound findings in polyneuropathy secondary to disulfiram.

    Science.gov (United States)

    Stone, Sarah L; Cartwright, Michael S; Panea, Oana R; Vann, Ryan C; Magruder, John L; Walker, Francis O

    2014-12-01

    Disulfiram toxicity can cause multiple neurologic problems, including a reversible distal sensorimotor axonal polyneuropathy. Although electrodiagnosis and biopsy results have been described in the diagnosis and management of patients with disulfiram associated polyneuropathy, neuromuscular ultrasound findings have not been reported. The authors present a case of electrodiagnostically confirmed axonal polyneuropathy with relative sural sparing secondary to disulfiram and describe the neuromuscular ultrasound findings in this individual. Ultrasound demonstrated distal enlargement with slight side-to-side asymmetry and normal proximal cross-sectional area in the lower extremity nerves. Neuromuscular ultrasound is another diagnostic modality that may be used to assist in the diagnosis of patients with polyneuropathy secondary to disulfiram.

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

    DEFF Research Database (Denmark)

    Brueckmann, B; Sasaki, N; Grobara, P;

    2015-01-01

    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......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...... neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio

  20. Neuromuscular Exercise Post Partial Medial Meniscectomy

    DEFF Research Database (Denmark)

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

    2015-01-01

    outcomes included additional measures of knee joint load distribution, patient-reported outcomes, maximal knee and hip muscle strength, and physical function measures. RESULTS: 60 out of 62 randomized participants (97%) completed the trial. There were no significant between-group differences in the change......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...... or a control group with no exercise. The exercise program included eight individual sessions with one of seven physiotherapists in private clinics, together with home exercises. Primary outcomes were the peak external knee adduction moment during normal pace walking and during a one-leg sit-to-stand. Secondary...

  1. Visual and tactile assessment of neuromuscular fade.

    Science.gov (United States)

    Brull, S J; Silverman, D G

    1993-08-01

    The accuracy of visual and tactile assessment of the neuromuscular fade in response to train-of-four (TOF) and double-burst stimulation (DBS) were compared to assess their relative utility in the clinical setting. For each of 74 data sets with a mechanographic TOF ratio less than 0.70, an observer (blinded to the presence or degree of fade) performed visual and tactile assessments of fade in response to TOF, DBS3,3, and DBS3,2 stimuli at low current (20 and 30 mA) and high current (50 and 60 mA). For the range of mechanographic TOF ratios between 0.41 and 0.70, visual assessment failed to identify TOF, DBS3,3, and DBS3,2 fade in 46%, 18%, and 14% of cases at high current and in 23%, 5%, and 0% of cases at low current, respectively. Tactile assessments failed to identify fade in 55%, 23%, and 14% of cases at high current and in 23%, 14%, and 14% of cases at low current. Overall, the ability to detect fade was comparable for visual and tactile assessments regardless of the method of neurostimulation (P = NS with paired t-test). However, the degree of overestimation of the fade ratio (i.e., quantitative assessment) tended to be less when using tactile means; the difference achieved significance for TOF at low current and DBS3,3 at both low and high currents. We conclude that the differences between the visual and tactile means of assessment are relatively small compared to the differences among the TOF and DBS patterns of neurostimulation. Both subjective techniques are often inadequate in settings in which assurance of full recovery of neuromuscular function is critical.

  2. Neuromuscular impairment following backpack load carriage.

    Science.gov (United States)

    Blacker, Sam D; Fallowfield, Joanne L; Bilzon, James L J; Willems, Mark E T

    2013-01-01

    Load Carriage using backpacks is an occupational task and can be a recreational pursuit. The aim of this study was to investigate the mechanisms responsible for changes in neuromuscular function of the m. quadriceps femoris following load carriage. The physiological responses of 10 male participants to voluntary and electrically stimulated isometric contractions were measured before and immediately after two hours of treadmill walking at 6.5 km•h(-1) during level walking with no load [LW], and level walking with load carriage (25 kg backpack) [LC]. Maximal voluntary contraction force decreased by 15 ± 11 % following LC (p=0.006), with no change following LW (p=0.292). Voluntary activation decreased after LW and LC (p=0.033) with no difference between conditions (p=0.405). Doublet contraction time decreased after both LW and LC (p=0.002), with no difference between conditions (p=0.232). There were no other changes in electrically invoked doublet parameters in either condition. The 20:50 Hz ratio did not change following LW (p=0.864) but decreased from 0.88 ± 0.04 to 0.84 ± 0.04 after LC (p=0.011) indicating reduced Ca2+ release from the sarcoplasmic reticulum during excitation contraction coupling. In conclusion, two hours of load carriage carrying a 25 kg back pack caused neuromuscular impairment through a decrease in voluntary activation (i.e. central drive) and fatigue or damage to the peripheral muscle, including impairment of the excitation contraction coupling process. This may reduce physical performance and increase the risk of musculoskeletal injury.

  3. Reactive Neuromuscular Training: A Multi-level Approach to Rehabilitation of the Unstable Shoulder.

    Science.gov (United States)

    Guido, John A; Stemm, John

    2007-05-01

    In this clinical commentary, the use of reactive neuromuscular training (RNT) will be discussed as part of an overall functional rehabilitation program in the treatment of the unstable glenohumeral joint. The RNT program is designed to restore the synchrony and synergy of muscle firing patterns about the shoulder, which are required for dynamic joint stability and fine motor control. Reactive neuromuscular training allows the clinician to bridge the gap between the achievement of clinical based goals and a return to athletic competition. The possible effects of RNT on central nervous system (CNS) programming to establish appropriate reflex responses and functional stability at the glenohumeral joint will be explored. The issues reviewed in this article will highlight the need for future research in this area.

  4. 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...

  5. The potential of disease management for neuromuscular hereditary disorders.

    Science.gov (United States)

    Chouinard, Maud-Christine; Gagnon, Cynthia; Laberge, Luc; Tremblay, Carmen; Côté, Charlotte; Leclerc, Nadine; Mathieu, Jean

    2009-01-01

    Neuromuscular hereditary disorders require long-term multidisciplinary rehabilitation management. Although the need for coordinated healthcare management has long been recognized, most neuromuscular disorders are still lacking clinical guidelines about their long-term management and structured evaluation plan with associated services. One of the most prevalent adult-onset neuromuscular disorders, myotonic dystrophy type 1, generally presents several comorbidities and a variable clinical picture, making management a constant challenge. This article presents a healthcare follow-up plan and proposes a nursing case management within a disease management program as an innovative and promising approach. This disease management program and model consists of eight components including population identification processes, evidence-based practice guidelines, collaborative practice, patient self-management education, and process outcomes evaluation (Disease Management Association of America, 2004). It is believed to have the potential to significantly improve healthcare management for neuromuscular hereditary disorders and will prove useful to nurses delivering and organizing services for this population.

  6. 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.

  7. Neuromuscular training for sports injury prevention: a systematic review

    National Research Council Canada - National Science Library

    Hübscher, Markus; Zech, Astrid; Pfeifer, Klaus; Hänsel, Frank; Vogt, Lutz; Banzer, Winfried

    2010-01-01

    The aim of this systematic review was to assess the effectiveness of proprioceptive/neuromuscular training in preventing sports injuries by using the best available evidence from methodologically well...

  8. 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

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

    NARCIS (Netherlands)

    Heerkens, Yvonne; Kuyk-Minis, Marie Antoinette van; Cup, Edith; Engels, Josephine; Engelen, Baziel van; Oostendorp, Rob

    2012-01-01

    To explore consultation reports for patient and employment characteristics and recommendations on employment regarding patients with neuromuscular diseases (NMDs). Eighty percent of the included consultation reports contained information on employment. Less than half the patients with NMD were emplo

  10. Effect of nimodipine and flunarizine on neuromuscular function in mice

    Directory of Open Access Journals (Sweden)

    Swapnil B. Kaikade

    2016-08-01

    Conclusions: Nimodipine has significant dose dependent depressant action on neuromuscular function while flunarizine has no effect on the above mentioned parameter. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1524-1527

  11. The function of neuromuscular compartments in human shoulder muscles

    National Research Council Canada - National Science Library

    Wickham, J B; Brown, J M M

    2012-01-01

    The aim of this study was to use a surface electromyographic (sEMG) technique with a ballistic isotonic shoulder joint adduction movement to determine the function of the neuromuscular compartments (NMCs...

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

    NARCIS (Netherlands)

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

  13. Chemosignals, hormones and mammalian reproduction.

    Science.gov (United States)

    Petrulis, Aras

    2013-05-01

    Many mammalian species use chemosignals to coordinate reproduction by altering the physiology and behavior of both sexes. Chemosignals prime reproductive physiology so that individuals become sexually mature and active at times when mating is most probable and suppress it when it is not. Once in reproductive condition, odors produced and deposited by both males and females are used to find and select individuals for mating. The production, dissemination and appropriate responses to these cues are modulated heavily by organizational and activational effects of gonadal sex steroids and thereby intrinsically link chemical communication to the broader reproductive context. Many compounds have been identified as "pheromones" but very few have met the expectations of that term: a unitary, species-typical substance that is both necessary and sufficient for an experience-independent behavioral or physiological response. In contrast, most responses to chemosignals are dependent or heavily modulated by experience, either in adulthood or during development. Mechanistically, chemosignals are perceived by both main and accessory (vomeronasal) olfactory systems with the importance of each system tied strongly to the nature of the stimulus rather than to the response. In the central nervous system, the vast majority of responses to chemosignals are mediated by cortical and medial amygdala connections with hypothalamic and other forebrain structures. Despite the importance of chemosignals in mammals, many details of chemical communication differ even among closely related species and defy clear categorization. Although generating much research and public interest, strong evidence for the existence of a robust chemical communication among humans is lacking.

  14. The sagital balance in idiopatic and neuromuscular scoliosis

    OpenAIRE

    Borges,Paulo Alvim; Ocampos, Guilherme Pereira; Mancuso Filho,José Antonio; Letaif,Olavo Biraghi; Marcon, Raphael Martus; Cristante, Alexandre Fogaça

    2014-01-01

    OBJECTIVES: To describe and compare the distribution of spinopelvic parameters (SPP) in a Brazilian population with idiopathic scoliosis (IS) and neuromuscular scoliosis (NMS), and evaluate the association between pelvic incidence (PI) and lumbar lordosis (LL). METHOD: Medical records investigation was performed. Sagital balance angles were measured in patients with neuromuscular and idiopathic scoliosis. RESULTS: IS sample means (in degrees): PI 55.55; Sacral Slope (SS) 45.35; Pelvic Tilt (P...

  15. The Mammalian Septin Interactome

    Science.gov (United States)

    Neubauer, Katharina; Zieger, Barbara

    2017-01-01

    Septins are GTP-binding and membrane-interacting proteins with a highly conserved domain structure involved in various cellular processes, including cytoskeleton organization, cytokinesis, and membrane dynamics. To date, 13 different septin genes have been identified in mammals (SEPT1 to SEPT12 and SEPT14), which can be classified into four distinct subgroups based on the sequence homology of their domain structure (SEPT2, SEPT3, SEPT6, and SEPT7 subgroup). The family members of these subgroups have a strong affinity for other septins and form apolar tri-, hexa-, or octameric complexes consisting of multiple septin polypeptides. The first characterized core complex is the hetero-trimer SEPT2-6-7. Within these complexes single septins can be exchanged in a subgroup-specific manner. Hexamers contain SEPT2 and SEPT6 subgroup members and SEPT7 in two copies each whereas the octamers additionally comprise two SEPT9 subgroup septins. The various isoforms seem to determine the function and regulation of the septin complex. Septins self-assemble into higher-order structures, including filaments and rings in orders, which are typical for different cell types. Misregulation of septins leads to human diseases such as neurodegenerative and bleeding disorders. In non-dividing cells such as neuronal tissue and platelets septins have been associated with exocytosis. However, many mechanistic details and roles attributed to septins are poorly understood. We describe here some important mammalian septin interactions with a special focus on the clinically relevant septin interactions. PMID:28224124

  16. Adrenomedullin in mammalian embryogenesis.

    Science.gov (United States)

    Garayoa, Mercedes; Bodegas, Elena; Cuttitta, Frank; Montuenga, Luis M

    2002-04-01

    Here are summarized data supporting that adrenomedullin (AM) is a multifunctional factor involved in the complex regulatory mechanisms of mammalian development. During rodent embryogenesis, AM is first expressed in the heart, followed by a broader but also defined spatio-temporal pattern of expression in vascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs. AM pattern of expression is suggestive of its involvement in the control of embryonic invasion, proliferation, and differentiation processes, probably through autocrine or paracrine modes of action. AM levels in fetoplacental tissues, uterus, maternal and umbilical plasma are highly increased during normal gestation. These findings in addition to other physiological and gene targeting studies support the importance of AM as a vasorelaxant factor implicated in the regulation of maternal vascular adaptation to pregnancy, as well as of fetal and fetoplacental circulations. AM is also present in amniotic fluid and milk, which is suggestive of additional functions in the maturation and immunological protection of the fetus. Altered expression of AM has been found in some gestational pathologies, although it is not yet clear whether this corresponds to causative or compensatory mechanisms. Future studies in regard to the distribution and expression levels of the molecules known to function as AM receptors, together with data on the action of complement factor H (an AM binding protein), may help to better define the roles of AM during embryonic development.

  17. Novel vibration-exercise instrument with dedicated adaptive filtering for electromyographic investigation of neuromuscular activation.

    Science.gov (United States)

    Xu, Lin; Rabotti, Chiara; Mischi, Massimo

    2013-03-01

    Vibration exercise (VE) has been suggested as an effective methodology to improve muscle strength and power performance. Several studies link the effects of vibration training to enhanced neuromuscular demand, typically ascribed to involuntary reflex mechanisms. However, the underlying mechanisms are still unclear, limiting the identification of the most appropriate vibration training protocols. This study concerns the realization of a new vibration exercise system for the upper limbs. Amplitude, frequency, and baseline of the vibrating force, which is generated by an electromechanical actuator, can be adjusted independently. A second order model is employed to identify the relation between the generated force and the input voltage driving the actuator. Our results show a high correlation (0.99) between the second order model fit and the measured data, ensuring accurate control on the supplied force. The level of neuromuscular demand imposed by the system on the targeted muscles can be estimated by electromyography (EMG). However, EMG measurements during VE can be severely affected by motion artifacts. An adaptive least mean square algorithm is proposed to remove motion artifacts from the measured EMG data. Preliminary validation with seven volunteers showed excellent motion artifact removal, enabling reliable evaluation of the neuromuscular activation.

  18. Laminin-database v.2.0: an update on laminins in health and neuromuscular disorders.

    Science.gov (United States)

    Golbert, Daiane C F; Santana-van-Vliet, Eliane; Mundstein, Alex S; Calfo, Vicente; Savino, Wilson; de Vasconcelos, Ana Tereza R

    2014-01-01

    The laminin (LM)-database, hosted at http://www.lm.lncc.br, was published in the NAR database 2011 edition. It was the first database that provided comprehensive information concerning a non-collagenous family of extracellular matrix proteins, the LMs. In its first version, this database contained a large amount of information concerning LMs related to health and disease, with particular emphasis on the haemopoietic system. Users can easily access several tabs for LMs and LM-related molecules, as well as LM nomenclatures and direct links to PubMed. The LM-database version 2.0 integrates data from several publications to achieve a more comprehensive knowledge of LMs in health and disease. The novel features include the addition of two new tabs, 'Neuromuscular Disorders' and 'miRNA--LM Relationship'. More specifically, in this updated version, an expanding set of data has been displayed concerning the role of LMs in neuromuscular and neurodegenerative diseases, as well as the putative involvement of microRNAs. Given the importance of LMs in several biological processes, such as cell adhesion, proliferation, differentiation, migration and cell death, this upgraded version expands for users a panoply of information, regarding complex molecular circuitries that involve LMs in health and disease, including neuromuscular and neurodegenerative disorders.

  19. Safe neuromuscular electrical stimulator designed for the elderly.

    Science.gov (United States)

    Krenn, Matthias; Haller, Michael; Bijak, Manfred; Unger, Ewald; Hofer, Christian; Kern, Helmut; Mayr, Winfried

    2011-03-01

    A stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge-balanced biphasic voltage-controlled stimulation channels. Additionally, the evoked myoelectric signal (M-wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand-alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials.

  20. Neuromuscular disorders in chronic alcohol intoxication

    Directory of Open Access Journals (Sweden)

    A. Yu. Emelyanova

    2015-01-01

    Full Text Available The paper reviews the present-day Russian and foreign literature on neuromuscular disorders in chronic alcohol intoxication. The most common manifestations of alcohol disease include alcoholic polyneuropathy (PNP and alcohol-induced skeletal muscle injury. The clinical polymorphism of alcoholic PNP is discussed. The paper considers a chronic sensory automatic form due to the direct toxic effects of ethanol and its metabolites during long-term alcohol intoxication, as well as acute/subacute sensorimotor neuropathy, the basis for the pathogenesis of which is B group vitamins, predominantly thiamine, deficiency that develops in the presence of drinking bouts concurrent with malnutrition and/or alcohol-related gastrointestinal tract diseases. In addition to nonuse of alcohol and a properly balanced diet, antioxidant therapy with alphalipoic acid and neurotropic B group vitamins is considered to be pathogenetic therapy for neuropathy. The most common and least studied clinicalform of alcohol-induced musculoskeletal injury is chronic alcoholic myopathy (AM, the diagnostic standard for which is morphometricand immunohistochemical examination of a muscle biopsy specimen. The morphological base for this form of myopathy is predominantly type 2 muscle fiber atrophy caused by impaired protein synthesis and a decreased regenerative potential of muscle fiber. The efficacy of antioxidants and leucine-containing amino acid mixtures in the treatment of chronic AM is discussed.

  1. Diagnostic Certified Assay: Neuromuscular and Cardiac Assessments

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    Rea Valaperta

    2013-01-01

    Full Text Available The expansion of the specific trinucleotide sequence, [CTG], is the molecular pathological mechanism responsible for the clinical manifestations of DM1. Many studies have described different molecular genetic techniques to detect DM1, but as yet there is no data on the analytical performances of techniques used so far in this disease. We therefore developed and validated a molecular method, “Myotonic Dystrophy SB kit,” to better characterize our DM1 population. 113 patients were examined: 20 DM1-positive, 11 DM1/DM2-negative, and13 DM1-negative/DM2-positive, who had a previous molecular diagnosis, while 69 were new cases. This assay correctly identified 113/113 patients, and all were confirmed by different homemade assays. Comparative analysis revealed that the sensitivity and the specificity of the new kit were very high (>99%. Same results were obtained using several extraction procedures and different concentrations of DNA. The distribution of pathologic alleles showed a prevalence of the “classical” form, while of the 96 nonexpanded alleles 19 different allelic types were observed. Cardiac and neuromuscular parameters were used to clinically characterize our patients and support the new genetic analysis. Our findings suggest that this assay appears to be a very robust and reliable molecular test, showing high reproducibility and giving an unambiguous interpretation of results.

  2. Sleep polygraphic parameters in neuromuscular diseases

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    Márcia Pradella

    1994-12-01

    Full Text Available In a polysomnography study of 32 neuromuscular patients - 22 with a form of muscular dystrophy, 3 with a form of congenital myopathy, 4 with a form of spinal muscular atrophy, 1 with a recurrent form of polymyositis and 1 with osteogenesis imperfecta syndrome - of which 21 were nonambulatory, we observed sleep related respiratory disturbances represented by: drops in oxygen saturation (SaO2, cardiac arrythmia, sleep disruption, apneas, tachypnea, tachycardia and snoring. Nine out of the cohort of 32 patients presented with significant desaturations periods. These patients presented with an associated restrictive syndrome and thoracic deformities, some with tachypnea and/or SaO2 below 90% during wakefulness. In this group, snoring was observed in those patients with a form of muscular dystrophy while tachypnea was observed in patients who presented the highest desaturations levels. Sleep quantification revealed an increase of stage 1 sleep coupled with a decrease or even total absence of REM sleep. This is, we believe, a likely consequence of episodic desaturations that may accompany sleep hypoventilation which is potentialised during REM sleep stage.

  3. Neuromuscular Fatigue During 200 M Breaststroke

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    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.

  4. Assessment of Motor Units in Neuromuscular Disease.

    Science.gov (United States)

    Henderson, Robert D; McCombe, Pamela A

    2017-01-01

    The motor unit comprises the anterior horn cell, its axon, and the muscle fibers that it innervates. Although the true number of motor units is unknown, the number of motor units appears to vary greatly between different muscles and between different individuals. Assessment of the number and function of motor units is needed in diseases of the anterior horn cell and other motor nerve disorders. Amyotrophic lateral sclerosis is the most important disease of anterior horn cells. The need for an effective biomarker for assessing disease progression and for use in clinical trials in amyotrophic lateral sclerosis has stimulated the study of methods to measure the number of motor units. Since 1970 a number of different methods, including the incremental, F-wave, multipoint, and statistical methods, have been developed but none has achieved widespread applicability. Two methods (MUNIX and the multipoint incremental method) are in current use across multiple centres and are discussed in detail in this review, together with other recently published methods. Imaging with magnetic resonance and ultrasound is increasingly being applied to this area. Motor unit number estimates have also been applied to other neuromuscular diseases such as spinal muscular atrophy, compression neuropathies, and prior poliomyelitis. The need for an objective measure for the assessment of motor units remains tantalizingly close but unfulfilled in 2016.

  5. Epigenetic regulation of the mammalian cell.

    Directory of Open Access Journals (Sweden)

    Keith Baverstock

    Full Text Available BACKGROUND: Understanding how mammalian cells are regulated epigenetically to express phenotype is a priority. The cellular phenotypic transition, induced by ionising radiation, from a normal cell to the genomic instability phenotype, where the ability to replicate the genotype accurately is compromised, illustrates important features of epigenetic regulation. Based on this phenomenon and earlier work we propose a model to describe the mammalian cell as a self assembled open system operating in an environment that includes its genotype, neighbouring cells and beyond. Phenotype is represented by high dimensional attractors, evolutionarily conditioned for stability and robustness and contingent on rules of engagement between gene products encoded in the genetic network. METHODOLOGY/FINDINGS: We describe how this system functions and note the indeterminacy and fluidity of its internal workings which place it in the logical reasoning framework of predicative logic. We find that the hypothesis is supported by evidence from cell and molecular biology. CONCLUSIONS: Epigenetic regulation and memory are fundamentally physical, as opposed to chemical, processes and the transition to genomic instability is an important feature of mammalian cells with probable fundamental relevance to speciation and carcinogenesis. A source of evolutionarily selectable variation, in terms of the rules of engagement between gene products, is seen as more likely to have greater prominence than genetic variation in an evolutionary context. As this epigenetic variation is based on attractor states phenotypic changes are not gradual; a phenotypic transition can involve the changed contribution of several gene products in a single step.

  6. Reaction of long-lived radicals and vitamin C in γ-irradiated mammalian cells and their model system at 295 K. Tunneling reaction in biological system

    Science.gov (United States)

    Matsumoto, Takuro; Miyazaki, Tetsuo; Kosugi, Yoshio; Kumada, Takayuki; Koyama, Sinji; Kodama, Seiji; Watanabe, Masami

    1997-05-01

    When golden hamster embryo (GHE) cells or concentrated albumin solution (0.1 kg dm -3) that is a model system of cells is irradiated with γ-rays at 295 K, organic radicals produced can be observed by ESR. The organic radicals survive at both 295 and 310 K for such a long time as 20 h. The long-lived radicals in GHE cells and the albumin solution react with vitamin C by the rate constants of 0.007 dm 3 mol -1 s -1 and 0.014 dm 3 mol -1 s -1, respectively. The long-lived radicals in human cells cause gene mutation, which is suppressed by addition of vitamin C. The isotope effect on the rate constant ( k) for the reaction of the long-lived radicals and vitamin C has been studied in the albumin solution by use of protonated vitamin C and deuterated vitamin C. The isotope effect ( kH/ kD) was more than 20 ≈ 50 and was interpreted in terms of tunneling reaction.

  7. Hierarchical rule-based monitoring and fuzzy logic control for neuromuscular block.

    Science.gov (United States)

    Shieh, J S; Fan, S Z; Chang, L W; Liu, C C

    2000-01-01

    The important task for anaesthetists is to provide an adequate degree of neuromuscular block during surgical operations, so that it should not be difficult to antagonize at the end of surgery. Therefore, this study examined the application of a simple technique (i.e., fuzzy logic) to an almost ideal muscle relaxant (i.e., rocuronium) at general anaesthesia in order to control the system more easily, efficiently, intelligently and safely during an operation. The characteristics of neuromuscular blockade induced by rocuronium were studied in 10 ASA I or II adult patients anaesthetized with inhalational (i.e., isoflurane) anaesthesia. A Datex Relaxograph was used to monitor neuromuscular block. And, ulnar nerve was stimulated supramaximally with repeated train-of-four via surface electrodes at the wrist. Initially a notebook personal computer was linked to a Datex Relaxograph to monitor electromyogram (EMG) signals which had been pruned by a three-level hierarchical structure of filters in order to design a controller for administering muscle relaxants. Furthermore, a four-level hierarchical fuzzy logic controller using the fuzzy logic and rule of thumb concept has been incorporated into the system. The Student's test was used to compare the variance between the groups. p control of muscle relaxation with a mean T1% error of -0.19 (SD 0.66) % accommodating a range in mean infusion rate (MIR) of 0.21-0.49 mg x kg(-1) x h(-1). When these results were compared with our previous ones using the same hierarchical structure applied to mivacurium, less variation in the T1% error (p controller activity of these two drugs showed no significant difference (p > 0.5). However, the consistent medium coefficient variance (CV) of the MIR of both rocuronium (i.e., 36.13 (SD 9.35) %) and mivacurium (i.e., 34.03 (SD 10.76) %) indicated a good controller activity. The results showed that a hierarchical rule-based monitoring and fuzzy logic control architecture can provide stable control

  8. Neuromuscular Fatigue after Submaximal Intermittent Contractions in Motorcycle Riders.

    Science.gov (United States)

    Torrado, P; Cabib, C; Morales, M; Valls-Sole, J; Marina, M

    2015-11-01

    Highly repetitive submaximal intermittent contractions of the forearm muscles during periods of 30-50 min partially explain why motorcycle races are so demanding for the neuromuscular system. This study investigated the contribution of central and peripheral mechanisms of fatigue on the exerted and contralateral extensor digitorum communis following an intermittent fatigue protocol (IFP) designed for motorcycle riders. 12 riders performed an IFP, which simulates the braking and throttle handle gesture. We examined the time course of recovery of maximal voluntary contraction (MVC), M-wave, motor evoked potential (MEP) to transcranial magnetic stimuli in relaxed and facilitated condition, and the cortical silent period (CSP) at time windows of 1, 3, 5, 10 and 20 min after the IFP. Whereas MVC, M-wave and MEP decreased, CSP lengthened significantly in the fatigued limb after completion of the IFP. Nevertheless, no differences were observed in the contralateral limb. All neurophysiological parameters reverted to baseline values in less than 20 min, while MVC remained lower in the exercised limb. No cross-over effects were observed in the contralateral non-exercised limb. Our results suggest that local factors are those mainly responsible for the incomplete MVC recovery after an intermittent muscle contraction protocol.

  9. Functional neuromuscular stimulation: outcomes in young people with tetraplegia.

    Science.gov (United States)

    Mulcahey, M J; Smith, B T; Betz, R R; Triolo, R J; Peckham, P H

    1994-01-01

    Percutaneous intramuscular functional neuromuscular stimulation (FNS) systems were fitted to the forearms of five adolescents with tetraplegia in an effort to provide active grasp and release. Two assessments designed at Case Western Reserve University to evaluate functional outcomes of FNS in adults were employed. The common object test (COT) was used to assess hand function during five activities of daily living (ADLs): eating, drinking, writing, brushing teeth and applying toothpaste. A usage survey provided information on the frequency of FNS use in environments outside of the laboratory. In addition, interviews were employed using open-ended questions to gain a deeper understanding of the perceptions of FNS in the adolescents' own environments. Based on the COT results, each adolescent was able to perform ADLs with and without FNS. However, FNS allowed unilateral function so that the extremity without FNS was freed to assist in balance or participate in bilateral tasks. Also, FNS reduced the need for multiple devices, providing users with the potential to perform activities in a variety of environments without transporting adaptive equipment. Those who reported using FNS most often obtained hard-bound school books, held pens during classroom and homework assignments, engaged in leisure activities and performed hygiene tasks. FNS was also used as a means to communicate and socialize through hand gestures. Well-known factors that influence the independence of people with tetraplegia also appeared to affect FNS use.

  10. Neuromuscular monitoring and postoperative residual curarisation: a meta-analysis.

    Science.gov (United States)

    Naguib, M; Kopman, A F; Ensor, J E

    2007-03-01

    We conducted a meta-analysis to examine the effect of intraoperative monitoring of neuromuscular function on the incidence of postoperative residual curarisation (PORC). PORC has been considered present when a patient has a train-of-four (TOF) ratio of < 0.7 or < 0.9. We analysed data from 24 trials (3375 patients) that were published between 1979 and 2005. We excluded data on mivacurium from this meta-analysis because only three studies had examined the incidence of PORC associated with its use. Long- and intermediate-acting neuromuscular blocking drugs had been given to 662 and 2713 patients, respectively. Neuromuscular function was monitored in 823 patients (24.4%). A simple peripheral nerve stimulator was used in 543 patients, and an objective monitor was used in 280. The incidence of PORC was found to be significantly lower after the use of intermediate neuromuscular blocking drugs. We could not demonstrate that the use of an intraoperative neuromuscular function monitor decreased the incidence of PORC.

  11. Current Status of Neuromuscular Reversal and Monitoring: Challenges and Opportunities.

    Science.gov (United States)

    Brull, Sorin J; Kopman, Aaron F

    2017-01-01

    Postoperative residual neuromuscular block has been recognized as a potential problem for decades, and it remains so today. Traditional pharmacologic antagonists (anticholinesterases) are ineffective in reversing profound and deep levels of neuromuscular block; at the opposite end of the recovery curve close to full recovery, anticholinesterases may induce paradoxical muscle weakness. The new selective relaxant-binding agent sugammadex can reverse any depth of block from aminosteroid (but not benzylisoquinolinium) relaxants; however, the effective dose to be administered should be chosen based on objective monitoring of the depth of neuromuscular block.To guide appropriate perioperative management, neuromuscular function assessment with a peripheral nerve stimulator is mandatory. Although in many settings, subjective (visual and tactile) evaluation of muscle responses is used, such evaluation has had limited success in preventing the occurrence of residual paralysis. Clinical evaluations of return of muscle strength (head lift and grip strength) or respiratory parameters (tidal volume and vital capacity) are equally insensitive at detecting neuromuscular weakness. Objective measurement (a train-of-four ratio greater than 0.90) is the only method to determine appropriate timing of tracheal extubation and ensure normal muscle function and patient safety.

  12. Fibromatosis: a potential sequela of neuromuscular choristoma.

    Science.gov (United States)

    Hébert-Blouin, Marie-Noëlle; Scheithauer, Bernd W; Amrami, Kimberly K; Durham, Susan R; Spinner, Robert J

    2012-02-01

    Neuromuscular choristoma (NMC) is a rare peripheral nerve lesion in which mature skeletal muscle fibers lie within the nerve and its fascicles. Given limited follow-up, its natural history is poorly understood. The occurrence of aggressive fibromatosis in one of the authors' patients and its occurrence in reported cases suggests an etiological relationship between the 2 lesions. This study attempts to explain the association and its frequency. All cases of NMCs seen in consultation or treated at the Mayo Clinic were identified. Demographic and clinical data were reviewed in cases with coexistent aggressive fibromatosis. Pathology and neuroimaging studies were reexamined. In addition, an extensive literature review was performed to explore the association of NMC with aggressive fibromatosis, with special attention given to pathological and imaging characteristics and the development of aggressive fibromatosis. The authors identified 10 patients with a diagnosis of NMC who were treated at the Mayo Clinic between 1992 and 2010. Four of 5 with adequate follow-up had developed a definite or suspected aggressive fibromatosis. A review of the initial pathological specimens in these cases revealed no evidence of fibromatosis, but all of the lesions exhibited accompanying hypocellular collagenous tissue. On MR images, all cases showed areas of low signal intensity, which significantly differed from muscle, nerve, and NMC components. On available serial MR imaging studies, aggressive fibromatosis seemed to originate in such lower-intensity regions. In the 18 previously reported cases of NMC, 5 patients developed recurrent masses diagnosed as either definite (2 cases) or possible (3 cases) fibromatosis. Review of the published imaging studies in these cases suggests the presence of lower intensity areas similar to those observed in the 10 patients treated at the Mayo Clinic. This study confirms that the development of aggressive fibromatosis in patients with NMC has been

  13. Aneuploidy in mammalian somatic cells in vivo.

    Science.gov (United States)

    Cimino, M C; Tice, R R; Liang, J C

    1986-01-01

    Aneuploidy is an important potential source of human disease and of reproductive failure. Nevertheless, the ability of chemical agents to induce aneuploidy has been investigated only sporadically in intact (whole-animal) mammalian systems. A search of the available literature from the EMCT Aneuploidy File (for years 1970-1983) provided 112 papers that dealt with aneuploidy in mammalian somatic cells in vivo. 59 of these papers did not meet minimal criteria for analysis and were rejected from subsequent review. Of the remaining 53 papers that dealt with aneuploidy induction by chemical agents in mammalian somatic cells in vivo, only 3 (6%) contained data that were considered to be supported conclusively by adequate study designs, execution, and reporting. These 3 papers dealt with 2 chemicals, one of which, mercury, was negative for aneuploidy induction in humans, and the other, pyrimethamine, was positive in an experimental rodent study. The majority of papers (94%) were considered inconclusive for a variety of reasons. The most common reasons for calling a study inconclusive were (a) combining data on hyperploidy with those on hypoploidy and/or polyploidy, (b) an inadequate or unspecified number of animals and/or cells per animal scored per treatment group, and (c) poor data presentation such that animal-to-animal variability could not be assessed. Suggestions for protocol development are made, and the future directions of research into aneuploidy induction are discussed.

  14. 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

  15. Reversal of profound rocuronium neuromuscular blockade by sugammadex in anesthetized rhesus monkeys.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the

  16. Real-world experience with neuromuscular blockade reversal.

    Science.gov (United States)

    Groudine, Scott B; Minkowitz, Harold S; Valentine, Danny L

    2017-11-01

    Neuromuscular blocking agents are used in many surgical procedures and have enabled new surgical advances. The expanded landscape of neuromuscular blockade (NMB) reversal drugs allows for fast and complete NMB reversal and the reduction of postoperative complications from residual block. In the United States, neostigmine/glycopyrrolate and sugammadex are the primary agents for pharmacologic antagonism of neuromuscular blocking agents. Whereas neostigmine and an anticholinergic have been available for decades, sugammadex has only recently become available. We present real-world cases in a variety of surgical procedures and clinical settings in which the use of NMB reversal agents played a significant role in the patients’ clinical outcome. Online access: http://courses.elseviercme.com/nmb/711.

  17. Fibromatosis arising in association with neuromuscular hamartoma of the mandible.

    Science.gov (United States)

    Taher, Leena Yaseen; Saleem, Muhammad; Velagapudi, Suresh; Dababo, Anas

    2013-09-01

    Aggressive fibromatosis is a benign but locally-aggressive tumor, which most often affects the muscles of the shoulder, the pelvic girdle, and the thigh. It usually affects adolescents and young adults. Desmoplastic fibroma, considered the bone counterpart of soft tissue fibromatosis, is a rare tumor that usually affects the metaphyseal or diaphyseal portions of long bones or, less commonly, the jaw. Neuromuscular hamartoma, a rare developmental lesion composed of mature elements of both striated muscle and nerve, is usually diagnosed in infants and children and affects large nerve trunks. Rarely, it can affect the head and neck region. Occasional cases showing an association between aggressive fibromatosis and neuromuscular hamartoma have been reported in the literature. Here we present a unique case of an adult patient with desmoplastic fibroma of the mandible in association with neuromuscular hamartoma.

  18. 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...... with muscle wasting due to neuromuscular conditions, however, a common belief has been that physical activity could accelerate degeneration of the diseased muscle and a careful approach to training has therefore been suggested. In this review, we describe the current knowledge about physical training...

  19. Perceived pain and temporomandibular disorders in neuromuscular diseases.

    Science.gov (United States)

    Fischer, Michael J; Riedlinger, Kathrin; Schoser, Benedikt; Bernateck, Michael

    2009-10-01

    Little is known about pain associated with temporomandibular disorders (TMD) in neuromuscular diseases. Inpatients (N = 134) with neuromuscular disorder diagnoses were given questionnaires to estimate pain localization and intensity. Research Diagnostic Criteria for Temporomandibular Disorders and the Temporomandibular Index (TMI) were utilized to assess TMD. Pain was reported by 116 patients (86%). Legs (52%) and arms (33%) were the most common locations for pain localization, but the highest Pearson correlations (TMI vs. perceived pain) appeared for pain located in the trunk and arms (0.861, P < 0.01). No correlation between TMI and diagnosis group existed except for "acquired myopathy" and "miscellaneous neuromuscular diseases." These results suggest that the degree of TMD does not correlate with pain according to disease, although common mechanisms might be responsible for pain development in specific body regions connected with TMD. Most important, higher levels of TMD are associated with higher levels of perceived pain.

  20. 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 instabil......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....

  1. Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals

    Science.gov (United States)

    KANEKO-ISHINO, Tomoko; ISHINO, Fumitoshi

    2015-01-01

    Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is “mammalian-specific genomic functions”, a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of “mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons”, based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID:26666304

  2. Train-of-four fade during onset of neuromuscular block with nondepolarising neuromuscular blocking agents.

    Science.gov (United States)

    Gibson, F M; Mirakhur, R K

    1989-04-01

    Fade in the train-of-four (TOF) responses during onset of neuromuscular block was studied following administration of atracurium (225 or 450 micrograms/kg), vecuronium (40 or 80 micrograms/kg), pancuronium (60 or 120 micrograms/kg) and tubocurarine (450 micrograms/kg). TOF ratios were measured at approximate heights of T1 (first response in the TOF) of 75, 50 and 25%. Fade in TOF increased as the height of T1 decreased, with maximum fade being observed at T1 of 25%. The greatest difference between relaxants was observed at T1 of 25%, vecuronium showing the least fade and pancuronium, atracurium and tubocurarine showing increasing fade, in that order. The difference between atracurium and tubocurarine or between vecuronium and pancuronium was not significant, but the degree of TOF fade was significantly greater with atracurium and tubocurarine in comparison to vecuronium or pancuronium.

  3. Urgencias en patología neuromuscular Emergencies in neuromuscular pathology

    Directory of Open Access Journals (Sweden)

    T. Ayuso

    2008-01-01

    Full Text Available 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 parálisis flácida aguda; puede ocasionar fallo respiratorio en un tercio de los casos precisando ventilación mecánica. El diagnóstico preciso de este síndrome permitirá iniciar tratamiento inmunomodulador, que ha demostrado que modifica el curso de la enfermedad. Además, la valoración clínica de los pacientes y el conocimiento de sencillos tests neurofisiológicos y de función respiratoria guiarán la decisión de ventilación mecánica evitando la intubación de urgencia. La urgencia más frecuente que ocasiona la MG es la crisis miasténica, definida por el deterioro en la función bulbar con insuficiencia respiratoria aguda y riesgo de parada respiratoria. Ocurre en un 15-20% de pacientes miasténicos y puede desencadenarse por múltiples factores. Además del diagnóstico preciso de la crisis es importante la supresión de los factores desencadenantes y medidas de soporte ventilatorio. Entre las medidas farmacológicas son la plasmaféresis y las inmunoglobulinas intravenosas los instrumentos más útiles en la actualidad; estos tratamientos no sustituyen la vigilancia intensiva y el reconocimiento de los signos inminentes de fallo respiratorio que implican soporte ventilatorio invasivo o no invasivo.Acute muscle weakness (AMW is the predominant symptom of neuromuscular emergencies, especially if it affects the respiratory or oropharyngeal musculature . AMW is a multi-etiological syndrome, with different lesion levels in the motor unit

  4. New techniques in the tissue diagnosis of gastrointestinal neuromuscular diseases

    Institute of Scientific and Technical Information of China (English)

    Charles H Knowles; Joanne E Martin

    2009-01-01

    Gastrointestinal neuromuscular diseases are a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular (including interstitial cell of Cajal) dysfunction. Common to most of these diseases are symptoms of impaired motor activity which manifest as slowed or obstructed transit with or without evidence of transient or persistent radiological visceral dilatation. A variety of histopathological techniques and allied investigations are being increasingly applied to tissue biopsies from such patients. This review outlines some of the more recent advances in this field, particularly in the most contentious area of small bowel disease manifesting as intestinal pseudo-obstruction.

  5. 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.

  6. Prevention and management of limb contractures in neuromuscular diseases.

    Science.gov (United States)

    Skalsky, Andrew J; McDonald, Craig M

    2012-08-01

    Limb contractures are a common impairment in neuromuscular diseases. They contribute to increased disability from decreased motor performance, mobility limitations, reduced functional range of motion, loss of function for activities of daily living, and increased pain. The pathogenesis of contractures is multifactorial. Myopathic conditions are associated with more severe limb contractures compared with neuropathic disorders. Although the evidence supporting the efficacy of multiple interventions to improve range of motion in neuromuscular diseases in a sustained manner is lacking, there are generally accepted principles with regard to splinting, bracing, stretching, and surgery that help minimize the impact or disability from contractures.

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

    OpenAIRE

    A.M. Labrador-Cerrato; P. Ortega Sánchez-Diezma; G. Lanzas Melendo; Gutiérrez-Ortega, C.

    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...

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

    DEFF Research Database (Denmark)

    Rathleff, Michael Skovdal; Samani, Afshin; Olesen, Jens L.

    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)....

  9. [Organization of therapeutic aid to patients with hereditary neuromuscular diseases].

    Science.gov (United States)

    Kalinin, V A; Temin, P A; Arkhipov, B A; Zavadenko, N N

    1989-01-01

    The paper summarizes experience gained for many years by the All-Union Research Methodological Center for Study of Hereditary Neuromuscular Diseases. The specialists of the Center render counselling and therapeutic assistance to patients afflicted with neuromuscular diseases. The counselling and diagnostic services are characterized by the fact that it is based on the activity of a large hospital intended for the treatment of various diseases. The problems which are being solved by the out- and inpatient services of the Center are considered in detail. The advantages of the setting up of the common in- and outpatient complex on the basis of the hospital intended for the treatment of various diseases are described.

  10. 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.

  11. Cellular and molecular characterization of multipolar Map5-expressing cells: a subset of newly generated, stage-specific parenchymal cells in the mammalian central nervous system.

    Science.gov (United States)

    Crociara, Paola; Parolisi, Roberta; Conte, Daniele; Fumagalli, Marta; Bonfanti, Luca

    2013-01-01

    Although extremely interesting in adult neuro-glio-genesis and promising as an endogenous source for repair, parenchymal progenitors remain largely obscure in their identity and physiology, due to a scarce availability of stage-specific markers. What appears difficult is the distinction between real cell populations and various differentiation stages of the same population. Here we focused on a subset of multipolar, polydendrocyte-like cells (mMap5 cells) expressing the microtubule associated protein 5 (Map5), which is known to be present in most neurons. We characterized the morphology, phenotype, regional distribution, proliferative dynamics, and stage-specific marker expression of these cells in the rabbit and mouse CNS, also assessing their existence in other mammalian species. mMap5 cells were never found to co-express the Ng2 antigen. They appear to be a population of glial cells sharing features but also differences with Ng2+progenitor cells. We show that mMap5 cells are newly generated, postmitotic parenchymal elements of the oligodendroglial lineage, thus being a stage-specific population of polydendrocytes. Finally, we report that the number of mMap5 cells, although reduced within the brain of adult/old animals, can increase in neurodegenerative and traumatic conditions.

  12. CRISPR系统与哺乳动物免疫系统的比较及其功能的研究进展%Analogy of CRISPR-Cas systems to mammalian immune systems and research progress in their functions

    Institute of Scientific and Technical Information of China (English)

    刘鸿博; 李浩; 邱少富; 宋宏彬

    2015-01-01

    The immune system of bacteria against phage shares a lot of similarity with that of mammals, especially the adaptive immune system.The elements and components of the bacterial adaptive immune system———clustered regularly interspaced short palindromic repeats ( CRISPR ) and the mammalian adaptive immune system have a lot of parallel mechanisms.We could acquire new understanding about the immune function of CRISPR systems through that analogy.In recent years, researchers have found CRISPR-Cas system can play significant roles in regulating bacterial growth and metabolism.These researches have revealed new functions of CRISPR beyond immunity.The ability of CRISPR to affect gene expression has attracted increasing attention.Further studies are needed to shed light on the complicated functions of CRISPR.%原核生物防御噬菌体入侵的机制与哺乳类免疫防御机制有很多相似之处,尤其是特异性免疫机制,原核生物的特异性免疫系统即成簇规律间隔短回文重复序列( clustered regularly interspaced short palindromic repeats, CRISPR)与哺乳类特异性免疫系统在很多环节体现了相似的规律。通过比较,能够加深对CRISPR的免疫功能的认识。近年发现,除了发挥特异性免疫功能,CRISPR系统还参与了许多细菌生长代谢过程的调控机制,调控基因表达的能力更是受到广泛的关注。 CRISPR系统功能的复杂程度远远超出免疫防御的范畴,值得深入研究。

  13. 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.

  14. Evolutionary dynamics of mammalian karyotypes

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2012-12-01

    Full Text Available This special volume of Cytogenetic and Genome Research (edited by Roscoe Stanyon, University of Florence and Alexander Graphodatsky, Siberian division of the Russian Academy of Sciences is dedicated to the fascinating long search of the forces behind the evolutionary dynamics of mammalian karyotypes, revealed after the hypotonic miracle of the 1950s....

  15. The shape of mammalian phylogeny

    DEFF Research Database (Denmark)

    Purvis, Andy; Fritz, Susanne A; Rodríguez, Jesús

    2011-01-01

    Mammalian phylogeny is far too asymmetric for all contemporaneous lineages to have had equal chances of diversifying. We consider this asymmetry or imbalance from four perspectives. First, we infer a minimal set of 'regime changes'-points at which net diversification rate has changed-identifying ...

  16. Technology of mammalian cell encapsulation

    NARCIS (Netherlands)

    Uludag, H; De Vos, P; Tresco, PA

    2000-01-01

    Entrapment of mammalian cells in physical membranes has been practiced since the early 1950s when it was originally introduced as a basic research tool. The method has since been developed based on the promise of its therapeutic usefulness in tissue transplantation. Encapsulation physically isolates

  17. Optogenetics for gene expression in mammalian cells.

    Science.gov (United States)

    Müller, Konrad; Naumann, Sebastian; Weber, Wilfried; Zurbriggen, Matias D

    2015-02-01

    Molecular switches that are controlled by chemicals have evolved as central research instruments in mammalian cell biology. However, these tools are limited in terms of their spatiotemporal resolution due to freely diffusing inducers. These limitations have recently been addressed by the development of optogenetic, genetically encoded, and light-responsive tools that can be controlled with the unprecedented spatiotemporal precision of light. In this article, we first provide a brief overview of currently available optogenetic tools that have been designed to control diverse cellular processes. Then, we focus on recent developments in light-controlled gene expression technologies and provide the reader with a guideline for choosing the most suitable gene expression system.

  18. Expression of the mammalian renal peptide transporter PEPT2 in the yeast Pichia pastoris and applications of the yeast system for functional analysis.

    Science.gov (United States)

    Döring, F; Michel, T; Rösel, A; Nickolaus, M; Daniel, H

    1998-01-01

    It has recently been identified the PEPT2 cDNA encodes the high affinity proton-coupled peptide transporter in rabbit kidney cortex. PEPT2 represents a 729 amino acid protein with 12 putative transmembrane domains that mediates H+/H3O+ dependent electrogenic transmembrane transport of di- and tripeptides and of selected peptidomimetics. Here the functional expression of PEPT2 in the methylotropic yeast Pichia pastoris is described under the control of a methanol inducible promoter. Western blot analysis of Pichia cell membranes prepared from a recombinant clone identified a protein with an apparent molecular mass of about 85-87 kDa. Peptide uptake into cells expressing PEPT2 was up to 80 times higher than in control cells. Cells of recombinant clones showed a saturable peptide transport activity for the hydrolysis resistant dipeptide 3H-D-Phe-Ala with an app. K0.5 of 0.143 +/- 0.016 mM. Inhibition of 3H-D-Phe-Ala uptake by selected di- and tripeptides and beta-lactam antibiotics revealed the same substrate specificity as obtained in renal membrane vesicles or for PEPT2 when expressed in Xenopus laevis oocytes. A novel fluorescence based assay for assessing transport function based on a coumarin-labeled fluorescent peptide analogue has also been developed. Moreover, using a histidyl auxotrophe strain a PEPT2 expressing cell clone in which transport function can be monitored by a simple yeast growth test was established. In conclusion, this is one of only a few reports on successful functional expression of mammalian membrane transport proteins in yeast. The high expression level will provide a simple means for future studies either on the structure-affinity relationship for substrate interaction with PEPT2 or for selection of mutants generated by random mutagenesis.

  19. Mammalian mismatch repair

    DEFF Research Database (Denmark)

    Pena Diaz, Javier; Jiricny, Josef

    2012-01-01

    A considerable surge of interest in the mismatch repair (MMR) system has been brought about by the discovery of a link between Lynch syndrome, an inherited predisposition to cancer of the colon and other organs, and malfunction of this key DNA metabolic pathway. This review focuses on recent...... advances in our understanding of the molecular mechanisms of canonical MMR, which improves replication fidelity by removing misincorporated nucleotides from the nascent DNA strand. We also discuss the involvement of MMR proteins in two other processes: trinucleotide repeat expansion and antibody maturation...

  20. 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 recep

  1. 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.

  2. Antagonism of non-depolarising neuromuscular block: current practice.

    Science.gov (United States)

    Kopman, A F; Eikermann, M

    2009-03-01

    There is now mounting evidence that even small degrees of postoperative residual neuromuscular block increases the incidence of adverse respiratory events in the Post Anaesthesia Care Unit and may increase longer-term morbidity as well. In the absence of quantitative neuromuscular monitoring, residual block is easily missed. A very strong case can be made for the routine administration of a non-depolarising antagonist unless it can be objectively demonstrated that complete recovery has occurred spontaneously. However, the use of acetylcholinesterase inhibitors is associated with the potential for cardiovascular and respiratory side-effects, so there are cogent reasons for using low doses when the level of neuromuscular block is not intense. As little as 0.015-0.025 mg.kg(-1) of neostigmine is required at a train-of-four count of four with minimal fade, whereas 0.04-0.05 mg.kg(-1) is needed at a train-of-four count of two or three. If only a single twitch or none at all can be evoked, neostigmine should not be expected to promptly reverse neuromuscular block, and antagonism is best delayed till a train-of-four-count of two is achieved.

  3. Neuromuscular Electrical Stimulation for Motor Restoration in Hemiplegia.

    Science.gov (United States)

    Knutson, Jayme S; Fu, Michael J; Sheffler, Lynne R; Chae, John

    2015-11-01

    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.

  4. 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

  5. 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...

  6. Neuromuscular and metabolic characteristics of elite basketball referees.

    Science.gov (United States)

    Bonganha, V; Cavaglieri, C R; Daniel, J F; Mercadante, L A; Montagner, P C; Borin, J P

    2013-06-01

    The dynamics of Basketball refereeing has changed and more recently the championships started to use the participation of three referees, but there is still a lack of information about the physical characteristics and performance of the referees. The aim of this study was to characterize the neuromuscular and metabolic performances and body composition of Brazilian elite basketball referees, with a level of national and international refereeing. Thirty-seven referees participated in the study (international level N.=17 and national level N.=20). We evaluated anthropometric and body composition variables, among them: height, body mass, body mass index (BMI) and body fat (%); metabolic parameters: lactate at rest and post-exercise; and neuromuscular performance: speed, explosive lower limbs strength, flexibility and aerobic capacity. The main results showed a statistically significant difference in age, in which the international referees were older than the national level (41.94±6.71; 37.30±7.23; P=0.036). There were not significant differences between the levels for neuromuscular and metabolic parameters and body composition. Comparing the results with athletes, the referees showed lower neuromuscular and metabolic parameters and the body composition showed higher body fat than basketball players. These data may represent physiological parameters to be considered in the prescription of physical training during the preparation and competition period.

  7. Neuromuscular training for rehabilitation of sports injuries: a systematic review.

    Science.gov (United States)

    Zech, Astrid; Hübscher, Markus; Vogt, Lutz; Banzer, Winfried; Hänsel, Frank; Pfeifer, Klaus

    2009-10-01

    Although proprioceptive and neuromuscular exercises are considered to be part and parcel of rehabilitation programs after sport injuries, there is an uncertainty regarding the effectiveness of corresponding training interventions. The objective of this review was to evaluate the effectiveness of proprioceptive and neuromuscular training (PT/NT) for the treatment of ankle, knee, and shoulder joint injuries. Two independent reviewers performed a literature search in various databases and reference lists of articles. Data of included trials were then extracted, and methodological quality was assessed by using predetermined forms. Fifteen trials met the inclusion criteria. PT/NT was effective at increasing functionality as well as at decreasing the incidence of recurrent injuries and "giving way" episodes after ankle sprains and in conservative treatment of anterior cruciate ligament injuries. However, conflicting results or no efficacy of training were reported for static postural control, joint position sense, neuromuscular control, joint laxity, and lower extremity strength. No study that examined PT/NT after shoulder injuries was found. From this review, it can be concluded that proprioceptive and neuromuscular interventions after ankle and knee joint injuries can be effective for the prevention of recurrent injuries and the improvement of joint functionality.

  8. Intraorbital neuromuscular choristoma adjacent to the optic nerve

    Directory of Open Access Journals (Sweden)

    Arie Perry, M.D.

    2017-03-01

    Full Text Available Neuromuscular choristoma is a rare tumor that incorporates mature skeletal muscle within fascicles of peripheral nerve. The etiology is poorly understood, yet most present in large nerves of children, with a tight link to post-operative fibromatosis recently appreciated. Herein, we report an exceptional intra-orbital example in a 53-year-old man with optic nerve compression.

  9. Optimising abdominal space with deep neuromuscular blockade in gynaecologic laparoscopy

    DEFF Research Database (Denmark)

    Madsen, Matias Vested; Gätke, M R; Springborg, H H

    2015-01-01

    neuromuscular blockade (NMB) would enlarge surgical space, measured as the distance from the sacral promontory to the trocar in patients undergoing gynaecologic laparoscopy. METHODS: Fourteen patients were randomised in an assessor-blinded crossover design. The distance from the sacral promontory to the trocar...

  10. Muscle ultrasound quantifies segmental neuromuscular outcome in pediatric myelomeningocele

    NARCIS (Netherlands)

    Verbeek, Renate J; Hoving, Eelco; Maurits, Natalia M; Brouwer, Oebele F; van der Hoeven, Johannes H; Sival, Deborah A

    2014-01-01

    In pediatric spina bifida aperta (SBA), non-invasive assessment of neuromuscular integrity by muscle ultrasound density (MUD) could provide important information about the clinical condition. We therefore aimed to determine the association between pediatric SBA MUD and segmental neurologic function.

  11. 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 i...

  12. 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 a

  13. 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

  14. 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

  15. 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

  16. Anaho Island: Mammalian species richness report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This study assessed the mammalian species richness on Anaho Island using live trapping between July 18th and July 23rd 2005. The last mammalian species richness...

  17. 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.

  18. Neuromuscular activity of Micrurus laticollaris (Squamata: Elapidae) venom in vitro.

    Science.gov (United States)

    Carbajal-Saucedo, Alejandro; Floriano, Rafael Stuani; Dal Belo, Cháriston André; Olvera-Rodríguez, Alejandro; Alagón, Alejandro; Rodrigues-Simioni, Léa

    2014-01-17

    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.

  19. Cytometry of mammalian sperm

    Energy Technology Data Exchange (ETDEWEB)

    Gledhill, B.L.

    1983-10-11

    Male germ cells respond dramatically to a variety of insults and are important reproductive dosimeters. Semen analyses are very useful in studies on the effects of drugs, chemicals, and environmental hazards on testicular function, male fertility and heritable germinal mutations. The accessibility of male cells makes them well suited for analytical cytology. We might automate the process of determining sperm morphology but should not do so solely for increased speed. Rather, richer tangible benefits will derive from cytometric evaluation through increased sensitivity, reduced subjectivity, standardization between investigators and laboratories, enhanced archival systems, and the benefits of easily exchanged standardized data. Inroads on the standardization of assays for motility and functional integrity are being made. Flow cytometric analysis of total DNA content of individual sperm is an insensitive means to detect exposure to reproductive toxins because of the small size and low frequency of the DNA content errors. Flow cytometry can be applied to determine the proportions of X- and Y-sperm in semen samples.

  20. A bicistronic baculovirus vector for transient and stable protein expression in mammalian cells.

    Science.gov (United States)

    Lackner, Andreas; Genta, Kathrin; Koppensteiner, Herwig; Herbacek, Irene; Holzmann, Klaus; Spiegl-Kreinecker, Sabine; Berger, Walter; Grusch, Michael

    2008-09-01

    Baculoviruses are widely used for protein production in insect cells, and their potential for gene transfer to mammalian cells is increasingly being recognized. Here we describe a baculovirus vector with a bicistronic mammalian expression cassette and demonstrate its suitability for efficient transient and stable protein expression in human glioblastoma cells. Bicistronic baculovirus vectors are safe, cost efficient, and easy to produce; thus, they represent an excellent gene transfer system for mammalian cells.

  1. The meiosis-specific modification of mammalian telomeres.

    Science.gov (United States)

    Shibuya, Hiroki; Watanabe, Yoshinori

    2014-01-01

    During meiosis, rapid chromosome movements within the nucleus enable homologous chromosomes to acquire physical juxtaposition. In most organisms, chromosome ends, telomeres, tethered to the transmembrane LINC-complex mediate this movement by transmitting cytoskeletal forces to the chromosomes. While the majority of molecular studies have been performed using lower eukaryotes as model systems, recent studies have identified mammalian meiotic telomere regulators, including the LINC-complex SUN1/KASH5 and the meiosis-specific telomere binding protein TERB1. This review highlights the molecular regulations of mammalian meiotic telomeres in comparison with other model systems and discusses some future perspectives.

  2. Bioenergetics of Mammalian Sperm Capacitation

    Directory of Open Access Journals (Sweden)

    Alessandra Ferramosca

    2014-01-01

    Full Text Available After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.

  3. Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction.

    Science.gov (United States)

    Plomp, Jaap J; Willison, Hugh J

    2009-08-15

    The outer leaflet of neuronal membranes is highly enriched in gangliosides. Therefore, specific neuronal roles have been attributed to this family of sialylated glycosphingolipids, e.g. in modulation of ion channels and transporters, neuronal interaction and recognition, temperature adaptation, Ca(2+) homeostasis, axonal growth, (para)node of Ranvier stability and synaptic transmission. Recent developmental, ageing and injury studies on transgenic mice lacking subsets of gangliosides indicate that gangliosides are involved in maintenance rather than development of the nervous system and that ganglioside family members are able to act in a mutually compensatory manner. Besides having physiological functions, gangliosides are the likely antigenic targets of autoantibodies present in Guillain-Barré syndrome (GBS), a group of neuropathies with clinical symptoms of motor- and/or sensory peripheral nerve dysfunction. Antibody binding to peripheral nerves is thought to either interfere with ganglioside function or activate complement, causing axonal damage and thereby disturbed action potential conduction. The presynaptic motor nerve terminal at the neuromuscular junction (NMJ) may be a prominent target because it is highly enriched in gangliosides and lies outside the blood-nerve barrier, allowing antibody access. The ensuing neuromuscular synaptopathy might contribute to the muscle weakness in GBS patients. Several groups, including our own, have studied the effects of anti-ganglioside antibodies in ex vivo and in vivo experimental settings at mouse NMJs. Here, after providing a background overview on ganglioside synthesis, localization and physiology, we will review those studies, which clearly show that anti-ganglioside antibodies are capable of binding to NMJs and thereby can exert a variety of pathophysiological effects. Furthermore, we will discuss the human clinical electrophysiological and histological evidence produced so far of the existence of a neuromuscular

  4. A Comparative Study of Sagittal Balance in Patients with Neuromuscular Scoliosis.

    Science.gov (United States)

    Borges, Paulo Alvim; Zelada, Flávio Gerardo Benites; Dos Santos Barros, Thiago Felipe; Letaif, Olavo Biraghi; da Rocha, Ivan Dias; Marcon, Raphael Martus; Cristante, Alexandre Fogaça; Barros-Filho, Tarcíso Eloy Pessoa

    2017-08-01

    Spinopelvic alignment has been associated with improved quality of life in patients with vertebral deformities, and it helps to compensate for imbalances in gait. Although surgical treatment of scoliosis in patients with neuromuscular spinal deformities promotes correction of coronal scoliotic deformities, it remains poorly established whether this results in large changes in sagittal balance parameters in this specific population. The objective of this study is to compare these parameters before and after the current procedure under the hypothesis is that there is no significant modification. Sampling included all records of patients with neuromuscular scoliosis with adequate radiographic records treated at Institute of Orthopedics and Traumatology of Clinics Hospital of University of São Paulo (IOT-HCFMUSP) from January 2009 to December 2013. Parameters analyzed were incidence, sacral inclination, pelvic tilt, lumbar lordosis, thoracic kyphosis, spinosacral angle, spinal inclination and spinopelvic inclination obtained using the iSite-Philips digital display system with Surgimap and a validated method for digital measurements of scoliosis radiographs. Comparison between the pre- and post-operative conditions involved means and standard deviations and the t-test. Based on 101 medical records only, 16 patients met the inclusion criteria for this study, including 7 males and 9 females, with an age range of 9-20 and a mean age of 12.9±3.06; 14 were diagnosed with cerebral palsy. No significant differences were found between pre and postoperative parameters. Despite correction of coronal scoliotic deformity in patients with neuromuscular deformities, there were no changes in spinopelvic alignment parameters in the group studied.

  5. Mitochondrial DNA triplication and punctual mutations in patients with mitochondrial neuromuscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Mkaouar-Rebai, Emna, E-mail: emna.mkaouar@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Felhi, Rahma; Tabebi, Mouna [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Alila-Fersi, Olfa; Chamkha, Imen [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Maalej, Marwa; Ammar, Marwa [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Kammoun, Fatma [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Keskes, Leila [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Hachicha, Mongia [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Fakhfakh, Faiza, E-mail: faiza.fakhfakh02@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia)

    2016-04-29

    Mitochondrial diseases are a heterogeneous group of disorders caused by the impairment of the mitochondrial oxidative phosphorylation system which have been associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear gene mutations. The clinical phenotypes are very diverse and the spectrum is still expanding. As brain and muscle are highly dependent on OXPHOS, consequently, neurological disorders and myopathy are common features of mtDNA mutations. Mutations in mtDNA can be classified into three categories: large-scale rearrangements, point mutations in tRNA or rRNA genes and point mutations in protein coding genes. In the present report, we screened mitochondrial genes of complex I, III, IV and V in 2 patients with mitochondrial neuromuscular disorders. The results showed the presence the pathogenic heteroplasmic m.9157G>A variation (A211T) in the MT-ATP6 gene in the first patient. We also reported the first case of triplication of 9 bp in the mitochondrial NC7 region in Africa and Tunisia, in association with the novel m.14924T>C in the MT-CYB gene in the second patient with mitochondrial neuromuscular disorder. - Highlights: • We reported 2 patients with mitochondrial neuromuscular disorders. • The heteroplasmic MT-ATP6 9157G>A variation was reported. • A triplication of 9 bp in the mitochondrial NC7 region was detected. • The m.14924T>C transition (S60P) in the MT-CYB gene was found.

  6. Molecular aspects of mammalian fertilization

    Institute of Scientific and Technical Information of China (English)

    Hector Serrano; Dolores Garcia-Suarez

    2001-01-01

    Mammalian fertilization is a highly regulated process, much of which are not clearly understood. Here we present some information in order to elaborate a working hypothesis for this process, beginning with the sperm modifications in the epidydimis up to sperm and egg plasmalemma interaction and fusion. We also discuss the still poorly understood capacitation process, the phenomenon of sperm chemo-attraction that brings the capacitated sperm to interact with the oocyte vestments and certain aspects of the acrosome reaction.

  7. 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.

  8. 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

  9. Regulation of Rap GTPases in mammalian neurons.

    Science.gov (United States)

    Shah, Bhavin; Püschel, Andreas W

    2016-10-01

    Small GTPases are central regulators of many cellular processes. The highly conserved Rap GTPases perform essential functions in the mammalian nervous system during development and in mature neurons. During neocortical development, Rap1 is required to regulate cadherin- and integrin-mediated adhesion. In the adult nervous system Rap1 and Rap2 regulate the maturation and plasticity of dendritic spine and synapses. Although genetic studies have revealed important roles of Rap GTPases in neurons, their regulation by guanine nucleotide exchange factors (GEFs) that activate them and GTPase activating proteins (GAPs) that inactivate them by stimulating their intrinsic GTPase activity is just beginning to be explored in vivo. Here we review how GEFs and GAPs regulate Rap GTPases in the nervous system with a focus on their in vivo function.

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

    Directory of Open Access Journals (Sweden)

    A.M. Labrador-Cerrato

    2015-03-01

    Full Text Available 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; Omniplaste®-E; observar la concordancia entre la prueba sit-and-reach y el test de Schober en la valoración de la ganancia de flexión lumbar. Material y métodos: Estudio piloto experimental a triple ciego. Se distribuyeron aleatoriamente 45 sujetos sanos de 20-55 años en tres grupos: 1 esparadrapo convencional; 2 Omniplaste®-E; 3 vendaje neuromuscular. En todos los participantes se evaluó la flexión del raquis lumbar mediante la prueba sit-and-reach y el test de Schober antes y después de la intervención siguiendo el mismo protocolo. Resultados: Considerado un intervalo de confianza del 95% y grado de significación estadística p<0,05 en todos los casos, se obtuvo un incremento estadísticamente significativo de la flexión lumbar en todos los grupos según la prueba sit-and-reach, que fue mayor en el grupo del vendaje neuromuscular (1,5 cm de mediana; p=0,011. Según el test de Schober, solamente el vendaje neuromuscular se mostró eficiente (p<0,001, incrementándose el valor basal en un 6,25% (1 cm de mediana. Conclusiones: La aplicación del vendaje neuromuscular sobre la columna lumbar mejora la flexión lumbar respecto a técnicas placebo a partir de los resultados obtenidos mediante el test de Schober, así como una mayor flexión global del tronco que estas técnicas según la prueba sit-and-reach. El test de Schober parece ser más fiable y preciso que la prueba sit-and-reach para estudios de este tipo.

  11. 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 embedding

  12. The effect of a Lucia jig for 30 minutes on neuromuscular re-programming, in normal subjects

    Directory of Open Access Journals (Sweden)

    Mariangela Salles Pereira Nassar

    2012-12-01

    Full Text Available The Lucia jig is a technique that promotes neuromuscular reprogramming of the masticatory system and allows the stabilization of the mandible without the interference of dental contacts, maintaining the mandible position in harmonic condition with the musculature in normal subjects or in patients with temporomandibular dysfunction (TMD. This study aimed to electromyographically analyze the activity (RMS of the masseter and temporal muscles in normal subjects (control group during the use of an anterior programming device, the Lucia jig, in place for 0, 5, 10, 20 and 30 minutes to demonstrate its effect on the stomatognathic system. Forty-two healthy dentate individuals (aged 21 to 40 years with normal occlusion and without parafunctional habits or temporomandibular dysfunction (RDC/TMD were evaluated on the basis of the electromyographic activity of the masseter and temporal muscles before placement of a neuromuscular re-programming device, the Lucia jig, on the upper central incisors. There were no statistically significant differences (p < 0.05 in the electromyographic activity of the masticatory muscles in the different time periods. The Lucia jig changed the electromyographic activity by promoting a neuromuscular reprogramming. In most of the time periods, it decreased the activation of the masticatory muscles, showing that this device has wide applicability in dentistry. The use of a Lucia jig over 0, 5, 10, 15, 20 and 30 minutes did not promote any statistically significant increase in muscle activity despite differences in the data, thus showing that this intra-oral device can be used in dentistry.

  13. Neuromuscular strain as a contributor to cognitive and other symptoms in chronic fatigue syndrome: hypothesis and conceptual model.

    Science.gov (United States)

    Rowe, Peter C; Fontaine, Kevin R; Violand, Richard L

    2013-01-01

    Individuals with chronic fatigue syndrome (CFS) have heightened sensitivity and increased symptoms following various physiologic challenges, such as orthostatic stress, physical exercise, and cognitive challenges. Similar heightened sensitivity to the same stressors in fibromyalgia (FM) has led investigators to propose that these findings reflect a state of central sensitivity. A large body of evidence supports the concept of central sensitivity in FM. A more modest literature provides partial support for this model in CFS, particularly with regard to pain. Nonetheless, fatigue and cognitive dysfunction have not been explained by the central sensitivity data thus far. Peripheral factors have attracted attention recently as contributors to central sensitivity. Work by Brieg, Sunderland, and others has emphasized the ability of the nervous system to undergo accommodative changes in length in response to the range of limb and trunk movements carried out during daily activity. If that ability to elongate is impaired-due to movement restrictions in tissues adjacent to nerves, or due to swelling or adhesions within the nerve itself-the result is an increase in mechanical tension within the nerve. This adverse neural tension, also termed neurodynamic dysfunction, is thought to contribute to pain and other symptoms through a variety of mechanisms. These include mechanical sensitization and altered nociceptive signaling, altered proprioception, adverse patterns of muscle recruitment and force of muscle contraction, reduced intra-neural blood flow, and release of inflammatory neuropeptides. Because it is not possible to differentiate completely between adverse neural tension and strain in muscles, fascia, and other soft tissues, we use the more general term "neuromuscular strain." In our clinical work, we have found that neuromuscular restrictions are common in CFS, and that many symptoms of CFS can be reproduced by selectively adding neuromuscular strain during the

  14. Cholinergic neuromuscular junctions in Brachionus calyciflorus and Lecane quadridentata (Rotifera:Monogononta)

    Institute of Scientific and Technical Information of China (English)

    Ignacio Alejandro Prez-Legaspi; Alma Lilin Guerrero-Barrera; Ivn Jos Galvn-Mendoza; Jos Luis Quintanar; Roberto Rico-Martnez

    2014-01-01

    Objective:To identify the presence of joint muscular and cholinergic systems in two freshwater rotifer species, Brachionus calyciflorus and Lecane quadridentata. Methods: The muscle actin fibers were stained with phalloidin-linked fluorescent dye, and acetylcholine was detected with Amplex Red Acetylcholine/Acetylcholinesterase Assay Kit, and then confocal scanning laser microscopy was used. Results:The musculature of Brachionus calyciflorus showed a pattern similar to other species of the same genus, while that of Lecane quadridentata was different from other rotifer genera described previously. The cholinergic system was determined by co-localization of both muscles and acetylcholine labels in the whole rotifer, suggesting the presence of neuromuscular junctions. Conclusions: The distribution pattern of muscular and acetylcholine systems showed considerable differences between the two species that might be related to different adaptations to particular ecological niches. The confirmation of a cholinergic system in rotifers contributes to the development of potential neuro-pharmacological and toxicological studies using rotifers as model organism.

  15. Redox regulation of mammalian sperm capacitation

    Directory of Open Access Journals (Sweden)

    Cristian O′Flaherty

    2015-01-01

    Full Text Available Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P H for sperm capacitation. Peroxiredoxins (PRDXs are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility.

  16. 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.

  17. [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.

  18. Supervised neuromuscular exercise prior to hip and knee replacement

    DEFF Research Database (Denmark)

    Fernandes, Linda; Roos, Ewa M; Overgaard, Søren

    2017-01-01

    BACKGROUND: There are indications of beneficial short-term effect of pre-operative exercise in reducing pain and improving activity of daily living after total hip replacement (THR) and total knee replacement (TKR) surgery. Though, information from studies conducting longer follow-ups and economic...... evaluations of exercise prior to THR and TKR is needed. The aim of the study was to analyse 12-month clinical effect and cost-utility of supervised neuromuscular exercise prior to THR and TKR surgery. METHODS: The study was conducted alongside a randomised controlled trial including 165 patients scheduled...... for standard THR or TKR at a hospital located in a rural area of Denmark. The patients were randomised to replacement surgery with or without an 8-week preoperative supervised neuromuscular exercise program (Clinical Trials registration no.: NCT01003756). Clinical effect was measured with Hip disability...

  19. 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

  20. Role of ortho-retronasal olfaction in mammalian cortical evolution.

    Science.gov (United States)

    Rowe, Timothy B; Shepherd, Gordon M

    2016-02-15

    Fossils of mammals and their extinct relatives among cynodonts give evidence of correlated transformations affecting olfaction as well as mastication, head movement, and ventilation, and suggest evolutionary coupling of these seemingly separate anatomical regions into a larger integrated system of ortho-retronasal olfaction. Evidence from paleontology and physiology suggests that ortho-retronasal olfaction played a critical role at three stages of mammalian cortical evolution: early mammalian brain development was driven in part by ortho-retronasal olfaction; the bauplan for neocortex had higher-level association functions derived from olfactory cortex; and human cortical evolution was enhanced by ortho-retronasal smell.

  1. Mammalian synthetic biology for studying the cell.

    Science.gov (United States)

    Mathur, Melina; Xiang, Joy S; Smolke, Christina D

    2017-01-02

    Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

  2. Rapid, modular and reliable construction of complex mammalian gene circuits.

    Science.gov (United States)

    Guye, Patrick; Li, Yinqing; Wroblewska, Liliana; Duportet, Xavier; Weiss, Ron

    2013-09-01

    We developed a framework for quick and reliable construction of complex gene circuits for genetically engineering mammalian cells. Our hierarchical framework is based on a novel nucleotide addressing system for defining the position of each part in an overall circuit. With this framework, we demonstrate construction of synthetic gene circuits of up to 64 kb in size comprising 11 transcription units and 33 basic parts. We show robust gene expression control of multiple transcription units by small molecule inducers in human cells with transient transfection and stable chromosomal integration of these circuits. This framework enables development of complex gene circuits for engineering mammalian cells with unprecedented speed, reliability and scalability and should have broad applicability in a variety of areas including mammalian cell fermentation, cell fate reprogramming and cell-based assays.

  3. 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.

  4. Increased virus replication in mammalian cells by blocking intracellular innate defense responses

    NARCIS (Netherlands)

    Vries, W. de; Haasnoot, J.; Velden, J. van der; Montfort, T. van; Zorgdrager, F.; Paxton, W.; Cornelissen, M.; Kuppeveld, F.J.M. van; Haan, P. de; Berkhout, B.

    2008-01-01

    The mammalian innate immune system senses viral infection by recognizing viral signatures and activates potent antiviral responses. Besides the interferon (IFN) response, there is accumulating evidence that RNA silencing or RNA interference (RNAi) serves as an antiviral mechanism in mammalian cells.

  5. Expression of a secreted protein in mammalian cells using baculovirus particles.

    Science.gov (United States)

    Jardin, Barbara Ann; Elias, Cynthia B; Prakash, Satya

    2012-01-01

    There are many methods presently available to produce recombinant proteins in mammalian systems. The BacMam system is a simple straightforward method which overlaps two well-established technologies, namely the BEVS insect cell system and the transduction of mammalian cells in vitro. This chapter describes a method for the study of gene expression in mammalian cells in a series of simple steps. Protocols outlined include the design and construction of the recombinant baculovirus, cell culture techniques required to maintain both insect and mammalian cells, generation of baculovirus stocks, and methods to obtain maximal and reproducible gene expression in mammalian cells. Currently available statistical techniques using factorial design of experiment to optimize conditions for recombinant protein in vitro are outlined. Then details with respect to process scale-up in disposable bioreactors are included.

  6. Basics of bone metabolism and osteoporosis in common pediatric neuromuscular disabilities.

    Science.gov (United States)

    Yaşar, Evren; Adigüzel, Emre; Arslan, Mutluay; Matthews, Dennis J

    2017-08-10

    Bone modeling is a process that starts with fetal life and continues during adolescence. Complex factors such as hormones, nutritional and environmental factors affect this process. In addition to these factors, physical conditioning and medications that have toxic effects on bony tissue should be carefully considered in patient follow-up. Osteoporosis is a significant problem in pediatric population because of ongoing growth and development of skeletal system. Two types of osteoporosis are primary and secondary types and children with neuromuscular disabilities constitute a major group with secondary osteoporosis. Low bone mass in patients with cerebral palsy, spina bifida, and Duchenne muscular dystrophy cause increased bone fragility in even slight traumas. Maximizing peak bone mass and prevention of bone loss are very important to reduce the fracture risk in neuromuscular diseases. This article aims to review the determinants of bone physiology and bone loss in children with cerebral palsy, spina bifida, and Duchenne muscular dystrophy. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  7. Safety and Efficacy of Subcutaneous Immunoglobulin in the Treatment of Neuromuscular Disorders.

    Science.gov (United States)

    Salameh, Johnny S; Deeb, Wissam; Burawski, Lauren; Wright, Suzanne; Souayah, Nizar

    2016-03-01

    Many neuromuscular diseases may be treated with immunoglobulins. In the United States, the major form of immunoglobulin used is intravenous (IV). Recently, there has been an increased interest in research regarding the use of subcutaneous immunoglobulin (SCIg), mainly for improved patient quality of life, convenience, potential for fewer systemic adverse events, and avoiding wear-off. The widespread use of the subcutaneous formulation in neurology has been affected by some limitations, mainly the smaller volume and higher frequency of infusions compared to IV administration. Also, there are different pharmacokinetic properties that should be considered to evaluate whether they change the immunomodulatory effect. There are several formulations available that address some limitations. Several studies have assessed efficacy, safety, and quality of life of SCIg in neurology. This review article summarizes the current evidence for the use of SCIg in neuromuscular diseases. It also addresses the pharmacokinetic differences and the different formulations available. The current available preliminary evidence indicates that SCIg is at least as effective as the IV formulations.

  8. Pre-pubertal males practising Taekwondo exhibit favourable postural and neuromuscular performance.

    Science.gov (United States)

    Jlid, Mohamed Chedly; Maffulli, Nicola; Souissi, Nisar; Chelly, Mohamed Souheil; Paillard, Thierry

    2016-01-01

    The postural and neuromuscular performances in healthy children taekwondo (TKD) practitioners in comparison with control children were examined. Seventeen healthy pre-pubertal males undertaking only physical education at school (age: 11.88 ± 0.33 years) and 12 pre-pubertal male TKD practitioners (>3 years, 4 sessions a week) (age 11.66 ± 0.49 years) were recruited. Performances in the dynamic postural control (Star Excursion Balance Test -SEBT), vertical jump [squat jump (SJ) and countermovement jump (CMJ)] and sprint running (distances: 5, 10, 20 and 30 m) tests were compared between the two groups. The performances of the TKD practitioners were better than those of the non-TKD active for the SEBT (for 14 of 16 conditions, p  0.05). TKD practice would stimulate sensory input and motor output of the postural system that would enhance its efficiency. In addition, the dynamic nature of TKD would develop the muscle power of the lower limbs. In our sample of healthy pre-pubertal males, TKD appears to improve postural and neuromuscular functions, but further research is required.

  9. Assessing tetraplegic patients' neuro-muscular adaptations to a six-week physiotherapeutic programme.

    Science.gov (United States)

    Oke, Kayode Israel; Kubeyinje, Oluwaseun S; Agwubike, Elias O

    2012-07-05

    Spinal cord injury is a life-transforming condition of sudden onset that can have devastating consequences. A multidisciplinary, functional goal-oriented programme is required to enable the tetraplegic patient live as fully and independently life as possible. Physiotherapy is a very important part of the multidisciplinary team required to prevent many of the immobilization complications that may result in serious functional limitations, reduce overall morbidity and achieve well patterned recovery. This study therefore highlights the neuromuscular adaptations of tetraplegic patients to physiotherapy over a period of six weeks. Fifteen patients participated in this study and the results showed that even though changes in the musculoskeletal parameters are inevitable in tetraplegics, the extent/degree of reduction of these parameters was grossly minimized in the studied subjects through the administration of physiotherapeutic measures. However, further research using a large sample size will be required to evaluate the physiologic adaptations of the neuromuscular system to the physiotherapy interventions among patients with spinal cord injury.

  10. Effectiveness of neuromuscular electrical stimulation in the functional knee rehabilitation in soldiers

    Directory of Open Access Journals (Sweden)

    R. Castillo-Lozano

    2015-12-01

    Full Text Available Background: The versatility of military physical therapist practice enables them not only to diagnose knee injuries but also to provide a wide range of definitive care and rehabilitation, reducing the need for costly evacuation. The aim this study was to evaluate the effectiveness of interventions by Neuromuscular Electrical Stimulation (NMES in the functional knee rehabilitation in soldiers and describe the main predictors and determinants in each intervention. Methods: A systematic search of the literature about NMES in physiotherapy was performed using the following electronic databases: Web of Science, PubMed, Cochrane, Physiotherapy Evidence Database (PEDro and CINAHL. The search strategy was: "neuromuscular electrical stimulation" and "physical therapy" and "strengthening" and "knee". Inclusion criteria were: original articles published and peer reviewed between 2004-2015, focusing on physiotherapy interventions by NMES on subjects older than 18 years. A total resulting from 46 studies was included in the study. Results: The results show the evidence on the effectiveness of NMES therapeutic/preventive purposes in the muscular system; and the importance of physical therapy in the army. Conclusion: As a method of functional knee rehabilitation, NMES proves effective in achieving the therapeutic/preventive objectives in soldiers. Level of Evidence: II. Systematic review of randomized clinical trials with homogeneity.

  11. Use of rocuronium and sugammadex under neuromuscular transmission monitoring in a patient with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Chryssoula Staikou

    2017-01-01

    Full Text Available Multiple sclerosis (MS is a potentially disabling disease characterized by demyelinating lesions in the central nervous system. One of the anesthetic challenges encountered in surgical patients with MS is the management of neuromuscular blockade (NMB and its reversal. We report a case of a 31-year-old female patient suffering from MS, who underwent gynecological surgery under general anesthesia with sevoflurane, fentanyl, and rocuronium which was successfully reversed with sugammadex. Neuromuscular transmission (NMT monitoring was used to guide the intraoperative doses of rocuronium and also the reversal of NMB by the use of sugammadex to ensure a safe tracheal extubation. In addition, delivered volatile was titrated according to anesthetic depth monitoring (Bispectral Index while esophageal temperature was also monitored for the maintenance of normothermia. Postoperatively, a multimodal analgesic scheme offered a high-quality analgesia and sleep, minimization of anxiety, and increased patient satisfaction. At 1-month follow-up, the patient's course was uncomplicated without any MS exacerbation. We consider that the use of rocuronium and sugammadex under NMT monitoring may represent a useful and safe choice in patients with MS.

  12. Myosin VI contributes to synaptic transmission and development at the Drosophila neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Campbell Shelagh

    2011-07-01

    Full Text Available Abstract Background Myosin VI, encoded by jaguar (jar in Drosophila melanogaster, is a unique member of the myosin superfamily of actin-based motor proteins. Myosin VI is the only myosin known to move towards the minus or pointed ends of actin filaments. Although Myosin VI has been implicated in numerous cellular processes as both an anchor and a transporter, little is known about the role of Myosin VI in the nervous system. We previously recovered jar in a screen for genes that modify neuromuscular junction (NMJ development and here we report on the genetic analysis of Myosin VI in synaptic development and function using loss of function jar alleles. Results Our experiments on Drosophila third instar larvae revealed decreased locomotor activity, a decrease in NMJ length, a reduction in synaptic bouton number, and altered synaptic vesicle localization in jar mutants. Furthermore, our studies of synaptic transmission revealed alterations in both basal synaptic transmission and short-term plasticity at the jar mutant neuromuscular synapse. Conclusions Altogether these findings indicate that Myosin VI is important for proper synaptic function and morphology. Myosin VI may be functioning as an anchor to tether vesicles to the bouton periphery and, thereby, participating in the regulation of synaptic vesicle mobilization during synaptic transmission.

  13. 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.

  14. Effects of Dynamic Neuromuscular Analysis Training on Static and Dynamic Balance in Indian Female Basketball Players

    Directory of Open Access Journals (Sweden)

    Archna Sharma

    2013-04-01

    Full Text Available The aim of this paper was to investigate the effects of dynamic neuromuscular analysis on static and dynamic balance of Indian state level female athletes. It was hypothesized that the training protocol would improve both static and dynamic components of the balance, improving dynamic balance more than static. A total of 43 randomly selected state level female basketball players aged 16 -18 years participated in the study. The subjects were further divided into two groups, viz. Dynamic Neuromuscular Analysis (DNA group (n=23 and control group (n = 20. Pre and post static balance was tested to all the subjects by Stork Balance Test (SBT and Balance Error Scoring System (BESS, and dynamic balance was measured by Star Excursion Balance Test (SEBT. DNA intervention of 90 minutes was given for 6 weeks while the control group followed traditional training. Results showed a significant improvement both in static and dynamic balance (p<0.001. It might be concluded that 6 week DNA training designed for the prevention of ACL injuries could also improve both static and dynamic balance in Indian female basketball players.

  15. Neuromuscular adaptations to isoload versus isokinetic eccentric resistance training.

    Science.gov (United States)

    Guilhem, Gaël; Cornu, Christophe; Maffiuletti, Nicola A; Guével, Arnaud

    2013-02-01

    The purpose of this study was to compare neuromuscular adaptations induced by work-matched isoload (IL) versus isokinetic (IK) eccentric resistance training. A total of 31 healthy subjects completed a 9-wk IL (n = 11) or IK (n = 10) training program for the knee extensors or did not train (control group; n = 10). The IL and IK programs consisted of 20 training sessions, which entailed three to five sets of eight repetitions in the respective modalities. The amount of work and the mean angular velocity were strictly matched between IL and IK conditions. Neuromuscular tests were performed before and after training and consisted of the assessment of quadriceps muscle strength, muscle architecture (vastus lateralis), EMG activity, and antagonist coactivation. IL, but not IK, eccentric resistance training enhanced eccentric strength at short muscle length (+20%), high-velocity eccentric strength (+15%), muscle thickness (+10%), and fascicle angle measured at rest (+11%; P eccentric movements (i.e., at short muscle lengths), which results in greater torque and angular velocities compared with IK actions, is the main determinant of strength and neuromuscular adaptations to eccentric training. These findings have important consequences for the optimization of IL and IK eccentric exercise for resistance training and rehabilitation purposes.

  16. 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.

  17. Neuromuscular responses to simulated brazilian jiu-jitsu fights.

    Science.gov (United States)

    da Silva, Bruno Victor Corrêa; Ide, Bernardo Neme; de Moura Simim, Mário Antônio; Marocolo, Moacir; da Mota, Gustavo Ribeiro

    2014-12-01

    The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ) fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m) undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest). Neuromuscular performance was measured by the bench press throw (BPT) and vertical counter movement jump (VCMJ) tests, assessed before the 1st fight (Pre) and after the last one (Post). Blood lactate (LA) was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power) was observed.

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

    Energy Technology Data Exchange (ETDEWEB)

    Schalke, B.C.G.; Rohkamm, R. (Neurologische Universitaetsklinik, Wuerzburg (Germany, F.R.)); Kaiser, W.

    1990-12-01

    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).

  19. 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.

  20. Muscle fiber hypotrophy with intact neuromuscular junctions. A study of a patient with congenital neuromuscular disease and ophthalmoplegia.

    Science.gov (United States)

    Bender, A N; Bender, M B

    1977-03-01

    An infant born with severe but nonprogressive somatic and cranial muscle weakness including bilateral external ophthalmoplegia was studied with a motor-point muscle biopsy. There was a strinking generalized decrease in the size of muscle fibers (hypotrophy), most marked in the type I fibers. Many of the small fibers were immature, resembling myotubes. Neuromuscular junctions on severely hypotrophic fibers were normal with esterase staining and by ultrastructural criteria. Although these are unusual clinical and biopsy characteristics, this infant's condition bears a resemblance to two other congenital nonprogressive neuromuscular diseases:myotubular myopathy and congenital fiber type disproportion. In these conditions and in our patient, there is no primary degenerative process affecting nerve or muscle but, rather, an apparent lack of maturation of fetal muscle fibers, indicating a defective normal trophic interaction between nerve and muscle.

  1. Neuromuscular electrical stimulation for mobility support of elderly

    Directory of Open Access Journals (Sweden)

    Winfried Mayr

    2015-10-01

    Full Text Available The stimulator for neuromuscular electrical stimulation for mobility support of elderly is not very complicated, but for application within "MOBIL" we have some additional demands to fulfill. First we have specific safety issues for this user group. A powerful compliance management system is crucial not only to guide daily application, but for creating hard data for the scientific outcome. We also need to assure easy handling of the stimulator, because the subjects are generally not able to cope with too difficult and complex motor skills. So, we developed five generations of stimulators and optimizing solutions after field tests. We are already planning the sixth generation with wireless control of the stimulation units by the central main handheld control unit. In a prototype, we have implemented a newly available high capacity memory, a breakthrough in “compliance data storage” as they offer the necessary high storage capacity and fast data handling for an affordable prize. The circuit also contains a 3D accelerometer sensor which acts as a further important safety features: if the control unit drops, this event is detected automatically by the sensor and activates an emergency switch-off that disables the stimulation to avoid associated risks. Further, we have implemented a hardware emergence shutdown and other safety measures. Finally, in the last example muscle torque measurements are referenced with compliance data. In the study normalized maximum voluntary contraction (MVC and maximum stimulation induced contraction (MSC were assessed in regular check-ups along the training period. With additional consideration of adjusted stimulation intensity for training out of the compliance data records we are able to estimate the induced contraction strength, which turned out to amount in average 11% of MVC. This value may seem on a first sight rather low, and ought to be considered in relation to the results at the end of the training period

  2. Fatigue in neuromuscular disorders: focus on Guillain–Barré syndrome and Pompe disease

    OpenAIRE

    2009-01-01

    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 into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular di...

  3. PICU EXTUBATION FAILURE: THE ROLE OF NEUROMUSCULAR DISORDERS

    Directory of Open Access Journals (Sweden)

    N. Billan MD,

    2007-02-01

    Full Text Available ObjectiveNeuromuscular disorders (diseases of the motor unit, can cause respiratory problems such as impaired cough reflex, chest deformity, recurrent pneumonia and acute respiratory failure; these are the worst most common complications of these diseases and the leading cause of death in such patients (1, 2. Their management hence, very often, entails admission to the Pediatric Intensive Care Unit (PICU (3,4 and during this phase, endotracheal intubation is almost always necessary, to maintain the patency of airways and to apply Positive Pressure Ventilation (PPV. However, endotracheal intubation is always temporary, and its success or failure depends on the timely decision of its termination to restore the normal respiration or to avoid the risk of recurring respiratory failure (5, 6. We designed this study to evaluate the role of neuromuscular disorders in causing extubation failure as compared to that of other risk factors.Materials & MethodsIn an analytical cross-sectional study, the risk factors of reintubation and duration of mechanical ventilation in two groups of 30 patients each, was compared, the first successful extubation and the second with extubation failure.ResultsNeuromuscular disorders (including Spinal Muscular Atrophy, Guillain- Barre' Syndrome, Congenital Myopathies and Muscular Dystrophies were the main underlying diseases in extubation-failure group (P= 0.0002. Hypercapnia (PaCO2>50mmHg was shown to be the most common cause of both the first intubation (P=0.001 and reintubation (P=0.004 in the group of patients who failed extubation. The mean duration of intubation and mechanical ventilation was longer in patients with neuromuscular disorders who had extubation failure (P= 0.01.ConclusionThis study showed that, as underlying problems, neuromuscular disorders are the most common causes of prolonged intubation which defeat weaning from the ventilator and result in reintubation by inducing hypercapnia. Therefore the weaning

  4. Ceramide signaling in mammalian epidermis.

    Science.gov (United States)

    Uchida, Yoshikazu

    2014-03-01

    Ceramide, the backbone structure of all sphingolipids, as well as a minor component of cellular membranes, has a unique role in the skin, by forming the epidermal permeability barrier at the extracellular domains of the outermost layer of the skin, the stratum corneum, which is required for terrestrial mammalian survival. In contrast to the role of ceramide in forming the permeability barrier, the signaling roles of ceramide and its metabolites have not yet been recognized. Ceramide and/or its metabolites regulate proliferation, differentiation, and apoptosis in epidermal keratinocytes. Recent studies have further demonstrated that a ceramide metabolite, sphingosine-1-phosphate, modulates innate immune function. Ceramide has already been applied to therapeutic approaches for treatment of eczema associated with attenuated epidermal permeability barrier function. Pharmacological modulation of ceramide and its metabolites' signaling can also be applied to cutaneous disease prevention and therapy. The author here describes the signaling roles of ceramide and its metabolites in mammalian cells and tissues, including the epidermis. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

  5. Neuromuscular dysfunction associated with delayed weaning from ...

    African Journals Online (AJOL)

    Yehia Khalil

    2012-03-21

    Mar 21, 2012 ... weaning from mechanical ventilation in patients with respiratory ... ratory system recovers from acute respiratory failure. Yet, invasive ..... vascular stroke, brain tumors and encephalopathy. ..... ventilator-induced lung injury.

  6. Use of neuromuscular monitoring to detect prolonged effect of succinylcholine or mivacurium

    DEFF Research Database (Denmark)

    Cassel, J; Staehr-Rye, A K; Nielsen, C V

    2014-01-01

    effect of the neuromuscular blocking agent was not discovered until after extubation. In the third patient, the lack of response to nerve stimulation was interpreted as a technical failure and the prolonged effect of succinylcholine was discovered when general anaesthesia was terminated. Both patients...... allowed a prolonged neuromuscular blockade to be discovered prior to tracheal extubation of the patient. The patient was extubated after successful reversal of the neuromuscular blockade. On the contrary, neuromuscular monitoring was not used during anaesthesia in the second patient; hence, the prolonged...

  7. A case series of re-establishment of neuromuscular block with rocuronium after sugammadex reversal.

    Science.gov (United States)

    Iwasaki, Hajime; Sasakawa, Tomoki; Takahoko, Kenichi; Takagi, Shunichi; Nakatsuka, Hideki; Suzuki, Takahiro; Iwasaki, Hiroshi

    2016-06-01

    We report the use of rocuronium to re-establish neuromuscular block after reversal with sugammadex. The aim of this study was to investigate the relationship between the dose of rocuronium needed to re-establish neuromuscular block and the time interval between sugammadex administration and re-administration of rocuronium. Patients who required re-establishment of neuromuscular block within 12 h after the reversal of rocuronium-induced neuromuscular block with sugammadex were included. After inducing general anesthesia and placing the neuromuscular monitor, the protocol to re-establish neuromuscular block was as follows. An initial rocuronium dose of 0.6 mg/kg was followed by additional 0.3 mg/kg doses every 2 min until train-of-four responses were abolished. A total of 11 patients were enrolled in this study. Intervals between sugammadex and second rocuronium were 12-465 min. Total dose of rocuronium needed to re-establish neuromuscular block was 0.6-1.2 mg/kg. 0.6 mg/kg rocuronium re-established neuromuscular block in all patients who received initial sugammadex more than 3 h previously. However, when the interval between sugammadex and second rocuronium was less than 2 h, more than 0.6 mg/kg rocuronium was necessary to re-establish neuromuscular block.

  8. Proprioceptive neuromuscular facilitation and strength training to gain muscle strength in elderly women

    National Research Council Canada - National Science Library

    Cesário, Denise Ferreira; Mendes, Geovânia Barbosa da Silva; Uchôa, Érica Patrícia Borba Lira; Veiga, Paulo Henrique Altran

    2014-01-01

    ...: To perform comparative analyze of results of proprioceptive neuromuscular facilitation (PNF) techniques and strength training to gain muscle strength of biceps and quadriceps and grip in the elderly...

  9. Enhancer evolution across 20 mammalian species

    DEFF Research Database (Denmark)

    Villar, Diego; Berthelot, Camille; Aldridge, Sarah;

    2015-01-01

    The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders...... by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements....... These results provide important insight into the functional genetics underpinning mammalian regulatory evolution....

  10. Recombinant Trichomonas vaginalis eIF-5A protein expressed from a eukaryotic system binds specifically to mammalian and putative trichomonal eIF-5A response elements (EREs).

    Science.gov (United States)

    Carvajal-Gamez, Bertha Isabel; Carrillo, Laura Vázquez; Torres-Romero, Julio César; Camacho-Nuez, Minerva; Ponce-Regalado, María Dolores; Camarillo, César López; Alvarez-Sánchez, María Elizbeth

    2016-12-01

    Trichomonas vaginalis eIF-5A-like protein (TveIF-5A) belongs to the highly conserved eIF-5A family of proteins that contains a unique polyamine-derived amino acid, hypusine. Recently, we determined that the polyamine putrescine is required for tveif-5a mRNA stability, and it is necessary for stability and maturation of the TveIF-5A protein. Eukaryotic eIF-5A is known to be involved in mRNA turnover and is capable of sequence-specific RNA binding to eIF-5A response elements (EREs). These ERE sequences are present in diverse mammalian mRNAs, including human cyclooxygenase-2 (cox-2). Here, we cloned the complete coding sequence of TveIF-5A and overexpressed it in a eukaryotic system. The recombinant protein (rTveIF-5A) was purified in soluble form using size-exclusion chromatography. Because of the polyamine-dependent regulation of TvCP39 (a protease of T. vaginalis) at the protein and RNA messenger (mRNA) levels, we looked for an ERE-like structure in the 3' region of tvcp39 mRNA. In RNA gel-shift assays, rTveIF-5A bound to transcripts at the EREs of cox-2 or tvcp39 mRNAs. This work shows the eIF-5A/ERE-like interaction in T. vaginalis.

  11. Manejo de longo prazo em crianças com transtornos neuromusculares Long-term management of children with neuromuscular disorders

    Directory of Open Access Journals (Sweden)

    Eugen-Matthias Strehle

    2009-10-01

    inherited myopathies and neuropathies. A patient cohort (n = 200 was evaluated using descriptive statistics. SUMMARY PF THE FINDINGS: Duchenne muscular dystrophy accounted for almost half of the diagnoses, followed by spinal muscular atrophy (12%, Becker muscular dystrophy and myotonic dystrophy (7% each. Sixteen patients (9% had an unknown myopathy. CONCLUSIONS: As with other chronic illnesses, these patients should be regularly reviewed by health professionals from an early age to increase life expectancy and improve quality of life. It is useful for physicians to take a structured approach when looking after children with neuromuscular disorders and to monitor all affected organ systems.

  12. Identification of an intestine-specific promoter and inducible expression of bacterial α-galactosidase in mammalian cells by a lac operon system

    Directory of Open Access Journals (Sweden)

    Ya-Feng Zhai

    2012-10-01

    Full Text Available Abstract Background α-galactosidase has been widely used in animal husbandry to reduce anti-nutritional factors (such as α-galactoside in feed. Intestine-specific and substrate inducible expression of α-galactosidase would be highly beneficial for transgenic animal production. Methods To achieve the intestine-specific and substrate inducible expression of α-galactosidase, we first identified intestine-specific promoters by comparing the transcriptional activity and tissue specificity of four intestine-specific promoters from human intestinal fatty acid binding protein, rat intestinal fatty acid binding protein, human mucin-2 and human lysozyme. We made two chimeric constructs combining the promoter and enhancer of human mucin-2, rat intestinal trefoil factor and human sucrase-isomaltase. Then a modified lac operon system was constructed to investigate the induction of α-galactosidase expression and enzyme activity by isopropyl β-D-1-thiogalactopyranoside (IPTG and an α-galactosidase substrate, α-lactose. We declared that the research carried out on human (Zhai Yafeng was in compliance with the Helsinki Declaration, and experimental research on animals also followed internationally recognized guidelines. Results The activity of the human mucin-2 promoter was about 2 to 3 times higher than that of other intestine-specific promoters. In the lac operon system, the repressor significantly decreased (P P Conclusions We have successfully constructed a high specificity inducible lac operon system in an intestine-derived cell line, which could be of great value for gene therapy applications and transgenic animal production.

  13. Mechanosensor Channels in Mammalian Somatosensory Neurons

    Directory of Open Access Journals (Sweden)

    Patrick Delmas

    2007-09-01

    Full Text Available Mechanoreceptive sensory neurons innervating the skin, skeletal muscles andviscera signal both innocuous and noxious information necessary for proprioception, touchand pain. These neurons are responsible for the transduction of mechanical stimuli intoaction potentials that propagate to the central nervous system. The ability of these cells todetect mechanical stimuli impinging on them relies on the presence of mechanosensitivechannels that transduce the external mechanical forces into electrical and chemical signals.Although a great deal of information regarding the molecular and biophysical properties ofmechanosensitive channels in prokaryotes has been accumulated over the past two decades,less is known about the mechanosensitive channels necessary for proprioception and thesenses of touch and pain. This review summarizes the most pertinent data onmechanosensitive channels of mammalian somatosensory neurons, focusing on theirproperties, pharmacology and putative identity.

  14. KN-93 inhibits IKr in mammalian cardiomyocytes.

    Science.gov (United States)

    Hegyi, Bence; Chen-Izu, Ye; Jian, Zhong; Shimkunas, Rafael; Izu, Leighton T; Banyasz, Tamas

    2015-12-01

    Calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 is widely used in multiple fields of cardiac research especially for studying the mechanisms of cardiomyopathy and cardiac arrhythmias. Whereas KN-93 is a potent inhibitor of CaMKII, several off-target effects have also been found in expression cell systems and smooth muscle cells, but there is no information on the KN93 side effects in mammalian ventricular myocytes. In this study we explore the effect of KN-93 on the rapid component of delayed rectifier potassium current (IKr) in the ventricular myocytes from rabbit and guinea pig hearts. Our data indicate that KN-93 exerts direct inhibitory effect on IKr that is not mediated via CaMKII. This off-target effect of KN93 should be taken into account when interpreting the data from using KN93 to investigate the role of CaMKII in cardiac function.

  15. Albendazole causes stage-dependent developmental toxicity and is deactivated by a mammalian metabolization system in a modified zebrafish embryotoxicity test.

    Science.gov (United States)

    Mattsson, Anna; Ullerås, Erik; Patring, Johan; Oskarsson, Agneta

    2012-08-01

    The zebrafish embryotoxicity test has previously been combined with an external metabolic activation system (MAS) to assess developmental toxicity of metabolites produced by maternal metabolism. Due to toxicity of MAS the exposure was limited to one early and short period. We have modified the method and included additional testing time points with extended exposure durations. Using the anthelmintic drug albendazole as a model substance, we demonstrated stage-dependent toxic effects at three windows of zebrafish embryo development, i.e. 2-3, 12-14 and 24-28h post fertilization, and showed that MAS, by metabolic deactivation, reduced the toxicity of albendazole at all time points. Chemical analysis confirmed that albendazole was efficiently metabolized by MAS to the corresponding sulfoxide and sulfone, which are non-toxic to zebrafish embryos. To conclude, the modified zebrafish embryotoxicity test with MAS can be expanded for assessment of metabolites at different developmental stages.

  16. Prenylation of a Rab1B mutant with altered GTPase activity is impaired in cell-free systems but not in intact mammalian cells.

    Science.gov (United States)

    Wilson, A L; Sheridan, K M; Erdman, R A; Maltese, W A

    1996-09-15

    Previous studies have reached differing conclusions as to whether or not guanine-nucleotide-dependent conformational changes affect the ability of Rab proteins to undergo post-translational modification by Rab:geranylgeranyltransferase (Rab-GGTase). We now show that the ability of a Rab1B mutant [Q67L (Gln-67-->Leu)] with reduced intrinsic GTPase activity to undergo geranylgeranylation in cell-free assays depends on the guanine nucleotide composition of the system. When GTP is the predominant nucleotide in the assay, Rab1BQ67L is a poor substrate. However, when GDP is present and GTP is omitted, prenylation of the Q67L mutant is comparable with that of the wild-type (WT) protein. These studies, coupled with the poor prenylation of Rab1BWT in the presence of the non-hydrolysable GTP analogue guanosine 5'-[gamma-thio]triphosphate, support the notion that Rab-GGTase prefers substrates in the GDP conformation. When the abilities of Rab1BQ67L and Rab1BWT to undergo prenylation were compared by metabolic labelling of transiently expressed proteins in cultured human 293 cells, we did not observe a decline in prenylation of the mutant protein as predicted on the basis of the cell-free assays. Moreover, the Q67L mutant was comparable with the wild-type Rab1B in its ability to associate with co-expressed Rab GDP dissociation inhibitors in 293 cells. These findings raise the possibility that unidentified proteins present in intact cells may compensate for the reduced intrinsic GTPase activity of the Q67L mutant, allowing a significant proportion of the nascent Rab1BQ67L to assume a GDP conformation. The differential prenylation of Rab1BQ67L in cell-free systems versus intact cells underscores the importance of evaluating the post-translational modification of specific Rab mutants in vivo, where poorly characterized regulatory proteins may have a significant effect on GTPase activity or nucleotide exchange rates.

  17. Mammalian skin evolution: a reevaluation.

    Science.gov (United States)

    Maderson, P F A

    2003-06-01

    A 1972 model for the evolutionary origin of hair suggested a primary mechanoreceptor role improving behavioral thermoregulation contributed to the success of late Paleozoic mammal-like reptiles. An insulatory role appeared secondarily subsequent to protohair multiplication. That model is updated in light of new data on (a) palaeoecology of mammalian ancestors; (b) involvement of HRPs in keratinization; (c) lipogenic lamellar bodies that form the barrier to cutaneous water loss; and (d) growth factors involved in hair follicle embryogenesis and turnover. It is now proposed that multiplication of sensory protohairs caused by mutations in patterning genes initially protected the delicate barrier tissues and eventually produced the minimal morphology necessary for an insulatory pelage. The latter permitted Mesozoic mammals to occupy the nocturnal niche 'in the shadow of dinosaurs'. When the giant reptiles became extinct, mammals underwent rapid radiation and reemerged as the dominant terrestrial vertebrates.

  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. Mammalian Mitochondrial ncRNA Database.

    Science.gov (United States)

    Anandakumar, Shanmugam; Vijayakumar, Saravanan; Arumugam, Nagarajan; Gromiha, M Michael

    2015-01-01

    Mammalian Mitochondrial ncRNA is a web-based database, which provides specific information on non-coding RNA in mammals. This database includes easy searching, comparing with BLAST and retrieving information on predicted structure and its function about mammalian ncRNAs. The database is available for free at http://www.iitm.ac.in/bioinfo/mmndb/.

  20. Comparison of mechanomyography and acceleromyography for the assessment of rocuronium induced neuromuscular block in myotonic dystrophy type 1.

    NARCIS (Netherlands)

    Vanlinthout, L.E.H.; Booij, L.H.D.J.; Egmond, J. van; Robertson, E.N.

    2010-01-01

    We measured acceleromyography and mechanomyography simultaneously with monitoring of rocuronium-induced neuromuscular block in four patients with myotonic dystrophy type 1. Furthermore, we compared neuromuscular block measures from these patients with those from normal controls from previous studies

  1. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

    NARCIS (Netherlands)

    Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

    2007-01-01

    Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were rando

  2. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study - Efficacy, safety, and pharmacokinetics

    NARCIS (Netherlands)

    Sparr, Harald J.; Vermeyen, Karel M.; Beaufort, Anton M.; Rietbergen, Henk; Proost, Johannes H.; Saldien, Vera; Velik-Salchner, Corinna; Wierda, J. Mark K. H.

    Background: Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated. Methods: Ninety-eight male adult patients were

  3. Neuromuscular Changes and Damage after Isoload versus Isokinetic Eccentric Exercise.

    Science.gov (United States)

    Doguet, Valentin; Nosaka, Kazunori; Plautard, Mathieu; Gross, Raphaël; Guilhem, GaËL; Guével, Arnaud; Jubeau, Marc

    2016-12-01

    This study compared the effects of isoload (IL) and isokinetic (IK) knee extensor eccentric exercises on changes in muscle damage and neuromuscular parameters to test the hypothesis that the changes would be different after IL and IK exercises. Twenty-two young men were paired based on their strength and placed in the IL (N = 11) or the IK (N = 11) group. The IL group performed 15 sets of 10 eccentric contractions with a 150% of predetermined one-repetition maximum load. The IK group performed 15 sets of several maximal eccentric contractions matched set by set for the total amount of work and mean angular velocity with the IL group. Muscle damage markers (voluntary isometric peak torque, muscle soreness, and creatine kinase activity) and neuromuscular variables (e.g., voluntary activation, H-reflex, M-wave, and evoked torque) were measured before, immediately after, and 24, 48, 72, and 96 h postexercise. Voluntary isometric peak torque decreased to the same extent (P = 0.94) in both groups immediately after (IL = -40.6% ± 13.8% vs IK = -42.4% ± 10.2%) to 96 h after the exercise (IL = -21.8% ± 28.5% vs IK = -26.7% ± 23.5%). Neither peak muscle soreness (IL = 48.1 ± 28.2 mm vs IK = 54.7 ± 28.9 mm, P = 0.57) nor creatine kinase activity (IL = 12,811 ± 22,654 U·L vs IK = 15,304 ± 24,739 U·L, P = 0.59) significantly differed between groups. H-reflex (IL = -23% vs IK = -35%) and M-wave (IL = -10% vs IK = -17%) significantly decreased immediately postexercise similarly between groups. The changes in muscle damage and neuromuscular function after the exercise are similar between IL and IK, suggesting that resistance modality has little effects on acute muscle responses.

  4. Quality of life after surgery for neuromuscular scoliosis

    Directory of Open Access Journals (Sweden)

    Peter Obid

    2013-02-01

    Full Text Available Surgery in patients with neuromuscular scoliosis is associated with a higher rate of complications. It is still controversially discussed whether the patients truly benefit from deformity correction. The purpose of this study is to investigate if the quality of life has been improved and if the patients and their caregivers are satisfied with the results of surgery. This is a retrospective clinical outcome study of 46 patients with neuromuscular scoliosis which were treated with primary stable posterior pedicle screw instrumentation and correction. To achieve fusion only autologous bone was used. Follow up was minimum 2 years and maximum 5 years with an average of 36 months. The patients and/or their caregivers received a questionnaire based on the PEDI (pediatric disability inventory and the GMFS (gross motor function score. The patients (and their caregivers were also asked if the quality of life has improved after surgery. Only 32 of 46 patients answered the questionnaire. The answers showed a high approval-rate regarding the patients satisfaction with the surgery and the improvement of quality of life. The questionnaire could be answered from 1 (I do not agree to 4 (I completely agree. The average agreement to the following statements was: i the quality of life has improved: 3.35; ii I am satisfied with surgery: 3.95; iii the operation has fulfilled my expectations: 3.76. The average age at surgery was 12.7 years. The mean pre-operative cobb-angle of the main curve was 83.1° with a correction post-operatively to a mean of 36.9° and 42.6° at final follow-up. That is an average correction of 56.9%. Although spinal fusion in neuromuscular scoliosis is associated with a higher rate of complications our results show that the patients and their caregivers are satisfied with the operation and the quality of life has improved after surgery.

  5. Case report: Neuromuscular block induced by rocuronium following sugammadex administration.

    Science.gov (United States)

    Askin, Tugba; Unver, Suheyla; Oguz, Deniz; Kutay, Kubra

    2017-02-01

    We present a case in which rocuronium was applied for muscle relaxation following the administration of sugammadex. An emergency surgery under general anesthesia was planned for a 43-year-old male patient due to an L1 vertebral corpus and right tibia-fibula shaft fracture. Anesthesia was induced with fentanyl, propofol and lidocaine. After applying only 30mg of the total induction dose of rocuronium, it was learned that the neurological examination should be controlled again from the surgeon because of the controversial of the neurological deficit. As a result, patient awakened from anesthesia. We administered 2mg/kg sugammadex and spontaneous breathing of patient returned immediately. The patient became conscious and orientated immediately afterwards. The neurological examination of the lower extremities was performed. The patient was anesthetized once again and 0.6mg/kg rocuronium was given in order to gain neoromuscular block approximately 10min after sugammadex administration. 2min later, the patient was smoothly intubated. Neuromuscular monitorization was not used because of emergency. We administered 2mg/kg sugammadex at the end of the procedure and the patient was extubated. The most suitable time for the re-establishment of rocuronium following sugammadex is currently unclear. This case showed that neuromuscular block can be effectively re-induced by rocuronium following the reversal of rocuronium-induced neuromuscular block with sugammadex. In this case, we consider that the ability to effectively reuse normal induction doses of rocuronium is an important clinical observation. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Clinical use of creatine in neuromuscular and neurometabolic disorders.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2007-01-01

    Many of the neuromuscular (e.g., muscular dystrophy) and neurometabolic (e.g., mitochondrial cytopathies) disorders share similar final common pathways of cellular dysfunction that may be favorably influenced by creatine monohydrate (CrM) supplementation. Studies using the mdx model of Duchenne muscular dystrophy have found evidence of enhanced mitochondrial function, reduced intra-cellular calcium and improved performance with CrM supplementation. Clinical trials in patients with Duchenne and Becker's muscular dystrophy have shown improved function, fat-free mass, and some evidence of improved bone health with CrM supplementation. In contrast, the improvements in function in myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth) have not been significant. Some studies in patients with mitochondrial cytopathies have shown improved muscle endurance and body composition, yet other studies did not find significant improvements in patients with mitochondrial cytopathy. Lower-dose CrM supplementation in patients with McArdle's disease (myophosphorylase deficiency) improved exercise capacity, yet higher doses actually showed some indication of worsened function. Based upon known cellular pathologies, there are potential benefits from CrM supplementation in patients with steroid myopathy, inflammatory myopathy, myoadenylate deaminase deficiency, and fatty acid oxidation defects. Larger randomized control trials (RCT) using homogeneous patient groups and objective and clinically relevant outcome variables are needed to determine whether creatine supplementation will be of therapeutic benefit to patients with neuromuscular or neurometabolic disorders. Given the relatively low prevalence of some of the neuromuscular and neurometabolic disorders, it will be necessary to use surrogate markers of potential clinical efficacy including markers of oxidative stress, cellular energy charge, and gene expression patterns.

  7. Neuromuscular Responses to Simulated Brazilian Jiu-Jitsu Fights

    Directory of Open Access Journals (Sweden)

    Corrêa da Silva Bruno Victor

    2014-12-01

    Full Text Available The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest. Neuromuscular performance was measured by the bench press throw (BPT and vertical counter movement jump (VCMJ tests, assessed before the 1st fight (Pre and after the last one (Post. Blood lactate (LA was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p < 0.05 increase in VCMJ performance (40.8 ± 5.5 cm Pre vs. 42.0 ± 5.8 cm Post, but no significant changes in the BPT (814 ± 167 W Pre vs. 835 ± 213 W Post were observed. LA concentration increased significantly (p < 0.05 at Post, both in the 1st min and the 15th min of recovery. We concluded that successive simulated BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power was observed.

  8. Dual-function vector for protein expression in both mammalian cells and Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Jespersen, Thomas; Grunnet, M; Angelo, K;

    2002-01-01

    will often engage both oocytes and mammalian cells. Efficient expression of a protein in both systems have thus far only been possible by subcloning the cDNA into two different vectors because several different molecular requirements should be fulfilled to obtain a high protein level in both mammalian cells...... and oocytes. To address this problem, we have constructed a plasmid vector, pXOOM, that can function as a template for expression in both oocytes and mammalian cells. By including all the necessary RNA stability elements for oocyte expression in a standard mammalian expression vector, we have obtained a dual......-function vector capable of supporting protein production in both Xenopus oocytes and CHO-K1 cells at an expression level equivalent to the levels obtained with vectors optimized for either oocyte or mammalian expression. Our functional studies have been performed with hERGI, KCNQ4, and Kv1.3 potassium channels....

  9. Photodynamic inactivation of mammalian viruses and bacteriophages.

    Science.gov (United States)

    Costa, Liliana; Faustino, Maria Amparo F; Neves, Maria Graça P M S; Cunha, Angela; Almeida, Adelaide

    2012-07-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  10. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  11. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Science.gov (United States)

    Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

    2012-01-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

  12. Cardiac involvement in children with neuro-muscular disorders

    Directory of Open Access Journals (Sweden)

    E. N. Arkhipova

    2015-01-01

    Full Text Available Many inherited neuromuscular disorders include cardiac involvement as a typical clinical feature. Among the most common of them is the group of muscular dystrophies. Dilated cardiomyopathy, ventricular arrhythmias, atrial fibrillations, atrioventricular and intraventricular conduction abnormalities, and sudden cardiac death are well known pathological findings in Duchenne muscular dystrophies, myotonic dystrophy type I and 2, Emery-Dreifuss muscular dystrophies and different types of limb-girdle muscular dystrophies and other disorders. Detection of cardiac pathology in patients with different muscular dystrophies is possible with ECG, echocardiography and cardiovascular magnetic resonance imaging, which are recommended for screening and early cardioprotective treatment.

  13. Preventing Ischial Pressure Ulcers: I. Review of Neuromuscular Electrical Stimulation

    Directory of Open Access Journals (Sweden)

    Hilton M. Kaplan

    2011-01-01

    Full Text Available Objective: Pressure ulcers (PUs are common and debilitating wounds that arise when immobilized patients cannot shift their weight. Treatment is expensive and recurrence rates are high. Pathophysiological mechanisms include reduced bulk and perfusion of chronically atrophic muscles as well as prolonged occlusion of blood flow to soft tissues from lack of voluntary postural shifting of body weight. This has suggested that PUs might be prevented by reanimating the paralyzed muscles using neuromuscular electrical stimulation (NMES. A review of the published literature over the past 2 decades is detailed.

  14. Calcium channels, neuromuscular synaptic transmission and neurological diseases.

    Science.gov (United States)

    Urbano, Francisco J; Pagani, Mario R; Uchitel, Osvaldo D

    2008-09-15

    Voltage-dependent calcium channels are essential in neuronal signaling and synaptic transmission, and their functional alterations underlie numerous human disorders whether monogenic (e.g., ataxia, migraine, etc.) or autoimmune. We review recent work on Ca(V)2.1 or P/Q channelopathies, mostly using neuromuscular junction preparations, and focus specially on the functional hierarchy among the calcium channels recruited to mediate neurotransmitter release when Ca(V)2.1 channels are mutated or depleted. In either case, synaptic transmission is greatly compromised; evidently, none of the reported functional replacements with other calcium channels compensates fully.

  15. MRI in neuromuscular disorders; MRT bei neuromuskulaeren Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Fischmann, Arne [Klinik St. Anna, Luzern (Switzerland). Inst. fuer Radiologie und Nuklearmedizin; Fischer, Dirk [Kantonsspital Bruderholz (Switzerland)

    2014-03-15

    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.)

  16. Assessing neuromuscular mechanisms in human-exoskeleton interaction.

    Science.gov (United States)

    Sylla, N; Bonnet, V; Venture, G; Armande, N; Fraisse, P

    2014-01-01

    In this study, we propose to evaluate a 7 DOF exoskeleton in terms of motion control. Using criteria from the human motor control literature, inverse optimization was performed to assess an industrial screwing movement. The results of our study show that the hybrid composition of the free arm movement was accurately determined. At contrary, when wearing the exoskeleton, which produces an arbitrary determined torque compensation, the motion is different from the naturally adopted one. This study is part of the evaluation and comprehension of the complex neuromuscular mechanism resulting in wearing an exoskeleton several hours per day for industrial tasks assistance.

  17. El vendaje neuromuscular en podología

    OpenAIRE

    Vázquez Amela, F. Xavier (Francesc Xavier); Verdaguer Sanmartí, Josefina; Lluch Fruns, Joan; Genís Barniol, Silvia

    2008-01-01

    Desde hace unos cinco años la introducción en España de los vendajes neuromusculares ha ido cobrando mayor relevancia, llegando el momento más álgido las imágenes de las olimpiadas de Beijing, donde se pudo observar el uso de este tipo de vendajes en muchas de las disciplinas deportivas. En este artículo pretendemos hacer una introducción general a este tipo de vendajes y la aplicación en patologías podales de gran incidencia en nuestras consultas.

  18. Active zone stability: insights from fly neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Xiaolin Tian

    2015-01-01

    Full Text Available The presynaptic active zone is a dynamic structure that orchestrates regulated release of neurotransmitters. Developmental and aging processes, and changes in neuronal network activity can all modulate the number, size and composition of active zone and thereby synaptic efficacy. However, very little is known about the mechanism that controls the structural stability of active zone. By studying a model synapse, the Drosophila neuromuscular junction, our recent work shed light on how two scaffolding proteins at the active zone regulate active zone stability by promoting a localized dephosphorylation event at the nerve terminal. Here we discuss the major insights from our findings and their implications for future research.

  19. Correction of organophosphate-induced neuromuscular blockade by diphenhydramine.

    Science.gov (United States)

    Clemmons, R M; Meyer, D J; Sundlof, S F; Rappaport, J J; Fossler, M E; Hubbell, J; Dorsey-Lee, M R

    1984-10-01

    Dogs exposed to topical organophosphate (fenthion) developed decreased plasma and muscle cholinesterase activities. After 2 doses were applied (1 week between doses), plasma concentrations declined 80% and muscle cholinesterase activity was reduced by 56%. Decremental responses to repetitive nerve stimulation developed after fenthion administration. Diphenhydramine, but not placebo, corrected the electrical abnormalities caused by organophosphate application, but without altering plasma or muscle cholinesterase activity. Control dogs housed in the same kennel demonstrated a slight decrease (18%) of plasma cholinesterase, which indicates that there may be potential cross contamination. Diphenydramine may be effective in treating organophosphate-induced neuromuscular weakness which is refractory to other forms of therapy.

  20. Time course and dimensions of postural control changes following neuromuscular training in youth field hockey athletes

    NARCIS (Netherlands)

    Zech, Astrid; Klahn, Philipp; Hoeft, Jon; Eulenburg, Christine Zu; Steib, Simon

    2014-01-01

    Purpose Injury prevention effects of neuromuscular training have been partly attributed to postural control adaptations. Uncertainty exists regarding the magnitude of these adaptations and on how they can be adequately monitored. The objective was to determine the time course of neuromuscular traini

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

    NARCIS (Netherlands)

    Viby-Mogensen, J; Ostergaard, D; Donati, F; Fisher, D; Hunter, J; Kampmann, JP; Kopman, A; Proost, JH; Rasmussen, SN; Skovgaard, LT; Varin, F; Wright, PMC

    2000-01-01

    In September 1997, an international consensus conference on standardization of studies of neuromuscular blocking agents was held in Copenhagen, Denmark. Based on the conference, a set of guidelines fur good clinical research practice (GCRT) in pharmacokinetic studies of neuromuscular blocking agents

  2. 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

  3. Motor function measure: validation of a short form for young children with neuromuscular diseases.

    Science.gov (United States)

    de Lattre, Capucine; Payan, Christine; Vuillerot, Carole; Rippert, Pascal; de Castro, Denis; Bérard, Carole; Poirot, Isabelle

    2013-11-01

    To validate a useful version of the Motor Function Measure (MFM) in children with neuromuscular diseases aged .90), and discriminant validity was good. The MFM-20 can be used as an outcome measure for assessment of motor function in young children with neuromuscular disease. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  4. The prejunctional inhibitory effect of suramin on neuromuscular transmission in vitro

    NARCIS (Netherlands)

    Henning, RH; Rowan, EG; Braga, MFM; Nelemans, A; Harvey, AL

    1996-01-01

    The P-2 purinoceptor antagonist suramin reverses skeletal muscle paralysis evoked by non-depolarizing neuromuscular blocking agents in vitro and in vivo. To further study the action of suramin on neuromuscular transmission, (miniature) endplate potentials ((m.)e.p.ps), motor nerve terminal currents

  5. Neuromuscular blockade for optimising surgical conditions during abdominal and gynaecological surgery

    DEFF Research Database (Denmark)

    Madsen, M V; Staehr-Rye, A K; Gätke, M R

    2015-01-01

    BACKGROUND: The level of neuromuscular blockade (NMB) that provides optimal surgical conditions during abdominal surgery has not been well established. The aim of this systematic review was to evaluate current evidence on the use of neuromuscular blocking agents in order to optimise surgical cond...

  6. Time course and dimensions of postural control changes following neuromuscular training in youth field hockey athletes

    NARCIS (Netherlands)

    Zech, Astrid; Klahn, Philipp; Hoeft, Jon; Eulenburg, Christine Zu; Steib, Simon

    2014-01-01

    Purpose Injury prevention effects of neuromuscular training have been partly attributed to postural control adaptations. Uncertainty exists regarding the magnitude of these adaptations and on how they can be adequately monitored. The objective was to determine the time course of neuromuscular traini

  7. Critical illness polyneuropathy and myopathy; a neuromuscular disorder encountered in the intensive care unit

    NARCIS (Netherlands)

    M-A.C.J. de Letter

    2001-01-01

    textabstractPatients with neuromuscular disorders encountered on the ICU can be divided into two main categories. One category has been admitted to the intensive care unit (ICU) due to an underlying neuromuscular disorder, mainly the Guillam Barre Syndrome ( GBS) and myasthenia gravis. The other cat

  8. Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Pol, F. van de; Bom, A.; Booij, L.H.D.J.

    2006-01-01

    BACKGROUND: Binding of the steroidal molecule of rocuronium by a cyclodextrin is a new concept for reversal of neuromuscular block. The present study evaluated the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative, to reverse constant neuromuscular block of about 90% induced

  9. Reversal of rocuronium-induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Booij, L.H.D.J.; Driessen, J.J.

    2009-01-01

    A case is reported in which a child with Duchenne muscular dystrophy received a dose of sugammadex to reverse a rocuronium-induced profound neuromuscular block. Sugammadex is the first selective relaxant binding agent and reverses rocuronium- and vecuronium-induced neuromuscular block. A fast and

  10. 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

  11. An 8-Week Neuromuscular Exercise Program for Patients With Mild to Moderate Knee Osteoarthritis

    DEFF Research Database (Denmark)

    Clausen, Brian; Holsgaard-Larsen, Anders; Roos, Ewa M

    2017-01-01

    OBJECTIVE:   To describe the feasibility of a neuromuscular exercise (NEMEX) program in patients with mild to moderate knee osteoarthritis (KOA). BACKGROUND:   Neuromuscular exercise has been increasingly used in patients with osteoarthritis to achieve sensorimotor control and improved daily func...

  12. Plantar flexor neuromuscular adjustments following match-play football in hot and cool conditions

    DEFF Research Database (Denmark)

    Girard, O; Nybo, Lars; Mohr, Magni;

    2015-01-01

    We assessed neuromuscular fatigue and recovery of the plantar flexors after playing football with or without severe heat stress. Neuromuscular characteristics of the plantar flexors were assessed in 17 male players at baseline and ∼30 min, 24, and 48 h after two 90-min football matches in tempera...

  13. Supercomplexes in the respiratory chains of yeast and mammalian mitochondria.

    Science.gov (United States)

    Schägger, H; Pfeiffer, K

    2000-04-17

    Around 30-40 years after the first isolation of the five complexes of oxidative phosphorylation from mammalian mitochondria, we present data that fundamentally change the paradigm of how the yeast and mammalian system of oxidative phosphorylation is organized. The complexes are not randomly distributed within the inner mitochondrial membrane, but assemble into supramolecular structures. We show that all cytochrome c oxidase (complex IV) of Saccharomyces cerevisiae is bound to cytochrome c reductase (complex III), which exists in three forms: the free dimer, and two supercomplexes comprising an additional one or two complex IV monomers. The distribution between these forms varies with growth conditions. In mammalian mitochondria, almost all complex I is assembled into supercomplexes comprising complexes I and III and up to four copies of complex IV, which guided us to present a model for a network of respiratory chain complexes: a 'respirasome'. A fraction of total bovine ATP synthase (complex V) was isolated in dimeric form, suggesting that a dimeric state is not limited to S.cerevisiae, but also exists in mammalian mitochondria.

  14. Lung development of monotremes: evidence for the mammalian morphotype.

    Science.gov (United States)

    Ferner, Kirsten; Zeller, Ulrich; Renfree, Marilyn B

    2009-02-01

    The reproductive strategies and the extent of development of neonates differ markedly between the three extant mammalian groups: the Monotremata, Marsupialia, and Eutheria. Monotremes and marsupials produce highly altricial offspring whereas the neonates of eutherian mammals range from altricial to precocial. The ability of the newborn mammal to leave the environment in which it developed depends highly on the degree of maturation of the cardio-respiratory system at the time of birth. The lung structure is thus a reflection of the metabolic capacity of neonates. The lung development in monotremes (Ornithorhynchus anatinus, Tachyglossus aculeatus), in one marsupial (Monodelphis domestica), and one altricial eutherian (Suncus murinus) species was examined. The results and additional data from the literature were integrated into a morphotype reconstruction of the lung structure of the mammalian neonate. The lung parenchyma of monotremes and marsupials was at the early terminal air sac stage at birth, with large terminal air sacs. The lung developed slowly. In contrast, altricial eutherian neonates had more advanced lungs at the late terminal air sac stage and postnatally, lung maturation proceeded rapidly. The mammalian lung is highly conserved in many respects between monotreme, marsupial, and eutherian species and the structural differences in the neonatal lungs can be explained mainly by different developmental rates. The lung structure of newborn marsupials and monotremes thus resembles the ancestral condition of the mammalian lung at birth, whereas the eutherian newborns have a more mature lung structure.

  15. Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction.

    Science.gov (United States)

    Borodinsky, Laura N; Spitzer, Nicholas C

    2007-01-02

    Signaling in the nervous system requires matching of neurotransmitter receptors with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine receptors are not fully understood. Because alterations in neuronal calcium spike activity alter transmitter specification in embryonic spinal neurons, we hypothesized that receptor expression in postsynaptic cells follows changes in transmitter expression to achieve this specific match. We find that embryonic vertebrate striated muscle cells normally express receptors for glutamate, GABA, and glycine as well as for acetylcholine. As maturation progresses, acetylcholine receptor expression prevails. Receptor selection is altered when early neuronal calcium-dependent activity is perturbed, and remaining receptor populations parallel changes in transmitter phenotype. In these cases, glutamatergic, GABAergic, and glycinergic synaptic currents are recorded from muscle cells, demonstrating that activity regulates matching of transmitters and their receptors in the assembly of functional synapses.

  16. 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.

  17. Evolution and Structure of Neuromuscular Systems in Spiralian Meiofauna

    DEFF Research Database (Denmark)

    Bekkouche, Nicolas Tarik

    Spiralia is a vast clade of Metazoa comprising large and well-known organisms, e.g., Annelida and Mollusca, but also many microscopic animals such as Gastrotricha or Gnathifera (including, Rotifera) of the often overlooked meiofauna. To date, the phylogeny and morphology of Spiralia have been...... difficult to resolve and understand. The present thesis focuses on spiralian meiofauna to i) reconstruct the phylogeny of this clade using transcriptomics and place enigmatic meiofaunal taxa and ii) resolve the morphology of three important taxa, mainly employing confocal laser scanning microscopy...... and immunohistochemistry: the spiralian incertae sedis, Lobatocerebrum, the recently described monospecific phylum Micrognathozoa (Gnathifera), and an early branching Gastrotricha, Diuronotus aspetos. The new spiralian phylogeny reveals with high support that the deepest branches of Spiralia consist of meiofaunal...

  18. Species differences in the effects of prostaglandins on inositol trisphosphate accumulation, phosphatidic acid formation, myosin light chain phosphorylation and contraction in iris sphincter of the mammalian eye: interaction with the cyclic AMP system.

    Science.gov (United States)

    Yousufzai, S Y; Chen, A L; Abdel-Latif, A A

    1988-12-01

    Comparative studies on the effects of prostaglandins (PGs) on 1,2-diacylglycerol, measured as phosphatidic acid (PA), and inositol trisphosphate (IP3) production, cyclic AMP (cAMP) formation, myosin light chain (MLC) phosphorylation and contraction in the iris sphincter smooth muscle of rabbit, bovine and other mammalian species were undertaken and functional and biochemical relationships between the IP3-Ca++ and cAMP second messenger systems were demonstrated. The findings obtained from these studies can be summarized as follows: 1) all PGs investigated, including PGE2, PGF2 alpha, PGF2 alpha-ester, PGE1 and PGA2 increased IP3 accumulation and PA formation, and the extent of stimulation was dependent on the animal species. Thus, PGF2 alpha-ester (1 microM), the most potent of the PGs, increased IP3 accumulation in rabbit and bovine sphincters by 33 and 58%, respectively, and increased PA formation by 67 and 56%, respectively. The PG increased IP3 accumulation in both rabbit and bovine sphincters very rapidly (T1/2 values about 26 sec) and in a dose-dependent manner. 2) The PG had no effect on MLC phosphorylation in the rabbit sphincter, but it increased that of the bovine by 36%. 3) The PG increased cAMP formation by 75% in the rabbit sphincter but it had no effect on that of the bovine. 4) The PG induced a maximal contractile response in the bovine sphincter but it had no effect on that of the rabbit. 5) In the bovine, PGA2 induced IP3 accumulation and contraction, without an effect on cAMP formation; however, in the rabbit, cat and dog it increased cAMP formation and had no effect on IP3 accumulation and contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Vellozia flavicans Mart. ex Schult. hydroalcoholic extract inhibits the neuromuscular blockade induced by Bothrops jararacussu venom

    Science.gov (United States)

    2014-01-01

    Background Snakebite is a significant public health issue in tropical countries. In Brazil, some of the most common snake envenomations are from Bothrops. Bothrops bites trigger local and systemic effects including edema, pain, erythema, cyanosis, infections, and necrosis. Vellozia flavicans is a plant from the Brazilian “cerrado” (savanna) that is popularly used as an anti-inflammatory medicine. Since inflammation develops quickly after Bothrops bites, which can lead to infection, the aim of the present study was to observe possible anti-snake venom and antimicrobial activities of V. flavicans (Vf). Methods The chromatographic profile of the main constituents from the Vf leaf hydroalcoholic extract was obtained by thin-layer chromatography (TLC). The anti-snake venom activity was measured by Vf’s ability to neutralize the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu) in a mouse phrenic nerve-diaphragm model (PND). After a 20 min incubation, preparations of PND were added to Tyrode’s solution (control); Vf (0.2, 0.5, 1, and 2 mg/mL); 40 μg/mL Bjssu; pre-incubation for 30 min with Bjssu and 1 mg/mL Vf; and a Bjssu pretreated preparation (for 10 min) followed by 1 mg/mL Vf. Myographic recording was performed, and the contractile responses were recorded. The antimicrobial activity (minimum inhibitory concentration [MIC] and minimum bactericidal concentration [MBC]) was obtained for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, using gentamicin and vancomycin as positive controls. Results TLC analysis yielded several compounds from Vf, such as flavonoids (quercetin) and phenolic acids (chlorogenic acid). Bjssu completely blocked the contractile responses of PND preparations, while Vf preserved 97% (±10%) of the contractile responses when incubated with Bjssu. In the PND pretreated with Bjssu, Vf was able to inhibit the neuromuscular blockade progress. MIC and MBC of Vf ranged

  20. Assembly, plasticity and selective vulnerability to disease of mouse neuromuscular junctions.

    Science.gov (United States)

    Santos, Alexandre Ferrão; Caroni, Pico

    2003-01-01

    Although physiological differences among neuromuscular junctions (NMJs) have long been known, NMJs have usually been considered as one type of synapse, restricting their potential value as model systems to investigate mechanisms controlling synapse assembly and plasticity. Here we discuss recent evidence that skeletal muscles in the mouse can be subdivided into two previously unrecognized subtypes, designated FaSyn and DeSyn muscles. These muscles differ in the pattern of neuromuscular synaptogenesis during embryonic development. Differences between classes are intrinsic to the muscles, and manifest in the absence of innervation or agrin. The distinct rates of synaptogenesis in the periphery may influence processes of circuit maturation through retrograde signals. While NMJs on FaSyn and DeSyn muscles exhibit a comparable anatomical organization in postnatal mice, treatments that challenge synaptic stability result in nerve sprouting, NMJ remodeling, and ectopic synaptogenesis selectively on DeSyn muscles. This anatomical plasticity of NMJs diminishes greatly between 2 and 6 months postnatally. NMJs lacking this plasticity are lost selectively and very early on in mouse models of motoneuron disease, suggesting that disease-associated motoneuron dysfunction may fail to initiate maintenance processes at "non-plastic" NMJs. Transgenic mice overexpressing growth-promoting proteins in motoneurons exhibit greatly enhanced stimulus-induced sprouting restricted to DeSyn muscles, supporting the notion that anatomical plasticity at the NMJ is primarily controlled by processes in the postsynaptic muscle. The discovery that entire muscles in the mouse differ substantially in the anatomical plasticity of their synapses establishes NMJs as a uniquely advantageous experimental system to investigate mechanisms controlling synaptic rearrangements at defined synapses in vivo.

  1. Neuromuscular rate of force development deficit in Parkinson disease.

    Science.gov (United States)

    Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

    2017-06-01

    Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

  2. Sarcocystis fayeri in skeletal muscle of horses with neuromuscular disease.

    Science.gov (United States)

    Aleman, Monica; Shapiro, Karen; Sisó, Silvia; Williams, Diane C; Rejmanek, Daniel; Aguilar, Beatriz; Conrad, Patricia A

    2016-01-01

    Recent reports of Sarcocystis fayeri-induced toxicity in people consuming horse meat warrant investigation on the prevalence and molecular characterization of Sarcocystis spp. infection in horses. Sarcocysts in skeletal muscle of horses have been commonly regarded as an incidental finding. In this study, we investigated the prevalence of sarcocysts in skeletal muscle of horses with neuromuscular disease. Our findings indicated that S. fayeri infection was common in young mature horses with neuromuscular disease and could be associated with myopathic and neurogenic processes. The number of infected muscles and number of sarcocysts per muscle were significantly higher in diseased than in control horses. S. fayeri was predominantly found in low oxidative highly glycolytic myofibers. This pathogen had a high glycolytic metabolism. Common clinical signs of disease included muscle atrophy, weakness with or without apparent muscle pain, gait deficits, and dysphagia in horses with involvement of the tongue and esophagus. Horses with myositis were lethargic, apparently painful, stiff, and reluctant to move. Similar to humans, sarcocystosis and cardiomyopathy can occur in horses. This study did not establish causality but supported a possible association (8.9% of cases) with disease. The assumption of Sarcocysts spp. being an incidental finding in every case might be inaccurate.

  3. Mammalian N-acetylglutamate synthase.

    Science.gov (United States)

    Morizono, Hiroki; Caldovic, Ljubica; Shi, Dashuang; Tuchman, Mendel

    2004-04-01

    N-Acetylglutamate synthase (NAGS, E.C. 2.3.1.1) is a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthetase I (CPSI). The mouse and human NAGS genes have been identified based on similarity to regions of NAGS from Neurospora crassa and cloned from liver cDNA libraries. These genes were shown to complement an argA- (NAGS) deficient Escherichia coli strain, and enzymatic activity of the proteins was confirmed by a new stable isotope dilution assay. The deduced amino acid sequence of mammalian NAGS contains a putative mitochondrial-targeting signal at the N-terminus. The mouse NAGS preprotein was overexpressed in insect cells to determine post-translational modifications and two processed proteins with different N-terminal truncations have been identified. Sequence analysis using a hidden Markov model suggests that the vertebrate NAGS protein contains domains with a carbamate kinase fold and an acyl-CoA N-acyltransferase fold, and protein crystallization experiments are currently underway. Inherited NAGS deficiency results in hyperammonemia, presumably due to the loss of CPSI activity. We, and others, have recently identified mutations in families with neonatal and late-onset NAGS deficiency and the identification of the gene has now made carrier testing and prenatal diagnosis feasible. A structural analog of NAG, carbamylglutamate, has been shown to bind and activate CPSI, and several patients have been reported to respond favorably to this drug (Carbaglu).

  4. Retinal research using the perfused mammalian eye.

    Science.gov (United States)

    Niemeyer, G

    2001-05-01

    The effort to isolate and maintain alive in vitro an intact mammalian eye is rewarded by the full control provided over the arterial input and exclusion of systemic regulatory or compensatory mechanisms. Electrical recording of typical light-evoked field potentials from retina and optic nerve can be complemented by single-cell recording. Thus, light-induced electrical activity reflects the function of the retinal pigment epithelium, of the layers of the retina and of the ganglion cells or their axons. Retinal function in vitro is documented by electrophysiological and morphological methods revealing subtle features of retinal information processing as well as optic nerve signals that approach-at threshold stimulus intensity-the human psychophysical threshold. Such sensitivity of third-order retinal neurons is described for the first time. This well controlled in vitro preparation has been used successfully for biophysical, metabolic and pharmacological studies. Examples are provided that demonstrate the marked sensibility of the rod system to changes in glucose supply. Moreover, histochemical identification of glycogen stores revealed labeling of the second- and third-order neurons subserving the rod system, in addition to labeling of Müller (glial) cells in the cat retina. The glycogen content of the cat retina is augmented by prolonged anesthesia, largely depleted by ischemia after enucleation and enhanced by insulin. Pharmacological experiments using agonists and antagonists of putative retinal neurotransmitters are summarized and outlined using the muscarinic cholinergic agonist QNB as an example. Actions and uptake of the neuromodulator adenosine are presented in detail, including inhibitory effects on physiologically characterized ganglion cells. Neuronal effects of adenosine are distinguished from those resulting from vasodilatation and from glycogenolysis induced by the neuromodulator. To open the blood-retina barrier, a hyperosmotic challenge can be

  5. How difficult is inference of mammalian causal gene regulatory networks?

    Directory of Open Access Journals (Sweden)

    Djordje Djordjevic

    Full Text Available Gene regulatory networks (GRNs play a central role in systems biology, especially in the study of mammalian organ development. One key question remains largely unanswered: Is it possible to infer mammalian causal GRNs using observable gene co-expression patterns alone? We assembled two mouse GRN datasets (embryonic tooth and heart and matching microarray gene expression profiles to systematically investigate the difficulties of mammalian causal GRN inference. The GRNs were assembled based on > 2,000 pieces of experimental genetic perturbation evidence from manually reading > 150 primary research articles. Each piece of perturbation evidence records the qualitative change of the expression of one gene following knock-down or over-expression of another gene. Our data have thorough annotation of tissue types and embryonic stages, as well as the type of regulation (activation, inhibition and no effect, which uniquely allows us to estimate both sensitivity and specificity of the inference of tissue specific causal GRN edges. Using these unprecedented datasets, we found that gene co-expression does not reliably distinguish true positive from false positive interactions, making inference of GRN in mammalian development very difficult. Nonetheless, if we have expression profiling data from genetic or molecular perturbation experiments, such as gene knock-out or signalling stimulation, it is possible to use the set of differentially expressed genes to recover causal regulatory relationships with good sensitivity and specificity. Our result supports the importance of using perturbation experimental data in causal network reconstruction. Furthermore, we showed that causal gene regulatory relationship can be highly cell type or developmental stage specific, suggesting the importance of employing expression profiles from homogeneous cell populations. This study provides essential datasets and empirical evidence to guide the development of new GRN inference

  6. How difficult is inference of mammalian causal gene regulatory networks?

    Science.gov (United States)

    Djordjevic, Djordje; Yang, Andrian; Zadoorian, Armella; Rungrugeecharoen, Kevin; Ho, Joshua W K

    2014-01-01

    Gene regulatory networks (GRNs) play a central role in systems biology, especially in the study of mammalian organ development. One key question remains largely unanswered: Is it possible to infer mammalian causal GRNs using observable gene co-expression patterns alone? We assembled two mouse GRN datasets (embryonic tooth and heart) and matching microarray gene expression profiles to systematically investigate the difficulties of mammalian causal GRN inference. The GRNs were assembled based on > 2,000 pieces of experimental genetic perturbation evidence from manually reading > 150 primary research articles. Each piece of perturbation evidence records the qualitative change of the expression of one gene following knock-down or over-expression of another gene. Our data have thorough annotation of tissue types and embryonic stages, as well as the type of regulation (activation, inhibition and no effect), which uniquely allows us to estimate both sensitivity and specificity of the inference of tissue specific causal GRN edges. Using these unprecedented datasets, we found that gene co-expression does not reliably distinguish true positive from false positive interactions, making inference of GRN in mammalian development very difficult. Nonetheless, if we have expression profiling data from genetic or molecular perturbation experiments, such as gene knock-out or signalling stimulation, it is possible to use the set of differentially expressed genes to recover causal regulatory relationships with good sensitivity and specificity. Our result supports the importance of using perturbation experimental data in causal network reconstruction. Furthermore, we showed that causal gene regulatory relationship can be highly cell type or developmental stage specific, suggesting the importance of employing expression profiles from homogeneous cell populations. This study provides essential datasets and empirical evidence to guide the development of new GRN inference methods for

  7. Functional expression of mammalian receptors and membrane channels in different cells.

    Science.gov (United States)

    Eifler, Nora; Duckely, Myriam; Sumanovski, Lazar T; Egan, Terrance M; Oksche, Alexander; Konopka, James B; Lüthi, Anita; Engel, Andreas; Werten, Paul J L

    2007-08-01

    In native tissues, the majority of medically important membrane proteins is only present at low concentrations, making their overexpression in recombinant systems a prerequisite for structural studies. Here, we explore the commonly used eukaryotic expression systems-yeast, baculovirus/insect cells (Sf9) and Semliki Forest Virus (SFV)/mammalian cells-for the expression of seven different eukaryotic membrane proteins from a variety of protein families. The expression levels, quality, biological activity, localization and solubility of all expressed proteins are compared in order to identify the advantages of one system over the other. SFV-transfected mammalian cell lines provide the closest to native environment for the expression of mammalian membrane proteins, and they exhibited the best overall performance. But depending on the protein, baculovirus-infected Sf9 cells performed almost as well as mammalian cells. The lowest expression levels for the proteins tested here were obtained in yeast.

  8. Nitric oxide negatively regulates mammalian adult neurogenesis

    Science.gov (United States)

    Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

    2003-08-01

    Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

  9. Crude subcellular fractionation of cultured mammalian cell lines

    OpenAIRE

    Holden Paul; Horton William A

    2009-01-01

    Abstract Background The expression and study of recombinant proteins in mammalian culture systems can be complicated during the cell lysis procedure by contaminating proteins from cellular compartments distinct from those within which the protein of interest resides and also by solubility issues that may arise from the use of a single lysis buffer. Partial subcellular fractionation using buffers of increasing stringency, rather than whole cell lysis is one way in which to avoid or reduce this...

  10. Endogenous peripheral neuromodulators of the mammalian taste bud.

    Science.gov (United States)

    Dando, Robin

    2010-10-01

    The sensitivity of the mammalian taste system displays a degree of plasticity based on short-term nutritional requirements. Deficiency in a particular substance may lead to a perceived increase in palatability of this substance, providing an additional drive to redress this nutritional imbalance through modification of intake. This alteration occurs not only in the brain but also, before any higher level processing has occurred, in the taste buds themselves. A brief review of recent advances is offered.

  11. Effect of methylprednisolone on mammalian neuronal networks in vitro.

    Science.gov (United States)

    Wittstock, Matthias; Rommer, Paulus S; Schiffmann, Florian; Jügelt, Konstantin; Stüwe, Simone; Benecke, Reiner; Schiffmann, Dietmar; Zettl, Uwe K

    2015-01-01

    Glucocorticosteroids (GCS) are widely used for the treatment of neurological diseases, e.g. multiple sclerosis. High levels of GCS are toxic to the central nervous system and can produce adverse effects. The effect of methylprednisolone (MP) on mammalian neuronal networks was studied in vitro. We demonstrate a dose-dependent excitatory effect of MP on cultured neuronal networks, followed by a shut-down of electrical activity using the microelectrode array technique.

  12. Enzymology of Mammalian DNA Methyltransferases.

    Science.gov (United States)

    Jurkowska, Renata Z; Jeltsch, Albert

    2016-01-01

    DNA methylation is currently one of the hottest topics in basic and biomedical research. Despite tremendous progress in understanding the structures and biochemical properties of the mammalian DNA nucleotide methyltransferases (DNMTs), principles of their regulation in cells have only begun to be uncovered. In mammals, DNA methylation is introduced by the DNMT1, DNMT3A, and DNMT3B enzymes, which are all large multi-domain proteins. These enzymes contain a catalytic C-terminal domain with a characteristic cytosine-C5 methyltransferase fold and an N-terminal part with different domains that interacts with other proteins and chromatin and is involved in targeting and regulation of the DNMTs. The subnuclear localization of the DNMT enzymes plays an important role in their biological function: DNMT1 is localized to replicating DNA via interaction with PCNA and UHRF1. DNMT3 enzymes bind to heterochromatin via protein multimerization and are targeted to chromatin by their ADD and PWWP domains. Recently, a novel regulatory mechanism has been discovered in DNMTs, as latest structural and functional data demonstrated that the catalytic activities of all three enzymes are under tight allosteric control of their N-terminal domains having autoinhibitory functions. This mechanism provides numerous possibilities for the precise regulation of the methyltransferases via controlling the binding and release of autoinhibitory domains by protein factors, noncoding RNAs, or by posttranslational modifications of the DNMTs. In this chapter, we summarize key enzymatic properties of DNMTs, including their specificity and processivity, and afterward we focus on the regulation of their activity and targeting via allosteric processes, protein interactors, and posttranslational modifications.

  13. Mammalian synthetic biology: emerging medical applications.

    Science.gov (United States)

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

    2015-05-06

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  14. Bats and Rodents Shape Mammalian Retroviral Phylogeny.

    Science.gov (United States)

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-11-09

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general.

  15. Rotation of single live mammalian cells using dynamic holographic optical tweezers

    Science.gov (United States)

    Bin Cao; Kelbauskas, Laimonas; Chan, Samantha; Shetty, Rishabh M.; Smith, Dean; Meldrum, Deirdre R.

    2017-05-01

    We report on a method for rotating single mammalian cells about an axis perpendicular to the optical system axis through the imaging plane using dynamic holographic optical tweezers (HOTs). Two optical traps are created on the opposite edges of a mammalian cell and are continuously transitioned through the imaging plane along the circumference of the cell in opposite directions, thus providing the torque to rotate the cell in a controlled fashion. The method enables a complete 360° rotation of live single mammalian cells with spherical or near-to spherical shape in 3D space, and represents a useful tool suitable for the single cell analysis field, including tomographic imaging.

  16. Consecuencias clínicas de las alteraciones neuromusculares en el paciente crítico Clinical consequences of neuromuscular impairments in critically ill patients

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    A. Mesejo

    2006-05-01

    de potenciales motores en la polineuropatía axonal. La crisis miasténica afecta a la unión neuromuscular y su diagnóstico suele ser más fácil al tener en la mayoría de los casos un diagnóstico previo de miastenia gravis.La debilidad muscular aumenta durante la actividad repetida (fatiga muscular y mejora con el reposo. Su confirmación diagnóstica se realiza con el test del edofronio y con la estimulación nerviosa repetitiva, que provoca una rápida disminución del 10-15% en la amplitud de las respuestas provocadas. La miopatía del paciente crítico se localiza en el músculo y provoca una debilidad generalizada con cuadriparesia, muy similar a la de la polineuropatía, que impide o retrasa la desconexión de la ventilación mecánica y que en sus grados avanzados puede provocar un aumento de CPK y mioglobina, junto con alteraciones en la exploración neurofisiológica. Esta última es difícil de discernir de la encontrada en la polineuropatía, aunque la normalidad en los potenciales de acción sensitiva y la redución en el potencial de ación motora con estimulación muscular directa, puede ayudar a diferenciarlos. El pronóstico funcional de las alteraciones musculares primarias suele ser bastante bueno, pero tanto la polineuropatía como la miopatía evolucionan lentamente a lo largo de semanas o meses, pudiendo quedar un importante déficit residual a los dos años en los casos más graves.Neuromuscular pathology in the critically ill patient develops within two settings: primary neurological diseases that require admission in the Intensive Care Medicine Unit for close monitoring or mechanical ventilation, and peripheral nervous system manifestations secondary to critical systemic diseases. The most frequent conditions in the first group are Guillain-Barré syndrome and Myasthenia Gravis, and in the second group, polyneuropathy and myopathy of the critically ill patient. The most commonly shared clinical pattern is the development of severe

  17. Functional study of mammalian Neph proteins in Drosophila melanogaster.

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    Martin Helmstädter

    Full Text Available Neph molecules are highly conserved immunoglobulin superfamily proteins (IgSF which are essential for multiple morphogenetic processes, including glomerular development in mammals and neuronal as well as nephrocyte development in D. melanogaster. While D. melanogaster expresses two Neph-like proteins (Kirre and IrreC/Rst, three Neph proteins (Neph1-3 are expressed in the mammalian system. However, although these molecules are highly abundant, their molecular functions are still poorly understood. Here we report on a fly system in which we overexpress and replace endogenous Neph homologs with mammalian Neph1-3 proteins to identify functional Neph protein networks required for neuronal and nephrocyte development. Misexpression of Neph1, but neither Neph2 nor Neph3, phenocopies the overexpression of endogenous Neph molecules suggesting a functional diversity of mammalian Neph family proteins. Moreover, structure-function analysis identified a conserved and specific Neph1 protein motif that appears to be required for the functional replacement of Kirre. Hereby, we establish D. melanogaster as a genetic system to specifically model molecular Neph1 functions in vivo and identify a conserved amino acid motif linking Neph1 to Drosophila Kirre function.

  18. Review of Quantitative Structure - Activity Relationships for Acute Mammalian Toxicity

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    Iglika Lessigiarska

    2006-12-01

    Full Text Available This paper reviews Quantitative Structure-Activity Relationship (QSAR models for acute mammalian toxicity published in the last decade. A number of QSAR models based on cytotoxicity data from mammalian cell lines are also included because of their possible use as a surrogate system for predicting acute toxicity to mammals. On the basis of the review, the following conclusions can be made: i a relatively small number of models for in vivo toxicity are published in the literature. This is due to the nature of the endpoint - acute systemic toxicity is usually related to whole body phenomena and therefore is very complex. The complexity of the mechanisms involved leads to difficulties in the QSAR modelling; ii most QSAR models identify hydrophobicity as a parameter of high importance for the modelled toxicity. In addition, many models indicate the role of the electronic and steric effects; iii most of the literature-based models are restricted to single chemical classes. Models based on more heterogeneous data sets are those incorporated in expert systems. In general, the QSAR models for mammalian toxicity identified in this review are considered useful for investigating the mechanisms of toxicity of defined chemical classes. However, for predictive purposes in the regulatory assessment of chemicals most of the models require additional information to satisfy internationally agreed validation principles. In addition, the development of new models covering larger chemical domains would be useful for the regulatory assessment of chemicals.

  19. [Usefulness of electromyography in diagnostics of the neuro-muscular diseases].

    Science.gov (United States)

    Kroczka, Sławomir; Steczkowska, Małgorzata; Kaciński, Marek

    2009-01-01

    in 2 others multifocal motor neuropathy with conduction block. In 7/36 patients familial sensory-motor polyneuropathy was diagnosed. Neuroboreliosis was cause of neuropathy in 2 children. In 1 child, segmental inflammation of anterior horns of the spinal cord evoked by Coxackie virus was revealed. Friedreich disease, Nieman-Pick disease, thoracic outlet syndrome was found in others. In 1 boy symptoms of polyneuropathy and encephaloptahy occurred in the course of tal intoxication. In group IV EMG examination showed myopathic injury of the muscles in 9 children. In 2 others the examination results were normal. Kearns-Syre syndrome was found in one of them and Duchenne disease in the second one, 16, 5 years old boy without pain complaints, Becker disease in 2 and in next 2 patients encephalopathy and in rare cases BaCM, congenital dystrophy and myotubular myopathy. SMA was diagnosed based on clinical manifestation and EMG examination in 18 patients. EMG examination showed lower motor neuron injury in every child with SMA type I and II. MG was diagnosed in 15 patients based on clinical manifestation and positive result of fatigability test. Ocular myasthenia was found in 2 patients, bulbar type of MG was found in 1 and systemic myasthenia in 12 children. In electrophysiological fatigability test amplitude of the first response was normal in every patient and decrease of amplitude in response 4:1 in patients with MG was from 26 to 88%. Electromyographic examination remains important diagnostic tool of neuromuscular disorders. In order to limit extension of differential diagnostics EMG should be performed in its early stage.

  20. INCIDENCE OF RESIDUAL NEUROMUSCULAR BLOCKADE AT TRACHEAL EXTUBATION: COMPARISON OF ATRACURIUM WITH VECURONIUM

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    Shwetha S

    2015-11-01

    Full Text Available BACKGROUND: Occurrence of undetected residual neuromuscular blockade is a common event in the post anaesthesia care unit. AIM: To compare the incidence and degree of residual neuromuscular blockade with the use of intermediate acting neuromuscular blocking agents Atracurium and Vecuronium. METHODS: 360 patients satisfying the inclusion and exclusion criteria were enrolled in the study and randomly allocated into one of the two study groups of 180 each to receive either Atracurium or Vecuronium intraoperatively. The anaesthesiologist blinded from the study extubated the patient based on the standard clinical criteria and the corresponding Train of Four(TOF ratios were noted by a blinded research assistant using a TOF watch (TOF- Watch® SX Organon, Ireland Ltd., Dublin, Ireland. Residual neuromuscular blockade was defined as a TOF ratio of 0.9 thirty minutes after tracheal extubation. CONCLUSION: We conclude from our study that significant post-operative residual curarization (TOF < 0.9 exists in majority of patients at the time of tracheal extubation (54.4% incidence despite the use of intermediate acting neuromuscular blocking drugs. The incidence and degree of post-operative residual curarization is significantly greater with Vecuronium compared to Atracurium. Thus we suggest that quantitative neuromuscular monitoring is required to assure complete neuromuscular recovery.

  1. Hacking the genetic code of mammalian cells.

    Science.gov (United States)

    Schwarzer, Dirk

    2009-07-06

    A genetic shuttle: The highlighted article, which was recently published by Schultz, Geierstanger and co-workers, describes a straightforward scheme for enlarging the genetic code of mammalian cells. An orthogonal tRNA/aminoacyl-tRNA synthetase pair specific for a new amino acid can be evolved in E. coli and subsequently transferred into mammalian cells. The feasibility of this approach was demonstrated by adding a photocaged lysine derivative to the genetic repertoire of a human cell line.

  2. Defining viability in mammalian cell cultures

    OpenAIRE

    Browne, Susan M.; Al-Rubeai, Mohamed

    2011-01-01

    Abstract A large number of assays are available to monitor viability in mammalian cell cultures with most defining loss of viability as a loss of plasma membrane integrity, a characteristic of necrotic cell death. However, the majority of cultured cells die by apoptosis and early apoptotic cells, although non-viable, maintain an intact plasma membrane and are thus ignored. Here we measure the viability of cultures of a number of common mammalian cell lines by assays that measure me...

  3. Neuromuscular Adaptations to Unilateral vs. Bilateral Strength Training in Women.

    Science.gov (United States)

    Botton, Cíntia E; Radaelli, Regis; Wilhelm, Eurico N; Rech, Anderson; Brown, Lee E; Pinto, Ronei S

    2016-07-01

    Botton, CE, Radaelli, R, Wilhelm, EN, Rech, A, Brown, LE, and Pinto, RS. Neuromuscular adaptations to unilateral vs. bilateral strength training in women. J Strength Cond Res 30(7): 1924-1932, 2016-Considering the bilateral deficit, the sum of forces produced by each limb in a unilateral condition is generally greater than that produced by them in a bilateral condition. Therefore, it can be speculated that performing unilateral strength exercises may allow greater training workloads and subsequently greater neuromuscular adaptations when compared with bilateral training. Hence, the purpose of this study was to compare neuromuscular adaptations with unilateral vs. bilateral training in the knee extensor muscles. Forty-three recreationally active young women were allocated to a control, unilateral (UG) or bilateral (BG) training group, which performed 2 times strength training sessions a week for 12 weeks. Knee extension one repetition maximum (1RM), maximal isometric strength, muscle electrical activity, and muscle thickness were obtained before and after the study period. Muscle strength was measured in unilateral (right + left) and bilateral tests. Both UG and BG increased similarly their unilateral 1RM (33.3 ± 14.3% vs. 24.6 ± 11.9%, respectively), bilateral 1RM (20.3 ± 6.8% vs. 28.5 ± 12.3%, respectively), and isometric strength (14.7 ± 11.3% vs. 13.1 ± 12.5%, respectively). The UG demonstrated greater unilateral isometric strength increase than the BG (21.4 ± 10.5% vs. 10.3 ± 11.1%, respectively) and only the UG increased muscle electrical activity. Muscle thickness increased similarly for both training groups. Neither group exhibited pretesting 1RM bilateral deficit values, but at post-testing, UG showed a significant bilateral deficit (-6.5 ± 7.8%) whereas BG showed a significant bilateral facilitation (5.9 ± 9.0%). Thus, performing unilateral or bilateral exercises was not a decisive factor for improving morphological adaptations and bilateral

  4. Review of Continuous Infusion Neuromuscular Blocking Agents in the Adult Intensive Care Unit.

    Science.gov (United States)

    Smetana, Keaton S; Roe, Neil A; Doepker, Bruce A; Jones, G Morgan

    The use of continuous infusion neuromuscular blocking agents remains controversial. The clinical benefit of these medications may be overshadowed by concerns of propagating intensive care unit-acquired weakness, which may prolong mechanical ventilation and impair the inability to assess neurologic function or pain. Despite these risks, the use of neuromuscular blocking agents in the intensive care unit is indicated in numerous clinical situations. Understanding pharmacologic nuances and clinical roles of these agents will aid in facilitating safe use in a variety of acute disease processes. This article provides clinicians with information regarding pharmacologic differences, indication for use, adverse effects, recommended doses, ancillary care, and monitoring among agents used for continuous neuromuscular blockade.

  5. Neuromuscular medicine competency in physical medicine and rehabilitation residents: a method of development and assessment.

    Science.gov (United States)

    Lin, Lei; Cuccurullo, Sara J; Innerfield, Caitlin E; Strax, Thomas E; Petagna, Anne

    2013-03-01

    This project endeavored to create an educational module including methodology to instruct physical medicine and rehabilitation residents in the evaluation and appropriate treatment of patients with neuromuscular disorders. It further sought to verify acquired competencies in neuromuscular rehabilitation through objective evaluation methodology. An American Association of Neuromuscular and Electrodiagnostic Medicine board-certified physician with 10 yrs of clinical experience in neuromuscular and general rehabilitation trained 19 residents using a standardized competency-based module. The residents were trained through clinical training, lectures, and review of self-assessment examination concepts from the American Academy of Physical Medicine & Rehabilitation syllabus provided in the Archives of Physical Medicine and Rehabilitation. After delivery of the educational module, knowledge acquisition and skill proficiency were measured in (1) completion of neuromuscular history and physical examination satisfactorily, (2) diagnosis and ability to design a patient care management plan via chart stimulated recall examinations, (3) physician-patient interaction via patient surveys, (4) physician-staff interaction via 360-degree global ratings, and (5) ability to write a comprehensive patient care report and to document a patient care management plan in accordance with Medicare guidelines via written patient reports. Assessment tools developed for this program address the basic competencies outlined by the Accreditation Council for Graduate Medical Education. To test the success of the standardized educational module, data were collected on an ongoing basis. The objective measures compared resident self-assessment examination scores in neuromuscular rehabilitation before and after the institution of the comprehensive neuromuscular competency module in the residency program. Nineteen (100%) of 19 residents successfully demonstrated proficiency in every segment of the

  6. The use of neuromuscular blocking agents in the ICU: where are we now?

    Science.gov (United States)

    Greenberg, Steven B; Vender, Jeffery

    2013-05-01

    Intensivists use neuromuscular blocking agents for a variety of clinical conditions, including for emergency intubation, acute respiratory distress syndrome, status asthmaticus, elevated intracranial pressure, elevated intra-abdominal pressure, and therapeutic hypothermia after ventricular fibrillation-associated cardiac arrest. The continued creation and use of evidence-based guidelines and protocols could ensure that neuromuscular blocking agents are used and monitored appropriately. A collaborative multidisciplinary approach coupled with constant review of the pharmacology, dosing, drug interactions, and monitoring techniques may reduce the adverse events associated with the use of neuromuscular blocking agents.

  7. Baculovirus ETL promoter acts as a shuttle promoter between insect cells and mammalian cells

    Institute of Scientific and Technical Information of China (English)

    Yu-kou LIU; Chih-chieh CHU; Tzong-yuan WU

    2006-01-01

    Aim:To identify a shuttle promoter that can mediate gene expression in both insect cells and mammalian cells to facilitate the development of a baculovirus vector-based mammalian cell gene delivery vehicle.Methods:Recombinant baculoviruses carrying the β-galactosidase reporter gene under the control of an early to late(ETL)promoter of the Autographa califomica multiple nuclear polyhedrosis virus(AcMNPV)or a cytomegalovirus immediate early promoter (CMV promoter)were constructed.COS1,HeLa,CHO-K1,hFob1.19,and MCF-7 mammalian cells were tested for the expression of β-galactosidase.Results:ETL promoter activity was higher in bone-derived hFob1.19 than in COS1,HeLa,CHOK1,or MCF-7 mammalian cells.The transient plasmid transfection assay indicated that ETL promoter activity in mammalian cells was dependent on baculovirus gene expression.Conclusion:ETL promoter activity in mammalian cells is baculovirus gene expression-dependent,and the shuttle promoter will facilitate the application of baculovirus expression vectors in mammalian cell expression systems and for gene therapy.

  8. Abdominal compartment syndrome successfully treated with neuromuscular blockade

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    Kris T Chiles

    2011-01-01

    Full Text Available A 48 year old male admitted to the intensive care unit after a cardiac arrest complicated by a stroke intra-operatively during automatic implantable cardioverter defibrillator placement. He post-operatively developed a rigid abdomen, elevated peak and plateau pressures, hypoxia and renal insufficiency. He was diagnosed with abdominal compartment syndrome with an intra-abdominal compartment pressure of 40mmHg. The patient was administered 10 mg of intravenous cisatracuriumbesylate in preparation for bedside surgical abdominal decompression. Cisatracurium eliminated the patients need for surgical intervention by reducing his abdominal compartment pressures to normal and improving his hypoxia and renal function. This case illustrates that neuromuscular blockade should be attempted in patients with abdominal compartment syndrome prior to surgical intervention.

  9. Isozyme patterns and protein profiles in neuromuscular disorders.

    Science.gov (United States)

    Edwards, Y H; Tipler, T D; Morgan-Hughes, J A; Neerunjun, J S; Hopkinson, D A

    1982-06-01

    The isozyme patterns of six different enzymes and the polypeptide profiles of soluble proteins have been examined in muscle biopsy specimens from 74 patients with a wide variety of neuromuscular disorders. About half of the samples showed unusual features in at least one, and often several, of the enzymes and proteins tested. The extent of the biochemical abnormalities was roughly proportional to the severity of the disorders. In all cases the unusual isozymes and polypeptide profiles seemed to reflect a reversion to the fetal pattern of gene expression. However, this change appeared to occur in extant muscle and was not dependent on the appearance of new muscle fibres. Among the enzymes, phosphoglycerate mutase followed by creatine kinase appeared to be the most sensitive index of muscle disorder. The extent of the change in the muscle creatine kinase isozyme pattern was not correlated with the levels of serum creatine kinase activity.

  10. Regional neuromuscular regulation within human rectus femoris muscle during gait.

    Science.gov (United States)

    Watanabe, Kohei; Kouzaki, Motoki; Moritani, Toshio

    2014-11-01

    The spatial distribution pattern of neuromuscular activation within the human rectus femoris (RF) muscle was investigated during gait by multi-channel surface electromyography (surface EMG). Eleven healthy men walked on a treadmill with three gait speeds (4, 5, and 6 km/h) and gradients (0°, 12.5°, and 25°). The spatial distribution of surface EMG was tested by central locus activation (CLA), which is calculated from 2-D multi-channel surface EMG with 46 surface electrodes. For all conditions, CLA was around the middle regions during the swing-to-stance transition and moved in a proximal direction during the stance phase and stance-to-swing transition (pphase significantly moved to proximal site with increasing gait speed (pphases, with increasing grade, CLA significantly moved distally (pgait cycle and is non-uniformly regulated longitudinally.

  11. Resúmenes de los trabajos sobre las Enfermedades Neuromusculares

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    Congreso Nacional de Neurología

    2010-03-01

    Full Text Available Las enfermedades neuromusculares constituyen un conjunto de afectaciones que afectan las neuronas motoras periférica, las vías motoras eferentes o los efectores (músculos esqueléticos. Sus manifestaciones clínicas son muy variadas y dependen de la causa y de los niveles de afectación. En este acápite se pueden encontrar los resúmenes de trabajos relacionados con el síndrome de Guillain Barre, polineuropatía diabética, Atrofia Muscular Espinal, Distrofia miotónica y otros todos presentados en el salón que abordó estas enfermedades.

  12. Alterations in neuromuscular function in girls with generalized joint hypermobility

    DEFF Research Database (Denmark)

    Jensen, Bente Rona; Melcher, Jesper Sandfeld; Melcher, Pia Grethe Sandfeld

    2016-01-01

    BACKGROUND: Generalized Joint Hypermobility (GJH) is associated with increased risk of musculoskeletal joint pain. We investigated neuromuscular performance and muscle activation strategy. METHODS: Girls with GJH and non-GJH (NGJH) performed isometric knee flexions (90°,110°,130°), and extensions...... (90°) at 20 % Maximum Voluntary Contraction, and explosive isometric knee flexions while sitting. EMG was recorded from knee flexor and extensor muscles. RESULTS: Early rate of torque development was 53 % faster for GJH. Reduced hamstring muscle activation in girls with GJH was found while knee...... extensor and calf muscle activation did not differ between groups. Flexion-extension and medial-lateral co-activation ratio during flexions were higher for girls with GJH than NGJH girls. CONCLUSIONS: Girls with GJH had higher capacity to rapidly generate force than NGJH girls which may reflect motor...

  13. Neuromuscular electrical stimulation for muscle wasting in heart failure patients.

    Science.gov (United States)

    Saitoh, Masakazu; Dos Santos, Marcelo Rodrigues; Anker, Markus; Anker, Stefan D; von Haehling, Stephan; Springer, Jochen

    2016-12-15

    Neuromuscular electrical stimulation (NMES) seems to be safe and beneficial in improvement in functional capacity, muscle strength, and quality of life when compared with conventional aerobic exercise, while the change in muscle fiber composition and muscle size was conflicting in patients with heart failure (HF). Moreover, NMES studies seem to have beneficial effects on pro-inflammatory cytokine, oxidative enzyme activity, and protein anabolic and catabolic metabolism that are the key molecular mechanism of muscle wasting in patients with HF. We review specific issues related to the effects of NMES on muscle wasting in patients with HF, whether NMES seems to be an alternative exercise modality preventing or improving in muscle wasting for HF patients who are unable or unwilling to engage in conventional exercise training; however no established strategies currently exist to focus on the patients with HF accompanied by muscle wasting. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Neuromuscular fatigue during dynamic maximal strength and hypertrophic resistance loadings.

    Science.gov (United States)

    Walker, Simon; Davis, Lisa; Avela, Janne; Häkkinen, Keijo

    2012-06-01

    The purpose of this study was to compare the acute neuromuscular fatigue during dynamic maximal strength and hypertrophic loadings, known to cause different adaptations underlying strength gain during training. Thirteen healthy, untrained males performed two leg press loadings, one week apart, consisting of 15 sets of 1 repetition maximum (MAX) and 5 sets of 10 repetition maximums (HYP). Concentric load and muscle activity, electromyography (EMG) amplitude and median frequency, was assessed throughout each set. Additionally, maximal bilateral isometric force and muscle activity was assessed pre-, mid-, and up to 30 min post-loading. Concentric load during MAX was decreased after set 10 (Pmuscle activity during HYP loading. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Active zone stability:insights from fly neuromuscular junction

    Institute of Scientific and Technical Information of China (English)

    Xiaolin Tian; Chunlai Wu

    2015-01-01

    The presynaptic active zone is a dynamic structure that orchestrates regulated release of neurotrans-mitters. Developmental and aging processes, and changes in neuronal network activity can all modulate the number, size and composition of active zone and thereby synaptic efifcacy. However, very little is known about the mechanism that controls the structural stability of active zone. By study-ing a model synapse, theDrosophila neuromuscular junction, our recent work shed light on how two scaffolding proteins at the active zone regulate active zone stability by promoting a localized dephos-phorylation event at the nerve terminal. Here we discuss the major insights from our ifndings and their implications for future research.

  16. Alterations in neuromuscular function in girls with generalized joint hypermobility

    DEFF Research Database (Denmark)

    Jensen, Bente Rona; Melcher, Jesper Sandfeld; Melcher, Pia Grethe Sandfeld;

    2016-01-01

    BACKGROUND: Generalized Joint Hypermobility (GJH) is associated with increased risk of musculoskeletal joint pain. We investigated neuromuscular performance and muscle activation strategy. METHODS: Girls with GJH and non-GJH (NGJH) performed isometric knee flexions (90°,110°,130°), and extensions...... (90°) at 20 % Maximum Voluntary Contraction, and explosive isometric knee flexions while sitting. EMG was recorded from knee flexor and extensor muscles. RESULTS: Early rate of torque development was 53 % faster for GJH. Reduced hamstring muscle activation in girls with GJH was found while knee...... adaptation to compensate for hypermobility. Higher medial muscle activation indicated higher levels of medial knee joint compression in girls with GJH. Increased flexion-extension co-activation ratios in GJH were explained by decreased agonist drive to the hamstrings....

  17. Neuropeptidomics applied to studies of mammalian reproduction

    Directory of Open Access Journals (Sweden)

    Le Thao T.

    2014-01-01

    Full Text Available Neuropeptidomics, a mass spectrometry-based technique which aims to uncover the complete suite of neuropeptides present in a tissue, organ or cell from the brain or nervous system, has found application in studies examining physiological responses (e.g. food intake, appetite and reproduction. Neuropeptides (and peptide hormones have long been known as regulators of mammalian physiological processes, particularly reproduction. These peptides are derived from precursor proteins and become active via proteolytic processes and post-translational modifications. A relatively large number of neuropeptides, mainly formed in the hypothalamus or the anterior pituitary of mammals, have been specifically associated with reproduction, including GnRH, NPY, PYY and kisspeptin. Here, we will present an overview of neuropeptides, their roles in reproduction and the application of neuropeptidomics in this field. We address the advantages of neuropeptidomics in reproductive studies including the high throughput identification, profiling and quantification of neuropeptides present in reproductive tissues and also discuss some of the challenges. The application of neuropeptidomics to the field of reproduction will provide the foundation for a greater understanding of how neuropeptides act to regulate reproductive function.

  18. Centrifugal innervation of the mammalian olfactory bulb.

    Science.gov (United States)

    Matsutani, Shinji; Yamamoto, Noboru

    2008-12-01

    Although it has been known for decades that the mammalian olfactory bulb receives a substantial number of centrifugal inputs from other regions of the brain, relatively few data have been available on the function of the centrifugal olfactory system. Knowing the role of the centrifugal projection and how it works is of critical importance to fully understanding olfaction. The centrifugal fibers can be classified into two groups, a group that release neuromodulators, such as noradrenaline, serotonin, or acetylcholine, and a group originating in the olfactory cortex. Accumulating evidence suggests that centrifugal neuromodulatory inputs are associated with acquisition of odor memory. Because the distribution of the terminals on these fibers is diffuse and widespread, the neuromodulatory inputs must affect diverse subsets of bulbar neurons at the same time. In contrast, knowledge of the role of centrifugal fibers from the olfactory cortical areas is limited. Judging from recent morphological evidence, these fibers may modify the activity of neurons located in sparse and discrete loci in the olfactory bulb. Given the modular organization of the olfactory bulb, centrifugal fibers from the olfactory cortex may help coordinate the activities of restricted subsets of neurons belonging to distinct functional modules in an odor-specific manner. Because the olfactory cortex receives inputs from limbic and neocortical areas in addition to inputs from the bulb, the centrifugal inputs from the cortex can modulate odor processing in the bulb in response to non-olfactory as well as olfactory cues.

  19. Sources of Error in Mammalian Genetic Screens

    Directory of Open Access Journals (Sweden)

    Laura Magill Sack

    2016-09-01

    Full Text Available Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs, from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc. This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias.

  20. Genetic modification of mammalian genome at chromosome level

    Directory of Open Access Journals (Sweden)

    OLEG L. SEROV

    2000-09-01

    Full Text Available The review is concerned with a progress in genetic modification of a mammalian genome in vitro and in vivo at chromosomal level. Recently three new approaches for the chromosome biotechnology have been developed: Using Cre/loxP-system a researcher is able to produce targeted rearrangements of whole chromosomes or their segments or particular genes within the genome, and therefore to modify the set, position and copy number of the endogenous elements of the genome. Mammalian artificial chromosomes (MACs provide a possibility to introduce into genome relatively large segments of alien chromosome material, either artificially constructed or derived from the genome of different species. Using ES-somatic cell hybrids allows to transfer whole chromosomes or their fragments between different genomes within and between species. Advantages and limitations of these approaches are discussed.