Potentiation in mouse lumbrical muscle without myosin light chain phosphorylation: Is resting calcium responsible?

PubMed Central

Smith, Ian C.; Gittings, William; Huang, Jian; McMillan, Elliott M.; Quadrilatero, Joe; Tupling, A. Russell

2013-01-01

The increase in isometric twitch force observed in fast-twitch rodent muscles during or after activity, known universally as potentiation, is normally associated with myosin regulatory light chain (RLC) phosphorylation. Interestingly, fast muscles from mice devoid of detectable skeletal myosin light chain kinase (skMLCK) retain a reduced ability to potentiate twitch force, indicating the presence of a secondary origin for this characteristic feature of the fast muscle phenotype. The purpose of this study was to assess changes in intracellular cytosolic free Ca2+ concentration ([Ca2+]i) after a potentiating stimulus in mouse lumbrical muscle (37°C). Lumbricals were loaded with the Ca2+-sensitive fluorescent indicators fura-2 or furaptra to detect changes in resting and peak, respectively, intracellular Ca2+ levels caused by 2.5 s of 20-Hz stimulation. Although this protocol produced an immediate increase in twitch force of 17 ± 3% (all data are n = 10) (P < 0.01), this potentiation dissipated quickly and was absent 30 s afterward. Fura-2 fluorescence signals at rest were increased by 11.1 ± 1.3% (P < 0.01) during potentiation, indicating a significant increase in resting [Ca2+]i. Interestingly, furaptra signals showed no change to either the amplitude or the duration of the intracellular Ca2+ transients (ICTs) that triggered potentiated twitches during this time (P < 0.50). Immunofluorescence work showed that 77% of lumbrical fibers expressed myosin heavy chain isoform IIx and/or IIb, but with low expression of skMLCK and high expression of myosin phosphatase targeting subunit 2. As a result, lumbrical muscles displayed no detectable RLC phosphorylation either at rest or after stimulation. We conclude that stimulation-induced elevations in resting [Ca2+]i, in the absence of change in the ICT, are responsible for a small-magnitude, short-lived potentiation of isometric twitch force. If operative in other fast-twitch muscles, this mechanism may complement the potentiating influence of myosin RLC phosphorylation. PMID:23401574

Effect of ADP on slow-twitch muscle fibres of the rat: implications for muscle fatigue.

PubMed

Macdonald, W A; Stephenson, D G

2006-05-15

Slow-twitch mechanically skinned fibres from rat soleus muscle were bathed in solutions mimicking the myoplasmic environment but containing different [ADP] (0.1 microm to 1.0 mm). The effect of ADP on sarcoplasmic reticulum (SR) Ca2+-content was determined from the magnitude of caffeine-induced force responses, while temporal changes in SR Ca2+-content allowed determination of the effective rates of the SR Ca2+-pump and of the SR Ca2+-leak. The SR Ca2+-pump rate, estimated at pCa (-log10[Ca2+]) 7.8, was reduced by 20% as the [ADP] was increased from 0.1 to 40 microm, with no further alteration when the [ADP] was increased to 1.0 mm. The SR Ca2+-leak rate constant was not altered by increasing [ADP] from 0.1 to 40 microm, but was increased by 26% when the [ADP] was elevated to 1.0 mm. This ADP-induced SR Ca2+-leak was insensitive to ruthenium red but was abolished by 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ), indicating that the leak pathway is via the SR Ca2+-pump and not the SR Ca2+-release channel. The decrease in SR Ca2+-pump rate and SR Ca2+-leak rate when [ADP] was increased led to a 40% decrease in SR Ca2+-loading capacity. Elevation of [ADP] had only minor direct effects on the contractile apparatus of slow-twitch fibres. These results suggest that ADP has only limited depressing effects on the contractility of slow-twitch muscle fibres. This is in contrast to the marked effects of ADP on force responses in fast-twitch muscle fibres and may contribute to the fatigue-resistant nature of slow-twitch muscle fibres.

Muscle Fatigue Affects the Interpolated Twitch Technique When Assessed Using Electrically-Induced Contractions in Human and Rat Muscles.

PubMed

Neyroud, Daria; Cheng, Arthur J; Bourdillon, Nicolas; Kayser, Bengt; Place, Nicolas; Westerblad, Håkan

2016-01-01

The interpolated twitch technique (ITT) is the gold standard to assess voluntary activation and central fatigue. Yet, its validity has been questioned. Here we studied how peripheral fatigue can affect the ITT. Repeated contractions at submaximal frequencies were produced by supramaximal electrical stimulations of the human adductor pollicis muscle in vivo and of isolated rat soleus fiber bundles; an extra stimulation pulse was given during contractions to induce a superimposed twitch. Human muscles fatigued by repeated 30-Hz stimulation trains (3 s on-1 s off) showed an ~80% reduction in the superimposed twitch force accompanied by a severely reduced EMG response (M-wave amplitude), which implies action potential failure. Subsequent experiments combined a less intense stimulation protocol (1.5 s on-3 s off) with ischemia to cause muscle fatigue, but which preserved M-wave amplitude. However, the superimposed twitch force still decreased markedly more than the potentiated twitch force; with ITT this would reflect increased "voluntary activation." In contrast, the superimposed twitch force was relatively spared when a similar protocol was performed in rat soleus bundles. Force relaxation was slowed by >150% in fatigued human muscles, whereas it was unchanged in rat soleus bundles. Accordingly, results similar to those in the human muscle were obtained when relaxation was slowed by cooling the rat soleus muscles. In conclusion, our data demonstrate that muscle fatigue can confound the quantification of central fatigue using the ITT.

ChpA Controls Twitching Motility and Broadly Affects Gene Expression in the Biological Control Agent Lysobacter enzymogenes.

PubMed

Zhou, Mimi; Shen, Danyu; Xu, Gaoge; Liu, Fengquan; Qian, Guoliang

2017-05-01

Lysobacter enzymogenes (L. enzymogenes) is an agriculturally important Gram-negative bacterium that employs T4P (type IV pili)-driven twitching motility to exhibit its antifungal function. Yet, it is still unclear how this bacterium regulates its twitching motility. Here, by using strain OH11 as the working model organism, we showed that a hybrid two-component system ChpA acts as a positive regulator in controlling twitching motility in L. enzymogenes. ChpA is a hybrid TCS (two-component transduction system) contains 7 domains including those for auto-phosphorylation and phosphate group transfer, as well as a phosphate receiver (REC) domain. Mutation of chpA completely abolished the wild-type twitching motility, as evidenced by the absence of mobile cells at the margin of the mutant colonies. Further studies of domain-deletion and phenotypic characterization reveal that domains responsible for phosphorylation and phosphotransfer, but not the REC domain, were indispensable for ChpA in regulating twitching motility. Transcriptome analyses of the chpA knockout strain indicated that ChpA was extensively involved in controlling expression of a wide variety of genes (totaling 243). The products of these differentially expressed genes were involved in multiple physiological and biological functions in L. enzymogenes. Thus, we have not only identified a new regulator controlling twitching motility in L. enzymogenes, but also provided the first report demonstrating the broad impact of the conserved ChpA in gene regulation in Gram-negative bacteria.

Lack of muscle contractile property changes at the time of perceived physical exhaustion suggests central mechanisms contributing to early motor task failure in patients with cancer-related fatigue.

PubMed

Kisiel-Sajewicz, Katarzyna; Davis, Mellar P; Siemionow, Vlodek; Seyidova-Khoshknabi, Dilara; Wyant, Alexandria; Walsh, Declan; Hou, Juliet; Yue, Guang H

2012-09-01

Fatigue is one of the most common symptoms reported by cancer survivors, and fatigue worsens when patients are engaged in muscle exertion, which results in early motor task failure. Central fatigue plays a significant role, more than muscle (peripheral) fatigue, in contributing to early task failure in cancer-related fatigue (CRF). The purpose of this study was to determine if muscle contractile property alterations (reflecting muscle fatigue) occurred at the end of a low-intensity muscle contraction to exhaustion and if these properties differed between those with CRF and healthy controls. Ten patients (aged 59.9±10.6 years, seven women) with advanced solid cancer and CRF and 12 age- and gender-matched healthy controls (aged 46.6±12.8 years, nine women) performed a sustained contraction of the right arm elbow flexion at 30% maximal level until exhaustion. Peak twitch force, time to peak twitch force, rate of peak twitch force development, and half relaxation time derived from electrical stimulation-evoked twitches were analyzed pre- and post-sustained contraction. CRF patients reported significantly greater fatigue as measured by the Brief Fatigue Inventory and failed the motor task earlier, 340±140 vs. 503±155 seconds in controls. All contractile property parameters did not change significantly in CRF but did change significantly in controls. CRF patients perceive physical exhaustion sooner during a motor fatigue task with minimal muscular fatigue. The observation supports that central fatigue is a more significant factor than peripheral fatigue in causing fatigue feelings and limits motor function in cancer survivors with fatigue symptoms. Copyright © 2012. Published by Elsevier Inc.

Deltoid, triceps, or both responses improve the success rate of the interscalene catheter surgical block compared with the biceps response.

PubMed

Borgeat, A; Ekatodramis, G; Guzzella, S; Ruland, P; Votta-Velis, G; Aguirre, J

2012-12-01

The influence of the muscular response elicited by neurostimulation on the success rate of interscalene block using a catheter (ISC) is unknown. In this investigation, we compared the success rate of ISC placement as indicated by biceps or deltoid, triceps, or both twitches. Three hundred (ASA I-II) patients presenting for elective arthroscopic rotator cuff repair were prospectively randomized to assessment by biceps (Group B) or deltoid, triceps, or both twitches (Group DT). All ISCs were placed with the aid of neurostimulation. The tip of the stimulating needle was placed after disappearance of either biceps or deltoid, triceps, or both twitches at 0.3 mA. The catheter was advanced 2-3 cm past the tip of the needle and the block was performed using 40 ml ropivacaine 0.5%. Successful block was defined as sensory block of the supraclavicular nerve and sensory and motor block involving the axillary, radial, median, and musculocutaneous nerves within 30 min. Success rate was 98.6% in Group DT compared with 92.5% in Group B (95% confidence interval 0.01-0.11; P<0.02). Supplemental analgesics during handling of the posterior part of the shoulder capsule were needed in two patients in Group DT and seven patients in Group B. Three patients in Group B had an incomplete radial nerve distribution anaesthesia necessitating general anaesthesia. One patient in Group B had an incomplete posterior block extension of the supraclavicular nerve. No acute or late complications were observed. Eliciting deltoid, triceps, or both twitches was associated with a higher success rate compared with eliciting biceps twitches during continuous interscalene block.

Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism.

PubMed

Marsili, Alessandro; Ramadan, Waile; Harney, John W; Mulcahey, Michelle; Castroneves, Luciana Audi; Goemann, Iuri Martin; Wajner, Simone Magagnin; Huang, Stephen A; Zavacki, Ann Marie; Maia, Ana Luiza; Dentice, Monica; Salvatore, Domenico; Silva, J Enrique; Larsen, P Reed

2010-12-01

Because of its large mass, relatively high metabolic activity and responsiveness to thyroid hormone, skeletal muscle contributes significantly to energy expenditure. Despite the presence of mRNA encoding the type 2 iodothyronine-deiodinase (D2), an enzyme that activates T(4) to T3, very low or undetectable activity has been reported in muscle homogenates of adult humans and mice. With a modified D2 assay, using microsomal protein, overnight incubation and protein from D2 knockout mouse muscle as a tissue-specific blank, we examined slow- and fast-twitch mouse skeletal muscles for D2 activity and its response to physiological stimuli. D2 activity was detectable in all hind limb muscles of 8- to 12-wk old C57/BL6 mice. Interestingly, it was higher in the slow-twitch soleus than in fast-twitch muscles (0.40 ± 0.06 vs. 0.076 ± 0.01 fmol/min · mg microsomal protein, respectively, P < 0.001). These levels are greater than those previously reported. Hypothyroidism caused a 40% (P < 0.01) and 300% (P < 0.001) increase in D2 activity after 4 and 8 wk treatment with antithyroid drugs, respectively, with no changes in D2 mRNA. Neither D2 mRNA nor activity increased after an overnight 4 C exposure despite a 10-fold increase in D2 activity in brown adipose tissue in the same mice. The magnitude of the activity, the fiber specificity, and the robust posttranslational response to hypothyroidism argue for a more important role for D2-generated T(3) in skeletal muscle physiology than previously assumed.

Type 2 Iodothyronine Deiodinase Levels Are Higher in Slow-Twitch than Fast-Twitch Mouse Skeletal Muscle and Are Increased in Hypothyroidism

PubMed Central

Marsili, Alessandro; Ramadan, Waile; Harney, John W.; Mulcahey, Michelle; Castroneves, Luciana Audi; Goemann, Iuri Martin; Wajner, Simone Magagnin; Huang, Stephen A.; Zavacki, Ann Marie; Maia, Ana Luiza; Dentice, Monica; Salvatore, Domenico; Silva, J. Enrique; Larsen, P. Reed

2010-01-01

Because of its large mass, relatively high metabolic activity and responsiveness to thyroid hormone, skeletal muscle contributes significantly to energy expenditure. Despite the presence of mRNA encoding the type 2 iodothyronine-deiodinase (D2), an enzyme that activates T4 to T3, very low or undetectable activity has been reported in muscle homogenates of adult humans and mice. With a modified D2 assay, using microsomal protein, overnight incubation and protein from D2 knockout mouse muscle as a tissue-specific blank, we examined slow- and fast-twitch mouse skeletal muscles for D2 activity and its response to physiological stimuli. D2 activity was detectable in all hind limb muscles of 8- to 12-wk old C57/BL6 mice. Interestingly, it was higher in the slow-twitch soleus than in fast-twitch muscles (0.40 ± 0.06 vs. 0.076 ± 0.01 fmol/min · mg microsomal protein, respectively, P < 0.001). These levels are greater than those previously reported. Hypothyroidism caused a 40% (P < 0.01) and 300% (P < 0.001) increase in D2 activity after 4 and 8 wk treatment with antithyroid drugs, respectively, with no changes in D2 mRNA. Neither D2 mRNA nor activity increased after an overnight 4 C exposure despite a 10-fold increase in D2 activity in brown adipose tissue in the same mice. The magnitude of the activity, the fiber specificity, and the robust posttranslational response to hypothyroidism argue for a more important role for D2-generated T3 in skeletal muscle physiology than previously assumed. PMID:20881246

Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve.

PubMed

Fisher, L E; Tyler, D J; Anderson, J S; Triolo, R J

2009-08-01

This study describes the stability and selectivity of four-contact spiral nerve-cuff electrodes implanted bilaterally on distal branches of the femoral nerves of a human volunteer with spinal cord injury as part of a neuroprosthesis for standing and transfers. Stimulation charge threshold, the minimum charge required to elicit a visible muscle contraction, was consistent and low (mean threshold charge at 63 weeks post-implantation: 23.3 +/- 8.5 nC) for all nerve-cuff electrode contacts over 63 weeks after implantation, indicating a stable interface with the peripheral nervous system. The ability of individual nerve-cuff electrode contacts to selectively stimulate separate components of the femoral nerve to activate individual heads of the quadriceps was assessed with fine-wire intramuscular electromyography while measuring isometric twitch knee extension moment. Six of eight electrode contacts could selectively activate one head of the quadriceps while selectively excluding others to produce maximum twitch responses of between 3.8 and 8.1 N m. The relationship between isometric twitch and tetanic knee extension moment was quantified, and selective twitch muscle responses scaled to between 15 and 35 N m in tetanic response to pulse trains with similar stimulation parameters. These results suggest that this nerve-cuff electrode can be an effective and chronically stable tool for selectively stimulating distal nerve branches in the lower extremities for neuroprosthetic applications.

Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve

PubMed Central

Fisher, L E; Tyler, D J; Anderson, J S; Triolo, R J

2010-01-01

This study describes the stability and selectivity of four-contact spiral nerve-cuff electrodes implanted bilaterally on distal branches of the femoral nerves of a human volunteer with spinal cord injury as part of a neuroprosthesis for standing and transfers. Stimulation charge threshold, the minimum charge required to elicit a visible muscle contraction, was consistent and low (mean threshold charge at 63 weeks post-implantation: 23.3 ± 8.5 nC) for all nerve-cuff electrode contacts over 63 weeks after implantation, indicating a stable interface with the peripheral nervous system. The ability of individual nerve-cuff electrode contacts to selectively stimulate separate components of the femoral nerve to activate individual heads of the quadriceps was assessed with fine-wire intramuscular electromyography while measuring isometric twitch knee extension moment. Six of eight electrode contacts could selectively activate one head of the quadriceps while selectively excluding others to produce maximum twitch responses of between 3.8 and 8.1 Nm. The relationship between isometric twitch and tetanic knee extension moment was quantified, and selective twitch muscle responses scaled to between 15 and 35 Nm in tetanic response to pulse trains with similar stimulation parameters. These results suggest that this nerve-cuff electrode can be an effective and chronically stable tool for selectively stimulating distal nerve branches in the lower extremities for neuroprosthetic applications. PMID:19602729

The effects of ramp stretches on active contractions in intact mammalian fast and slow muscle fibres.

PubMed

Mutungi, G; Ranatunga, K W

2001-01-01

The effects of a ramp stretch (amplitude <6% muscle fibre length (L0), speed < 13L0 s(-1)) on twitch tension and twitch tension re-development were examined in intact mammalian (rat) fast and slow muscle fibre bundles. The experiments were done in vitro at 20 degrees C and at an initial sarcomere length of 2.68 microm. In both fibre types, a stretch applied during the rising phase of the twitch response (including the time of stimulation) increased the re-developed twitch tension (15-35%). A stretch applied before the stimulus had little or no effect on the twitch myogram in fast muscle fibres, but it increased the twitch tension (approximately 5%) in slow muscle fibres. A similar stretch had little or no effect on tetanic tension in either muscle fibre type. In general, the results indicate that the contractile-activation mechanism may be stretch sensitive and this is particularly pronounced in slow muscle fibres. Recorded at a high sampling rate and examined at an appropriate time scale, the transitory tension response to a stretch rose in at least two phases; an initial rapid tension rise to a break (break point tension, P1a) followed by a slower tension rise (apparent P2a) to a peak reached at the end of the stretch. Plotted against stretch velocity, P1a tension increased in direct proportion to stretch velocity (viscous-like) whereas, P2a tension (calculated as peak tension minus P1a tension) increased with stretch velocity to a plateau (visco-elastic). Examined at the peak of a twitch, P1a tension had a slope (viscosity coefficient) of 1.8 kN m(-2) per L0 s(-1) in fast fibres and 4.7 kN m(-2) per L0 s(-1) in slow muscle fibres. In the same preparations, P2a tension had a relaxation time of 8 ms in the fast muscle fibres and 25 ms in the slow muscle fibres. The amplitudes of both tension components scaled with the instantaneous twitch tension in qualitatively the same way as the instantaneous fibre stiffness. These fast/slow fibre type differences probably reflect differences in their cross-bridge kinetics.

Human skeletal muscle responses to spaceflight and possible countermeasures

NASA Technical Reports Server (NTRS)

Gollnick, Philip D.; Edgerton, V. Reggie; Saltin, Bengt

1990-01-01

The current status of knowledge concerning the effects of unweighting skeletal muscle is summarized. The results of both ground-based and space-based animal studies are reviewed which show that there is rapid loss in muscle mass, primarily in slow-twitch muscle, of the rat during unweighting of muscle. There is also a shift in the myosin isoforms with muscles such that slow-twitch muscles take on many of the characteristics of fast-twitch muscles. Ground-based studies in human suggest that programs of electrical stimulation can be developed to simulate normal muscular contractions. Attempts to develop countermeasures to the adverse effects of space travel on muscular functions in humans have not been successful to date.

Effect of ADP on slow-twitch muscle fibres of the rat: implications for muscle fatigue

PubMed Central

Macdonald, W A; Stephenson, D G

2006-01-01

Slow-twitch mechanically skinned fibres from rat soleus muscle were bathed in solutions mimicking the myoplasmic environment but containing different [ADP] (0.1 μm to 1.0 mm). The effect of ADP on sarcoplasmic reticulum (SR) Ca2+-content was determined from the magnitude of caffeine-induced force responses, while temporal changes in SR Ca2+-content allowed determination of the effective rates of the SR Ca2+-pump and of the SR Ca2+-leak. The SR Ca2+-pump rate, estimated at pCa (−log10[Ca2+]) 7.8, was reduced by 20% as the [ADP] was increased from 0.1 to 40 μm, with no further alteration when the [ADP] was increased to 1.0 mm. The SR Ca2+-leak rate constant was not altered by increasing [ADP] from 0.1 to 40 μm, but was increased by 26% when the [ADP] was elevated to 1.0 mm. This ADP-induced SR Ca2+-leak was insensitive to ruthenium red but was abolished by 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ), indicating that the leak pathway is via the SR Ca2+-pump and not the SR Ca2+-release channel. The decrease in SR Ca2+-pump rate and SR Ca2+-leak rate when [ADP] was increased led to a 40% decrease in SR Ca2+-loading capacity. Elevation of [ADP] had only minor direct effects on the contractile apparatus of slow-twitch fibres. These results suggest that ADP has only limited depressing effects on the contractility of slow-twitch muscle fibres. This is in contrast to the marked effects of ADP on force responses in fast-twitch muscle fibres and may contribute to the fatigue-resistant nature of slow-twitch muscle fibres. PMID:16556653

Paying the piper: the cost of Ca2+ pumping during the mating call of toadfish

PubMed Central

Harwood, Claire L; Young, Iain S; Tikunov, Boris A; Hollingworth, Stephen; Baylor, Stephen M; Rome, Lawrence C

2011-01-01

Abstract Superfast fibres of toadfish swimbladder muscle generate a series of superfast Ca2+ transients, a necessity for high-frequency calling. How is this accomplished with a relatively low rate of Ca2+ pumping by the sarcoplasmic reticulum (SR)? We hypothesized that there may not be complete Ca2+ saturation and desaturation of the troponin Ca2+ regulatory sites with each twitch during calling. To test this, we determined the number of regulatory sites by measuring the concentration of troponin C (TNC) molecules, 33.8 μmol per kg wet weight. We then estimated how much SR Ca2+ is released per twitch by measuring the recovery oxygen consumption in the presence of a crossbridge blocker, N-benzyl-p-toluene sulphonamide (BTS). The results agreed closely with SR release estimates obtained with a kinetic model used to analyse Ca2+ transient measurements. We found that 235 μmol of Ca2+ per kg muscle is released with the first twitch of an 80 Hz stimulus (15oC). Release per twitch declines dramatically thereafter such that by the 10th twitch release is only 48 μmol kg−1 (well below the concentration of TNC Ca2+ regulatory sites, 67.6 μmol kg−1). The ATP usage per twitch by the myosin crossbridges remains essentially constant at ∼25 μmol kg−1 throughout the stimulus period. Hence, for the first twitch, ∼80% of the energy goes into pumping Ca2+ (which uses 1 ATP per 2 Ca2+ ions pumped), but by the 10th and subsequent twitches the proportion is ∼50%. Even though by the 10th stimulus the Ca2+ release per twitch has dropped 5-fold, the Ca2+ remaining in the SR has declined by only ∼18%; hence dwindling SR Ca2+ content is not responsible for the drop. Rather, inactivation of the Ca2+ release channel by myoplasmic Ca2+ likely explains this reduction. If inactivation did not occur, the SR would run out of Ca2+ well before the end of even a 40-twitch call. Hence, inactivation of the Ca2+ release channel plays a critical role in swimbladder muscle during normal in vivo function. PMID:21946852

Trigeminal Proprioception Evoked by Strong Stretching of the Mechanoreceptors in Müller's Muscle Induces Reflex Contraction of the Orbital Orbicularis Oculi Slow-Twitch Muscle Fibers.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya; Ban, Midori; Yuzuriha, Shunsuke

2014-01-01

The mixed orbicularis oculi muscle lacks an intramuscular proprioceptive system such as muscle spindles, to induce reflex contraction of its slow-twitch fibers. We evaluated whether the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction of the slow-twitch fibers of the orbicularis oculi in addition to those of the levator and frontalis muscles. We evaluated in patients with aponeurosis-disinserted blepharoptosis whether strong stretching of the mechanoreceptors in Müller's muscle from upgaze with unilateral lid load induced reflex contraction of the orbicularis oculi slow-twitch fibers and whether anesthesia of Müller's muscle precluded the contraction. We compared the electromyographic responses of the bilateral orbicularis oculi muscles to unilateral intraoperative direct stimulation of the trigeminal proprioceptive nerve with those to unilateral transcutaneous electrical stimulation of the supraorbital nerve. Upgaze with a unilateral 3-g lid load induced reflex contraction of the bilateral orbicularis oculi muscles with ipsilateral dominance. Anesthesia of Müller's muscle precluded the reflex contraction. The orbicularis oculi reflex evoked by stimulation of the trigeminal proprioceptive nerve differed from that by electrical stimulation of the supraorbital nerve in terms of the intensity of current required to induce the reflex, the absence of R1, and duration. The mechanoreceptors in Müller's muscle functions as an extramuscular proprioceptive system to induce reflex contraction of the orbital orbicularis oculi slow-twitch fibers. Whereas reflex contraction of the pretarsal orbicularis fast-twitch fibers functions in spontaneous or reflex blinking, that of the orbital orbicularis oculi slow-twitch fibers may factor in grimacing and blepharospasm.

Trigeminal Proprioception Evoked by Strong Stretching of the Mechanoreceptors in Müller's Muscle Induces Reflex Contraction of the Orbital Orbicularis Oculi Slow-Twitch Muscle Fibers

PubMed Central

Ban, Ryokuya; Ban, Midori; Yuzuriha, Shunsuke

2014-01-01

Objective: The mixed orbicularis oculi muscle lacks an intramuscular proprioceptive system such as muscle spindles, to induce reflex contraction of its slow-twitch fibers. We evaluated whether the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction of the slow-twitch fibers of the orbicularis oculi in addition to those of the levator and frontalis muscles. Methods: We evaluated in patients with aponeurosis-disinserted blepharoptosis whether strong stretching of the mechanoreceptors in Müller's muscle from upgaze with unilateral lid load induced reflex contraction of the orbicularis oculi slow-twitch fibers and whether anesthesia of Müller's muscle precluded the contraction. We compared the electromyographic responses of the bilateral orbicularis oculi muscles to unilateral intraoperative direct stimulation of the trigeminal proprioceptive nerve with those to unilateral transcutaneous electrical stimulation of the supraorbital nerve. Results: Upgaze with a unilateral 3-g lid load induced reflex contraction of the bilateral orbicularis oculi muscles with ipsilateral dominance. Anesthesia of Müller's muscle precluded the reflex contraction. The orbicularis oculi reflex evoked by stimulation of the trigeminal proprioceptive nerve differed from that by electrical stimulation of the supraorbital nerve in terms of the intensity of current required to induce the reflex, the absence of R1, and duration. Conclusions: The mechanoreceptors in Müller's muscle functions as an extramuscular proprioceptive system to induce reflex contraction of the orbital orbicularis oculi slow-twitch fibers. Whereas reflex contraction of the pretarsal orbicularis fast-twitch fibers functions in spontaneous or reflex blinking, that of the orbital orbicularis oculi slow-twitch fibers may factor in grimacing and blepharospasm. PMID:25210572

Fiber-type-specific sensitivities and phenotypic adaptations to dietary fat overload differentially impact fast- versus slow-twitch muscle contractile function in C57BL/6J mice.

PubMed

Ciapaite, Jolita; van den Berg, Sjoerd A; Houten, Sander M; Nicolay, Klaas; van Dijk, Ko Willems; Jeneson, Jeroen A

2015-02-01

High-fat diets (HFDs) have been shown to interfere with skeletal muscle energy metabolism and cause peripheral insulin resistance. However, understanding of HFD impact on skeletal muscle primary function, i.e., contractile performance, is limited. Male C57BL/6J mice were fed HFD containing lard (HFL) or palm oil (HFP), or low-fat diet (LFD) for 5weeks. Fast-twitch (FT) extensor digitorum longus (EDL) and slow-twitch (ST) soleus muscles were characterized with respect to contractile function and selected biochemical features. In FT EDL muscle, a 30%-50% increase in fatty acid (FA) content and doubling of long-chain acylcarnitine (C14-C18) content in response to HFL and HFP feeding were accompanied by increase in protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial oxidative phosphorylation complexes and acyl-CoA dehydrogenases involved in mitochondrial FA β-oxidation. Peak force of FT EDL twitch and tetanic contractions was unaltered, but the relaxation time (RT) of twitch contractions was 30% slower compared to LFD controls. The latter was caused by accumulation of lipid intermediates rather than changes in the expression levels of proteins involved in calcium handling. In ST soleus muscle, no evidence for lipid overload was found in any HFD group. However, particularly in HFP group, the peak force of twitch and tetanic contractions was reduced, but RT was faster than LFD controls. The latter was associated with a fast-to-slow shift in troponin T isoform expression. Taken together, these data highlight fiber-type-specific sensitivities and phenotypic adaptations to dietary lipid overload that differentially impact fast- versus slow-twitch skeletal muscle contractile function. Copyright © 2015 Elsevier Inc. All rights reserved.

Twitch analysis as an approach to motor unit activation during electrical stimulation.

PubMed

Heyters, M; Carpentier, A; Duchateau, J; Hainaut, K

1994-12-01

The mechanical twitch in response to increasing electrical stimulus intensity, delivered both over the motor point and motor nerve, was recorded in the first dorsal interosseous (FDI) and the adductor pollicis (AP), and only over the motor point in the soleus (Sol), lateral (LG), and medial (MG) gastrocnemius muscles of human subjects. The relationship between intensity of electrical stimulation (ES) and twitch torque showed a positive linear regression in all muscles. In the FDI and AP the relationship was not significantly different when ES was applied at the motor point or over the motor nerve. At small intensities of activation, ES induced larger twitch torques in the MG and LG, which contain a roughly equal proportion of slow and fast motor units (MUs) compared to the Sol, which is composed mainly of slow type fibres. Moreover, the relationship between ES intensity and twitch time-to-peak is best fitted in all muscles by a power curve that shows a greater twitch time-to-peak range in its initial part for muscles containing a larger proportion of fast MUs (LG, MG) than for muscles mainly composed of slow MUs (Sol). In conclusion, these results induced by ES at the motor point and/or over the motor nerve confirm the concept of a reversed sequence of MU activation, as compared to voluntary contractions, and document this viewpoint in muscles of different function and composition. The reversed sequence of MU activation is more clearly evident during motor point ES.

Optimized ratiometric calcium sensors for functional in vivo imaging of neurons and T lymphocytes.

PubMed

Thestrup, Thomas; Litzlbauer, Julia; Bartholomäus, Ingo; Mues, Marsilius; Russo, Luigi; Dana, Hod; Kovalchuk, Yuri; Liang, Yajie; Kalamakis, Georgios; Laukat, Yvonne; Becker, Stefan; Witte, Gregor; Geiger, Anselm; Allen, Taylor; Rome, Lawrence C; Chen, Tsai-Wen; Kim, Douglas S; Garaschuk, Olga; Griesinger, Christian; Griesbeck, Oliver

2014-02-01

The quality of genetically encoded calcium indicators (GECIs) has improved dramatically in recent years, but high-performing ratiometric indicators are still rare. Here we describe a series of fluorescence resonance energy transfer (FRET)-based calcium biosensors with a reduced number of calcium binding sites per sensor. These 'Twitch' sensors are based on the C-terminal domain of Opsanus troponin C. Their FRET responses were optimized by a large-scale functional screen in bacterial colonies, refined by a secondary screen in rat hippocampal neuron cultures. We tested the in vivo performance of the most sensitive variants in the brain and lymph nodes of mice. The sensitivity of the Twitch sensors matched that of synthetic calcium dyes and allowed visualization of tonic action potential firing in neurons and high resolution functional tracking of T lymphocytes. Given their ratiometric readout, their brightness, large dynamic range and linear response properties, Twitch sensors represent versatile tools for neuroscience and immunology.

The augmenting action of banana tree juice on skeletal muscle contraction.

PubMed

Singh, Y N; Dryden, W F

1990-01-01

An extract obtained from juice expressed from the stem of the plantain banana tree (Musa sapientum L., var. paradisiaca) induces twitch augmentation in skeletal muscles. The mechanism of this action was investigated in the mouse hemi-diaphragm preparation. Directly evoked twitches and potassium induced (K+) contractures were both augmented by the extract. Twitch augmentation was partly dependent on extracellular Ca2+. The action on K(+)-contractures was unaffected by tetrodotoxin, but the rate of relaxation was enhanced in the absence of extracellular calcium (0[Ca2+]o). Muscle contracture induced by high concentrations of extract was also augmented in 0[Ca2+]o and in the presence of the Ca2(+)-channel blocking agent, nifedipine. The time course of the contracture was shortened in 0[Ca2+]o, but not by nifedipine. Nifedipine enhanced the augmenting effect of the extract on twitches but shortened the time-course of this action. In addition, a muscle contracture was superimposed on the twitching muscle at higher concentrations of nifedipine. Manganese, on the other hand, reduced or abolished the augmenting action of the extract. The results are consistent with an action of banana tree juice on the molecule responsible for excitation-contraction coupling in skeletal muscle, resulting in a labilization of intracellular Ca2+.

Maximal Voluntary Activation of the Elbow Flexors Is under Predicted by Transcranial Magnetic Stimulation Compared to Motor Point Stimulation Prior to and Following Muscle Fatigue

PubMed Central

Cadigan, Edward W. J.; Collins, Brandon W.; Philpott, Devin T. G.; Kippenhuck, Garreth; Brenton, Mitchell; Button, Duane C.

2017-01-01

Transcranial magnetic (TMS) and motor point stimulation have been used to determine voluntary activation (VA). However, very few studies have directly compared the two stimulation techniques for assessing VA of the elbow flexors. The purpose of this study was to compare TMS and motor point stimulation for assessing VA in non-fatigued and fatigued elbow flexors. Participants performed a fatigue protocol that included twelve, 15 s isometric elbow flexor contractions. Participants completed a set of isometric elbow flexion contractions at 100, 75, 50, and 25% of maximum voluntary contraction (MVC) prior to and following fatigue contractions 3, 6, 9, and 12 and 5 and 10 min post-fatigue. Force and EMG of the bicep and triceps brachii were measured for each contraction. Force responses to TMS and motor point stimulation and EMG responses to TMS (motor evoked potentials, MEPs) and Erb's point stimulation (maximal M-waves, Mmax) were also recorded. VA was estimated using the equation: VA% = (1−SITforce/PTforce) × 100. The resting twitch was measured directly for motor point stimulation and estimated for both motor point stimulation and TMS by extrapolation of the linear regression between the superimposed twitch force and voluntary force. MVC force, potentiated twitch force and VA significantly (p < 0.05) decreased throughout the elbow flexor fatigue protocol and partially recovered 10 min post fatigue. VA was significantly (p < 0.05) underestimated when using TMS compared to motor point stimulation in non-fatigued and fatigued elbow flexors. Motor point stimulation compared to TMS superimposed twitch forces were significantly (p < 0.05) higher at 50% MVC but similar at 75 and 100% MVC. The linear relationship between TMS superimposed twitch force and voluntary force significantly (p < 0.05) decreased with fatigue. There was no change in triceps/biceps electromyography, biceps/triceps MEP amplitudes, or bicep MEP amplitudes throughout the fatigue protocol at 100% MVC. In conclusion, motor point stimulation as opposed to TMS led to a higher estimation of VA in non-fatigued and fatigued elbow flexors. The decreased linear relationship between TMS superimposed twitch force and voluntary force led to an underestimation of the estimated resting twitch force and thus, a reduced VA. PMID:28979211

Maximal Voluntary Activation of the Elbow Flexors Is under Predicted by Transcranial Magnetic Stimulation Compared to Motor Point Stimulation Prior to and Following Muscle Fatigue.

PubMed

Cadigan, Edward W J; Collins, Brandon W; Philpott, Devin T G; Kippenhuck, Garreth; Brenton, Mitchell; Button, Duane C

2017-01-01

Transcranial magnetic (TMS) and motor point stimulation have been used to determine voluntary activation (VA). However, very few studies have directly compared the two stimulation techniques for assessing VA of the elbow flexors. The purpose of this study was to compare TMS and motor point stimulation for assessing VA in non-fatigued and fatigued elbow flexors. Participants performed a fatigue protocol that included twelve, 15 s isometric elbow flexor contractions. Participants completed a set of isometric elbow flexion contractions at 100, 75, 50, and 25% of maximum voluntary contraction (MVC) prior to and following fatigue contractions 3, 6, 9, and 12 and 5 and 10 min post-fatigue. Force and EMG of the bicep and triceps brachii were measured for each contraction. Force responses to TMS and motor point stimulation and EMG responses to TMS (motor evoked potentials, MEPs) and Erb's point stimulation (maximal M-waves, M max ) were also recorded. VA was estimated using the equation: VA% = (1- SITforce / PTforce ) × 100. The resting twitch was measured directly for motor point stimulation and estimated for both motor point stimulation and TMS by extrapolation of the linear regression between the superimposed twitch force and voluntary force. MVC force, potentiated twitch force and VA significantly ( p < 0.05) decreased throughout the elbow flexor fatigue protocol and partially recovered 10 min post fatigue. VA was significantly ( p < 0.05) underestimated when using TMS compared to motor point stimulation in non-fatigued and fatigued elbow flexors. Motor point stimulation compared to TMS superimposed twitch forces were significantly ( p < 0.05) higher at 50% MVC but similar at 75 and 100% MVC. The linear relationship between TMS superimposed twitch force and voluntary force significantly ( p < 0.05) decreased with fatigue. There was no change in triceps/biceps electromyography, biceps/triceps MEP amplitudes, or bicep MEP amplitudes throughout the fatigue protocol at 100% MVC. In conclusion, motor point stimulation as opposed to TMS led to a higher estimation of VA in non-fatigued and fatigued elbow flexors. The decreased linear relationship between TMS superimposed twitch force and voluntary force led to an underestimation of the estimated resting twitch force and thus, a reduced VA.

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

NASA Astrophysics Data System (ADS)

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

1994-08-01

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

Dihydrotestosterone activates the MAPK pathway and modulates maximum isometric force through the EGF receptor in isolated intact mouse skeletal muscle fibres.

PubMed

Hamdi, M M; Mutungi, G

2010-02-01

It is generally believed that steroid hormones have both genomic and non-genomic (rapid) actions. Although the latter form an important component of the physiological response of these hormones, little is known about the cellular signalling pathway(s) mediating these effects and their physiological functions in adult mammalian skeletal muscle fibres. Therefore, the primary aim of this study was to investigate the non-genomic actions of dihydrotestosterone (DHT) and their physiological role in isolated intact mammalian skeletal muscle fibre bundles. Our results show that treating the fibre bundles with physiological concentrations of DHT increases both twitch and tetanic contractions in fast twitch fibres. However, it decreases them in slow twitch fibres. These changes in force are accompanied by an increase in the phosphorylation of MAPK/ERK1/2 in both fibre types and that of regulatory myosin light chains in fast twitch fibres. Both effects were insensitive to inhibitors of Src kinase, androgen receptor, insulin-like growth factor 1 receptor and platelet-derived growth factor receptor. However, they were abolished by the MAPK/ERK1/2 kinase inhibitor PD98059 and the epidermal growth factor (EGF) receptor inhibitor tyrphostin AG 1478. In contrast, testosterone had no effect on force and increased the phosphorylation of ERK1/2 in slow twitch fibres only. From these results we conclude that sex steroids have non-genomic actions in isolated intact mammalian skeletal muscle fibres. These are mediated through the EGF receptor and one of their main physiological functions is the enhancement of force production in fast twitch skeletal muscle fibres.

Enhancement by oxotremorine of acetylcholine release from the rat phrenic nerve.

PubMed Central

Das, M; Ganguly, D K; Vedasiromoni, J R

1978-01-01

Oxotremorine (10.5 micron) produced a paralytic effect on twitch responses of rat diaphragm in vitro to direct and indirect stimulation. 2 The paralytic effect of oxotremorine was absent when the diaphragm was stimulated directly in the presence of hemicholinium-3 (0.42 mM), at a time when twitch responses to indirect stimulation ceased completely. 3 Oxotremorine, at two different pharmacologically active doses, strikingly increased the resting as well as electrically evoked release of acetylcholine into the bathing fluid from the phrenic nerve-diaphragm preparation. 4 This presynaptic effect of oxotremorine may explain its pharmacological effects at the cholinergic synapses studied so far. PMID:203356

Age effects on rat hindlimb muscle atrophy during suspension unloading

NASA Technical Reports Server (NTRS)

Steffen, Joseph M.; Fell, Ronald D.; Geoghegan, Thomas E.; Ringel, Lisa C.; Musacchia, X. J.

1990-01-01

The effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450-g) and juvenile (200-g) rats after 1, 7, or 14 days of whole-body suspension. Quantitatively and qualitatively the soleus, gastrocnemius, plantaris, and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicates a less rapid rate of response in adult muscles.

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

PubMed Central

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

2012-01-01

Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca2+ handling and contractile function using fast- and slow-twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast-twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca2+] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca2+ handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow-twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca2+ handling in fast-twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness. PMID:22687611

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

PubMed

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

2012-08-01

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

Mitochondrial oxidative enzyme activity in individual fibre types in hypo- and hyperthyroid rat skeletal muscles.

PubMed

Johnson, M A; Turnbull, D M

1984-04-01

Quantitative cytochemical and biochemical techniques have been used in combination to study the response of mitochondrial oxidative enzymes in individual muscle fibre types to hypo- and hyperthyroidism. Hypothyroidism resulted in decreased activity of succinate dehydrogenase (SDH), L-glycerol-3-phosphate dehydrogenase (L-GPDH), and D-3-hydroxybutyrate dehydrogenase (D-HBDH) in all fibre types of both slow-twitch soleus and fast-twitch extensor digitorum longus (e.d.l.) muscles. In hyperthyroidism, only L-GPDH activity increased in e.d.l. but more marked increases were seen in soleus muscles, which also showed increased SDH activity. In addition to these alterations in the enzyme activity in individual fibre types the metabolic profile of the muscle is further modified by the hormone-induced interconversion of slow- to fast-twitch fibres and vice versa.

Electrical Stimulation of Artificial Heart Muscle: A Look Into the Electrophysiologic and Genetic Implications.

PubMed

Mohamed, Mohamed A; Islas, Jose F; Schwartz, Robert J; Birla, Ravi K

Development of tissue-engineered hearts for treatment of myocardial infarction or biologic pacemakers has been hindered by the production of mostly arrhythmic or in-synergistic constructs. Electrical stimulation (ES) of these constructs has been shown to produce tissues with greater twitch force and better adrenergic response. To further our understanding of the mechanisms underlying the effect of ES, we fabricated a bioreactor capable of delivering continuous or intermittent waveforms of various types to multiple constructs simultaneously. In this study, we examined the effect of an intermittent biphasic square wave on our artificial heart muscle (AHM) composed of neonatal rat cardiac cells and fibrin gel. Twitch forces, spontaneous contraction rates, biopotentials, gene expression profiles, and histologic observations were examined for the ES protocol over a 12 day culture period. We demonstrate improved consistency between samples for twitch force and contraction rate, and higher normalized twitch force amplitudes for electrically stimulated AHMs. Improvements in electrophysiology within the AHM were noted by higher conduction velocities and lower latency in electrical response for electrically stimulated AHMs. Genes expressing key electrophysiologic and structural markers peaked at days 6 and 8 of culture, only a few days after the initiation of ES. These results may be used for optimization strategies to establish protocols for producing AHMs capable of replacing damaged heart tissue in either a contractile or electrophysiologic capacity. Optimized AHMs can lead to alternative treatments to heart failure and alleviate the limited donor supply crisis.

Electrical Stimulation of Artificial Heart Muscle: a look into the electrophysiological and genetic implications

PubMed Central

Mohamed, Mohamed A; Islas, Jose F; Schwartz, Robert J; Birla, Ravi K

2016-01-01

Development of tissue-engineered hearts for treatment of myocardial infarction or biological pacemakers has been hindered by the production of mostly arrhythmic or in-synergistic constructs. Electrical stimulation (ES) of these constructs has been shown to produce tissues with greater twitch force and better adrenergic response. In order to further our understanding of the mechanisms underlying the effect of ES, we fabricated a bioreactor capable of delivering continuous or intermittent waveforms of various types to multiple constructs simultaneously. In this study, we examined the effect of an intermittent biphasic square wave on our artificial heart muscle (AHM) composed of neonatal rat cardiac cells and fibrin gel. Twitch forces, spontaneous contraction rates, biopotentials, gene expression profiles, and histological observations were examined for the ES protocol over a 12 day culture period. We demonstrate improved consistency between samples for twitch force and contraction rate, and higher normalized twitch force amplitudes for electrically stimulated AHM. Improvements in electrophysiology within the AHM was noted by higher conduction velocities and lower latency in electrical response for electrically stimulated AHM. Genes expressing key electrophysiological and structural markers peaked at days 6 and 8 of culture, only a few days after the initiation of ES. These results may be used for optimization strategies to establish protocols for producing AHM capable of replacing damaged heart tissue in either a contractile or electrophysiological capacity. Optimized AHM can lead to alternative treatments to heart failure and alleviate the limited donor supply crisis. PMID:28459744

Impact of titin strain on the cardiac slow force response.

PubMed

Ait-Mou, Younss; Zhang, Mengjie; Martin, Jody L; Greaser, Marion L; de Tombe, Pieter P

2017-11-01

Stretch of myocardium, such as occurs upon increased filling of the cardiac chamber, induces two distinct responses: an immediate increase in twitch force followed by a slower increase in twitch force that develops over the course of several minutes. The immediate response is due, in part, to modulation of myofilament Ca 2+ sensitivity by sarcomere length (SL). The slowly developing force response, termed the Slow Force Response (SFR), is caused by a slowly developing increase in intracellular Ca 2+ upon sustained stretch. A blunted immediate force response was recently reported for myocardium isolated from homozygous giant titin mutant rats (HM) compared to muscle from wild-type littermates (WT). Here, we examined the impact of titin isoform on the SFR. Right ventricular trabeculae were isolated and mounted in an experimental chamber. SL was measured by laser diffraction. The SFR was recorded in response to a 0.2 μm SL stretch in the presence of [Ca 2+ ] o  = 0.4 mM, a bathing concentration reflecting ∼50% of maximum twitch force development at 25 °C. Presence of the giant titin isoform (HM) was associated with a significant reduction in diastolic passive force upon stretch, and ∼50% reduction of the magnitude of the SFR; the rate of SFR development was unaffected. The sustained SL stretch was identical in both muscle groups. Therefore, our data suggest that cytoskeletal strain may underlie directly the cellular mechanisms that lead to the increased intracellular [Ca 2+ ] i that causes the SFR, possibly by involving cardiac myocyte integrin signaling pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides.

PubMed

Flitney, F W; Singh, J

1980-07-01

1. A study has been made of a well documented but poorly understood response of the isolated frog ventricle to treatment with exogenous adenosine 5' triphosphate (ATP). Measurements of membrane potential, isometric twitch tension and levels of endogenous 3',5'-cyclic nucleotides have been made at various times during the ATP-induced response. 2. ATP elicits a characteristic triphasic response, which comprises an initial, abrupt increase in contractility, rising to a maximum within a few beats (first phase); followed by a period when the twitch amplitude falls, sometimes to below the control level (second phase); and superceded by a more slowly developing and longer-lasting increase in contractile force (third phase). The response is unaffected by atropine, propranolol or phentolamine. However, the prostaglandin synthetase inhibitor indomethacin depresses the first phase and entirely suppresses the third phase. 3. The inotropic effects of ATP are accompanied by changes in the shape of the action potential. These effects are dose-related. The duration of the action potential (D-30mV) and its positive overshoot (O) are increased during all phases of the response, for [ATP]o's up to 10(-5) M. However, at higher [ATP]o's, D-30mV and O ar both reduced during the second phase (but not the first or third phase), when isometric twitch tension is also depressed. The relationship between action potential duration and twitch tension (P) for different [ATP]o's is linear for all three phases of the response, but the slopes of the curves (delta P/delta D) are markedly different, indicating that the sensitivity of the contractile system to membrane depolarization is not constant, but varies continuously throughout the response. 4. ATP has a potent stimulatory effect on the metabolism of endogenous 3',5'-cyclic nucleotides. The time courses of the changes in adenosine 3','5-cyclic monophosphate (3',5'-cyclic AMP) and guanosine 3',5'-cyclic monophosphate (3',5'-cyclic GMP) are complex, but the accompanying change in isometric twitch tension is paralleled closely by corresponding changes in the ratio 3',5'cyclic AMP:3',5'-cyclic GMP. 5. It is concluded that ATP exerts a dual effect on the ventricle and that the contractile response is regulated by changes in the metabolism of 3',5'-cyclic nucleotides. The effects of indomethacin indicate a possible involvement of prostaglandins in mediating the ATP response. It is suggested that the initial effect of ATP on the ventricle is to increase the permeability of the fibres to Ca2+. 6. The relationship between 3',5' cyclic nucleotide levels and ventricular contractility is discussed. It is postulated that the antagonistic effects of 3',5'-cyclic AMP and 3',5'-cyclic GMP are expressed at the level of certain phosphoproteins which regulate both the availability of Ca2+ and the sensitivity of the contractile proteins to Ca2+.

Characterization of the head-twitch response induced by hallucinogens in mice: detection of the behavior based on the dynamics of head movement.

PubMed

Halberstadt, Adam L; Geyer, Mark A

2013-06-01

The head-twitch response (HTR) is a rapid side-to-side rotational head movement that occurs in rats and mice after administration of serotonergic hallucinogens and other 5-HT2A agonists. The HTR is widely used as a behavioral assay for 5-HT2A activation and to probe for interactions between the 5-HT2A receptor and other transmitter systems. High-speed video recordings were used to analyze the head movement that occurs during head twitches in C57BL/6J mice. Experiments were also conducted in C57BL/6J mice to determine whether a head-mounted magnet and a magnetometer coil could be used to detect the HTR induced by serotonergic hallucinations based on the dynamics of the response. Head movement during the HTR was highly rhythmic and occurred within a specific frequency range (mean head movement frequency of 90.3 Hz). Head twitches produced wave-like oscillations of magnetometer coil voltage that matched the frequency of head movement during the response. The magnetometer coil detected the HTR induced by the serotonergic hallucinogens 2,5-dimethoxy-4-iodoamphetamine (DOI; 0.25, 0.5, and 1.0 mg/kg, i.p.) and lysergic acid diethylamide (LSD; 0.05, 0.1, 0.2, and 0.4 mg/kg, i.p.) with extremely high sensitivity and specificity. Magnetometer coil recordings demonstrated that the non-hallucinogenic compounds (+)-amphetamine (2.5 and 5.0 mg/kg, i.p.) and lisuride (0.8, 1.6, and 3.2 mg/kg, i.p.) did not induce the HTR. These studies confirm that a magnetometer coil can be used to detect the HTR induced by hallucinogens. The use of magnetometer-based HTR detection provides a high-throughput, semi-automated assay for this behavior, and offers several advantages over traditional assessment methods.

Characterization of the head-twitch response induced by hallucinogens in mice: detection of the behavior based on the dynamics of head movement

PubMed Central

Halberstadt, Adam L.; Geyer, Mark A.

2013-01-01

Rationale The head-twitch response (HTR) is a rapid side-to-side rotational head movement that occurs in rats and mice after administration of serotonergic hallucinogens and other 5-HT2A agonists. The HTR is widely used as a behavioral assay for 5-HT2A activation and to probe for interactions between the 5-HT2A receptor and other transmitter systems. Objective High-speed video recordings were used to analyze the head movement that occurs during head twitches in C57BL/6J mice. Experiments were also conducted in C57BL/6J mice to determine whether a head-mounted magnet and a magnetometer coil could be used to detect the HTR induced by serotonergic hallucinations based on the dynamics of the response. Results Head movement during the HTR was highly rhythmic and occurred within a specific frequency range (mean reciprocation frequency of 90.3 Hz). Head twitches produced wave-like oscillations of magnetometer coil voltage that matched the frequency of head movement during the response. The magnetometer coil detected the HTR induced by the serotonergic hallucinogens 2,5-dimethoxy-4-iodoamphetamine (DOI; 0.25, 0.5, and 1.0 mg/kg, IP) and lysergic acid diethylamide (LSD; 0.05, 0.1, 0.2, and 0.4 mg/kg, IP) with extremely high sensitivity and specificity. Magnetometer coil recordings demonstrated that the non-hallucinogenic compounds (+)-amphetamine (2.5 and 5.0 mg/kg, IP) and lisuride (0.8, 1.6, and 3.2 mg/kg, IP) did not induce the HTR. Conclusions These studies confirm that a magnetometer coil can be used to detect the HTR induced by hallucinogens. The use of magnetometer-based HTR detection provides a high-throughput, semi-automated assay for this behavior, and offers several advantages over traditional assessment methods. PMID:23407781

Expression of multiple slow myosin heavy chain genes reveals a diversity of zebrafish slow twitch muscle fibres with differing requirements for Hedgehog and Prdm1 activity.

PubMed

Elworthy, Stone; Hargrave, Murray; Knight, Robert; Mebus, Katharina; Ingham, Philip W

2008-06-01

The zebrafish embryo develops a series of anatomically distinct slow twitch muscle fibres that characteristically express genes encoding lineage-specific isoforms of sarcomeric proteins such as MyHC and troponin. We show here that different subsets of these slow fibres express distinct members of a tandem array of slow MyHC genes. The first slow twitch muscle fibres to differentiate, which are specified by the activity of the transcription factor Prdm1 (also called Ubo or Blimp1) in response to Hedgehog (Hh) signalling, express the smyhc1 gene. Subsequently, secondary slow twitch fibres differentiate in most cases independently of Hh activity. We find that although some of these later-forming fibres also express smyhc1, others express smyhc2 or smyhc3. We show that the smyhc1-positive fibres express the ubo (prdm1) gene and adopt fast twitch fibre characteristics in the absence of Prdm1 activity, whereas those that do not express smyhc1 can differentiate independently of Prdm1 function. Conversely, some smyhc2-expressing fibres, although independent of Prdm1 function, require Hh activity to form. The adult trunk slow fibres express smyhc2 and smyhc3, but lack smyhc1 expression. The different slow fibres in the craniofacial muscles variously express smyhc1, smyhc2 and smyhc3, and all differentiate independently of Prdm1.

Hybrid assemblies of ATP-sensitive K+ channels determine their muscle-type-dependent biophysical and pharmacological properties.

PubMed

Tricarico, Domenico; Mele, Antonietta; Lundquist, Andrew L; Desai, Reshma R; George, Alfred L; Conte Camerino, Diana

2006-01-24

ATP-sensitive K(+) channels (K(ATP)) are an octameric complex of inwardly rectifying K(+) channels (Kir6.1 and Kir6.2) and sulfonylurea receptors (SUR1 and SUR2A/B), which are involved in several diseases. The tissue-selective expression of the subunits leads to different channels; however, the composition and role of the functional channel in native muscle fibers is not known. In this article, the properties of K(ATP) channels of fast-twitch and slow-twitch muscles were compared by combining patch-clamp experiments with measurements of gene expression. We found that the density of K(ATP) currents/area was muscle-type specific, being higher in fast-twitch muscles compared with the slow-twitch muscle. The density of K(ATP) currents/area was correlated with the level of Kir6.2 expression. SUR2A was the most abundant subunit expressed in all muscles, whereas the vascular SUR2B subunit was expressed but at lower levels. A significant expression of the pancreatic SUR1 was also found in fast-twitch muscles. Pharmacological experiments showed that the channel response to the SUR1 agonist diazoxide, SUR2A/B agonist cromakalim, SUR1 antagonist tolbutamide, and the SUR1/SUR2A/B-antagonist glibenclamide matched the SURs expression pattern. Muscle-specific K(ATP) subunit compositions contribute to the physiological performance of different muscle fiber types and determine the pharmacological actions of drugs modulating K(ATP) activity in muscle diseases.

Calcium-Enhanced Twitching Motility in Xylella fastidiosa Is Linked to a Single PilY1 Homolog

PubMed Central

Cruz, Luisa F.; Parker, Jennifer K.; Cobine, Paul A.

2014-01-01

The plant-pathogenic bacterium Xylella fastidiosa is restricted to the xylem vessel environment, where mineral nutrients are transported through the plant host; therefore, changes in the concentrations of these elements likely impact the growth and virulence of this bacterium. Twitching motility, dependent on type IV pili (TFP), is required for movement against the transpiration stream that results in basipetal colonization. We previously demonstrated that calcium (Ca) increases the motility of X. fastidiosa, although the mechanism was unknown. PilY1 is a TFP structural protein recently shown to bind Ca and to regulate twitching and adhesion in bacterial pathogens of humans. Sequence analysis identified three pilY1 homologs in X. fastidiosa (PD0023, PD0502, and PD1611), one of which (PD1611) contains a Ca-binding motif. Separate deletions of PD0023 and PD1611 resulted in mutants that still showed twitching motility and were not impaired in attachment or biofilm formation. However, the response of increased twitching at higher Ca concentrations was lost in the pilY1-1611 mutant. Ca does not modulate the expression of any of the X. fastidiosa PilY1 homologs, although it increases the expression of the retraction ATPase pilT during active movement. The evidence presented here suggests functional differences between the PilY1 homologs, which may provide X. fastidiosa with an adaptive advantage in environments with high Ca concentrations, such as xylem sap. PMID:25217013

Calcium-Enhanced Twitching Motility in Xylella fastidiosa Is Linked to a Single PilY1 Homolog.

PubMed

Cruz, Luisa F; Parker, Jennifer K; Cobine, Paul A; De La Fuente, Leonardo

2014-12-01

The plant-pathogenic bacterium Xylella fastidiosa is restricted to the xylem vessel environment, where mineral nutrients are transported through the plant host; therefore, changes in the concentrations of these elements likely impact the growth and virulence of this bacterium. Twitching motility, dependent on type IV pili (TFP), is required for movement against the transpiration stream that results in basipetal colonization. We previously demonstrated that calcium (Ca) increases the motility of X. fastidiosa, although the mechanism was unknown. PilY1 is a TFP structural protein recently shown to bind Ca and to regulate twitching and adhesion in bacterial pathogens of humans. Sequence analysis identified three pilY1 homologs in X. fastidiosa (PD0023, PD0502, and PD1611), one of which (PD1611) contains a Ca-binding motif. Separate deletions of PD0023 and PD1611 resulted in mutants that still showed twitching motility and were not impaired in attachment or biofilm formation. However, the response of increased twitching at higher Ca concentrations was lost in the pilY1-1611 mutant. Ca does not modulate the expression of any of the X. fastidiosa PilY1 homologs, although it increases the expression of the retraction ATPase pilT during active movement. The evidence presented here suggests functional differences between the PilY1 homologs, which may provide X. fastidiosa with an adaptive advantage in environments with high Ca concentrations, such as xylem sap. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Slow to fast alterations in skeletal muscle fibers caused by clenbuterol, a beta(2)-receptor agonist

NASA Technical Reports Server (NTRS)

Zeman, Richard J.; Ludemann, Robert; Easton, Thomas G.; Etlinger, Joseph D.

1988-01-01

The effects of a beta(2)-receptor agonist, clenbuterol, and a beta(2) antagonist, butoxamine, on the skeletal muscle fibers of rats were investigated. It was found that chronic treatment of rats with clenbuterol caused hypertrophy of histochemically identified fast-twitch, but not slow-twitch, fibers within the soleus, while in the extensor digitorum longus the mean areas of both fiber types were increased; in both muscles, the ratio of the number of fast-twitch to slow-twitch fibers was increased. In contrast, a treatment with butoxamine caused a reduction of the fast-twitch fiber size in both muscles, and the ratio of the fast-twitch to slow-twitch fibers was decreased.

[Case of anti VGKC-complex antibody associated disorder presenting with severe pain and fasciculations predominant in unilateral upper extremity].

PubMed

Hara, Kenju; Watanabe, Osamu; Shibano, Ken; Ishiguro, Hideaki

2012-01-01

A 21-year-old man complained of severe pain and muscle twitching localized in his right arm. Neurological examination showed muscle fasciculations in his right forearm but no myokymia or myotonia. Needle electromyography revealed fibrillation potentials in his biceps brachii muscle and extensor carpi radialis muscle at rest but no myokymic discharges. His serum anti-voltage-gated potassium channel (VGKC)-complex antibody level was significantly high (194.2pM; controls <100pM). Although anticonvulsant therapy relieved his pain, he was readmitted to our hospital because of severe pain in his left arm and both thighs three months later. A high-dose intravenous immunoglobulin (IVIG) therapy followed by steroid pulse therapy relieved his pain. This case with neither muscle cramp nor myokymia expands the phenotype of anti VGKC-complex antibody associated disorder.

Responses of neuromuscular systems under gravity or microgravity environment.

PubMed

Ishihara, Akihiko; Kawano, Fuminori; Wang, Xiao Dong; Ohira, Yoshinobu

2004-11-01

Hindlimb suspension of rats induces induces fiber atrophy and type shift of muscle fibers. In contrast, there is no change in the cell size or oxidative enzyme activity of spinal motoneurons innervating muscle fibers. Growth-related increases in the cell size of muscle fibers and their spinal motoneurons are inhibited by hindlimb suspension. Exposure to microgravity induces atrophy of fibers (especially slow-twitch fibers) and shift of fibers from slow- to fast-twitch type in skeletal muscles (especially slow, anti-gravity muscles). In addition, a decrease in the oxidative enzyme activity of spinal motoneurons innervating slow-twitch fibers and of sensory neurons in the dorsal root ganglion is observed following exposure to microgravity. It is concluded that neuromuscular activities are important for maintaining metabolism and function of neuromuscular systems at an early postnatal development and that gravity effects both efferent and afferent neural pathways.

The influence of rat suspension-hypokinesia on the gastrocnemius muscle

NASA Technical Reports Server (NTRS)

Templeton, G. H.; Padalino, M.; Manton, J.; Leconey, T.; Hagler, H.; Glasberg, M.

1984-01-01

Hind-limb hypokinesia was induced in rats by the Morey method to characterize the response of the gastrocnemius muscle. A comparison of rats suspended for 2 weeks with weight, sex, and litter-matched control rats indicate no difference in gastrocnemius wet weight, contraction, or one-half relaxation times, but less contractile function as indicated by lowered dP/dt. Myosin ATPase staining identified uniform Type I (slow-twitch) and II (fast-twitch) atrophy in the muscles from 4 of 10 rats suspended for 2 weeks and 1 of 12 rats suspended for 4 weeks; muscles from three other rats of the 4-week group displayed greater Type I atrophy. Other histochemical changes were characteristic of a neuropathy. These data together with recently acquired soleus data (29) indicate the Morey model, like space flight, evokes greater changes in the Type I or slow twitch fibers of the gastrocnemius and soleus muscles.

Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives.

PubMed

Nakagawasai, Osamu; Arai, Yuichiro; Satoh, Shin-etsu; Satoh, Nobunori; Neda, Mitsuro; Hozumi, Masato; Oka, Ryusho; Hiraga, Hajime; Tadano, Takeshi

2004-01-01

It is well known that head-twitch response (HTR) in mice represents hallucinations, since administration of lysergic acid diethylamide (LSD) produces hallucinations in humans, and the HTR in mice is induced by administration of LSD as a hallucinogen. The HTR is produced by excitation of 5-hydroxytryptamine (5-HT)2A receptors. In this paper, we review the mechanisms of HTR induced by various drugs such as 5-HT precursor, 5-HT receptor agonist, 5-HT releaser, hallucinogenic compounds, benzodiazepins and cannabinoid. The response induced by HTR-inducers is significantly enhanced by combined treatment with a non-selective form of monoamine oxidase (MAO) inhibitor. Thus, the relationship between MAO activity and HTR caused by these drugs (especially, alpha-methylated analogous compounds which 5-fluoro-alpha-methyltryptamine, 6-fluoro-alpha-methyltryptamine and p-hydroxyamphetamine) is presented in detail.

Electrical stimulation to the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle induces involuntary reflex contraction of the frontalis muscles.

PubMed

Matsuo, Kiyoshi; Osada, Yoshiro; Ban, Ryokuya

2013-02-01

The levator and frontalis muscles lack interior muscle spindles, despite consisting of slow-twitch fibres that involuntarily sustain eyelid-opening and eyebrow-raising against gravity. To compensate for this anatomical defect, this study hypothetically proposes that initial voluntary contraction of the levator fast-twitch muscle fibres stretches the mechanoreceptors in Müller's muscle and evokes proprioception, which continuously induces reflex contraction of slow-twitch fibres of the levator and frontalis muscles. This study sought to determine whether unilateral transcutaneous electrical stimulation to the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle could induce electromyographic responses in the frontalis muscles, with monitoring responses in the orbicularis oculi muscles. The study population included 27 normal subjects and 23 subjects with aponeurotic blepharoptosis, who displayed persistently raised eyebrows on primary gaze and light eyelid closure. The stimulation induced a short-latency response in the ipsilateral frontalis muscle of all subjects and long-latency responses in the bilateral frontalis muscles of normal subjects. However, it did not induce long-latency responses in the bilateral frontalis muscles of subjects with aponeurotic blepharoptosis. The orbicularis oculi muscles showed R1 and/or R2 responses. The stimulation might reach not only the proprioceptive fibres, but also other sensory fibres related to the blink or corneal reflex. The experimental system can provoke a monosynaptic short-latency response in the ipsilateral frontalis muscle, probably through the mesencephalic trigeminal proprioceptive neuron and the frontalis motor neuron, and polysynaptic long-latency responses in the bilateral frontalis muscles through an unknown pathway. The latter neural circuit appeared to be engaged by the circumstances of aponeurotic blepharoptosis.

A comparison of rat myosin from fast and slow skeletal muscle and the effect of disuse

NASA Technical Reports Server (NTRS)

Unsworth, B. R.; Witzmann, F. A.; Fitts, R. H.

1981-01-01

Certain enzymatic and structural features of myosin, purified from rat skeletal muscles representative of the fast twitch glycolytic (type IIb), the fast twitch oxidative (type IIa), and the slow twitch oxidative (type I) fiber, were determined and the results were compared with the measured contractile properties. Good correlation was found between the shortening velocities and Ca(2+)-activated ATPase activity for each fiber type. Short term hind limb immobilization caused prolongation of contraction time and one-half relaxation time in the fast twitch muscles and a reduction of these contractile properties in slow twitch soleus. Furthermore, the increased maximum shortening velocity in the immobilized soleus could be correlated with increased Ca(2+)-ATPase, but no change was observed in the enzymatic activity of the fast twitch muscles. No alteration in light chain distribution with disuse was observed in any of the fiber types. The myosin from slow twitch soleus could be distinguished from fast twitch myosins on the basis of the pattern of peptides generated by proteolysis of the heavy chains. Six weeks of hind limb immobilization resulted in both an increased ATPase activity and an altered heavy chain primary structure in the slow twitch soleus muscle.

Development of a Novel Method for Analyzing Pseudomonas aeruginosa Twitching Motility and Its Application to Define the AmrZ Regulon

PubMed Central

Xu, Binjie; Wozniak, Daniel J.

2015-01-01

Twitching motility is an important migration mechanism for the Gram-negative bacterium Pseudomonas aeruginosa. In the commonly used subsurface twitching assay, the sub-population of P. aeruginosa with active twitching motility is difficult to harvest for high-throughput studies. Here we describe the development of a novel method that allows efficient isolation of bacterial sub-populations conducting highly active twitching motility. The transcription factor AmrZ regulates multiple P. aeruginosa virulence factors including twitching motility, yet the mechanism of this activation remains unclear. We therefore set out to understand this mechanism by defining the AmrZ regulon using DNA microarrays in combination with the newly developed twitching motility method. We discovered 112 genes in the AmrZ regulon and many encode virulence factors. One gene of interest and the subsequent focus was lecB, which encodes a fucose-binding lectin. DNA binding assays revealed that AmrZ activates lecB transcription by directly binding to its promoter. The lecB gene was previously shown to be required for twitching motility in P. aeruginosa strain PAK; however, our lecB deletion had no effect on twitching motility in strain PAO1. Collectively, in this study a novel condition was developed for quantitative studies of twitching motility, under which the AmrZ regulon was defined. PMID:26309248

Prdm1a and miR-499 act sequentially to restrict Sox6 activity to the fast-twitch muscle lineage in the zebrafish embryo.

PubMed

Wang, XinGang; Ono, Yosuke; Tan, Swee Chuan; Chai, Ruth JinFen; Parkin, Caroline; Ingham, Philip W

2011-10-01

Sox6 has been proposed to play a conserved role in vertebrate skeletal muscle fibre type specification. In zebrafish, sox6 transcription is repressed in slow-twitch progenitors by the Prdm1a transcription factor. Here we identify sox6 cis-regulatory sequences that drive fast-twitch-specific expression in a Prdm1a-dependent manner. We show that sox6 transcription subsequently becomes derepressed in slow-twitch fibres, whereas Sox6 protein remains restricted to fast-twitch fibres. We find that translational repression of sox6 is mediated by miR-499, the slow-twitch-specific expression of which is in turn controlled by Prdm1a, forming a regulatory loop that initiates and maintains the slow-twitch muscle lineage.

Model-based sensorimotor integration for multi-joint control: development of a virtual arm model.

PubMed

Song, D; Lan, N; Loeb, G E; Gordon, J

2008-06-01

An integrated, sensorimotor virtual arm (VA) model has been developed and validated for simulation studies of control of human arm movements. Realistic anatomical features of shoulder, elbow and forearm joints were captured with a graphic modeling environment, SIMM. The model included 15 musculotendon elements acting at the shoulder, elbow and forearm. Muscle actions on joints were evaluated by SIMM generated moment arms that were matched to experimentally measured profiles. The Virtual Muscle (VM) model contained appropriate admixture of slow and fast twitch fibers with realistic physiological properties for force production. A realistic spindle model was embedded in each VM with inputs of fascicle length, gamma static (gamma(stat)) and dynamic (gamma(dyn)) controls and outputs of primary (I(a)) and secondary (II) afferents. A piecewise linear model of Golgi Tendon Organ (GTO) represented the ensemble sampling (I(b)) of the total muscle force at the tendon. All model components were integrated into a Simulink block using a special software tool. The complete VA model was validated with open-loop simulation at discrete hand positions within the full range of alpha and gamma drives to extrafusal and intrafusal muscle fibers. The model behaviors were consistent with a wide variety of physiological phenomena. Spindle afferents were effectively modulated by fusimotor drives and hand positions of the arm. These simulations validated the VA model as a computational tool for studying arm movement control. The VA model is available to researchers at website http://pt.usc.edu/cel .

Postjunctional inhibition of contractor responses in the mouse vas deferens by rat and human calcitonin gene-related peptides (CGRP).

PubMed Central

Al-Kazwini, S. J.; Craig, R. K.; Marshall, I.

1986-01-01

The effects of rat and human alpha-calcitonin gene-related peptide (CGRP) were compared in the mouse and rabbit isolated vas deferens preparation contracted by either field stimulation or acetylcholine. The peptides were about equipotent at inhibiting twitch responses of the mouse vas deferens to field stimulation at 0.2 Hz (IC50 12 +/- 4 nM and 15 +/- 3 nM, rat and human alpha-CGRP respectively). Rat alpha-CGRP was less potent at inhibiting responses to 10 Hz than to either 0.2 Hz or 1.0 Hz stimulation. The potency of rat alpha-CGRP at 1.0 Hz was unaltered by halving the calcium concentration of the Krebs solution. The inhibitory effect of human alpha-CGRP was not antagonized by either propranolol (300 nM) or idazoxan (300 nM), although in the same tissues these latter two drugs reduced responses to isoprenaline and clonidine respectively. Rat alpha-CGRP (100 nM) and human alpha-CGRP (1.0 microM) did not alter the uptake of [3H]-noradrenaline (30 nM) into mice isolated vasa deferentia. Rat alpha-CGRP (3-100 nM) did not alter the fractional release per pulse (1.0 Hz, 100 pulses) of tritium from vasa preloaded with [3H]-noradrenaline, although at the same time the peptide inhibited responses of the smooth muscle to field stimulation. Rat and human alpha-CGRP were equipotent at inhibiting contractions of the mouse vas deferens evoked by acetylcholine although the peptides were less potent than against twitch responses. In the rabbit vas deferens neither rat nor human alpha-CGRP (3 nM-1 microM) inhibited either twitch responses or acetylcholine contractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3486688

Calorie restriction enhances insulin-stimulated glucose uptake and Akt phosphorylation in both fast-twitch and slow-twitch skeletal muscle of 24-month-old rats.

PubMed

Sequea, Donel A; Sharma, Naveen; Arias, Edward B; Cartee, Gregory D

2012-12-01

Calorie restriction (CR) induces enhanced insulin-stimulated glucose uptake in fast-twitch (type II) muscle from old rats, but the effect of CR on slow-twitch (type I) muscle from old rats is unknown. The purpose of this study was to assess insulin-stimulated glucose uptake and phosphorylation of key insulin signaling proteins in isolated epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles from 24-month-old ad libitum fed and CR (consuming 65% of ad libitum, intake) rats. Muscles were incubated with and without 1.2 nM insulin. CR versus ad libitum rats had greater insulin-stimulated glucose uptake and Akt phosphorylation (pAkt) on T308 and S473 for both muscles incubated with insulin. GLUT4 protein abundance and phosphorylation of the insulin receptor (Y1162/1163) and AS160 (T642) were unaltered by CR in both muscles. These results implicate enhanced pAkt as a potential mechanism for the CR-induced increase in insulin-stimulated glucose uptake by the fast-twitch epitrochlearis and slow-twitch soleus of old rats.

Visualization of Twitching Motility and Characterization of the Role of the PilG in Xylella fastidiosa.

PubMed

Shi, Xiangyang; Lin, Hong

2016-04-08

Xylella fastidiosa is a Gram-negative non-flagellated bacterium that causes a number of economically important diseases of plants. The twitching motility provides X. fastidiosa a means for long-distance intra-plant movement and colonization, contributing toward pathogenicity in X. fastidiosa. The twitching motility of X. fastidiosa is operated by type IV pili. Type IV pili of Xylella fastidiosa are regulated by pilG, a chemotaxis regulator in Pil-Chp operon encoding proteins that are involved with signal transduction pathways. To elucidate the roles of pilG in the twitching motility of X. fastidiosa, a pilG-deficient mutant XfΔpilG and its complementary strain XfΔpilG-C containing native pilG were developed. A microfluidic chambers integrated with a time-lapse image recording system was used to observe twitching motility in XfΔpilG, XfΔpilG-C and its wild type strain. Using this recording system, it permits long-term spatial and temporal observations of aggregation, migration of individual cells and populations of bacteria via twitching motility. X. fastidiosa wild type and complementary XfΔpilG-C strain showed typical twitching motility characteristics directly observed in the microfluidic flow chambers, whereas mutant XfΔpliG exhibited the twitching deficient phenotype. This study demonstrates that pilG contributes to the twitching motility of X. fastidiosa. The microfluidic flow chamber is used as a means for observing twitching motility.

Glycogen depletion according to muscle and fibre types in response to dyadic encounters in pigs (Sus scrofa domesticus)--relationships with plasma epinephrine and aggressive behaviour.

PubMed

Fernandez, X; Meunier-Salaün, M C; Ecolan, P

1994-12-01

Changes in glycogen content according to fibre type were assessed in a predominantly white (Longissimus) and a predominantly red (Semispinalis) pig muscle, in response to dyadic encounters involving aggressive interactions. Tested animals showed significantly lower glycogen levels than the control in the Semispinalis, but not in the Longissimus muscle. Histological treatment of muscle serial cuts followed by computerized image analysis showed that the observed decrease in muscle Semispinalis glycogen level occurred only in fast-twitch fibres. Total glycogen and glycogen contents in fast-twitch fibres of the Semispinalis muscle were closely and negatively related to aggressive behaviour, but not with plasma epinephrine levels during and at the end of the encounters. The present results provide indirect evidences suggesting a major influence of fighting-induced physical activity on muscle glycogen depletion in response to aggressive interactions in pigs.

Sarcomere length-dependence of activity-dependent twitch potentiation in mouse skeletal muscle

PubMed Central

Rassier, Dilson E; MacIntosh, Brian R

2002-01-01

Background It has been reported that potentiation of a skeletal muscle twitch response is proportional to muscle length with a negative slope during staircase, and a positive slope during posttetanic potentiation. This study was done to directly compare staircase and posttetanic responses with measurement of sarcomere length to compare their length-dependence. Methods Mouse extensor digitorum longus (EDL) muscles were dissected to small bundles of fibers, which permit measurement of sarcomere length (SL), by laser diffraction. In vitro fixed-end contractions of EDL fiber bundles were elicited at 22°C and 35°C at sarcomere lengths ranging from 2.35 μm to 3.85 μm. Twitch contractions were assessed before and after 1.5 s of 75 Hz stimulation at 22°C or during 10 s of 10 Hz stimulation at 22°C or 35°C. Results Staircase potentiation was greater at 35°C than 22°C, and the relative magnitude of the twitch contraction (Pt*/Pt) was proportional to sarcomere length with a negative slope, over the range 2.3 μm – 3.7 μm. Linear regression yielded the following: Pt*/Pt = -0.59·SL+3.27 (r2 = 0.74); Pt*/Pt = -0.39·SL+2.34 (r2 = 0.48); and Pt*/Pt = -0.50·SL+2.45 (r2 = 0.80) for staircase at 35°C, and 22°C and posttetanic response respectively. Posttetanic depression rather than potentiation was present at long SL. This indicates that there may be two processes operating in these muscles to modulate the force: one that enhances and a second that depresses the force. Either or both of these processes may have a length-dependence of its mechanism. Conclusion There is no evidence that posttetanic potentiation is fundamentally different from staircase in these muscles. PMID:12475395

Validation of jump squats as a practical measure of post-activation potentiation.

PubMed

Nibali, Maria L; Chapman, Dale W; Robergs, Robert A; Drinkwater, Eric J

2013-03-01

To determine if post-activation potentiation (PAP) can augment sports performance, it is pertinent that researchers be confident that any enhancement in performance is attributable to the PAP phenomenon. However, obtaining mechanistic measures of PAP in the daily training environment of highly trained athletes is impractical. We sought to validate jump squats as a practical measure with ecological validity to sports performance against a mechanistic measure of PAP. We assessed the evoked muscle twitch properties of the knee extensors and jump squat kinetics of 8 physically trained males in response to a 5-repetition-maximum back squat conditioning stimulus (CS). Evoked muscle twitch, followed by 3 jump squats, was assessed before and at 4, 8, and 12 min post CS. Time intervals were assessed on separate occasions using a Latin square design. Linear regression was used to determine the relationship between post-pre changes in kinetic variables and muscle twitch peak force (Ft) and twitch rate of force development (RFDt). Large correlations were observed for both concentric relative and absolute mean power and Ft (r = 0.50 ± 0.30) and RFDt (r = 0.56 ± 0.27 and r = 0.58 ± 0.26). Concentric rate of force development (RFD) showed moderate correlations with Ft (r = 0.45 ± 0.33) and RFDt (r = 0.49 ± 0.32). Small-to-moderate correlations were observed for a number of kinetic variables (r = -0.42-0.43 ± 0.32-0.38). Jump squat concentric mean power and RFD are valid ecological measures of muscle potentiation, capable of detecting changes in athletic performance in response to the PAP phenomenon.

Selective modification of the pyruvate dehydrogenase kinase isoform profile in skeletal muscle in hyperthyroidism: implications for the regulatory impact of glucose on fatty acid oxidation.

PubMed

Sugden, M C; Lall, H S; Harris, R A; Holness, M J

2000-11-01

The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC). Immunoblot analysis with antibodies raised against recombinant PDK isoforms demonstrated changes in PDK isoform expression in response to experimental hyperthyroidism (100 microg/100 g body weight; 3 days) that was selective for fast-twitch vs slow-twitch skeletal muscle in that PDK2 expression was increased in the fast-twitch skeletal muscle (the anterior tibialis) (by 1. 6-fold; P<0.05) but not in the slow-twitch muscle (the soleus). PDK4 protein expression was increased by experimental hyperthyroidism in both muscle types, there being a greater response in the anterior tibialis (4.2-fold increase; P<0.05) than in the soleus (3.2-fold increase; P<0.05). The hyperthyroidism-associated up-regulation of PDK4 expression was observed in conjunction with suppression of skeletal-muscle PDC activity, but not suppression of glucose uptake/phosphorylation, as measured in vivo in conscious unrestrained rats (using the 2-[(3)H]deoxyglucose technique). We propose that increased PDK isoform expression contributes to the pathology of hyperthyroidism and to PDC inactivation by facilitating the operation of the glucose --> lactate --> glucose (Cori) and glucose --> alanine --> glucose cycles. We also propose that enhanced relative expression of the pyruvate-insensitive PDK isoform (PDK4) in skeletal muscle in hyperthyroidism uncouples glycolytic flux from pyruvate oxidation, sparing pyruvate for non-oxidative entry into the tricarboxylic acid (TCA) cycle, and thereby supporting entry of acetyl-CoA (derived from fatty acid oxidation) into the TCA cycle.

The Action of Botulinum Toxin at the Neuromuscular Junction

DTIC Science & Technology

1980-12-22

fast - twitch " (gastrocnemius) and " slow - twitch " (soleus) muscles ... muscle fibers -"_re not significantly affected by the toxin. It is interesting to note that, although fast - twitch and slow - twitch mucles were...Duchen LW: An electron microscopic study of the changes induced by borulinum o::in in the motor end-plates of slow and fast skeletal muscle fibres of

Models of disuse - A comparison of hindlimb suspension and immobilization

NASA Technical Reports Server (NTRS)

Fitts, R. H.; Metzger, J. M.; Riley, D. A.; Unsworth, B. R.

1986-01-01

The effects of 1 and 2 weeks of hindlimb suspension (HS) on the contractile properties of fast- and slow-twitch skeletal muscles of male Sprague Dawley rats are studied and compared with hindlimb immobilization (HI) data. The optimal length and contractile properties of the slow-twitch soleus, fast-twitch extensor digitorum longus, and the vastus lateralis are measured. It is observed that HS and HI affect slow-twitch muscles; isometric twitch duration in the slow-twitch soleus is decreased. Soleus muscle mass and peak tetanic tension declines with disuse. A major difference in the influence of HS and HI on the maximal speed of soleus muscle shortening, V(max) is detected; HS produced a twofold increase in V(max) compared to control data and HI had no significant effect on V(max). The relation between V(max) and myosin concentration is analyzed. The data reveal that HS modifies slow-twitch muscle yielding hybrid fibers with elevated shortening velocities and this change may be dependent on the elimination of load-bearing contractions.

Recovery in skeletal muscle contractile function after prolonged hindlimb immobilization

NASA Technical Reports Server (NTRS)

Fitts, R. H.; Brimmer, C. J.

1985-01-01

The effect of three-month hindlimb immobilization (IM) in rats on contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus, and fast-twitch superficial region of the vastus lateralis were measured after 0, 14, 28, 60, and 90 days of recovery on excized, horizontally suspended muscles stimulated electrically to maximal twitch tension. IM caused decreases in muscle-to-body weight ratios for all muscles, with no complete recovery even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than those of the slow-twitch SOL. The SOL isometric twitch duration was shortened, due to reduced contraction and half-relaxation time, both of which returned to control levels after 14 days of recovery. The peak tetanic tension, P(O), g/sq cm,, decreased with IM by 46 percent in the SOL, but recovered by the 28th day. The maximum shortening velocity was not altered by IM in any of the muscles. Thus, normal contractile function could recover after prolonged limb IM.

Weakfish sonic muscle: influence of size, temperature and season.

PubMed

Connaughton, M A; Fine, M L; Taylor, M H

2002-08-01

The influence of temperature, size and season on the sounds produced by the sonic muscles of the weakfish Cynoscion regalis are categorized and used to formulate a hypothesis about the mechanism of sound generation by the sonic muscle and swimbladder. Sounds produced by male weakfish occur at the time and location of spawning and have been observed in courtship in captivity. Each call includes a series of 6-10 sound pulses, and each pulse expresses a damped, 2-3 cycle acoustic waveform generated by single simultaneous twitches of the bilateral sonic muscles. The sonic muscles triple in mass during the spawning season, and this hypertrophy is initiated by rising testosterone levels that trigger increases in myofibrillar and sarcoplasmic cross-sectional area of sonic muscle fibers. In response to increasing temperature, sound pressure level (SPL), dominant frequency and repetition rate increase, and pulse duration decreases. Likewise, SPL and pulse duration increase and dominant frequency decreases with fish size. Changes in acoustic parameters with fish size suggest the possibility that drumming sounds act as an 'honest' signal of male fitness during courtship. These parameters also correlate with seasonally increasing sonic muscle mass. We hypothesize that sonic muscle twitch duration rather than the resonant frequency of the swimbladder determines dominant frequency. The brief (3.5 ms), rapidly decaying acoustic pulses reflect a low-Q, broadly tuned resonator, suggesting that dominant frequency is determined by the forced response of the swimbladder to sonic muscle contractions. The changing dominant frequency with temperature in fish of the same size further suggests that frequency is not determined by the natural frequency of the bladder because temperature is unlikely to affect resonance. Finally, dominant frequency correlates with pulse duration (reflecting muscle twitch duration), and the inverse of the period of the second cycle of acoustic energy approximates the recorded frequency. This paper demonstrates for the first time that the dominant frequency of a fish sound produced by a single muscle twitch is apparently determined by the velocity of the muscle twitch rather than the natural frequency of the swimbladder.

NEOCORTICAL ACTIVATION OF THE HIPPOCAMPUS DURING SLEEP IN INFANT RATS

PubMed Central

Mohns, Ethan J.; Blumberg, Mark S.

2010-01-01

We recently reported that the majority of hippocampal neurons in newborn rats increase their activity in association with myoclonic twitches, which are indicative of active sleep. Because spindle bursts in the developing somatosensory neocortex occur in response to sensory feedback from myoclonic twitching, we hypothesized that the state-dependent activity of the newborn hippocampus arises from sensory feedback that sequentially activates the neocortex and then hippocampus, constituting an early form of neocortical-hippocampal communication. Here, in unanesthetized 5–6-day-old rats, we test this hypothesis by recording simultaneously from forelimb and barrel regions of somatosensory neocortex and dorsal hippocampus during periods of spontaneous sleep and wakefulness and in response to peripheral stimulation. Myoclonic twitches were consistently followed by neocortical spindle bursts, which were in turn consistently followed by bursts of hippocampal unit activity; moreover, spindle burst power was positively correlated with hippocampal unit activity. In addition, exogenous stimulation consistently evoked this neocortical-to-hippocampal sequence of activation. Finally, parahippocampal lesions that disrupted functional connections between the neocortex and hippocampus effectively disrupted the transmission of both spontaneous and evoked neocortical activity to the hippocampus. These findings suggest that sleep-related motor activity contributes to the development of neocortical and hippocampal circuits and provides a foundation upon which coordinated activity between these two forebrain structures develops. PMID:20203203

Characterization of kinin receptors modulating neurogenic contractions of the mouse isolated vas deferens.

PubMed

Maas, J; Rae, G A; Huidobro-Toro, J P; Calixto, J B

1995-04-01

1. This study analyses the receptors mediating the effects of bradykinin (BK) and analogues on neurogenic twitch contractions of the mouse isolated vas deferens evoked, in the presence of captopril (3 microM), by electrical field stimulation with trains of 4 rectangular 0.5 ms pulses of supramaximal strength, delivered at a frequency of 10 Hz every 20 s. 2. BK (0.1-300 nM) induced a graded potentiation of twitches, with an EC50 (geometric mean and 95% confidence limits) of 4.5 nM (1.7-11.6) and an Emax of 315 +/- 19 mg per 10 mg of wet tissue (n = 6). Similar results were obtained in tissues challenged with Lys-BK, [Hyp3]-BK, Met,Lys-BK and the selective B2 receptor agonist [Tyr(Me)8]-BK (0.1-300 nM). 3. The selective B2 receptor antagonists, Hoe 140 (1-10 nM) and NPC 17731 (3-30 nM), caused graded rightward shifts of the curve to BK-induced twitch potentiation, yielding apparent pA2 values of 9.65 +/- 0.09 and 9.08 +/- 0.13, respectively, and Schild plot slopes not different from 1. Both antagonists (100 nM) failed to modify similar twitch potentiations induced by substance P (3 nM) or endothelin-1 (1 nM). Preincubation with the selective B1 receptor antagonist, [Leu8,des-Arg9]-BK (1 microM), increased the potentiating effect of BK on twitches at 30-300 nM. 4. In contrast to BK, the selective B1 receptor agonist, [des-Arg9]-BK (0.3-1000 nM) reduced the amplitude of twitches in a graded fashion, with an IC50 of 13.7 nM (10.4-16.1) and an Imax of 175 +/- 11 mg (n = 4). The twitch depression induced by [des-Arg9]-BK (300 nM) was not affected by Hoe140 (30nM) or NPC 17731 (100nM), but was abolished by the selective B1 receptor antagonist,[Leu8,des-Arg9]-BK (1 microM), which did not modify the twitch inhibitory effect of clonidine (1 nM) or morphine (300 nM).5. In non-stimulated preparations, BK (100 nM) also potentiated, in a Hoe 140-sensitive (10 nM)manner, the contractions induced by ATP (100 microM), but not by noradrenaline (10 microM), whereas[des-Arg9]-BK (300 nM) did not modify the contractions induced by either agonist.6. It is concluded that the mouse vas deferens expresses both B1 and B2 receptors, which modulate sympathetic neurotransmission in opposing ways. Neurogenic contractions are inhibited by stimulation of possibly prejunctional B, receptors, whereas activation of B2 receptors increases twitch contractions,in part by amplifying the responsiveness of the smooth muscle cells to the sympathetic co-transmitter ATP.

Actions of the selective inhibitor of cholinesterase tetramonoisopropyl pyrophosphortetramide on the rat phrenic nerve-diaphragm preparation

PubMed Central

Heffron, P. F.

1972-01-01

1. Tetramonoisopropyl pyrophosphortetramide (iso-OMPA) added for 15 min to the rat isolated phrenic nerve-diaphragm in a concentration of 30 μM, produced a complete selective and stable inhibition of cholinesterase. A concentration of 3 μM produced near complete inhibition of cholinesterase, and a concentration of 300 μM also inhibited acetylcholinesterase marginally. 2. Inhibition of cholinesterase was associated with a sustained increase in the neuromuscular blocking action of exogenous butyrylcholine but not of exogenous acetylcholine. Iso-OMPA, 300 μM, in addition caused transient increases in the sensitivity of the rat diaphragm to exogenous acetylcholine and butyrylcholine. In the same concentration, it had a curare-like action on the frog rectus abdominis muscle preparation. 3. Iso-OMPA, 30 μM, caused reversible increases in the amplitude of the twitch response and tetanic responses, which were of a similar magnitude in the indirectly stimulated preparation and the directly stimulated curarized preparation. Caffeine had a similar effect on the twitch response and its effectiveness was increased by iso-OMPA, and vice-versa. Amongst anticholinesterases, octamethyl pyrophosphortetramide and tetraethylpyrophosphate also enhanced the amplitude of the tetanic response, but paraoxon, dyflos, and mipafox did not. 4. It is concluded that iso-OMPA, in concentrations (3 and 30 μM) which in 15 min give near maximal or maximal selective inhibition of cholinesterase, has no effect on the transmission of nerve impulses at the neuromuscular junction, but enhances reversibly the amplitude of the contractile response to stimulation by a direct action upon the muscle fibre, which involves a mechanism related to but not identical with that by which caffeine potentiates twitch tension. In higher concentrations, iso-OMPA has a curare-like action at the neuromuscular junction. PMID:4347708

Do imipramine and dihydroergosine possess two components - one stimulating 5-HT sub 1 and the other inhibiting 5-HT sub 2 receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pericic, D.; Mueck-Seler, D.

1990-01-01

The mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-included stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT{sub 1} receptor sites, but not by ritanserin, a specific 5-HT{sub 2} receptor antagonist. (-) -Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. As expected, 8-OH-DPAT, a selective 5-HT{sub 1A} receptor agonist, stimulated, and 5-HT{sub 1B} agonists CGS 12066B and 1-(trifluoromethylphenyl) piperazine (TFMPP) failed to stimulatemore » the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer that after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for {sup 3}H-ketanserin binding sites than imipramine.« less

Electrical and Mechanical Responses in Deep Abdominal Extensor Muscles of Crayfish and Lobster

PubMed Central

Abbott, Bernard C.; Parnas, I.

1965-01-01

Electrical and mechanical studies have been made of the deep abdominal extensor muscles, medial (DEAM) and lateral (DEAL), of crayfish and lobster. The medial muscle responds to direct (intracellular) and indirect stimulation with a transient membrane depolarization which exhibits the properties of a propagated non-decremental action potential but does not overshoot the zero level. The amplitude is about 30 mv in crayfish and 50 mv in lobster. It is followed by a fast all-or-none twitch whose duration at 20°C is 30 to 50 msec. and whose developed tension is 500 gm/cm2 or about half the tetanic value. Membrane potential is K+-dependent and immersion in high K+ induces a brief transient tension rise as in other twitch-type muscles. The action potential and twitch are normal even if all external Na+ is replaced with sucrose but vary with external Ca++, the action potential increasing 8 to 10 mv for a twofold increase in Ca++. The lateral muscle (DEAL) is much slower and responds to intracellular stimulation only with an electrotonic or a local response. Mechanical responses and relaxation speeds are slow with minimal duration of contraction of 0.5 to 2 seconds. Immersion in high K solutions induces large maintained tensions. Sarcomere length in the fast DEAM is uniform and about 2 µ at rest, but in the DEAL speed is less and sarcomere length is greater averaging about 4.5 µ but with a mixed population of fibers. PMID:14324996

Comparison of collagen fibre architecture between slow-twitch cranial and fast-twitch caudal parts of broiler M. latissimus dorsi.

PubMed

Nakamura, Y N; Iwamoto, H; Tabata, S; Ono, Y

2003-07-01

1. Collagen fibre architectures of perimysium and endomysium in the slow-twitch cranial and fast-twitch caudal parts of broiler M. latissimus dorsi were compared. 2. Type I and III collagens were distributed in both perimysium and endomysium as indicated by their positive immunohistochemical reactions to polyclonal antibodies. 3. Cells invested by endomysium with no myofibres were larger in the cranial part because of the presence of larger slow-twitch myofibres. The honeycomb structure of endomysium was divided into several parts by thick perimysium. 4. The thick perimysial collagen fibres with parallel fibrils, which were interconnected by the loose reticular fibrils and thin fibres, were more numerous and thicker in the cranial part than the caudal. 5. Thick endomysial sidewall of cells in the cranial part was composed of a rougher reticulum of slightly thicker collagen fibrils compared with the thin sidewall in the caudal part. 6. These results indicated that both perimysial constitutions of collagen fibres and endomysial collagen fibrils had attained much larger growth in the slow-twitch cranial part than the fast-twitch caudal in broiler latissimus dorsi muscle.

Conflicting effects of fatigue and potentiation on voluntary force.

PubMed

Behm, David G; Button, Duane C; Barbour, Glen; Butt, Jeremy C; Young, Warren B

2004-05-01

The objective of this study was to investigate whether a warm-up consisting of a series of maximal contractions would augment the force and activation of subsequent leg extensor contractions. Both voluntary and evoked isometric contractions were tested to determine the mechanisms underlying the response. Nine subjects were tested for twitch, tetanic, submaximal (30%), and maximal voluntary contractile (MVC) properties before and after (1, 5, 10, and 15 minutes) one to three 10-second MVCs. MVC force either did not change following 1-2 MVCs or was depressed at 10 and 15 minutes after 3 MVCs. MVC activation was decreased (4.4-6.9%) throughout recovery, whereas submaximal contractions were minimally affected. Although overall, twitches were potentiated (15.5-19.8%) posttest, 3 MVCs had significantly greater twitch potentiation than 1 or 2 MVCs at 5 and 10 minutes. Results suggest that voluntary and evoked contractions respond differently to prior 10-second MVCs. In the present study, a warm-up routine of 1-3 MVCs of a 10-second duration did not enhance subsequent voluntary performance.

Intracellular calcium movements during excitation–contraction coupling in mammalian slow-twitch and fast-twitch muscle fibers

PubMed Central

Hollingworth, Stephen

2012-01-01

In skeletal muscle fibers, action potentials elicit contractions by releasing calcium ions (Ca2+) from the sarcoplasmic reticulum. Experiments on individual mouse muscle fibers micro-injected with a rapidly responding fluorescent Ca2+ indicator dye reveal that the amount of Ca2+ released is three- to fourfold larger in fast-twitch fibers than in slow-twitch fibers, and the proportion of the released Ca2+ that binds to troponin to activate contraction is substantially smaller. PMID:22450485

HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice.

PubMed

Holloway, Terrell; Moreno, Jose L; González-Maeso, Javier

2016-07-09

The heteromeric receptor complex between 5-HT2A and mGlu2 has been implicated in some of the behavioral phenotypes in mouse models of psychosis(1,2). Consequently, investigation of structural details of the interaction between 5-HT2A and mGlu2 affecting schizophrenia-related behaviors represents a powerful translational tool. As previously shown, the head-twitch response (HTR) in mice is elicited by hallucinogenic drugs and this behavioral response is absent in 5-HT2A knockout (KO) mice(3,4). Additionally, by conditionally expressing the 5-HT2A receptor only in cortex, it was demonstrated that 5-HT2A receptor-dependent signaling pathways on cortical pyramidal neurons are sufficient to elicit head-twitch behavior in response to hallucinogenic drugs(3). Finally, it has been shown that the head-twitch behavioral response induced by the hallucinogens DOI and lysergic acid diethylamide (LSD) is significantly decreased in mGlu2-KO mice(5). These findings suggest that mGlu2 is at least in part necessary for the 5-HT2A receptor-dependent psychosis-like behavioral effects induced by LSD-like drugs. However, this does not provide evidence as to whether the 5-HT2A-mGlu2 receptor complex is necessary for this behavioral phenotype. To address this question, herpes simplex virus (HSV) constructs to express either mGlu2 or mGlu2ΔTM4N (mGlu2/mGlu3 chimeric construct that does not form the 5-HT2A-mGlu2 receptor complex) in the frontal cortex of mGlu2-KO mice were used to examine whether this GPCR heteromeric complex is needed for the behavioral effects induced by LSD-like drugs(6).

American football and other sports injuries may cause migraine/persistent pain decades later and can be treated successfully with electrical twitch-obtaining intramuscular stimulation (ETOIMS).

PubMed

Chu, J; McNally, S; Bruyninckx, F; Neuhauser, D

2017-04-01

Autonomous twitch elicitation at myofascial trigger points from spondylotic radiculopathies-induced denervation supersensitivity can provide favourable pain relief using electrical twitch-obtaining intramuscular stimulation (ETOIMS). To provide objective evidence that ETOIMS is safe and efficacious in migraine and persistent pain management due to decades-old injuries to head and spine from paediatric American football. An 83-year-old mildly hypertensive patient with 25-year history of refractory migraine and persistent pain self-selected to regularly receive fee-for-service ETOIMS 2/week over 20 months. He had 180 sessions of ETOIMS. Pain levels, blood pressure (BP) and heart rate/pulse were recorded before and immediately after each treatment alongside highest level of clinically elicitable twitch forces/session, session duration and intervals between treatments. Twitch force grades recorded were from 1 to 5, grade 5 twitch force being strongest. Initially, there was hypersensitivity to electrical stimulation with low stimulus parameters (500 µs pulse-width, 30 mA stimulus intensity, frequency 1.3 Hz). This resolved with gradual stimulus increments as tolerated during successive treatments. By treatment 27, autonomous twitches were noted. Spearman's correlation coefficients showed that pain levels are negatively related to twitch force, number of treatments, treatment session duration and directly related to BP and heart rate/pulse. Treatment numbers and session durations directly influence twitch force. At end of study, headaches and quality of life improved, hypertension resolved and antihypertensive medication had been discontinued. Using statistical process control methodology in an individual patient, we showed long-term safety and effectiveness of ETOIMS in simultaneous diagnosis, treatment, prognosis and prevention of migraine and persistent pain in real time obviating necessity for randomised controlled studies.

Effects of drugs affecting endogenous amines or cyclic nucleotides on ethanol withdrawal head twitches in mice.

PubMed Central

Collier, H O; Hammond, M D; Schneider, C

1976-01-01

1 Twenty-four hours after ethanol withdrawal, dependent mice exhibited frequent head twitching. Naive mice exhibited similar twitching 15 min after treatment with 5-hydroxytryptophan (5-HTP) or 6 h after alpha-methyl-p-tyrosine (AMPT). Ethanol lessened the incidence of head twitches induced by any of these treatments. 5-HTP and AMPT each increased the incidence of head twitches induced by withdrawal of ethanol from dependent mice. 2 Drugs that affect the amount or activity of endogenous amines or cyclic nucleotides modified the incidence of head twitches. Nearly all drugs acted in the same direction on twitching elicited by any of these three treatments. 3 The incidence was lessened by: (a) methysergide, methergoline, MA 1420, p-chlorophenylalanine and p-chloroamphetamine; (b) dopamine, noradrenaline, L-DOPA, amphetamine and apomorphine; (c) hyoscine and nicotine; and (d) adenosine triphosphate, dibutyryl cyclic adenosine-3',5'-monophosphate (db cyclic AMP) and prostaglandins E1 and E2. 4 The incidence was increased by: (a) acetylcholine, carbachol and physostigmine; and (b) guanosine triphosphate, dibutyryl cyclic guanosine monophosphate (db cyclic GMP), theophylline and 3-isobutyl-1-methyl-xanthine. 5 These findings suggest that head twitching induced by these three treatments arises from a common biochemical mechanism, which may ultimately be a change in favour of cyclic GMP of the balance between this nucleotide and cyclic AMP within appropriate neurones. This imbalance appears to be elicited or increased by 5-hydroxytryptamine and acetylcholine and to be decreased by dopamine, noradrenaline and E prostaglandins. 6 Neither actinomycin D nor cycloheximide, given during the induction of ethanol dependence, altered the incidence of head twitches after ethanol withdrawal. PMID:987821

Central and peripheral cardiovascular responses to electrically induced and voluntary leg exercise

NASA Technical Reports Server (NTRS)

Saltin, B.; Strange, S.; Bangsbo, J.; Kim, C. K.; Duvoisin, M.; Hargens, A.; Gollnick, P. D.

1990-01-01

With long missions in space countermeasures have to be used to secure safe operations in space and a safe return to Earth. Exercises of various forms have been used, but the question has arisen whether electrically induced contractions of muscle especially sensitive to weightlessness and crucial for man's performance would aid in maintaining their optimal function. The physiological responses both to short term and prolonged dynamic exercise performed either voluntarily or induced by electrical stimulation were considered. The local and systemic circulatory responses were similar for the voluntary and electrically induced contractions. The metabolic response was slightly more pronounced with electrical stimulation. This could be a reflection of not only slow twitch (type 1) but also fast twitch (type 2) fibers being recruited when the contractions were induced electrically. Intramuscular pressure recordings indicated that the dominant fraction of the muscle group was engaged regardless of mode of activation. Some 70 percent of the short term peak voluntary exercise capacity could be attained with electrical stimulation. Thus, electrically induced contractions of specific muscle groups should indeed be considered as an efficient countermeasure.

Twitching in Sensorimotor Development from Sleeping Rats to Robots

PubMed Central

Marques, Hugo Gravato; Iida, Fumiya

2013-01-01

It is still not known how the “rudimentary” movements of fetuses and infants are transformed into the coordinated, flexible, and adaptive movements of adults. In addressing this important issue, we consider a behavior that has been perennially viewed as a functionless by-product of a dreaming brain: the jerky limb movements called myoclonic twitches. Recent work has identified the neural mechanisms that produce twitching as well as those that convey sensory feedback from twitching limbs to the spinal cord and brain. In turn, these mechanistic insights have helped inspire new ideas about the functional roles that twitching might play in the self-organization of spinal and supraspinal sensorimotor circuits. Striking support for these ideas is coming from the field of developmental robotics: When twitches are mimicked in robot models of the musculoskeletal system, basic neural circuitry self-organizes. Mutually inspired biological and synthetic approaches promise not only to produce better robots, but also to solve fundamental problems concerning the developmental origins of sensorimotor maps in the spinal cord and brain. PMID:23787051

Decreased muscle endurance associated with diabetic neuropathy may be attributed partially to neuromuscular transmission failure

PubMed Central

Kimpinski, Kurt; Doherty, Timothy J.; Rice, Charles L.

2015-01-01

Diabetic polyneuropathy (DPN) can cause muscle atrophy, weakness, contractile slowing, and neuromuscular transmission instability. Our objective was to assess the response of the impaired neuromuscular system of DPN in humans when stressed with a sustained maximal voluntary contraction (MVC). Baseline MVC and evoked dorsiflexor contractile properties were assessed in DPN patients (n = 10) and controls (n = 10). Surface electromyography was used to record tibialis anterior evoked maximal compound muscle action potentials (CMAPs) and neuromuscular activity during MVCs. Participants performed a sustained isometric dorsiflexion MVC for which task termination was determined by the inability to sustain ≥60% MVC torque. The fatigue protocol was immediately followed by a maximal twitch, with additional maximal twitches and MVCs assessed at 30 s and 2 min postfatigue. DPN patients fatigued ∼21% more quickly than controls (P < 0.05) and featured less relative electromyographic activity during the first one-third of the fatigue protocol compared with controls (P < 0.05). Immediately following fatigue, maximal twitch torque was reduced similarly (∼20%) in both groups, and concurrently CMAPs were reduced (∼12%) in DPN patients, whereas they were unaffected in controls (P > 0.05). Twitch torque and CMAP amplitude recovered to baseline 30 s postfatigue. Additionally, at 30 s postfatigue, both groups had similar (∼10%) reductions in MVC torque relative to baseline, and MVC strength recovered by 2 min postfatigue. We conclude DPN patients possess less endurance than controls, and neuromuscular transmission failure may contribute to this greater fatigability. PMID:25663671

Recovery from Short Term Intense Exercise: Its Relation to Capillary Supply and Lactate Release,

DTIC Science & Technology

1982-01-01

accumulate at a higher rate in fast twitch (FT or Type II) than in slow twitch (ST or Type I) fibers of exercised muscles . Lactate form- ed and accumulated...is made up by a high percentage of FT fibers than can be expected in a " slow twitch " muscle . Moreover, the over-all metabolic profile of the ST fiber...local muscular fatigue. Eur. J. Appl. Physiol. 38, 9-15 (1978b) Baldwin, K.M., Tipton, C.M.: Work and metabolic patterns of fast and slow twitch

Experiment K-6-10. Effects of zero gravity on myofibril protein content and isomyosin distribution in rodent skeletal muscle

NASA Technical Reports Server (NTRS)

Baldwin, K.; Herrick, R.; Oganov, V.

1990-01-01

The purpose of this experiment was to investigate the effects of 12 days of zero gravity (0G) exposure (Cosmos 1887 Biosputnik) on the enzymatic properties, protein content, and isomyosin distribution of the myofibril fraction of the slow-twitch vastus intermedius (VI) and the fast-twitch vastus lateralis (VL) muscles of adult male rats. Measurements were obtained on three experimental groups (n=5 each group) designated as flight-group (FG), vivarium-control (VC), and synchronous-control (SC). Body weight of the FG was significantly lower than the two control groups (p less than 0.05). Compared to the two control groups, VI weight was lower by 23 percent (p less than 0.10); whereas no such reduction was observed for the VL muscle. Myofibril yields (mg protein/g of muscle) in the VI were 35 percent lower in the FG compared to the controls (p less than 0.05); whereas, no such pattern was apparent for the VL muscle. When myofibril yields were expressed on a muscle basis (mg/g x muscle weight), the loss of myofibril protein was more exaggerated and suggests that myofibril protein degradation is an early event in the muscle atrophy response to 0G. Analysis of myosin isoforms indicated that slow-myosin was the primary isoform lost in the calculated degradation of total myosin. No evidence of loss of the fast isomyosins was apparent for either muscle following space flight. Myofibril ATPase activity of the VI was increased in the FG compared to controls, which is consistent with the observation of preferential slow-myosin degradation. These data suggest that muscles containing a high percent of slow-twitch fibers undergo greater degrees of myofibril protein degradation than do muscles containing predominantly fast-twitch fibers in response to a relatively short period of 0G exposure, and the primary target appears to be the slow-myosin molecule.

Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors, in mice

PubMed Central

Gray, Bradley W.; Bailey, Jessica M.; Smith, Douglas; Hansen, Martin; Kristensen, Jesper L.

2014-01-01

Rationale 2-([2-(4-cyano-2,5-dimethoxyphenyl)ethylamino]methyl)phenol (25CN-NBOH) is structurally similar to N-benzyl substituted phenethylamine hallucinogens currently emerging as drugs of abuse. 25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro, but has not been behaviorally characterized. Objective 25CN-NBOH was compared to the traditional phenethylamine hallucinogen R(−)-2,5-dimethoxy-4-iodoamphetamine (DOI) using mouse models of drug-elicited head twitch behavior and drug discrimination. Methods Drug-elicited head twitches were quantified for 10 min following administration of various doses of either DOI or 25CN-NBOH, with and without pretreatments of 0.01 mg/kg 5-HT2A antagonist M100907 or 3.0 mg/kg 5-HT2C antagonist RS102221. The capacity of 25CN-NBOH to attenuate DOI-elicited head twitch was also investigated. Mice were trained to discriminate DOI or M100907 from saline, and 25CN-NBOH was tested for generalization. Results 25CN-NBOH induced a head twitch response in the mouse that was lower in magnitude than that of DOI, blocked by M100907, but not altered by RS102221. DOI-elicited head twitch was dose-dependently attenuated by 25CN-NBOH pretreatment. 25CN-NBOH produced an intermediate degree of generalization (55%) for the DOI training dose, and these interoceptive effects were attenuated by M100907. Finally, 25CN-NBOH did not generalize to M100907 at any dose, but ketanserin fully substituted in these animals. Conclusions 25CN-NBOH was behaviorally active, but less effective than DOI in two mouse models of hallucinogenic effects. The effectiveness with which M100907 antagonized the behavioral actions of 25CN-NBOH strongly suggests that the 5-HT2A receptor is an important site of agonist action for this compound in vivo. PMID:25224567

Effects of changes in dietary fatty acids on isolated skeletal muscle functions in rats.

PubMed

Ayre, K J; Hulbert, A J

1996-02-01

The effects of manipulating dietary levels of essential polyunsaturated fatty acids on the function of isolated skeletal muscles in male Wistar rats were examined. Three isoenergetic diets were used: an essential fatty acid-deficient diet (EFAD), a diet high in essential (n-6) fatty acids [High (n-6)], and a diet enriched with essential (n-3) fatty acids [High (n-3)]. After 9 wk, groups of rats on each test diet were fed a stock diet of laboratory chow for a further 6 wk. Muscle function was examined by using a battery of five tests for soleus (slow twitch) and extensor digitorum longus (EDL; fast twitch). Tests included single muscle twitches, sustained tetanic contractions, posttetanic potentiation, sustained high-frequency stimulation, and intermittent low-frequency stimulation. Results for muscles from the High (n-6) and High (n-3) groups were very similar. However, the EFAD diet resulted in significantly lower muscular tensions and reduced response times compared with the High (n-6) and High (n-3) diets. Peak twitch tension in soleus muscles was 16-21% less in the EFAD group than in the High (n-6) and High (n-3) groups, respectively [analysis of variance (ANOVA), P < 0.01). During high-frequency stimulation, EDL muscles from the EFAD rats fatigued 32% more quickly (ANOVA, P < 0.01)]. Also, twitch contraction and half-relaxation times were significantly 5-7% reduced in the EFAD group (ANOVA, P < 0.01). During intermittent low-frequency stimulation, soleus muscles from the EFAD group generated 25-28% less tension than did the other groups (ANOVA, P < 0.01), but in EDL muscles from the EFAD group, endurance was 20% greater than in the High (n-6) group (ANOVA, P < 0.05). After 6 wk on the stock diet, there were no longer any differences between the dietary groups. Manipulation of dietary fatty acids results in significant, but reversible, effects in muscles of rats fed an EFAD diet.

The role of Sox6 in zebrafish muscle fiber type specification.

PubMed

Jackson, Harriet E; Ono, Yosuke; Wang, Xingang; Elworthy, Stone; Cunliffe, Vincent T; Ingham, Philip W

2015-01-01

The transcription factor Sox6 has been implicated in regulating muscle fiber type-specific gene expression in mammals. In zebrafish, loss of function of the transcription factor Prdm1a results in a slow to fast-twitch fiber type transformation presaged by ectopic expression of sox6 in slow-twitch progenitors. Morpholino-mediated Sox6 knockdown can suppress this transformation but causes ectopic expression of only one of three slow-twitch specific genes assayed. Here, we use gain and loss of function analysis to analyse further the role of Sox6 in zebrafish muscle fiber type specification. The GAL4 binary misexpression system was used to express Sox6 ectopically in zebrafish embryos. Cis-regulatory elements were characterized using transgenic fish. Zinc finger nuclease mediated targeted mutagenesis was used to analyse the effects of loss of Sox6 function in embryonic, larval and adult zebrafish. Zebrafish transgenic for the GCaMP3 Calcium reporter were used to assay Ca2+ transients in wild-type and mutant muscle fibres. Ectopic Sox6 expression is sufficient to downregulate slow-twitch specific gene expression in zebrafish embryos. Cis-regulatory elements upstream of the slow myosin heavy chain 1 (smyhc1) and slow troponin c (tnnc1b) genes contain putative Sox6 binding sites required for repression of the former but not the latter. Embryos homozygous for sox6 null alleles expressed tnnc1b throughout the fast-twitch muscle whereas other slow-specific muscle genes, including smyhc1, were expressed ectopically in only a subset of fast-twitch fibers. Ca2+ transients in sox6 mutant fast-twitch fibers were intermediate in their speed and amplitude between those of wild-type slow- and fast-twitch fibers. sox6 homozygotes survived to adulthood and exhibited continued misexpression of tnnc1b as well as smaller slow-twitch fibers. They also exhibited a striking curvature of the spine. The Sox6 transcription factor is a key regulator of fast-twitch muscle fiber differentiation in the zebrafish, a role similar to that ascribed to its murine ortholog.

A comparative study of charge movement in rat and frog skeletal muscle fibres.

PubMed

Hollingworth, S; Marshall, M W

1981-12-01

1. The middle of the fibre voltage--clamp technique (Adrian & Marshall, 1977), modified where necessary for electrically short muscle fibres, has been used to measure non-linear charge movements in mammalian fast twitch (rat extensor digitorum longus), mammalian slow twitch (rat soleus) and frog (sartorius) muscles. 2. The maximum amount of charge moved in mammalian fast twitch muscle at 2 degrees C in hypertonic solution, was 3--5 times greater than in slow twitch muscle. The voltage distribution of fast twitch charge was 10--15 mV more positive when compared to slow twitch. 3. In both mammalian muscle types hypertonic Ringer solution negatively shifted the voltage distribution of charge some 6 mV. The steepness of charge moved around mechanical threshold was unaffected by hypertonicity. 4. The amount of charge in frog sartorius fibres at 2 degrees C in hypertonic solution was about half of that in rat fast twitch muscle; the voltage distribution of the frog charge was similar to rat soleus muscle. 5. Warming between 2 and 15 degrees C had no effect on either the amount of steady-state distribution of charge in mammalian or frog muscles. 6. At 2 degrees C, the kinetics of charge movement in fast and slow twitch mammalian muscles were similar and 2--3 times faster than frog muscle at the same temperature. In fast and slow mammalian fibres at 2 degrees C similar times were taken to shift the same fractions of the total amount of charge. The Q10 of charge movement kinetics was between 1.2 and 2.0 in the three muscles studied.

Length dependence of force generation exhibit similarities between rat cardiac myocytes and skeletal muscle fibres.

PubMed

Hanft, Laurin M; McDonald, Kerry S

2010-08-01

According to the Frank-Starling relationship, increased ventricular volume increases cardiac output, which helps match cardiac output to peripheral circulatory demand. The cellular basis for this relationship is in large part the myofilament length-tension relationship. Length-tension relationships in maximally calcium activated preparations are relatively shallow and similar between cardiac myocytes and skeletal muscle fibres. During twitch activations length-tension relationships become steeper in both cardiac and skeletal muscle; however, it remains unclear whether length dependence of tension differs between striated muscle cell types during submaximal activations. The purpose of this study was to compare sarcomere length-tension relationships and the sarcomere length dependence of force development between rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres. Muscle cell preparations were calcium activated to yield 50% maximal force, after which isometric force and rate constants (k(tr)) of force development were measured over a range of sarcomere lengths. Myofilament length-tension relationships were considerably steeper in fast-twitch fibres compared to slow-twitch fibres. Interestingly, cardiac myocyte preparations exhibited two populations of length-tension relationships, one steeper than fast-twitch fibres and the other similar to slow-twitch fibres. Moreover, myocytes with shallow length-tension relationships were converted to steeper length-tension relationships by protein kinase A (PKA)-induced myofilament phosphorylation. Sarcomere length-k(tr) relationships were distinct between all three cell types and exhibited patterns markedly different from Ca(2+) activation-dependent k(tr) relationships. Overall, these findings indicate cardiac myocytes exhibit varied length-tension relationships and sarcomere length appears a dominant modulator of force development rates. Importantly, cardiac myocyte length-tension relationships appear able to switch between slow-twitch-like and fast-twitch-like by PKA-mediated myofibrillar phosphorylation, which implicates a novel means for controlling Frank-Starling relationships.

Juxtaposition of the changes in intracellular calcium and force during staircase potentiation at 30 and 37°C

PubMed Central

Vandenboom, Rene

2014-01-01

Ca2+ entry during the action potential stimulates muscle contraction. During repetitive low frequency stimulation, skeletal muscle undergoes staircase potentiation (SP), a progressive increase in the peak twitch force induced by each successive stimulus. Multiple mechanisms, including myosin regulatory light chain phosphorylation, likely contribute to SP, a temperature-dependent process. Here, we used the Ca2+-sensitive fluorescence indicators acetoxymethyl (AM)-furaptra and AM-fura-2 to examine the intracellular Ca2+ transient (ICT) and the baseline Ca2+ level at the onset of each ICT during SP at 30 and 37°C in mouse lumbrical muscle. The stimulation protocol, 8 Hz for 8 s, resulted in a 27 ± 3% increase in twitch force at 37°C and a 7 ± 2% decrease in twitch force at 30°C (P < 0.05). Regardless of temperature, the peak rate of force production (+df/dt) was higher in all twitches relative to the first twitch (P < 0.05). Consistent with the differential effects of stimulation on twitch force at the two temperatures, raw ICT amplitude decreased during repetitive stimulation at 30°C (P < 0.05) but not at 37°C. Cytosolic Ca2+ accumulated during SP such that baseline Ca2+ at the onset of ICTs occurring late in the train was higher (P < 0.05) than that of those occurring early in the train. ICT duration increased progressively at both temperatures. This effect was not entirely proportional to the changes in twitch duration, as twitch duration characteristically decreased before increasing late in the protocol. This is the first study identifying a changing ICT as an important, and temperature-sensitive, modulator of muscle force during repetitive stimulation. Moreover, we extend previous observations by demonstrating that contraction-induced increases in baseline Ca2+ coincide with greater +df/dt but not necessarily with higher twitch force. PMID:25422504

Differential effect of denervation on free radical scavenging enzymes in slow and fast muscle of rat

NASA Technical Reports Server (NTRS)

Asayama, K.; Dettbarn, W. D.; Burr, I. M.

1985-01-01

To determine the effect of denervation on the free radical scavenging systems in relation to the mitochondrial oxidative metabolism in the slow twitch soleus and fast twitch extensor digitorum longus (EDL) muscles, the sciatic nerve of the rat was crushed in the mid-thigh region and the muscle tissue levels of 5 enzymes were studied 2 and 5 weeks following crush. Radioimmunoassays were utilized for the selective measurement of cuprozinc (cytosolic) and mangano (mitochondrial) superoxide dismutases. These data represent the first systematic report of free radical scavening systems in slow and fast muscles in response to denervation. Selective modification of cuprozinc and manganosuperoxide dismutases and differential regulation of GSH-peroxidase was demonstrated in slow and fast muscle.

Metabotropic Glutamate2 Receptors Play a Key Role in Modulating Head Twitches Induced by a Serotonergic Hallucinogen in Mice

PubMed Central

Benvenga, Mark J.; Chaney, Stephen F.; Baez, Melvyn; Britton, Thomas C.; Hornback, William J.; Monn, James A.; Marek, Gerard J.

2018-01-01

There is substantial evidence that glutamate can modulate the effects of 5-hydroxytryptamine2A (5-HT2A) receptor activation through stimulation of metabotropic glutamate2/3 (mGlu2/3) receptors in the prefrontal cortex. Here we show that constitutive deletion of the mGlu2 gene profoundly attenuates an effect of 5-HT2A receptor activation using the mouse head twitch response (HTR). MGlu2 and mGlu3 receptor knockout (KO) as well as age-matched ICR (CD-1) wild type (WT) mice were administered (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and observed for head twitch activity. DOI failed to produce significant head twitches in mGlu2 receptor KO mice at a dose 10-fold higher than the peak effective dose in WT or mGlu3 receptor KO mice. In addition, the mGlu2/3 receptor agonist LY379268, and the mGlu2 receptor positive allosteric modulator (PAM) CBiPES, potently blocked the HTR to DOI in WT and mGlu3 receptor KO mice. Conversely, the mGlu2/3 receptor antagonist LY341495 (10 mg/kg) increased the HTR produced by DOI (3 mg/kg) in mGlu3 receptor KO mice. Finally, the mGlu2 receptor potentiator CBiPES was able to attenuate the increase in the HTR produced by LY341495 in mGlu3 receptor KO mice. Taken together, all of these results are consistent with the hypothesis that that DOI-induced head twitches are modulated by mGlu2 receptor activation. These results also are in keeping with a critical autoreceptor function for mGlu2 receptors in the prefrontal cortex with differential effects of acute vs. chronic perturbation (e.g., constitutive mGlu2 receptor KO mice). The robust attenuation of DOI-induced head twitches in the mGlu2 receptor KO mice appears to reflect the critical role of glutamate in ongoing regulation of 5-HT2A receptors in the prefrontal cortex. Future experiments with inducible knockouts for the mGlu2 receptor and/or selective mGlu3 receptor agonists/PAMs/antagonists could provide an important tools in understanding glutamatergic modulation of prefrontal cortical 5-HT2A receptor function. PMID:29599719

Motor nerve transplantation.

PubMed

Gray, W P; Keohane, C; Kirwan, W O

1997-10-01

The motor nerve transplantation (MNT) technique is used to transfer an intact nerve into a denervated muscle by harvesting a neurovascular pedicle of muscle containing motor endplates from the motor endplate zone of a donor muscle and implanting it into a denervated muscle. Thirty-six adult New Zealand White rabbits underwent reinnervation of the left long peroneal (LP) muscle (fast twitch) with a motor nerve graft from the soleus muscle (slow twitch). The right LP muscle served as a control. Reinnervation was assessed using microstimulatory single-fiber electromyography (SFEMG), alterations in muscle fiber typing and grouping, and isometric response curves. Neurofilament antibody was used for axon staining. The neurofilament studies provided direct evidence of nerve growth from the motor nerve graft into the adjacent denervated muscle. Median motor endplate jitter was 13 microsec preoperatively, and 26 microsec at 2 months, 29.5 microsec at 4 months, and 14 microsec at 6 months postoperatively (p < 0.001). Isometric tetanic tension studies showed a progressive functional recovery in the reinnervated muscle over 6 months. There was no histological evidence of aberrant reinnervation from any source outside the nerve pedicle. Isometric twitch responses and adenosine triphosphatase studies confirmed the conversion of the reinnervated LP muscle to a slow-type muscle. Acetylcholinesterase studies confirmed the presence of functioning motor endplates beneath the insertion of the motor nerve graft. It is concluded that the MNT technique achieves motor reinnervation by growth of new nerve fibers across the pedicle graft into the recipient muscle.

Selected Contribution: Skeletal muscle focal adhesion kinase, paxillin, and serum response factor are loading dependent

NASA Technical Reports Server (NTRS)

Gordon, S. E.; Fluck, M.; Booth, F. W.

2001-01-01

This investigation examined the effect of mechanical loading state on focal adhesion kinase (FAK), paxillin, and serum response factor (SRF) in rat skeletal muscle. We found that FAK concentration and tyrosine phosphorylation, paxillin concentration, and SRF concentration are all lower in the lesser load-bearing fast-twitch plantaris and gastrocnemius muscles compared with the greater load-bearing slow-twitch soleus muscle. Of these three muscles, 7 days of mechanical unloading via tail suspension elicited a decrease in FAK tyrosine phosphorylation only in the soleus muscle and decreases in FAK and paxillin concentrations only in the plantaris and gastrocnemius muscles. Unloading decreased SRF concentration in all three muscles. Mechanical overloading (via bilateral gastrocnemius ablation) for 1 or 8 days increased FAK and paxillin concentrations in the soleus and plantaris muscles. Additionally, whereas FAK tyrosine phosphorylation and SRF concentration were increased by < or =1 day of overloading in the soleus muscle, these increases did not occur until somewhere between 1 and 8 days of overloading in the plantaris muscle. These data indicate that, in the skeletal muscles of rats, the focal adhesion complex proteins FAK and paxillin and the transcription factor SRF are generally modulated in association with the mechanical loading state of the muscle. However, the somewhat different patterns of adaptation of these proteins to altered loading in slow- vs. fast-twitch skeletal muscles indicate that the mechanisms and time course of adaptation may partly depend on the prior loading state of the muscle.

Subthreshold muscle twitches dissociate oscillatory neural signatures of conflicts from errors.

PubMed

Cohen, Michael X; van Gaal, Simon

2014-02-01

We investigated the neural systems underlying conflict detection and error monitoring during rapid online error correction/monitoring mechanisms. We combined data from four separate cognitive tasks and 64 subjects in which EEG and EMG (muscle activity from the thumb used to respond) were recorded. In typical neuroscience experiments, behavioral responses are classified as "error" or "correct"; however, closer inspection of our data revealed that correct responses were often accompanied by "partial errors" - a muscle twitch of the incorrect hand ("mixed correct trials," ~13% of the trials). We found that these muscle twitches dissociated conflicts from errors in time-frequency domain analyses of EEG data. In particular, both mixed-correct trials and full error trials were associated with enhanced theta-band power (4-9Hz) compared to correct trials. However, full errors were additionally associated with power and frontal-parietal synchrony in the delta band. Single-trial robust multiple regression analyses revealed a significant modulation of theta power as a function of partial error correction time, thus linking trial-to-trial fluctuations in power to conflict. Furthermore, single-trial correlation analyses revealed a qualitative dissociation between conflict and error processing, such that mixed correct trials were associated with positive theta-RT correlations whereas full error trials were associated with negative delta-RT correlations. These findings shed new light on the local and global network mechanisms of conflict monitoring and error detection, and their relationship to online action adjustment. © 2013.

Chronic hypobaric hypoxia increases isolated rat fast-twitch and slow-twitch limb muscle force and fatigue.

PubMed

El-Khoury, R; Bradford, A; O'Halloran, K D

2012-01-01

Chronic hypoxia alters respiratory muscle force and fatigue, effects that could be attributed to hypoxia and/or increased activation due to hyperventilation. We hypothesized that chronic hypoxia is associated with phenotypic change in non-respiratory muscles and therefore we tested the hypothesis that chronic hypobaric hypoxia increases limb muscle force and fatigue. Adult male Wistar rats were exposed to normoxia or hypobaric hypoxia (PB=450 mm Hg) for 6 weeks. At the end of the treatment period, soleus (SOL) and extensor digitorum longus (EDL) muscles were removed under pentobarbitone anaesthesia and strips were mounted for isometric force determination in Krebs solution in standard water-jacketed organ baths at 25 °C. Isometric twitch and tetanic force, contractile kinetics, force-frequency relationship and fatigue characteristics were determined in response to electrical field stimulation. Chronic hypoxia increased specific force in SOL and EDL compared to age-matched normoxic controls. Furthermore, chronic hypoxia decreased endurance in both limb muscles. We conclude that hypoxia elicits functional plasticity in limb muscles perhaps due to oxidative stress. Our results may have implications for respiratory disorders that are characterized by prolonged hypoxia such as chronic obstructive pulmonary disease (COPD).

Torque decrease during submaximal evoked contractions of the quadriceps muscle is linked not only to muscle fatigue.

PubMed

Matkowski, Boris; Lepers, Romuald; Martin, Alain

2015-05-01

The aim of this study was to analyze the neuromuscular mechanisms involved in the torque decrease induced by submaximal electromyostimulation (EMS) of the quadriceps muscle. It was hypothesized that torque decrease after EMS would reflect the fatigability of the activated motor units (MUs), but also a reduction in the number of MUs recruited as a result of changes in axonal excitability threshold. Two experiments were performed on 20 men to analyze 1) the supramaximal twitch superimposed and evoked at rest during EMS (Experiment 1, n = 9) and 2) the twitch response and torque-frequency relation of the MUs activated by EMS (Experiment 2, n = 11). Torque loss was assessed by 15 EMS-evoked contractions (50 Hz; 6 s on/6 s off), elicited at a constant intensity that evoked 20% of the maximal voluntary contraction (MVC) torque. The same stimulation intensity delivered over the muscles was used to induce the torque-frequency relation and the single electrical pulse evoked after each EMS contraction (Experiment 2). In Experiment 1, supramaximal twitch was induced by femoral nerve stimulation. Torque decreased by ~60% during EMS-evoked contractions and by only ~18% during MVCs. This was accompanied by a rightward shift of the torque-frequency relation of MUs activated and an increase of the ratio between the superimposed and posttetanic maximal twitch evoked during EMS contraction. These findings suggest that the torque decrease observed during submaximal EMS-evoked contractions involved muscular mechanisms but also a reduction in the number of MUs recruited due to changes in axonal excitability. Copyright © 2015 the American Physiological Society.

[The relationship between contractile characteristics and fiber type conversion in hind-limb unloading mice soleus].

PubMed

Li, Li; Liu, Hong-Ju; Yang, Ming-Hao; Li, Jing-Long; Wang, Lu; Chen, Xiao-Ping; Fan, Ming

2012-03-01

To explore the relationship between contractile characteristics and fiber type conversion in hind-limb unloading mice soleus. After 28-day hind-limb unloading and muscle atrophy, we used the method of isolated muscle perfusion with different stimulated protocols to determine the changes in contractile characteristics including the isometric twitch force and tetanus force and fatigue index of slow twitch muscle in mice. The muscle myofibrillar composition and fiber type conversion were detected by immunofluorescence staining and real-time PCR. The isometric twitch force and the tetanus force and fatigue index were decreased progressively in 28-day unloaded mice soleus, with the increase in fast twitch fiber subtype and the decrease in slow twitch fiber subtype. The alteration of contractile characteristics is relevant to the slow-to-fast fiber conversion in mice soleus after 28-day hind-limb unloading.

Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload

NASA Technical Reports Server (NTRS)

Carlson, C. J.; Fan, Z.; Gordon, S. E.; Booth, F. W.

2001-01-01

Knowledge of the molecular mechanisms by which skeletal muscle hypertrophies in response to increased mechanical loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. To gain insight into potential early signaling mechanisms associated with skeletal muscle hypertrophy, the temporal pattern of mitogen-activated protein kinase (MAPK) phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activity during the first 24 h of muscle overload was determined in the rat slow-twitch soleus and fast-twitch plantaris muscles after ablation of the gastrocnemius muscle. p38alpha MAPK phosphorylation was elevated for the entire 24-h overload period in both muscles. In contrast, Erk 2 and p54 JNK phosphorylation were transiently increased by overload, returning to the levels of sham-operated controls by 24 h. PI3-kinase activity was increased by muscle overload only at 12 h of overload and only in the plantaris muscle. In summary, sustained elevation of p38alpha MAPK phosphorylation occurred early in response to muscle overload, identifying this pathway as a potential candidate for mediating early hypertrophic signals in response to skeletal muscle overload.

The Click and Twitch in Contemporary Poetry.

ERIC Educational Resources Information Center

Meredith, Bernard

It is the creative writing instructor's role to help the student turn "twitch" poems into "click" poems ("twitch" being a kind of verbal hypertension that takes shape in the absence of anything humanly important to say on the poet's part and "click" being the finished poem that makes a sound like the click of the lid on a perfectly made box).…

Development and use of the incremental twitch subtraction MUNE method in mice.

PubMed

Hegedus, Janka; Jones, Kelvin E; Gordon, Tessa

2009-01-01

We have used a technique to estimate the number of functioning motor units (MUNE) innervating a muscle in mice based on twitch tension. The MUNE technique was verified by modeling twitch tensions from isolated ventral root stimulation. Analysis by twitch tensions allowed us to identify motor unit fiber types. The MUNE technique was used to compare normal mice with transgenic superoxide dismutase-1 mutation (G94A) mice to assess the time course of motor unit loss with respect to fiber type. Motor unit loss was found to occur well in advance of behavioral changes and the degree of reinnervation is dependent upon motor unit fiber types.

Time-related changes in firing rates are influenced by recruitment threshold and twitch force potentiation in the first dorsal interosseous.

PubMed

Miller, Jonathan D; Herda, Trent J; Trevino, Michael A; Sterczala, Adam J; Ciccone, Anthony B

2017-08-01

What is the central question of this study? The influences of motor unit recruitment threshold and twitch force potentiation on the changes in firing rates during steady-force muscular contractions are not well understood. What is the main finding and its importance? The behaviour of motor units during steady force was influenced by recruitment threshold, such that firing rates decreased for lower-threshold motor units but increased for higher-threshold motor units. In addition, individuals with greater changes in firing rates possessed greater twitch force potentiation. There are contradictory reports regarding changes in motor unit firing rates during steady-force contractions. Inconsistencies are likely to be the result of previous studies disregarding motor unit recruitment thresholds and not examining firing rates on a subject-by-subject basis. It is hypothesized that firing rates are manipulated by twitch force potentiation during contractions. Therefore, in this study we examined time-related changes in firing rates at steady force in relationship to motor unit recruitment threshold in the first dorsal interosseous and the influence of twitch force potentiation on such changes in young versus aged individuals. Subjects performed a 12 s steady-force contraction at 50% maximal voluntary contraction, with evoked twitches before and after the contraction to quantify potentiation. Firing rates, in relationship to recruitment thresholds, were determined at the beginning, middle and end of the steady force. There were no firing rate changes for aged individuals. For the young, firing rates decreased slightly for lower-threshold motor units but increased for higher-threshold motor units. Twitch force potentiation was greater for young than aged subjects, and changes in firing rates were correlated with twitch force potentiation. Thus, individuals with greater increases in firing rates of higher-threshold motor units and decreases in lower-threshold motor units possessed greater twitch force potentiation. Overall, changes in firing rates during brief steady-force contractions are dependent on recruitment threshold and explained in part by twitch force potentiation. Given that firing rate changes were measured in relationship to recruitment threshold, this study illustrates a more complete view of firing rate changes during steady-force contractions. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Effect of limb immobilization on skeletal muscle

NASA Technical Reports Server (NTRS)

Booth, F. W.

1982-01-01

Current knowledge and questions remaining concerning the effects of limb immobilization on skeletal muscle is reviewed. The most dramatic of these effects is muscle atrophy, which has been noted in cases of muscles fixed at or below their resting length. Immobilization is also accompanied by a substantial decrease in motoneuronal discharges, which results in the conversion of slow-twitch muscle to muscle with fast-twitch characteristics. Sarcolemma effects include no change or a decrease in resting membrane potential, the appearance of extrajunctional acetylcholine receptors, and no change in acetylcholinesterase activity. Evidence of changes in motoneuron after hyperpolarization characteristics suggests that the muscle inactivity is responsible for neuronal changes, rather than vice versa. The rate of protein loss from atrophying muscles is determined solely by the first-order rate constant for degradation. Various other biochemical and functional changes have been noted, including decreased insulin responsiveness and protein synthesis. The model of limb immobilization may also be useful for related studies of muscle adaptation.

Effects of capsaicin in the motor nerve.

PubMed

Pettorossi, V E; Bortolami, R; Della Torre, G; Brunetti, O

1994-08-01

The injection of capsaicin into the lateral gastrocnemius (LG) muscle of the rat induced an immediate and sustained reduction in the A delta and C components of the compound action potential (CAP) of the LG motor nerve. Conversely, the drug did not immediately affect the CAP wave belonging to fast-conducting fibers or the motor responses to LG nerve stimulation. It seems that capsaicin only affects the group III and IV afferents of LG nerve. However, a week after the injection the capsaicin also altered the motor responses, as shown by the threshold enhancement and amplitude reduction of the muscle twitch and by the decrease of the A alpha-beta CAP components. This late motor impairment was attributed to a central depression following a reduction of capsaicin-sensitive neuron input into the CNS. However, this motor effect was transient since the LG nerve regained the preinjection excitability level in a week and the muscle twitch amplitude reached the control value in a month.

A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles.

PubMed

Piette, Antoine Boulanger; Dufresne, Sébastien S; Frenette, Jérôme

2016-10-28

Cumulative evidence indicates that statins induce myotoxicity. However, the lack of understanding of how statins affect skeletal muscles at the structural, functional, and physiological levels hampers proper healthcare management. The purpose of the present study was to investigate the early after-effects of lovastatin on the slow-twitch soleus (Sol) and fast-twitch extensor digitorum longus (EDL) muscles. Adult C57BL/6 mice were orally administrated with placebo or lovastatin [50 mg/kg/d] for 28 days. At the end of the treatment, the isometric ex vivo contractile properties of the Sol and EDL muscles were measured. Subtetanic and tetanic contractions were assessed and contraction kinetics were recorded. The muscles were then frozen for immunohistochemical analyses. Data were analyzed by two-way ANOVA followed by an a posteriori Tukey's test. The short-term lovastatin treatment did not induce muscle mass loss, muscle fiber atrophy, or creatine kinase (CK) release. It had no functional impact on slow-twitch Sol muscles. However, subtetanic stimulations at 10 Hz provoked greater force production in fast-twitch EDL muscles. The treatment also decreased the maximal rate of force development (dP/dT) of twitch contractions and prolonged the half relaxation time (1/2RT) of tetanic contractions of EDL muscles. An early short-term statin treatment induced subtle but significant changes in some parameters of the contractile profile of EDL muscles, providing new insights into the selective initiation of statin-induced myopathy in fast-twitch muscles.

Interpolated twitches in fatiguing single mouse muscle fibres: implications for the assessment of central fatigue

PubMed Central

Place, Nicolas; Yamada, Takashi; Bruton, Joseph D; Westerblad, Håkan

2008-01-01

An electrically evoked twitch during a maximal voluntary contraction (twitch interpolation) is frequently used to assess central fatigue. In this study we used intact single muscle fibres to determine if intramuscular mechanisms could affect the force increase with the twitch interpolation technique. Intact single fibres from flexor digitorum brevis of NMRI mice were dissected and mounted in a chamber equipped with a force transducer. Free myoplasmic [Ca2+] ([Ca2+]i) was measured with the fluorescent Ca2+ indicator indo-1. Seven fibres were fatigued with repeated 70 Hz tetani until 40% initial force with an interpolated pulse evoked every fifth tetanus. Results showed that the force generated by the interpolated twitch increased throughout fatigue, being 9 ± 1% of tetanic force at the start and 19 ± 1% at the end (P < 0.001). This was not due to a larger increase in [Ca2+]i induced by the interpolated twitch during fatigue but rather to the fact that the force–[Ca2+]i relationship is sigmoidal and fibres entered a steeper part of the relationship during fatigue. In another set of experiments, we observed that repeated tetani evoked at 150 Hz resulted in more rapid fatigue development than at 70 Hz and there was a decrease in force (‘sag’) during contractions, which was not observed at 70 Hz. In conclusion, the extent of central fatigue is difficult to assess and it may be overestimated when using the twitch interpolation technique. PMID:18403421

Twitch and tetanic force responses and longitudinal propagation of action potentials in skinned skeletal muscle fibres of the rat

PubMed Central

Posterino, G S; Lamb, G D; Stephenson, D G

2000-01-01

Transverse electrical field stimulation (50 V cm−1, 2 ms duration) of mechanically skinned skeletal muscle fibres of the rat elicited twitch and tetanic force responses (36 ± 4 and 83 ± 4 % of maximum Ca2+-activated force, respectively; n = 23) closely resembling those in intact fibres. The responses were steeply dependent on the field strength and were eliminated by inclusion of 10 μm tetrodotoxin (TTX) in the (sealed) transverse tubular (T-) system of the skinned fibres and by chronic depolarisation of the T-system. Spontaneous twitch-like activity occurred sporadically in many fibres, producing near maximal force in some instances (mean time to peak: 190 ± 40 ms; n = 4). Such responses propagated as a wave of contraction longitudinally along the fibre at a velocity of 13 ± 3 mm s−1 (n = 7). These spontaneous contractions were also inhibited by inclusion of TTX in the T-system and by chronic depolarisation. We examined whether the T-tubular network was interconnected longitudinally using fibre segments that were skinned for only ∼2/3 of their length, leaving the remainder of each segment intact with its T-system open to the bathing solution. After such fibres were exposed to TTX (60 μm), the adjacent skinned region (with its T-system not open to the solution) became unresponsive to subsequent electrical stimulation in ∼50 % of cases (7/15), indicating that TTX was able to diffuse longitudinally inside the fibre via the tubular network over hundreds of sarcomeres. These experiments show that excitation–contraction coupling in mammalian muscle fibres involves action potential propagation both transversally and longitudinally within the tubular system. Longitudinal propagation of action potentials inside skeletal muscle fibres is likely to be an important safety mechanism for reducing conduction failure during fatigue and explains why, in developing skeletal muscle, the T-system first develops as an internal longitudinal network. PMID:10944176

Identification of an operon, Pil-Chp, that controls twitching motility and virulence in Xylella fastidiosa.

PubMed

Cursino, Luciana; Galvani, Cheryl D; Athinuwat, Dusit; Zaini, Paulo A; Li, Yaxin; De La Fuente, Leonardo; Hoch, Harvey C; Burr, Thomas J; Mowery, Patricia

2011-10-01

Xylella fastidiosa is an important phytopathogenic bacterium that causes many serious plant diseases, including Pierce's disease of grapevines. Disease manifestation by X. fastidiosa is associated with the expression of several factors, including the type IV pili that are required for twitching motility. We provide evidence that an operon, named Pil-Chp, with genes homologous to those found in chemotaxis systems, regulates twitching motility. Transposon insertion into the pilL gene of the operon resulted in loss of twitching motility (pilL is homologous to cheA genes encoding kinases). The X. fastidiosa mutant maintained the type IV pili, indicating that the disrupted pilL or downstream operon genes are involved in pili function, and not biogenesis. The mutated X. fastidiosa produced less biofilm than wild-type cells, indicating that the operon contributes to biofilm formation. Finally, in planta the mutant produced delayed and less severe disease, indicating that the Pil-Chp operon contributes to the virulence of X. fastidiosa, presumably through its role in twitching motility.

The impact of magnesium on isometric twitch parameters and resting membrane potential of the skeletal muscle in diabetic rats.

PubMed

Pelit, Aykut; Emre, Mustafa; Dağli, Kenan; Tuli, Abdullah

2013-04-01

To present the relationship between oral magnesium supplementation, blood glucose, and changes in isometric twitch parameters, resting membrane potential (RMP), in the gastrocnemius muscle in diabetic rats. Sixty rats were used in this study. The rats were divided into four groups: control (drinking tap water, Group I, n = 15), control with treated with magnesium sulfate (10 g/L) (Group II, n = 15), diabetic (Group III, n = 15), and diabetic with treated with magnesium sulfate (10 g/L) (Group IV, n = 15). In Group II and IV, the level of plasma magnesium was increased comparing to those of the control group (p < 0.05). Isometric twitch tensions were decreased significantly in the Group III, but Group IV isometric twitch tensions were increased significantly. Group IV RMP values were close to the Group I. Hyperglycemia decreases gastrocnemius muscle isometric twitch tension and increases RMP in diabetic rats. Magnesium treatment can prevent these diabetic complications.

Dihydrotestosterone treatment rescues the decline in protein synthesis as a result of sarcopenia in isolated mouse skeletal muscle fibres.

PubMed

Wendowski, Oskar; Redshaw, Zoe; Mutungi, Gabriel

2017-02-01

Sarcopenia, the progressive decline in skeletal muscle mass and function with age, is a debilitating condition. It leads to inactivity, falls, and loss of independence. Despite this, its cause(s) and the underlying mechanism(s) are still poorly understood. In this study, small skeletal muscle fibre bundles isolated from the extensor digitorum longus (a fast-twitch muscle) and the soleus (a slow-twitch muscle) of adult mice of different ages (range 100-900 days old) were used to investigate the effects of ageing and dihydrotestosterone (DHT) treatment on protein synthesis as well as the expression and function of two amino acid transporters; the sodium-coupled neutral amino acid transporter (SNAT) 2, and the sodium-independent L-type amino-acid transporter (LAT) 2. At all ages investigated, protein synthesis was always higher in the slow-twitch than in the fast-twitch muscle fibres and decreased with age in both fibre types. However, the decline was greater in the fast-twitch than in the slow-twitch fibres and was accompanied by a reduction in the expression of SNAT2 and LAT2 at the protein level. Again, the decrease in the expression of the amino acid transporters was greater in the fast-twitch than in the slow-twitch fibres. In contrast, ageing had no effect on SNAT2 and LAT2 expressions at the mRNA level. Treating the muscle fibre bundles with physiological concentrations (~2 nM) of DHT for 1 h completely reversed the effects of ageing on protein synthesis and the expression of SNAT2 and LAT2 protein in both fibre types. From the observations that ageing is accompanied by a reduction in protein synthesis and transporter expression and that these effects are reversed by DHT treatment, we conclude that sarcopenia arises from an age-dependent reduction in protein synthesis caused, in part, by the lack of or by the low bioavailability of the male sex steroid, DHT.

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

PubMed

Trinh, Huong H; Lamb, Graham D

2006-07-01

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

Mucosal fluid glycoprotein DMBT1 suppresses twitching motility and virulence of the opportunistic pathogen Pseudomonas aeruginosa

PubMed Central

Evans, David J.; Fleiszig, Suzanne M. J.

2017-01-01

It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition of twitching by tear fluid was dose-dependent with dilutions to 6.25% retaining activity. Purified lactoferrin, lysozyme, and contrived tears containing these, and many other, tear components lacked the activity. Systematic protein fractionation, mass spectrometry, and immunoprecipitation identified the glycoprotein DMBT1 (Deleted in Malignant Brain Tumors 1) in tear fluid as required. DMBT1 purified from human saliva also inhibited twitching, as well as P. aeruginosa traversal of human corneal epithelial cells in vitro, and reduced disease pathology in a murine model of corneal infection. DMBT1 did not affect PilA expression, nor bacterial intracellular cyclicAMP levels, and suppressed twitching motility of P. aeruginosa chemotaxis mutants (chpB, pilK), and an adenylate cyclase mutant (cyaB). However, dot-immunoblot assays showed purified DMBT1 binding of pili extracted from PAO1 suggesting that twitching inhibition may involve a direct interaction with pili. The latter could affect extension or retraction of pili, their interactions with biotic or abiotic surfaces, or cause their aggregation. Together, the data suggest that DMBT1 inhibition of twitching motility contributes to the mechanisms by which mucosal fluids protect against P. aeruginosa infection. This study also advances our understanding of how mucosal fluids protect against infection, and suggests directions for novel biocompatible strategies to protect our surface epithelia against a major opportunistic pathogen. PMID:28489917

A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres

PubMed Central

Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

2013-01-01

Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nm and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres. PMID:23878367

A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres.

PubMed

Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

2013-10-15

Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nM and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres.

The role of the sarcoplasmic reticulum in the generation of high heart rates and blood pressures in reptiles.

PubMed

Galli, Gina L J; Gesser, Hans; Taylor, Edwin W; Shiels, Holly A; Wang, Tobias

2006-05-01

The functional significance of the sarcoplasmic reticulum (SR) in the generation of high heart rates and blood pressures was investigated in four species of reptile; the turtle, Trachemys scripta; the python, Python regius, the tegu lizard, Tupinanvis merianae, and the varanid lizard, Varanus exanthematicus. Force-frequency trials and imposed pauses were performed on ventricular and atrial tissue from each species with and without the SR inhibitor ryanodine, and in the absence and presence of adrenaline. In all species, an imposed pause of 1 or 5 min caused a post-rest decay of force, and a negative force-frequency response was observed in all species within their in vivo frequency range of heart rates. These relationships were not affected by either ryanodine or adrenaline. In ventricular strips from varanid lizards and pythons, ryanodine caused significant reductions in twitch force within their physiologically relevant frequency range. In atrial tissue from the tegu and varanid lizards, SR inhibition reduced twitch force across the whole of their physiological frequency range. In contrast, in the more sedentary species, the turtle and the python, SR inhibition only decreased twitch force at stimulation frequencies above maximal in vivo heart rates. Adrenaline caused an increase in twitch force in all species studied. In ventricular tissue, this positive inotropic effect was sufficient to overcome the negative effects of ryanodine. In atrial tissue however, adrenaline could only ameliorate the negative effects of ryanodine at the lower pacing frequencies. Our results indicate that reptiles recruit Ca2+ from the SR for force development in a frequency and tissue dependent manner. This is discussed in the context of the development of high reptilian heart rates and blood pressures.

Neuromuscular pharmacodynamics of mivacurium in adults with major burns.

PubMed

Han, T-H; Martyn, J A J

2011-05-01

Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns. Thirty adults with 35 (13)% [mean (sd)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch™. Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured. Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P<0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre(-1); P<0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P<0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r=-0.6; P<0.001). The dibucaine numbers were not different. The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors.

Measuring Dynamic Kidney Function in an Undergraduate Physiology Laboratory

ERIC Educational Resources Information Center

Medler, Scott; Harrington, Frederick

2013-01-01

Most undergraduate physiology laboratories are very limited in how they treat renal physiology. It is common to find teaching laboratories equipped with the capability for high-resolution digital recordings of physiological functions (muscle twitches, ECG, action potentials, respiratory responses, etc.), but most urinary laboratories still rely on…

Muscle Responses to Stimulation of the Tadpole Tail

ERIC Educational Resources Information Center

Funkhouser, Anne

1976-01-01

Describes use of tail muscles and spinal cord in the tadpole as an alternative source for muscle-and-nerve experiments. Includes explanation of simple dissection and preparation of tadpole; instructions for experiments such as threshold, strength of stimulus, frequency of stimulus, single twitch, tetanus, fatigue, effects of temperature on…

Coexistence of twitch potentiation and tetanic force decline in rat hindlimb muscle

NASA Technical Reports Server (NTRS)

Rankin, Lucinda L.; Enoka, Roger M.; Volz, Kathryn A.; Stuart, Douglas G.

1988-01-01

The effect of whole-muscle fatigue on the isometric twitch was investigated in various hindlimb muscles of anesthetized rats, using an experimental protocol designed to assess the levels of fatigability in motor units. The results of EMG and force measurements revealed the existence of a linear relationship between fatigability and the magnitude of the twitch force following the fatigue test in both soleus and extensor digitorum longus muscles.

Diastolic scattered light fluctuation, resting force and twitch force in mammalian cardiac muscle

PubMed Central

Lakatta, E. G.; Lappé, D. L.

1981-01-01

1. When coherent light was passed through isolated isometric cardiac muscles during the diastolic or resting period, intensity fluctuations were observed in the scattered field. The frequency of these intensity fluctuations (f½) varied with many experimental interventions known to enhance Ca2+ flux into the cell. 2. In rat muscles stimulated at low frequencies (0.1 ± 2.0 min-1) stepwise increases (0.4-10 mm) of [Ca2+] in the bathing fluid ([Ca2+]e), or addition of ouabain (10-6-6 × 10-4 m) to the perfusate caused stepwise increases in f½. These were paralleled by increments in resting force (RF) such that the changes in f½ and RF were highly correlated. Substitution of K+ for Na+ in the perfusate resulted in parallel transients in RF and f½. 3. In contrast to the rat, most cat muscles stimulated at low frequencies in the steady state exhibited neither diastolic intensity fluctuations nor Ca2+-dependent changes in RF in [Ca2+]e of 10 mm or less; when [Ca2+]e was increased to 12-32 mm, however, steady-state Ca2+-dependent f½ and RF were observed. In a given [Ca2+]e reduction of [Na+]e increased f½. In the transient state following cessation of regular stimulation at more rapid rates (12-96 min-1) intensity fluctuations were present in all [Ca2+]e and decayed with time (seconds to minutes); the f½ and time course of the decay of the fluctuations were determined by the rate of prior stimulation and [Ca2+]e. 4. Maximum potentiation of twitch force in response to the above inotropic interventions was associated with an optimal level of f½ which was similar in both species; when higher levels of f½ were produced by more intense inotropic intervention, twitch force declined. Over the range of inotropic intervention up to and including that at which maximum twitch potentiation occurred, the increase in diastolic f½ predicted the extent of twitch potentiation with a high degree of accuracy (r > 0.97) both in the transient and steady states. 5. In contrast to the other inotropic interventions studied, catecholamines were unique in that neither f½ nor RF increased over a full range of concentrations that resulted in maximum potentiation of the twitch. 6. It is concluded from these observations that f½ reflects diastolic Ca2+-dependent myofilament interaction; the increase in the extent of this interaction by inotropic interventions that do not alter the affinity of the myofilaments for Ca2+ probably reflects an increase in diastolic myoplasmic [Ca2+], an optimal level of which is associated with maximal potentiation of twitch force; the difference in f½ in rat and cat muscles under a given set of in vitro conditions may be related to the marked species difference in the effectiveness of excitation—contraction coupling. PMID:7310715

Developmental changes in the activation properties and ultrastructure of fast- and slow-twitch muscles from fetal sheep.

PubMed

West, J M; Barclay, C J; Luff, A R; Walker, D W

1999-04-01

At early stages of muscle development, skeletal muscles contract and relax slowly, regardless of whether they are destined to become fast- or slow-twitch. In this study, we have characterised the activation profiles of developing fast- and slow-twitch muscles from a precocial species, the sheep, to determine if the activation profiles of the muscles are characteristically slow when both the fast- and slow-twitch muscles have slow isometric contraction profiles. Single skinned muscle fibres from the fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus muscles from fetal (gestational ages 70, 90, 120 and 140 days; term 147 days) and neonatal (8 weeks old) sheep were used to determine the isometric force-pCa (pCa = -log10[Ca2+]) and force-pSr relations during development. Fast-twitch mammalian muscles generally have a greatly different sensitivity to Ca2+ and Sr2+ whereas slow-twitch muscles have a similar sensitivity to these divalent cations. At all ages studied, the force-pCa and force-pSr relations of the FDL muscle were widely separated. The mean separation of the mid-point of the curves (pCa50-pSr50) was approximately 1.1. This is typical of adult fast-twitch muscle. The force-pCa and force-pSr curves for soleus muscle were also widely separated at 70 and 90 days gestation (pCa50-pSr50 approximately 0.75); between 90 days and 140 days this separation decreased significantly to approximately 0.2. This leads to a paradoxical situation whereby at early stages of muscle development the fast muscles have contraction dynamics of slow muscles but the slow muscles have activation profiles more characteristic of fast muscles. The time course for development of the FDL and soleus is different, based on sarcomere structure with the soleus muscle developing clearly defined sarcomere structure earlier in gestation than the FDL. At 70 days gestation the FDL muscle had no clearly defined sarcomeres. Force (N cm-2) increased almost linearly between 70 and 140 days gestation in both muscle types and there was no difference between the Ca(2+)- and Sr(2+)-activated force throughout development.

Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats.

PubMed

Ghosh, Arijit; Dhumal, V R; Tilak, A V; Das, Nina; Singh, Amarinder; Bondekar, Abhijit A

2011-01-01

To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions.

Evaluation of nootropic and neuroprotective effects of low dose aspirin in rats

PubMed Central

Ghosh, Arijit; Dhumal, V. R.; Tilak, A. V.; Das, Nina; Singh, Amarinder; Bondekar, Abhijit A.

2011-01-01

Objective: To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Materials and Methods: Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Results: Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Conclusion: Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions. PMID:21701638

The Pseudomonas aeruginosa ribbon-helix-helix DNA-binding protein AlgZ (AmrZ) controls twitching motility and biogenesis of type IV pili.

PubMed

Baynham, Patricia J; Ramsey, Deborah M; Gvozdyev, Borys V; Cordonnier, Ellen M; Wozniak, Daniel J

2006-01-01

Pseudomonas aeruginosa is an opportunistic pathogen that is commonly found in water and soil. In order to colonize surfaces with low water content, P. aeruginosa utilizes a flagellum-independent form of locomotion called twitching motility, which is dependent upon the extension and retraction of type IV pili. This study demonstrates that AlgZ, previously identified as a DNA-binding protein absolutely required for transcription of the alginate biosynthetic operon, is required for twitching motility. AlgZ may be required for the biogenesis or function of type IV pili in twitching motility. Transmission electron microscopy analysis of an algZ deletion in nonmucoid PAO1 failed to detect surface pili. To examine expression and localization of PilA (the major pilin subunit), whole-cell extracts and cell surface pilin preparations were analyzed by Western blotting. While the PilA levels present in whole-cell extracts were similar for wild-type P. aeruginosa and P. aeruginosa with the algZ deletion, the amount of PilA on the surface of the cells was drastically reduced in the algZ mutant. Analysis of algZ and algD mutants indicates that the DNA-binding activity of AlgZ is essential for the regulation of twitching motility and that this is independent of the role of AlgZ in alginate expression. These data show that AlgZ DNA-binding activity is required for twitching motility independently of its role in alginate production and that this involves the surface localization of type IV pili. Given this new role in twitching motility, we propose that algZ (PA3385) be designated amrZ (alginate and motility regulator Z).

Myosin content of individual human muscle fibers isolated by laser capture microdissection.

PubMed

Stuart, Charles A; Stone, William L; Howell, Mary E A; Brannon, Marianne F; Hall, H Kenton; Gibson, Andrew L; Stone, Michael H

2016-03-01

Muscle fiber composition correlates with insulin resistance, and exercise training can increase slow-twitch (type I) fibers and, thereby, mitigate diabetes risk. Human skeletal muscle is made up of three distinct fiber types, but muscle contains many more isoforms of myosin heavy and light chains, which are coded by 15 and 11 different genes, respectively. Laser capture microdissection techniques allow assessment of mRNA and protein content in individual fibers. We found that specific human fiber types contain different mixtures of myosin heavy and light chains. Fast-twitch (type IIx) fibers consistently contained myosin heavy chains 1, 2, and 4 and myosin light chain 1. Type I fibers always contained myosin heavy chains 6 and 7 (MYH6 and MYH7) and myosin light chain 3 (MYL3), whereas MYH6, MYH7, and MYL3 were nearly absent from type IIx fibers. In contrast to cardiomyocytes, where MYH6 (also known as α-myosin heavy chain) is seen solely in fast-twitch cells, only slow-twitch fibers of skeletal muscle contained MYH6. Classical fast myosin heavy chains (MHC1, MHC2, and MHC4) were present in variable proportions in all fiber types, but significant MYH6 and MYH7 expression indicated slow-twitch phenotype, and the absence of these two isoforms determined a fast-twitch phenotype. The mixed myosin heavy and light chain content of type IIa fibers was consistent with its role as a transition between fast and slow phenotypes. These new observations suggest that the presence or absence of MYH6 and MYH7 proteins dictates the slow- or fast-twitch phenotype in skeletal muscle. Copyright © 2016 the American Physiological Society.

Myosin content of individual human muscle fibers isolated by laser capture microdissection

PubMed Central

Stone, William L.; Howell, Mary E. A.; Brannon, Marianne F.; Hall, H. Kenton; Gibson, Andrew L.; Stone, Michael H.

2015-01-01

Muscle fiber composition correlates with insulin resistance, and exercise training can increase slow-twitch (type I) fibers and, thereby, mitigate diabetes risk. Human skeletal muscle is made up of three distinct fiber types, but muscle contains many more isoforms of myosin heavy and light chains, which are coded by 15 and 11 different genes, respectively. Laser capture microdissection techniques allow assessment of mRNA and protein content in individual fibers. We found that specific human fiber types contain different mixtures of myosin heavy and light chains. Fast-twitch (type IIx) fibers consistently contained myosin heavy chains 1, 2, and 4 and myosin light chain 1. Type I fibers always contained myosin heavy chains 6 and 7 (MYH6 and MYH7) and myosin light chain 3 (MYL3), whereas MYH6, MYH7, and MYL3 were nearly absent from type IIx fibers. In contrast to cardiomyocytes, where MYH6 (also known as α-myosin heavy chain) is seen solely in fast-twitch cells, only slow-twitch fibers of skeletal muscle contained MYH6. Classical fast myosin heavy chains (MHC1, MHC2, and MHC4) were present in variable proportions in all fiber types, but significant MYH6 and MYH7 expression indicated slow-twitch phenotype, and the absence of these two isoforms determined a fast-twitch phenotype. The mixed myosin heavy and light chain content of type IIa fibers was consistent with its role as a transition between fast and slow phenotypes. These new observations suggest that the presence or absence of MYH6 and MYH7 proteins dictates the slow- or fast-twitch phenotype in skeletal muscle. PMID:26676053

Effect of carbohydrate supplementation on postexercise GLUT-4 protein expression in skeletal muscle.

PubMed

Kuo, C H; Hunt, D G; Ding, Z; Ivy, J L

1999-12-01

The effect of carbohydrate supplementation on skeletal muscle glucose transporter GLUT-4 protein expression was studied in fast-twitch red and white gastrocnemius muscle of Sprague-Dawley rats before and after glycogen depletion by swimming. Exercise significantly reduced fast-twitch red muscle glycogen by 50%. During a 16-h exercise recovery period, muscle glycogen returned to control levels (25.0 +/- 1.4 micromol/g) in exercise-fasted rats (24.2 +/- 0. 3 micro). However, when carbohydrate supplementation was provided during and immediately postexercise by intubation, muscle glycogen increased 77% above control (44.4 +/- 2.1 micromol/g). Exercise-fasting resulted in an 80% increase in fast-twitch red muscle GLUT-4 mRNA but only a 43% increase in GLUT-4 protein concentration. Conversely, exercise plus carbohydrate supplementation elevated fast-twitch red muscle GLUT-4 protein concentration by 88% above control, whereas GLUT-4 mRNA was increased by only 40%. Neither a 16-h fast nor carbohydrate supplementation had an effect on fast-twitch red muscle GLUT-4 protein concentration or on GLUT-4 mRNA in sedentary rats, although carbohydrate supplementation increased muscle glycogen concentration by 40% (35.0 +/- 0.9 micromol/g). GLUT-4 protein in fast-twitch white muscle followed a pattern similar to fast-twitch red muscle. These results indicate that carbohydrate supplementation, provided with exercise, will enhance GLUT-4 protein expression by increasing translational efficiency. Conversely, postexercise fasting appears to upregulate GLUT-4 mRNA, possibly to amplify GLUT-4 protein expression on an increase in glucose availability. These regulatory mechanisms may help control muscle glucose uptake in accordance with glucose availability and protect against postexercise hypoglycemia.

Swimming and twitching motility are essential for attachment and virulence of Pantoea ananatis in onion seedlings.

PubMed

Weller-Stuart, Tania; Toth, Ian; De Maayer, Pieter; Coutinho, Teresa

2017-06-01

Pantoea ananatis is a widespread phytopathogen with a broad host range. Despite its ability to infect economically important crops, such as maize, rice and onion, relatively little is known about how this bacterium infects and colonizes host tissue or spreads within and between hosts. To study the role of motility in pathogenicity, we analysed both swimming and twitching motility in P. ananatis LMG 20103. Genetic recombineering was used to construct four mutants affected in motility. Two flagellar mutants were disrupted in the flgK and motA genes, required for flagellar assembly and flagellar rotation, respectively. Similarly, two twitching motility mutants were generated, impaired in the structure (pilA) and functioning (pilT) of the type IV pili. The role of swimming and twitching motility during the infection cycle of P. ananatis in onion seedlings was determined by comparing the mutant- and wild-type strains using several in vitro and in planta assays. From the results obtained, it was evident that flagella aid P. ananatis in locating and attaching to onion leaf surfaces, as well as in pathogenicity, whereas twitching motility is instrumental in the spread of the bacteria on the surface once attachment has occurred. Both swimming and twitching motility contribute towards the ability of P. ananatis to cause disease in onions. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Fatigue and contraction of slow and fast muscles in hypokinetic/hypodynamic rats

NASA Technical Reports Server (NTRS)

Fell, R. D.; Gladden, L. B.; Steffen, J. M.; Musacchia, X. J.

1985-01-01

The effects of hypokinesia/hypodynamia (H/H) on the fatigability and contractile properties of the rat soleus (S) and gastrocnemius (G) muscles have been investigated experimentally. Whole body suspension for one week was used to induce H/H, and fatigue was brought on by train stimulation for periods of 45 and 16 minutes. Following stimulation, rapid rates of fatigue were observed in the G-muscles of the suspended rats, while minimal fatigue was observed in the S-muscles. The twitch and tetanic contractile properties of the muscles were measured before and after train stimulation. It is found that H/H suspension increased twitch tension in the G-muscles, but did not change any contractile properties in the S-muscles. The peak twitch, train, tetanic tensions and time to peak were unchanged in the S-muscles of the suspended rats. On the basis of the experimental results, it is concluded that 1 wk of muscle atropy induced by H/H significantly increases fatigability in G-muscles, but does not affect the contractile properties of fast-twitch and slow-twitch muscles.

Clindamycin enhances a nondepolarizing neuromuscular blockade.

PubMed

Becker, L D; Miller, R D

1976-07-01

Neuromuscular blockades induced by clindamycin alone and with d-tubocurarine or pancuronium were examined in the in-vitro guinea pig lumbrical muscle-nerve preparation. Clindamycin, 80-240 mug/ml, initially increased twitch tension. With higher concentrations (180-240 mug/ml) twitch tension subsequently decreased. With 15 to 20 per cent depression of twitch tension by clindamycin, neostigmine (5-20 ng/ml) or calcium (81 mug/ml) slightly but not completely antagonized the blockade. Clindamycin, 40 mug/ml, a dose that did not depress twitch tension, potentiated d-tubocurarine- or pancuronium-induced neuromuscular bloackade. Plasma concentrations of clindamycin of 10-40 mug/ml were recommended for treating serious infections. The authors conclude that the administration of clindamycin may augment nondepolarizing blockade in man, and antagonism by neostigmine and calcium may be incomplete.

Mathematical modelling of the active hearing process in mosquitoes

PubMed Central

Avitabile, D.; Homer, M.; Champneys, A. R.; Jackson, J. C.; Robert, D.

2010-01-01

Insects have evolved diverse and delicate morphological structures in order to capture the inherently low energy of a propagating sound wave. In mosquitoes, the capture of acoustic energy and its transduction into neuronal signals are assisted by the active mechanical participation of the scolopidia. We propose a simple microscopic mechanistic model of the active amplification in the mosquito species Toxorhynchites brevipalpis. The model is based on the description of the antenna as a forced-damped oscillator coupled to a set of active threads (ensembles of scolopidia) that provide an impulsive force when they twitch. This twitching is in turn controlled by channels that are opened and closed if the antennal oscillation reaches a critical amplitude. The model matches both qualitatively and quantitatively with recent experiments: spontaneous oscillations, nonlinear amplification, hysteresis, 2 : 1 resonances, frequency response and gain loss owing to hypoxia. The numerical simulations presented here also generate new hypotheses. In particular, the model seems to indicate that scolopidia located towards the tip of Johnston's organ are responsible for the entrainment of the other scolopidia and that they give the largest contribution to the mechanical amplification. PMID:19447819

Dihydrotestosterone treatment rescues the decline in protein synthesis as a result of sarcopenia in isolated mouse skeletal muscle fibres

PubMed Central

Wendowski, Oskar; Redshaw, Zoe

2016-01-01

Abstract Background Sarcopenia, the progressive decline in skeletal muscle mass and function with age, is a debilitating condition. It leads to inactivity, falls, and loss of independence. Despite this, its cause(s) and the underlying mechanism(s) are still poorly understood. Methods In this study, small skeletal muscle fibre bundles isolated from the extensor digitorum longus (a fast‐twitch muscle) and the soleus (a slow‐twitch muscle) of adult mice of different ages (range 100–900 days old) were used to investigate the effects of ageing and dihydrotestosterone (DHT) treatment on protein synthesis as well as the expression and function of two amino acid transporters; the sodium‐coupled neutral amino acid transporter (SNAT) 2, and the sodium‐independent L‐type amino‐acid transporter (LAT) 2. Results At all ages investigated, protein synthesis was always higher in the slow‐twitch than in the fast‐twitch muscle fibres and decreased with age in both fibre types. However, the decline was greater in the fast‐twitch than in the slow‐twitch fibres and was accompanied by a reduction in the expression of SNAT2 and LAT2 at the protein level. Again, the decrease in the expression of the amino acid transporters was greater in the fast‐twitch than in the slow‐twitch fibres. In contrast, ageing had no effect on SNAT2 and LAT2 expressions at the mRNA level. Treating the muscle fibre bundles with physiological concentrations (~2 nM) of DHT for 1 h completely reversed the effects of ageing on protein synthesis and the expression of SNAT2 and LAT2 protein in both fibre types. Conclusion From the observations that ageing is accompanied by a reduction in protein synthesis and transporter expression and that these effects are reversed by DHT treatment, we conclude that sarcopenia arises from an age‐dependent reduction in protein synthesis caused, in part, by the lack of or by the low bioavailability of the male sex steroid, DHT. PMID:27239418

The role of frequency in the effects of long-term intermittent stimulation of denervated slow-twitch muscle in the rat.

PubMed Central

Al-Amood, W S; Lewis, D M

1987-01-01

1. Rat soleus muscle was denervated by sciatic transection and electrically stimulated for periods of between 3 and 9 weeks with intermittent 1 s bursts of pulses. Most of the bursts were either repeated every 90 s and pulses within them had frequencies between 10 and 100 Hz, or had a frequency of 50 Hz and were repeated at intervals between 60 and 600 s. Comparisons were made with continuous stimulation at 10 Hz. 2. At the end of the period of stimulation, isometric twitches and tetani were measured and, in a proportion, also isotonic shortening velocity. 3. Isometric twitch duration (contraction and relaxation) decreased with time of stimulation. Very similar effects were seen in all animals in which intermittent stimulation had been used. There was a significant relationship between the change in twitch duration and the frequency used within the bursts of chronic stimulation, with slightly larger effects at frequencies of 40 and 60 Hz. The lowest burst repetition rate produced the largest effects. 4. It was confirmed that similar changes were found in denervated muscles that were not stimulated, although these changes were smaller and developed more slowly. 5. The extreme loss of tetanic tension induced in the muscle by denervation was reduced by chronic stimulation, with no significant difference between different regimes, although there were small differences which showed the same patterns of effectiveness described for twitch durations. 6. Continuous stimulation at 10 Hz maintained the twitch contraction and relaxation phases at the values found 3 weeks after denervation, that is it prevented secondary shortening of the twitch. Continuous stimulation reduced tension loss but was, perhaps, less effective than intermittent stimulation. 7. Twitch-tetanus ratio increased with denervation with little spontaneous reversal later. Stimulation at all frequencies reduced the ratio, but it did not reach normal values. 8. Isotonic shortening velocity was measured in many of the muscles. Maximum velocity was estimated and normalized by muscle length.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 3 PMID:3446785

Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

PubMed

Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V; Halama, Marek; Wieczorek, Piotr P

2015-03-27

The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

Differential expression of FGF receptors and of myogenic regulatory factors in primary cultures of satellite cells originating from fast (EDL) and slow (Soleus) twitch rat muscles.

PubMed

Martelly, I; Soulet, L; Bonnavaud, S; Cebrian, J; Gautron, J; Barritault, D

2000-11-01

In the rat, the fast and slow twitch muscles respectively Extensor digitorum longus (EDL) and Soleus present differential characteristics during regeneration. This suggests that their satellite cells responsible for muscle growth and repair represent distinct cellular populations. We have previously shown that satellite cells dissociated from Soleus and grown in vitro proliferate more readily than those isolated from EDL muscle. Fibroblast growth factors (FGFs) are known as regulators of myoblast proliferation and several studies have revealed a relationship between the response of myoblasts to FGF and the expression of myogenic regulatory factors (MRF) of the MyoD family by myoblasts. Therefore, we presently examined the possibility that the satellite cells isolated from EDL and Soleus muscles differ in the expression of FGF receptors (FGF-R) and of MRF expression. FGF-R1 and -R4 were strongly expressed in proliferating cultures whereas FGF-R2 and R3 were not detected in these cultures. In differentiating cultures, only -R1 was present in EDL satellite cells while FGF-R4 was also still expressed in Soleus cells. Interestingly, the unconventional receptor for FGF called cystein rich FGF receptor (CFR), of yet unknown function, was mainly detected in EDL satellite cell cultures. Soleus and EDL satellite cell cultures also differed in the expression MRFs. These results are consistent with the notion that satellite cells from fast and slow twitch muscles belong to different types of myogenic cells and suggest that satellite cells might play distinct roles in the formation and diversification of fast and slow fibres.

Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice

PubMed Central

Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V.; Halama, Marek; Wieczorek, Piotr P.

2015-01-01

The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers. PMID:25826052

Neuromuscular activity of the venoms of the Colombian coral snakes Micrurus dissoleucus and Micrurus mipartitus: an evolutionary perspective.

PubMed

Renjifo, Camila; Smith, Eric N; Hodgson, Wayne C; Renjifo, Juan M; Sanchez, Armando; Acosta, Rodrigo; Maldonado, Jairo H; Riveros, Alain

2012-01-01

The venoms of coral snakes (genus Micrurus) are known to induce a broad spectrum of pharmacological activities. While some studies have investigated their potential human effects, little is known about their mechanism of action in terms of the ecological diversity and evolutionary relationships among the group. In the current study we investigated the neuromuscular blockade of the venom of two sister species Micrurus mipartitus and Micrurus dissoleucus, which exhibit divergent ecological characteristics in Colombia, by using the chick biventer cervicis nerve-muscle preparation. We also undertook a phylogenetic analysis of these species and their congeners, in order to provide an evolutionary framework for the American coral snakes. The venom of M. mipartitus caused a concentration-dependant inhibition (3-10 μg/ml) of nerve-mediated twitches and significantly inhibited contractile responses to exogenous ACh (1 mM), but not KCl (40 mM), indicating a postsynaptic mechanism of action. The inhibition of indirect twitches at the lower venom dose (3 μg/ml) showed to be triphasic and the effect was further attenuated when PLA2 was inhibited. M. dissoleucus venom (10-50 μg/ml) failed to produce a complete blockade of nerve-mediated twitches within a 3 h time period and significantly inhibited contractile responses to exogenous ACh (1 mM) and KCl (40 mM), indicating both postsynaptic and myotoxic mechanisms of action. Myotoxic activity was confirmed by morphological studies of the envenomed tissues. Our results demonstrate a hitherto unsuspected diversity of pharmacological actions in closely related species which exhibit divergent ecological characteristics; these results have important implications for both the clinical management of Coral snake envenomings and the design of Micrurus antivenom. Copyright © 2011 Elsevier Ltd. All rights reserved.

Moving People from Science Adjacent to Science Doers with Twitch.tv

NASA Astrophysics Data System (ADS)

Gay, Pamela L.; CosmoQuest

2017-10-01

The CosmoQuest community is testing the ability to attract people from playing online videogames to doing fully online citizen science by engaging people through the Twitch.tv streaming platform. Twitch.tv launched in 2011 as an online platform for video gamers to stream their gameplay while providing narrative. In its six years of regular growth, the platform has added support for people playing non-video games, and for those participating in non-game activities. As part of their expansion, in April 2017, Twitch.tv hosted a science week during which they streamed the Cosmos series and allowed different feeds provide real-time commentary. They also hosted panel discussions on a variety of science topics. CosmoQuest participated in this event and used it as a jumping off point for beginning to interact with Twitch.tv community members online. With CosmoQuest’s beta launch of Image Detectives, they expanded their use of this streaming platform to include regular “office hours”, during which team members did science with CosmoQuest’s online projects, took questions from community members, and otherwise promoted the CosmoQuest community. This presentation examines this case study, and looks at how well different kinds of Twitter engagements attracted audiences, the conversion rate from viewer to subscriber, and at how effectively CosmoQuest was able to migrate users from viewing citizen science on Twitch.tv to participating in citizen science on CosmoQuest.org.This project was supported through NASA cooperative agreement NNX17AD20A.

Toward a comprehensive hybrid physical-virtual reality simulator of peripheral anesthesia with ultrasound and neurostimulator guidance.

PubMed

Samosky, Joseph T; Allen, Pete; Boronyak, Steve; Branstetter, Barton; Hein, Steven; Juhas, Mark; Nelson, Douglas A; Orebaugh, Steven; Pinto, Rohan; Smelko, Adam; Thompson, Mitch; Weaver, Robert A

2011-01-01

We are developing a simulator of peripheral nerve block utilizing a mixed-reality approach: the combination of a physical model, an MRI-derived virtual model, mechatronics and spatial tracking. Our design uses tangible (physical) interfaces to simulate surface anatomy, haptic feedback during needle insertion, mechatronic display of muscle twitch corresponding to the specific nerve stimulated, and visual and haptic feedback for the injection syringe. The twitch response is calculated incorporating the sensed output of a real neurostimulator. The virtual model is isomorphic with the physical model and is derived from segmented MRI data. This model provides the subsurface anatomy and, combined with electromagnetic tracking of a sham ultrasound probe and a standard nerve block needle, supports simulated ultrasound display and measurement of needle location and proximity to nerves and vessels. The needle tracking and virtual model also support objective performance metrics of needle targeting technique.

Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy.

PubMed

Petchey, Louisa K; Risebro, Catherine A; Vieira, Joaquim M; Roberts, Tom; Bryson, John B; Greensmith, Linda; Lythgoe, Mark F; Riley, Paul R

2014-07-01

Correct regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-related homeobox factor 1 (Prox1) during mouse heart development in the direct transcriptional repression of the fast-twitch skeletal muscle genes troponin T3, troponin I2, and myosin light chain 1. A proportion of cardiac-specific Prox1 knockout mice survive beyond birth with hearts characterized by marked overexpression of fast-twitch genes and postnatal development of a fatal dilated cardiomyopathy. Through conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved requirement for Prox1 in the repression of troponin T3, troponin I2, and myosin light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1 ablation as sufficient to cause a switch from a slow- to fast-twitch muscle phenotype. Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease.

Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

PubMed Central

Petchey, Louisa K.; Risebro, Catherine A.; Vieira, Joaquim M.; Roberts, Tom; Bryson, John B.; Greensmith, Linda; Lythgoe, Mark F.; Riley, Paul R.

2014-01-01

Correct regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-related homeobox factor 1 (Prox1) during mouse heart development in the direct transcriptional repression of the fast-twitch skeletal muscle genes troponin T3, troponin I2, and myosin light chain 1. A proportion of cardiac-specific Prox1 knockout mice survive beyond birth with hearts characterized by marked overexpression of fast-twitch genes and postnatal development of a fatal dilated cardiomyopathy. Through conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved requirement for Prox1 in the repression of troponin T3, troponin I2, and myosin light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1 ablation as sufficient to cause a switch from a slow- to fast-twitch muscle phenotype. Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease. PMID:24938781

Dynamic formation of microenvironments at the myotendinous junction correlates with muscle fiber morphogenesis in zebrafish

PubMed Central

Snow, Chelsi J.; Henry, Clarissa A.

2009-01-01

Muscle development involves the specification and morphogenesis of muscle fibers that attach to tendons. After attachment, muscles and tendons then function as an integrated unit to transduce force to the skeletal system and stabilize joints. The attachment site is the myotendinous junction, or MTJ, and is the primary site of force transmission. We find that attachment of fast-twitch myofibers to the MTJ correlates with the formation of novel microenvironments within the MTJ. The expression or activation of two proteins involved in anchoring the intracellular cytoskeleton to the extracellular matrix, Focal adhesion kinase (Fak) and β-dystroglycan is up-regulated. Conversely, the extracellular matrix protein Fibronectin (Fn) is down-regulated. This degradation of Fn as fast-twitch fibers attach to the MTJ results in Fn protein defining a novel microenvironment within the MTJ adjacent to slow-twitch, but not fast-twitch, muscle. Interestingly, however, Fak, laminin, Fn and β-dystroglycan concentrate at the MTJ in mutants that do not have slow-twitch fibers. Taken together, these data elucidate novel and dynamic microenvironments within the MTJ and indicate that MTJ morphogenesis is spatially and temporally complex. PMID:18783736

Measurement of Contractile Stress Generated by Cultured Rat Muscle on Silicon Cantilevers for Toxin Detection and Muscle Performance Enhancement

DTIC Science & Technology

2010-06-01

muscle . J Clin Invest 117: 2388–2391. 13. Close R (1964) Dynamic properties of fast and slow skeletal muscles of the rat during development. J Physiol...cultured skeletal muscle [30], which reported average peak twitch stress values of 2.9 kPa (reported as specific peak twitch force in units of kN/m2), but...demonstrates that the myotubes were driven down a path towards a more mature phenotype, in the process developing fast - twitch isoforms of myosin, while

Autonomic components of Complex Regional Pain Syndrome (CRPS) are favourably affected by Electrical Twitch-Obtaining Intramuscular Stimulation (ETOIMS): effects on blood pressure and heart rate.

PubMed

Chu, Jennifer; Bruyninckx, Frans; Neuhauser, Duncan V

2017-07-01

Favourable pain relief results on evoking autonomous twitches at myofascial trigger points with Electrical Twitch Obtaining Intramuscular Stimulation (ETOIMS). To document autonomic nervous system (ANS) dysfunction in Complex Regional Pain Syndrome (CRPS) from blood pressure (BP) and pulse/heart rate changes with ETOIMS. A patient with persistent pain regularly received serial ETOIMS sessions of 60, 90, 120 or ≥150 min over 24 months. Outcome measures include BP: systolic, diastolic, pulse pressure and pulse/heart rate, pre-session/immediate-post-session summed differences (SDPPP index), and pain reduction. His results were compared with that of two other patients and one normal control. Each individual represented the following maximal elicitable twitch forces (TWF) graded 1-5: maximum TWF2: control subject; maximum TWF3: CRPS patient with suspected ANS dysfunction; and maximum TWF4 and TWF5: two patients with respective slow-fatigue and fast-fatigue twitches who during ETOIMS had autonomous twitching at local and remote myotomes simultaneously from denervation supersensitivity. ETOIMS results between TWFs were compared using one-way analysis of variance test. The patients showed immediate significant pain reduction, BP and pulse/heart rate changes/reduction(s) except for diastolic BP in the TWF5 patient. TWF2 control subject had diastolic BP reduction with ETOIMS but not with rest. Linear regression showed TWF grade to be the most significant variable in pain reduction, more so than the number of treatments, session duration and treatment interval. TWF grade was the most important variable in significantly reducing outcome measures, especially pulse/heart rate. Unlike others, the TWF3 patient had distinctive reductions in SDPPP index. Measuring BP and pulse/heart rate is clinically practical for alerting ANS dysfunction maintained CRPS. SDPPP index (≥26) and pulse/heart rate (≥8) reductions with almost every ETOIMS treatment, plus inability to evoke autonomous twitches due to pain-induced muscle hypertonicity, are pathognomonic of this problem.

Hexamethonium produces both twitch and tetanic depression without fade in common African toad (Bufo regularis).

PubMed

Ajibola, E S; Adebayo, A O; Thomas, F C; Rahman, S A; Gbadebo, A M; Odunbaku, T A

2009-12-01

The study was designed to investigate the nature of the cholinoceptors at the sciatic nerve-gastrocnemius muscle junction of the common African toad (Bufo regularis). Using myographic technique, the twitch properties of the sciatic-gastrocnemius muscle preparation of the common African toad was studied. Both the twitch height and peak tetanic height were measured as a percentage of control. Hexamethonium at a concentration of 0.1 mM significantly [P<0.05] reduced the mean twitch height from 2.62 cm to 1.0 cm and mean peak tetanic height from 5.38 cm to 4.32 cm. Hexamethonium, however does not produce tetanic fade at the same concentration. We hypothesized that the cholinoceptors of the neuromuscular junction of the common African toad (Bufo regularis) resemble the developing synapse of African clawed toad (Xenopus laevis) and may contain muscarinic M1 autoreceptors at the pre juntional membrane.

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

PubMed

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

2018-01-01

High-intensity muscle actions have the potential to temporarily improve muscle contractile properties (i.e., postactivation potentiation, PAP) thereby inducing acute performance enhancements. There is evidence that balance training can improve performance during strength exercises. Taking these findings together, the purpose of this study was to examine the acute effects of a combined balance and strength (B+S) exercise vs. a strength only (S) exercise on twitch contractile properties, maximum voluntary strength, and jump performance in young athletes. Female elite young soccer players ( N = 12) aged 14-15 years conducted three experimental conditions in randomized order: S included 3 sets of 8-10 dynamic leg extensions at 80% of the 1-repetition maximum, B+S consisted of 3 sets of 40 s double-leg stances on a balance board prior to leg extensions (same as S), and a resting control period. Before and 7 min after exercise, participants were tested for their electrically-evoked isometric twitches (i.e., twitch peak torque, twitch rate of torque development) and maximal voluntary contraction (MVC) torque of the plantar flexor muscles. Additionally, countermovement (CMJ) and drop jump (DJ) performances (i.e., CMJ/DJ height, DJ ground contact time) were assessed. Significant effects of condition on twitch contractile properties ( p < 0.05, d = 1.1) and jump performance outputs ( p < 0.05, 1.1 ≤ d ≤ 1.2) were found. Post-hoc tests revealed that S compared to control produced larger PAP for twitch peak torques by trend ( p = 0.07, d = 1.8, 33 vs. 21%) and significantly larger PAP for twitch rate of torque development ( p < 0.05, d = 2.4, 55 vs. 43%). Following B+S compared to control, significant improvements in CMJ height ( p < 0.01, d = 1.9, 3%) and DJ contact time were found ( p < 0.01, d = 2.0, 10%). This study revealed protocol-specific acute performance improvements. While S resulted in significant increases in twitch contractile properties, B+S produced significant enhancements in jump performance. It is concluded that PAP effects in the plantar flexors may not directly translate to improved jump performance in female elite young soccer players. Therefore, the observed gains in jump performance following B+S are most likely related to neuromuscular changes (e.g., intramuscular coordination) rather than improved contractile properties.

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

PubMed Central

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

2018-01-01

High-intensity muscle actions have the potential to temporarily improve muscle contractile properties (i.e., postactivation potentiation, PAP) thereby inducing acute performance enhancements. There is evidence that balance training can improve performance during strength exercises. Taking these findings together, the purpose of this study was to examine the acute effects of a combined balance and strength (B+S) exercise vs. a strength only (S) exercise on twitch contractile properties, maximum voluntary strength, and jump performance in young athletes. Female elite young soccer players (N = 12) aged 14–15 years conducted three experimental conditions in randomized order: S included 3 sets of 8–10 dynamic leg extensions at 80% of the 1-repetition maximum, B+S consisted of 3 sets of 40 s double-leg stances on a balance board prior to leg extensions (same as S), and a resting control period. Before and 7 min after exercise, participants were tested for their electrically-evoked isometric twitches (i.e., twitch peak torque, twitch rate of torque development) and maximal voluntary contraction (MVC) torque of the plantar flexor muscles. Additionally, countermovement (CMJ) and drop jump (DJ) performances (i.e., CMJ/DJ height, DJ ground contact time) were assessed. Significant effects of condition on twitch contractile properties (p < 0.05, d = 1.1) and jump performance outputs (p < 0.05, 1.1 ≤ d ≤ 1.2) were found. Post-hoc tests revealed that S compared to control produced larger PAP for twitch peak torques by trend (p = 0.07, d = 1.8, 33 vs. 21%) and significantly larger PAP for twitch rate of torque development (p < 0.05, d = 2.4, 55 vs. 43%). Following B+S compared to control, significant improvements in CMJ height (p < 0.01, d = 1.9, 3%) and DJ contact time were found (p < 0.01, d = 2.0, 10%). This study revealed protocol-specific acute performance improvements. While S resulted in significant increases in twitch contractile properties, B+S produced significant enhancements in jump performance. It is concluded that PAP effects in the plantar flexors may not directly translate to improved jump performance in female elite young soccer players. Therefore, the observed gains in jump performance following B+S are most likely related to neuromuscular changes (e.g., intramuscular coordination) rather than improved contractile properties. PMID:29628898

Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness

PubMed Central

Stuart, Charles A.; Lee, Michelle L.; South, Mark A.; Howell, Mary E.A.; Cartwright, Brian M.; Ramsey, Michael W.; Stone, Michael H.

2016-01-01

Only half of pre-diabetic, subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pre-training characteristics favoring a positive response to exercise training. Thirty non-diabetic, subjects who are obese volunteered for eight weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and GLUT4 expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pre-training baseline. PMID:27379957

The ineffectiveness of (±)-carnitine preventing the twitchings of striated frog muscle in 0.7% sodium chloride solution

PubMed Central

Friebel, H.

1959-01-01

The spontaneous twitchings of isolated frog sartorius muscles in 0.7% NaCl solution have been studied. Addition of 1 mg./ml. of (±)-carnitine hydrochloride, or of (±)-carnitine base, to the bath fluid had no influence on the spontaneous activity of the muscles, their excitability or their ability to liberate potassium. This indicates that carnitine is not a natural inhibitor of striated frog muscle. Fluids enriched with potassium either from twitching muscle or by addition of KCl inhibited the activity of muscles reversibly. PMID:13825014

Can fast-twitch muscle fibres be selectively recruited during lengthening contractions? Review and applications to sport movements.

PubMed

Chalmers, Gordon R

2008-01-01

Literature examining the recruitment order of motor units during lengthening (eccentric) contractions was reviewed to determine if fast-twitch motor units can be active while lower threshold slow-twitch motor units are not active. Studies utilizing surface electromyogram (EMG) amplitude, single motor unit activity, spike amplitude-frequency analyses, EMG power spectrum, mechanomyographic, and phosphocreatine-to-creatine ratio (PCr/Cr) techniques were reviewed. Only single motor unit and PCr/Cr data were found to be suitable to address the goals of this review. Nine of ten single motor unit studies, examining joint movement velocities up to 225 degrees/s and forces up to 53% of a maximum voluntary contraction, found that the size principle of motor unit recruitment applied during lengthening contractions. Deviation from the size principle was demonstrated by one study examining movements within a small range of low velocities and modest forces, although other studies examining similar low forces and lengthening velocities reported size-ordered recruitment. The PCr/Cr data demonstrated the activation of all fibre types in lengthening maximal contractions. Most evidence indicates that for lengthening contractions of a wide range of efforts and speeds, fast-twitch muscle fibres cannot be selectively recruited without activity of the slow-twitch fibres of the same muscle.

Use of a fiber glass optical system to measure the contractile characteristics of a single isolated muscle cell

NASA Astrophysics Data System (ADS)

Chen, Chulung; Yin, Shizhuo; Li, Jiang; Yu, Francis T. S.; Cheung, Joseph Y.; Zhang, Xueqian; Lei, Xiaoxiao; Wu, Zhongkong

1998-05-01

Cell is the basic structural and fundamental unit of all organisms; the smallest structure capable of performing all the activities vital to life. One goal of current research interest is to learn how the muscle varies the strength of its contraction in response to electric stimuli. A wide variety of techniques have been developed to monitor the mechanical response of isolated cardiac myocytes. Some success has been reported either with the use of intact rat myocytes supported by suction micropipettes or in guinea pig myocytes adhering to glass beams. However, the usual measuring techniques exhibit destructive contact performance on live cells. They could not solve the problem, since the cell may die during or after the time-consuming attachment process at the beginning of each experiment. In contrast, a novel optical system, which consists of a microglass tube with an inner diameter the same size of a real cardiac cell, is proposed to simulate real cell's twitch process. the physical parameters of synthetic cell are well known. By comparing the dynamics of the real cell with that of the simulated cell, the twitch characteristics of the real cell can be measured.

Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model

PubMed Central

Canal, Clint E.; Morgan, Drake

2013-01-01

Two primary animal models persist for assessing hallucinogenic potential of novel compounds and for examining the pharmacological and neurobiological substrates underlying the actions of classical hallucinogens, the two-lever drug discrimination procedure and the drug-induced head-twitch response (HTR) in rodents. The substituted amphetamine hallucinogen, serotonin 2 (5-HT2) receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI) has emerged as the most popular pharmacological tool used in HTR studies of hallucinogens. Synthesizing classic, recent, and relatively overlooked findings, addressing ostensibly conflicting observations, and considering contemporary theories in receptor and behavioural pharmacology, this review provides an up-to-date and comprehensive synopsis of DOI and the HTR model, from neural mechanisms to utility for understanding psychiatric diseases. Also presented is support for the argument that, although both the two-lever drug discrimination and the HTR models in rodents are useful for uncovering receptors, interacting proteins, intracellular signalling pathways, and neurochemical processes affected by DOI and related classical hallucinogens, results from both models suggest they are not reporting hallucinogenic experiences in animals. PMID:22517680

Effects of Allyl Isothiocyanate, Acetaminophen, and Dipyrone in the Guinea-Pig Ileum.

PubMed

Donnerer, Josef; Liebmann, Ingrid

2017-01-01

Allyl isothiocyanate (AITC, mustard oil, 50-200 µmol/l), depending on specific dosages, inhibited the cholinergic twitch response in the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. AITC also induced short-lasting contractile responses, and decreases of the basal tone of the LMMP strip at low concentrations and increases at high concentrations. Hexamethonium, a blocker of nicotinic ganglionic transmission, was able to prevent the AITC-evoked inhibitory effect, an effect that was also observed with the opioid antagonist naloxone. The P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid and guanethidine had no significant influence on the inhibitory effect of AITC. Since AITC also reduced the electrical stimulation-induced myogenic smooth muscle contractions in the LMMP preparation, its contractile and relaxant actions can be regarded as neurogenic and myogenic in nature. The analgesics, acetaminophen (paracetamol, 100-500 µmol/l) and dipyrone (metamizole, 100-500 µmol/l), reduced both the cholinergic twitch and the myogenic contractions in the LMMP strip to the same extent; therefore, their action in the intestinal smooth muscle can be regarded as myogenic spasmolytic in nature. © 2016 S. Karger AG, Basel.

Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging.

PubMed

Jayasinghe, Isuru D; Munro, Michelle; Baddeley, David; Launikonis, Bradley S; Soeller, Christian

2014-10-06

Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Altered fast- and slow-twitch muscle fibre characteristics in female mice with a (S248F) knock-in mutation of the brain neuronal nicotinic acetylcholine receptor.

PubMed

Cannata, David J; Finkelstein, David I; Gantois, Ilse; Teper, Yaroslav; Drago, John; West, Jan M

2009-01-01

We generated a mouse line with a missense mutation (S248F) in the gene (CHRNA4) encoding the alpha4 subunit of neuronal nicotinic acetylcholine receptor (nAChR). Mutant mice demonstrate brief nicotine induced dystonia that resembles the clinical events seen in patients with the same mutation. Drug-induced dystonia is more pronounced in female mice, thus our aim was to determine if the S248F mutation changed the properties of fast- and slow-twitch muscle fibres from female mutant mice. Reverse transcriptase-PCR confirmed CHRNA4 gene expression in the brain but not skeletal muscles in normal and mutant mice. Ca(2+) and Sr(2+) force activation curves were obtained using skinned muscle fibres prepared from slow-twitch (soleus) and fast-twitch (EDL) muscles. Two significant results were found: (1) the (pCa(50) - pSr(50)) value from EDL fibres was smaller in mutant mice than in wild type (1.01 vs. 1.30), (2) the percentage force produced at pSr 5.5 was larger in mutants than in wild type (5.76 vs. 0.24%). Both results indicate a shift to slow-twitch characteristics in the mutant. This conclusion is supported by the identification of the myosin heavy chain (MHC) isoforms. Mutant EDL fibres expressed MHC I (usually only found in slow-twitch fibres) as well as MHC IIa. Despite the lack of spontaneous dystonic events, our findings suggest that mutant mice may be having subclinical events or the mutation results in a chronic alteration to muscle neural input.

Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging

PubMed Central

Jayasinghe, Isuru D.; Munro, Michelle; Baddeley, David; Launikonis, Bradley S.; Soeller, Christian

2014-01-01

Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. PMID:25100314

Age-related differences in twitch properties and muscle activation of the first dorsal interosseous.

PubMed

Miller, Jonathan D; Herda, Trent J; Trevino, Michael A; Sterczala, Adam J; Ciccone, Anthony B; Nicoll, Justin X

2017-06-01

To examine twitch force potentiation and twitch contraction duration, as well as electromyographic amplitude (EMG RMS ) and motor unit mean firing rates (MFR) at targeted forces between young and old individuals in the first dorsal interosseous (FDI). Ultrasonography was used to assess muscle quality. Twenty-two young (YG) (age=22.6±2.7years) and 14 older (OD) (age=62.1±4.7years) individuals completed conditioning contractions at 10% and 50% maximal voluntary contraction, (MVC) during which EMG RMS and MFRs were assessed. Evoked twitches preceded and followed the conditioning contractions. Ultrasound images were taken to quantify muscle quality (cross-sectional area [CSA] and echo intensity [EI]). No differences were found between young and old for CSA, pre-conditioning contraction twitch force, or MFRs (P>0.05). However, OD individuals exhibited greater EI and contraction duration (P<0.05), and EMG RMS (YG=35.4±8.7%, OD=43.4±13.2%; P=0.034). Twitch force potentiation was lower for OD (0.311±0.15N) than YG (0.619±0.26N) from pre- to post-50% conditioning contraction (P<0.001). Lower levels of potentiation with elongated contraction durations likely contributed to greater muscle activation during the conditioning contractions in the OD rather than altered MFRs. Ultrasonography suggested age-related changes in muscle structure contributed to altered contractile properties in the OD. Greater muscle activation requirements can have negative implications on fatigue resistance at low to moderate intensities in older individuals. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Cortical relapses in multiple sclerosis.

PubMed

Puthenparampil, Marco; Poggiali, Davide; Causin, Francesco; Rolma, Giuseppe; Rinaldi, Francesca; Perini, Paola; Gallo, Paolo

2016-08-01

Multiple sclerosis (MS) is a white and grey matter disease of the central nervous system (CNS). It is recognized that cortical damage (i.e. focal lesions and atrophy) plays a role in determining the accumulation of physical and cognitive disability that is observed in patients with progressive MS. To date, an association of cortical lesions with clinical relapses has not been described. We report clinical and magnetic resonance imaging (MRI) findings of five relapsing-remitting MS (RRMS) patients who had clinical relapses characterized by the acute appearance of cortical symptoms, due to the development of large, snake-like, cortical inflammatory lesions. Symptoms were: acute Wernicke's aphasia mimicking stroke; agraphia with acalculia, not associated to a motor deficit nor linguistic disturbance; hyposthenia of the left arm, followed by muscle twitching of the hand, spreading to arm and face; acute onset of left lower limb paroxysmal hypertonia; and temporal lobe status epilepticus, with psychotic symptoms. Cortical relapses may occur in MS. MRI examination in MS should include sequences, such as double inversion recovery (DIR) or phase sensitive inversion recovery (PSIR), that are aimed at visualizing cortical lesions, especially in the presence of symptoms of cortical dysfunction. Our observation further stresses and extends the clinical relevance of cortical pathology in MS. © The Author(s), 2015.

Properties of slow- and fast-twitch muscle fibres in a mouse model of amyotrophic lateral sclerosis.

PubMed

Atkin, Julie D; Scott, Rachel L; West, Jan M; Lopes, Elizabeth; Quah, Alvin K J; Cheema, Surindar S

2005-05-01

This investigation was undertaken to determine if there are altered histological, pathological and contractile properties in presymptomatic or endstage diseased muscle fibres from representative slow-twitch and fast-twitch muscles of SOD1 G93A mice in comparison to wildtype mice. In presymptomatic SOD1 G93A mice, there was no detectable peripheral dysfunction, providing evidence that muscle pathology is secondary to motor neuronal dysfunction. At disease endstage however, single muscle fibre contractile analysis demonstrated that fast-twitch muscle fibres and neuromuscular junctions are preferentially affected by amyotrophic lateral sclerosis-induced denervation, being unable to produce the same levels of force when activated by calcium as muscle fibres from their age-matched controls. The levels of transgenic SOD1 expression, aggregation state and activity were also examined in these muscles but there no was no preference for muscle fibre type. Hence, there is no simple correlation between SOD1 protein expression/activity, and muscle fibre type vulnerability in SOD1 G93A mice.

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units

PubMed Central

Sanchez, Gabriel N.; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L.; Schnitzer, Mark J.

2017-01-01

SUMMARY Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle’s contractile units. Despite the motor unit’s centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. PMID:26687220

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units.

PubMed

Sanchez, Gabriel N; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L; Schnitzer, Mark J

2015-12-16

Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle's contractile units. Despite the motor unit's centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. Copyright © 2015 Elsevier Inc. All rights reserved.

EXERCISE, MANUAL THERAPY AND POSTURAL RE-EDUCATION FOR UNCONTROLLED EAR TWITCHING AND RELATED IMPAIRMENTS AFTER WHIPLASH INJURY: A CASE REPORT.

PubMed

Flanders, Kelsey; Feldner, Heather

2017-10-01

Whiplash Associated Disorders and the interventions used to remediate them are well documented in physical therapy literature. However, specific interventions for spasms of the neck musculature that also involve constant ear twitching have yet to be addressed. The purpose of this case report is twofold. First, to describe comprehensive physical therapy management and outcomes for a subject with uncontrolled ear twitching and related musculoskeletal impairments, and second, to discuss the physical therapist's approach to evidence-based care when faced with a paucity of literature addressing physical therapy interventions for subjects with uncontrolled ear twitching. The subject was a 14-year-old female who sustained a right anterolateral whiplash injury when struck in the head by a volleyball seven months prior to physical therapy. Beginning five months after that injury, she experienced uncontrolled and constant superior/inferior movement of her right ear (hereafter described in this report as a twitch) in addition to facial and cervical pain from her initial injury. She was unable to participate in high school athletics due to her pain. A multimodal treatment approach including exercise, manual therapy, and postural reeducation was utilized during the subject's episode of care. After eight treatment sessions, the subjects's cervical range of motion and upper extremity strength improved. The reported frequency of ear twitching decreased, as did reports of neck and shoulder pain. In addition, her Neck Disability Index improved from a score of 22, indicating moderate disability, to 9, indicating mild disability and she was able to return to sport activity. With limited research to direct intervention, clinical reasoning was utilized to formulate an effective therapeutic intervention. A combination of manual therapy, exercise, and postural reeducation intervention was effective for this subject and could assist in guiding interventions for similarly unique clinical presentations in the future. Further research is needed to examine the etiology of ear twitching caused by muscle spasm and to develop additional evidence-based interventions for Whiplash Associated Disorders. Level 4.

Rocuronium duration of action under sevoflurane, desflurane or propofol anaesthesia.

PubMed

Maidatsi, P G; Zaralidou, A Th; Gorgias, N K; Amaniti, E N; Karakoulas, K A; Giala, M M

2004-10-01

We conducted a prospective randomized study to evaluate whether the duration of action of a single bolus dose of rocuronium is influenced by maintenance of anaesthesia with sevoflurane, desflurane or propofol infusion. Fifty-seven ASA I-II patients undergoing elective abdominal surgery were enrolled in this study. Anaesthesia was induced with thiopental 3-5 mg kg(-1) or propofol 2.5 mg kg(-1) and fentanyl 5 microg kg(-1) and tracheal intubation was facilitated with rocuronium 0.9 mg kg(-1). Thereafter patients were randomly allocated to three different groups to receive sevoflurane, desflurane or propofol for maintenance of anaesthesia. Recovery of neuromuscular function was monitored by single twitch stimulation of the ulnar nerve and by recording the adductor pollicis response using accelerometry. Intergroup recovery times to 5% of control value of single twitch were analysed using analysis of variance with Bonferroni correction. The mean (95% confidence interval) recovery time to 5% of control value of single twitch during desflurane anaesthesia was 90.18 (86.11-94.25) min. Significantly shorter recovery times were observed during sevoflurane or propofol anaesthesia, 58.86 (54.73-62.99) min and 51.11 (45.47-56.74) min, respectively (P < 0.001). There were also significant differences in the recovery time between groups receiving desflurane vs. sevoflurane (P < 0.001) and desflurane vs. propofol (P < 0.001). Desflurane anaesthesia significantly prolongs the duration of action of rocuronium at 0.9 mg kg(-1) single bolus dose, compared to sevoflurane or propofol anaesthesia maintenance regimens.

Twitching motility and biofilm formation are associated with tonB1 in Xylella fastidiosa.

PubMed

Cursino, Luciana; Li, Yaxin; Zaini, Paulo A; De La Fuente, Leonardo; Hoch, Harvey C; Burr, Thomas J

2009-10-01

A mutation in the Xylella fastidiosa tonB1 gene resulted in loss of twitching motility and in significantly less biofilm formation as compared with a wild type. The altered motility and biofilm phenotypes were restored by complementation with a functional copy of the gene. The mutation affected virulence as measured by Pierce's disease symptoms on grapevines. The role of TonB1 in twitching and biofilm formation appears to be independent of the characteristic iron-uptake function of this protein. This is the first report demonstrating a functional role for a tonB homolog in X. fastidiosa.

Enhancement and diminution of mechanical tension evoked by staircase and by tetanus in rat muscle

PubMed Central

Krarup, Christian

1981-01-01

1. Potentiation of the isometric twitch tension was compared during and after the staircase and after tetanic stimuli in the fast-twitch extensor digitorum longus muscle of adult Lewis rats at 37-38°C. 2. With up to 250 stimuli the potentiation rose with an increase in both the frequency and number of stimuli in the staircase (2-5/sec) and the tetanus (100-167/sec). After a tetanus of 375 stimuli (125/sec) the potentiation was smaller. The potentiation 2 sec after a tetanus of 250 stimuli (167/sec) was + 132 ± 5% (n = 21, s.e. of mean) which was greater (P < 0·001) than at the 250th stimulus at 5/sec, +92±3% (n = 21, s.e. of mean). 3. After the staircase the decay of potentiation was initially slow and later more rapid. This was taken to indicate both the recovery of a process that diminished twitch tension and the decay of a process causing potentiation. After 250 stimuli (5/sec) the rate of decay of the processes causing diminution and potentiation had time constants of 34·5 ± 3·8 sec (n = 18, s.e. of mean) and 102·2 ± 6·6 sec (n = 20, s.e. of mean) respectively. Compared with the potentiation, the process causing diminution became relatively more pronounced the greater the frequency of stimuli. 4. The decay of post-tetanic potentiation showed an initial rapid and a later slower phase of decay. After a tetanus of 250 stimuli (167/sec) the rates of decay had time constants of 5·7 ± 0·8 sec (n = 16, s.e. of mean) and 113·5 ± 8·7 sec (n = 19, s.e. of mean) respectively. 5. Compared with the unpotentiated response the time course of the twitch was shortened initially in the staircase and when the post-tetanic potentiation was low. The contraction time was then increasingly prolonged the greater the potentiation and the greater the number of stimuli in the staircase and in the tetanus. The half-relaxation time was the more prolonged the greater the number of stimuli. 6. Potentiation can be described in terms of a two-compartment model of processes which show saturation. Both compartments were activated in a tetanus whereas only the compartment with a slow rate of decay was activated in the staircase. It is speculated that the two compartments are related to the excitation—contraction coupling. The process that caused diminution of twitch tension during the staircase may be due to fatigue. It is suggested that the energy consumption in 250 twitches is about 10 times greater than in a tetanus of 250 stimuli which may explain the presence of fatigue after the staircase whereas it was absent after the tetanus. PMID:7264972

Osteoprotegerin and β2-Agonists Mitigate Muscular Dystrophy in Slow- and Fast-Twitch Skeletal Muscles.

PubMed

Dufresne, Sébastien S; Boulanger-Piette, Antoine; Frenette, Jérôme

2017-03-01

Our recent work showed that daily injections of osteoprotegerin (OPG)-immunoglobulin fragment complex (OPG-Fc) completely restore the function of fast-twitch extensor digitorum longus muscles in dystrophic mdx mice, a murine model of Duchenne muscular dystrophy. However, despite marked improvements, OPG-Fc was not as effective in preventing the loss of function of slow-twitch soleus and diaphragm muscles. Because β 2 -agonists enhance the function of slow- and fast-twitch dystrophic muscles and because their use is limited by their adverse effects on bone and cardiac tissues, we hypothesized that OPG-Fc, a bone and skeletal muscle protector, acts synergistically with β 2 -agonists and potentiates their positive effects on skeletal muscles. We observed that the content of β 2 -adrenergic receptors, which are mainly expressed in skeletal muscle, is significantly reduced in dystrophic muscles but is rescued by the injection of OPG-Fc. Most important, OPG-Fc combined with a low dose of formoterol, a member of a new generation of β 2 -agonists, histologically and functionally rescued slow-twitch dystrophic muscles. This combination of therapeutic agents, which have already been tested and approved for human use, may open up new therapeutic avenues for Duchenne muscular dystrophy and possibly other neuromuscular diseases. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Comparative morphometry of fibers and capillaries in soleus following weightlessness (SL-3) and suspension

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Steffen, Joseph M.; Fell, R. D.; Dombrowski, M. J.

1988-01-01

This work is a continuation of efforts to assess responses of rat skeletal muscle to weightlessness (W) and earthside laboratory experiments with unloading of hind limbs. The soleus is a slow-twitch, load-bearing (antigravity) muscle. Both exposure to W and to the hypokinesia/hypodynamia of whole-body suspension (WBS) results in soleus atrophy. Cross-sectional areas of both slow- and fast-twitch fibers decrease during 7 days of W or 7 or 14 days of WBS. Density and area changes tended to reverse to control levels during 7 days of recovery (R) following WBS. Capillary density was increased with 7 days of W or 7 or 14 days of WBS. During 7 days of R the capillary density returned toward control levels. In summary, the reduction in fiber cross-sectional areas and the increase in fiber and capillary densities support the hypothesis that in both W and WBS there is a loss in soleus muscle cell mass and not in fiber numbers.

Swimming, swarming, twitching, and chemotactic responses of Cupriavidus metallidurans CH34 and Pseudomonas putida mt2 in the presence of cadmium.

PubMed

Shamim, Saba; Rehman, Abdul; Qazi, Mahmood Hussain

2014-04-01

To use of microorganisms for bioremediation purposes, the study of their motility behavior toward metals is essential. In the present study, Cupriavidus metallidurans CH34 and Pseudomonas putida mt2 were used as cadmium (Cd)-resistant and -sensitive bacteria, respectively, to evaluate the effects of Cd on their motility behaviors. Potassium morpholinopropane sulfonate (MOPS) buffer was used to observe the motility behavior of both isolates. Movement of mt2 was less in MOPS buffer compared with CH34, likely reflecting the mono-flagellated nature of mt2 and the peritrichous nature of CH34. The swimming, swarming, twitching, and chemotaxis behaviors of mt2 were greater in the presence of glucose than that of Cd. mt2 exhibited negative motility behaviors when exposed to Cd, but the opposite effect was seen in CH34. Cd was found to be a chemorepellent for mt2 but a chemoattractant for CH34, suggesting that CH34 is a potential candidate for metal (Cd) bioremediation.

Intramuscular variations of proteome and muscle fiber type distribution in semimembranosus and semitendinosus muscles associated with pork quality.

PubMed

Kim, Gap-Don; Yang, Han-Sul; Jeong, Jin-Yeon

2018-04-01

Proteome analysis was performed to understand intramuscular variations in muscle fiber distribution in semimembranosus (SM) and semitendinosus (ST) muscles associated with pork quality. Fifteen SM and ST muscles were separated into dark and light portions. The relative area of oxidative fiber was higher (P < .0001) in dark portion than that in light portion, while glycolytic fiber types were distributed primarily (P < .01) in light portions regardless of muscle types. Myosin-1, myosin-4, troponin complex (fast), myosin light chains, and metabolic enzymes responsible for fast-twitch glycolytic types were overexpressed in light portions (P < .05). However, myosin-2, myosin-7, myoglobin, and mitochondrial oxidative metabolic enzymes were closely related to slow-twitch oxidative fibers. These resulted in high pH, redness, and tenderness but low lightness and drip loss of pork quality. In conclusion, differentially expressed muscle proteins are associated with fiber type (oxidative vs. glycolytic) distribution, resulting in intramuscular variations of pork quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fuel trafficking in muscle—potential role of myoglobin/lipid binding

USDA-ARS?s Scientific Manuscript database

Myoglobin is one of the most abundant proteins in skeletal muscle (type 1, "slow twitch" fibers) and cardiomyocytes, and supports oxidative combustion of fuels. Myoglobin-abundant muscle types are adept at fatty acid oxidation, in contrast to "white" (type 2, "fast twitch") fibers that tend to rely ...

Muscle Fiber Types and Training.

ERIC Educational Resources Information Center

Karp, Jason R.

2001-01-01

The specific types of fibers that make up individual muscles greatly influence how people will adapt to their training programs. This paper explains the complexities of skeletal muscles, focusing on types of muscle fibers (slow-twitch and fast-twitch), recruitment of muscle fibers to perform a motor task, and determining fiber type. Implications…

Caffeine-induced increase in voluntary activation and strength of the quadriceps muscle during isometric, concentric and eccentric contractions.

PubMed

Behrens, Martin; Mau-Moeller, Anett; Weippert, Matthias; Fuhrmann, Josefin; Wegner, Katharina; Skripitz, Ralf; Bader, Rainer; Bruhn, Sven

2015-05-13

This study investigated effects of caffeine ingestion (8 mg/kg) on maximum voluntary torque (MVT) and voluntary activation of the quadriceps during isometric, concentric and eccentric contractions. Fourteen subjects ingested caffeine and placebo in a randomized, controlled, counterbalanced, double-blind crossover design. Neuromuscular tests were performed before and 1 h after oral caffeine and placebo intake. MVTs were measured and the interpolated twitch technique was applied during isometric, concentric and eccentric contractions to assess voluntary activation. Furthermore, normalized root mean square of the EMG signal was calculated and evoked spinal reflex responses (H-reflex evoked at rest and during weak isometric voluntary contraction) as well as twitch torques were analyzed. Caffeine increased MVT by 26.4 N m (95%CI: 9.3-43.5 N m, P = 0.004), 22.5 N m (95%CI: 3.1-42.0 N m, P = 0.025) and 22.5 N m (95%CI: 2.2-42.7 N m, P = 0.032) for isometric, concentric and eccentric contractions. Strength enhancements were associated with increases in voluntary activation. Explosive voluntary strength and voluntary activation at the onset of contraction were significantly increased following caffeine ingestion. Changes in spinal reflex responses and at the muscle level were not observed. Data suggest that caffeine ingestion induced an acute increase in voluntary activation that was responsible for the increased strength regardless of the contraction mode.

Possible involvement of AMPK in acute exercise-induced expression of monocarboxylate transporters MCT1 and MCT4 mRNA in fast-twitch skeletal muscle.

PubMed

Takimoto, Masaki; Takeyama, Mirei; Hamada, Taku

2013-11-01

The regulatory mechanisms responsible for acute exercise-induced expression of monocarboxylate transporters MCT1 and MCT4 mRNA in skeletal muscle remain unclear. 5'-adenosine-activated protein kinase (AMPK) is a key signaling molecule that regulates gene expression at the mRNA level. We examined whether AMPK activation is involved in acute exercise-induced expression of MCT1 and MCT4 mRNA in fast-twitch muscle. Male Sprague-Dawley rats were subjected to an acute bout of either 5min high-intensity intermittent swimming (HIS) or 6-h low-intensity prolonged swimming (LIS). The effects of acute exercise on the phosphorylation of AMPK (p-AMPK), calcium/calmodulin pendent kinase II (p-CaMKII), p38 mitogen-activated protein kinase (p-p38MAPK), and MCTs mRNA were analyzed in vivo. To observe the direct effects of AMPK activation on MCTs mRNA, the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), caffeine, and dantrolene were analyzed in vitro using an isolated muscle incubation model. The p-AMPK increased in response to both HIS and LIS, although the p-CaMKII and p-p38MAPK were increased only following HIS. Irrespective of exercise intensity, MCT1 and MCT4 mRNA was also transiently upregulated by both HIS and LIS. Direct exposure of the epitrochlearis muscle to 0.5mmol/L AICAR or 1mmol/L caffeine, which activated p-AMPK increased both MCT1 and MCT4 mRNA levels. When pAMPK was inhibited by dantrolene, neither MCT1 nor MCT4 mRNA was increased. These results suggest that acute exercise-induced increases in MCT1 and MCT4 mRNA expression may be possibly mediated by AMPK activation, at least in part in fast-twitch muscle. © 2013.

β2-Adrenergic Receptor Activation Suppresses the Rat Phenethylamine Hallucinogen-Induced Head Twitch Response: Hallucinogen-Induced Excitatory Post-synaptic Potentials as a Potential Substrate

PubMed Central

Marek, Gerard J.; Ramos, Brian P.

2018-01-01

5-Hydroxytryptamine2A (5-HT2A) receptors are enriched in layers I and Va of the rat prefrontal cortex and neocortex and their activation increases the frequency of glutamatergic excitatory post-synaptic potentials/currents (EPSP/Cs) onto layer V pyramidal cells. A number of other G-protein coupled receptors (GPCRs) are also enriched in cortical layers I and Va and either induce (α1-adrenergic and orexin2) or suppress (metabotropic glutamate2 [mGlu2], adenosine A1, μ-opioid) both 5-HT-induced EPSCs and head twitches or head shakes induced by the phenethylamine hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Another neurotransmitter receptor also localized to apparent thalamocortical afferents to layers I and Va of the rat prefrontal cortex and neocortex is the β2-adrenergic receptor. Therefore, we conducted preliminary electrophysiological experiments with rat brain slices examining the effects of epinephrine on electrically-evoked EPSPs following bath application of DOI (3 μM). Epinephrine (0.3–10 μM) suppressed the late EPSPs produced by electrical stimulation and DOI. The selective β2-adrenergic receptor antagonist ICI-118,551 (300 nM) resulted in a rightward shift of the epinephrine concentration-response relationship. We also tested the selective β2-adrenergic receptor agonist clenbuterol and the antagonist ICI-118,551 on DOI-induced head twitches. Clenbuterol (0.3–3 mg/kg, i.p.) suppressed DOI (1.25 mg/kg, i.p.)-induced head twitches. This clenbuterol effect appeared to be at least partially reversed by the selective β2-adrenergic receptor antagonist ICI-118,553 (0.01–1 mg/kg, i.p.), with significant reversal at doses of 0.1 and 1 mg/kg. Thus, β2-adrenergic receptor activation reverses the effects of phenethylamine hallucinogens in the rat prefrontal cortex. While Gi/Go-coupled GPCRs have previously been shown to suppress both the electrophysiological and behavioral effects of 5-HT2A receptor activation in the mPFC, the present work appears to extend this suppressant action to a Gs-coupled GPCR. Furthermore, the modulation of 5-HT2A receptor activation-induced glutamate release onto mPFC layer V pyramidal neurons apical dendrites by a range GPCRs in rat brain slices appears to results in behaviorally salient effects of relevance when screening for novel CNS therapeutic drugs. PMID:29472863

Performing Play: Cultural Production on Twitch.tv

ERIC Educational Resources Information Center

Pellicone, Anthony James

2017-01-01

Streaming is an emerging practice of videogame culture, where a player broadcasts a live capture of their game-play to an audience. Every day Twitch.tv, the most popular streaming platform, features thousands of streams broadcast to millions of viewers. Streams are detailed multimedia artifacts, and their study allows us to understand how the…

Isometric contractions of motor units in a fast twitch muscle of the cat

PubMed Central

Bagust, J.; Knott, Sarah; Lewis, D. M.; Luck, J. C.; Westerman, R. A.

1973-01-01

1. Isosmetric contractions of cat flexor digitorum longus whole muscles and of functionally isolated motor units have been measured under conditions similar to those used by Buller & Lewis (1965a). 2. Motor unit twitch time to peak was inversely related to axonal conduction velocity. The logarithm of tetanic tension was directly related to conduction velocity. These relationships suggest that each motoneurone has an influence on the muscle fibres which it innervates. 3. The ratio of twitch to tetanic tension was directly related to the time to peak of the motor unit. This fact might be explained by variation between motor units of the duration of `active state'. 4. The muscle length at which tension was maximal varied between motor units and the optima were found over the range of muscle lengths which could occur in the body. Slow motor units had longer optimal lengths. 5. The sample of motor units was considered to be unbiased because the distribution of axon conduction velocities was compatible with reported motor fibre diameter spectra of the muscle nerve. The mean motor unit tetanic tension gave a reasonable estimate of the number of α-motor axons in the muscle nerve. Twitch tensions gave a value that was 40% higher. 6. Motor unit and whole muscle data were in good agreement for length-tetanus tension curves, for times to peak and for twitch-tetanus ratios at long muscle lengths. PMID:4715372

Effects of subacute pyridostigmine administration on mammalian skeletal muscle function. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adler, M.; Deshpande, S.S.; Foster, R.E.

1992-12-31

The subacute effects of pyridostigmine bromide were investigated on the contractile properties of rat extensor digitorum longus (EDL) and diaphragm muscles. The cholinesterase inhibitor was delivered via subcutaneously implanted osmotic minipumps (Alzet) at 9 microns g h-1 (low dose) or 60 micro g h-1 (high dose). Animals receiving high-dose pyridostigmine pumps exhibited marked alterations in muscle properties within the first day of exposure that persisted for the remaining 13 days. With 0.1 Hz stimulation, EDL twitch tensions of treated animals were elevated relative to control. Repetitive stimulation at frequencies > 1 Hz led a use-dependent depression in the amplitude ofmore » successive twitches during the train. Recovery from pyridostigmine was essentially complete by 1 day of withdrawal. Rats implanted with low-dose pyridostigmine pumps showed little or no alteration of in vivo twitch tensions during the entire 14 days of treatment. Diaphragm and EDL muscles excised from pyridostigmine-treated rats and tested in vitro showed no significant alterations in twitch and tetanic tensions and displayed the same sensitivity as muscles of control animals to subsequent pyridostigmine exposures. In the presence of atropine, subacutely administered pyridostigmine protected rats from two LD5O doses of the irreversible cholinesterase inhibitor, soman. In the absence of atropine, the LD50 of soman was not altered by subacute pyridostigmine treatment. Extensor digitorum longus; diaphragm; twitch tension; ACh release; subacute; Alzet pumps; tolerance; anticholinesterase; pyridostigmine; soman.« less

Anatomic and physiological characteristics of the ferret lateral rectus muscle and abducens nucleus.

PubMed

Bishop, Keith N; McClung, J Ross; Goldberg, Stephen J; Shall, Mary S

2007-11-01

The ferret has become a popular model for physiological and neurodevelopmental research in the visual system. We believed it important, therefore, to study extraocular whole muscle as well as single motor unit physiology in the ferret. Using extracellular stimulation, 62 individual motor units in the ferret abducens nucleus were evaluated for their contractile characteristics. Of these motor units, 56 innervated the lateral rectus (LR) muscle alone, while 6 were split between the LR and retractor bulbi (RB) muscle slips. In addition to individual motor units, the whole LR muscle was evaluated for twitch, tetanic peak force, and fatigue. The abducens nucleus motor units showed a twitch contraction time of 15.4 ms, a mean twitch tension of 30.2 mg, and an average fusion frequency of 154 Hz. Single-unit fatigue index averaged 0.634. Whole muscle twitch contraction time was 16.7 ms with a mean twitch tension of 3.32 g. The average fatigue index of whole muscle was 0.408. The abducens nucleus was examined with horseradish peroxidase conjugated with the subunit B of cholera toxin histochemistry and found to contain an average of 183 motoneurons. Samples of LR were found to contain an average of 4,687 fibers, indicating an LR innervation ratio of 25.6:1. Compared with cat and squirrel monkeys, the ferret LR motor units contract more slowly yet more powerfully. The functional visual requirements of the ferret may explain these fundamental differences.

Evidence that the Na+-K+ leak/pump ratio contributes to the difference in endurance between fast- and slow-twitch muscles.

PubMed

Clausen, T; Overgaard, K; Nielsen, O B

2004-02-01

Muscles containing predominantly fast-twitch (type II) fibres [ext. dig. longus (EDL)] show considerably lower contractile endurance than muscles containing mainly slow-twitch (type I) fibres (soleus). To assess whether differences in Na+-K+ fluxes and excitability might contribute to this phenomenon, we compared excitation-induced Na+-K+ leaks, Na+ channels, Na+-K+ pump capacity, force and compound action potentials (M-waves) in rat EDL and soleus muscles. Isolated muscles were mounted for isometric contractions in Krebs-Ringer bicarbonate buffer and exposed to direct or indirect continuous or intermittent electrical stimulation. The time-course of force decline and concomitant changes in Na+-K+ exchange and M-waves were recorded. During continuous stimulation at 60-120 Hz, EDL showed around fivefold faster rate of force decline than soleus. This was associated with a faster loss of excitability as estimated from the area and amplitude of the M-waves. The net uptake of Na+ and the release of K+ per action potential were respectively 6.5- and 6.6-fold larger in EDL than in soleus, which may in part be due to the larger content of Na+ channels in EDL. During intermittent stimulation with 1 s 60 Hz pulse trains, EDL showed eightfold faster rate of force decline than soleus. The considerably lower contractile endurance of fast-twitch compared with slow-twitch muscles reflects differences in the rate of excitation-induced loss of excitability. This is attributed to the much larger excitation-induced Na+ influx and K+ efflux, leading to a faster rise in [K+]o in fast-twitch muscles. This may only be partly compensated by the concomitant activation of the Na+-K+ pumps, in particular in fibres showing large passive Na+-K+ leaks or reduced content of Na+-K+ pumps. Thus, endurance depends on the leak/pump ratio for Na+ and K+.

Train-of-four recovery precedes twitch recovery during reversal with sugammadex in pediatric patients: A retrospective analysis.

PubMed

Vieira Carlos, Ricardo; Luis Abramides Torres, Marcelo; de Boer, Hans Donald

2018-04-01

After reversal of a rocuronium-induced neuromuscular blockade with sugammadex, the recovery of train-of-four ratio to 0.9 is faster than recovery of first twitch of the train-of-four to 90% in adults. These findings after reversal of neuromuscular blockade with sugammadex have not yet been investigated in pediatric patients. The aim of this retrospective analysis was to investigate the relationship of the recovery of first twitch of the train-of-four height and train-of-four ratio after reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric patients. Patients ASA I-III, aged 2-11 years, and who underwent abdominal and/or perineal surgery were included in the analysis. After extracting the necessary data from the hospital database, the patients were divided into 2 groups based on the dose of sugammadex received: group A: 2 mg.kg -1 for reversal of moderate neuromuscular blockade and group B: 4 mg.kg -1 for reversal of deep neuromuscular blockade. The relationship of the recovery of first twitch of the train-of-four height and train-of-four ratio in these 2 groups were analyzed. Data from 43 pediatric patients aged 2-11 years could be analyzed. The first twitch of the train-of-four height at the recovery of train-of-four ratio to 0.9 in group B was statistically significantly lower compared with group A. This height 3 and 5 minutes after the train-of-four ratio reached 0.9 showed no statistically significant differences between groups. The results were in line with the results found in adults and showed that the train-of-four ratio recovered to 0.9 was faster than first twitch of the train-of-four height recovered to the same level. © 2018 John Wiley & Sons Ltd.

Characterization of kinin receptors modulating neurogenic contractions of the mouse isolated vas deferens.

PubMed Central

Maas, J; Rae, G A; Huidobro-Toro, J P; Calixto, J B

1995-01-01

1. This study analyses the receptors mediating the effects of bradykinin (BK) and analogues on neurogenic twitch contractions of the mouse isolated vas deferens evoked, in the presence of captopril (3 microM), by electrical field stimulation with trains of 4 rectangular 0.5 ms pulses of supramaximal strength, delivered at a frequency of 10 Hz every 20 s. 2. BK (0.1-300 nM) induced a graded potentiation of twitches, with an EC50 (geometric mean and 95% confidence limits) of 4.5 nM (1.7-11.6) and an Emax of 315 +/- 19 mg per 10 mg of wet tissue (n = 6). Similar results were obtained in tissues challenged with Lys-BK, [Hyp3]-BK, Met,Lys-BK and the selective B2 receptor agonist [Tyr(Me)8]-BK (0.1-300 nM). 3. The selective B2 receptor antagonists, Hoe 140 (1-10 nM) and NPC 17731 (3-30 nM), caused graded rightward shifts of the curve to BK-induced twitch potentiation, yielding apparent pA2 values of 9.65 +/- 0.09 and 9.08 +/- 0.13, respectively, and Schild plot slopes not different from 1. Both antagonists (100 nM) failed to modify similar twitch potentiations induced by substance P (3 nM) or endothelin-1 (1 nM). Preincubation with the selective B1 receptor antagonist, [Leu8,des-Arg9]-BK (1 microM), increased the potentiating effect of BK on twitches at 30-300 nM. 4. In contrast to BK, the selective B1 receptor agonist, [des-Arg9]-BK (0.3-1000 nM) reduced the amplitude of twitches in a graded fashion, with an IC50 of 13.7 nM (10.4-16.1) and an Imax of 175 +/- 11 mg (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7606350

No regional difference in cisatracurium dose-response and time-course-of-action between patients in China and Bosnia.

PubMed

Dahaba, A A; Suljevic, I; Bornemann, H; Wu, X-M; Metzler, H

2011-03-01

Variability in drug response could result from a variety of genetic and environmental factors that are often hard to define or quantify. A number of studies demonstrated regional geographic variations in potency of neuromuscular blocking agents (NMBAs). The aim of our study was to compare dose-response and time-course-of-action of cisatracurium besylate, an NMBA eliminated via the Hoffman degradation, in two countries with different life habits, diet, and ambient conditions; being Han Chinese in China and Caucasians in Bosnia. Neuromuscular block of cisatracurium 20 µg kg(-1), followed by four incremental 10 µg kg(-1) doses, and the remainder of 100 µg kg(-1) was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, The Netherlands). Dose-response curves were created using log-dose-probit-response transformation. There were no significant differences in cisatracurium mean (95% confidence intervals) ED(50), ED(90), and ED(95) (effective doses for 50%, 90%, and 95% first twitch depression) in Caucasian [39.1 (35.7-42.3), 50.6 (45.5-54.3), and 54.4 (49.8-58.9) µg kg(-1)] compared with Chinese patients [39.2 (35.1-43.1), 52.4 (47.9-56.8), and 56.9 (52.8-61.9) µg kg(-1)], respectively. There were no significant differences in mean (sd) Dur(25) and Dur(0.9) (time until 25% first twitch and 0.9 train-of-four ratio recoveries) in Caucasian [47.1 (6.4) and 77.5 (9.1) min)] compared with Chinese patients [(45.9 (4.7) and 72.3 (9.1) min)], respectively. Cisatracurium dose-response relationship and time-course-of-action were not influenced by geographic location. Thus, cisatracurium would not require dose adjustments between patients living in the two geographic locations.

Cardiac troponin T and fast skeletal muscle denervation in ageing

PubMed Central

Xu, Zherong; Feng, Xin; Dong, Juan; Wang, Zhong‐Min; Lee, Jingyun; Furdui, Cristina; Files, Daniel Clark; Beavers, Kristen M.; Kritchevsky, Stephen; Milligan, Carolanne; Jin, Jian‐Ping; Delbono, Osvaldo

2017-01-01

Abstract Background Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast‐twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow‐twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre‐type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle‐specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown. Methods Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real‐time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ. Results Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region—but mainly in the fast‐twitch, not the slow‐twitch, muscle of old mice. We further found that the protein kinase A (PKA) RIα subunit was largely removed from, while PKA RIIα and RIIβ are enriched at, the NMJ—again, preferentially in fast‐twitch but not slow‐twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RIα and reduced PKA RIIα at the NMJ; (ii) decreased the levels of gene expression of muscle denervation markers; and (iii) enhanced neurotransmission efficiency at NMJ. Conclusions Cardiac troponin T at the NMJ region contributes to NMJ functional decline with ageing mainly in the fast‐twitch skeletal muscle through interfering with PKA signalling. This knowledge could inform useful targets for prevention and therapy of age‐related decline in muscle function. PMID:28419739

Effects provoked by chronic undernourishment on the fibre type composition and contractility of fast muscles in male and female developing rats.

PubMed

Pereyra-Venegas, J; Segura-Alegría, B; Guadarrama-Olmos, J C; Mariscal-Tovar, S; Quiróz-González, S; Jiménez-Estrada, I

2015-10-01

In this study, we compare the effects of pre- and post-natal food deprivation on the relative proportion of fibre types and contractile responses in the extensor digitorum longus (EDL) muscle of female and male rats at different post-natal ages. EDL muscles from undernourished male (UM) rats showed a higher proportion of Type IIB than IIA fibres and larger normalized twitch responses (with respect to muscle weight) than those of controls (CM). In contrast, EDL muscles from control (CF) and undernourished female rats (UF) showed no significant differences in their fibre type composition and normalized twitch forces at most of the ages analysed. Our data are indicative that the EDL muscles from undernourished males are more susceptible to the effects exerted by low food income than the EDL muscles from female rats. It is proposed that changes in the reactive oxygen species (ROS) concentration and hormonal factors, due to undernutrition, are involved in the alterations observed in the fibre type composition and force production of EDL muscles in undernourished male rats and that estrogens may have an antioxidant protective role on the undernourished EDL muscles in female rats. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Quantifying Ca2+ release and inactivation of Ca2+ release in fast- and slow-twitch muscles.

PubMed

Barclay, C J

2012-12-01

The aims of this study were to quantify the Ca(2+) release underlying twitch contractions of mammalian fast- and slow-twitch muscle and to comprehensively describe the transient inactivation of Ca(2+) release following a stimulus. Experiments were performed using bundles of fibres from mouse extensor digitorum longus (EDL) and soleus muscles. Ca(2+) release was quantified from the amount of ATP used to remove Ca(2+) from the myoplasm following stimulation. ATP turnover by crossbridges was blocked pharmacologically (N-benzyl-p-toluenesulphonamide for EDL, blebbistatin for soleus) and muscle heat production was used as an index of Ca(2+) pump ATP turnover. At 20°C, Ca(2+) release in response to a single stimulus was 34 and 84 μmol (kg muscle)(-1) for soleus and EDL, respectively, and increased with temperature (30°C: soleus, 61 μmol kg(-1); EDL, 168 μmol kg(-1)). Delivery of another stimulus within 100 ms of the first produced a smaller Ca(2+) release. The maximum magnitude of the decrease in Ca(2+) release was greater in EDL than soleus. Ca(2+) release recovered with an exponential time course which was faster in EDL (mean time constant at 20°C, 32.1 ms) than soleus (65.6 ms) and faster at 30°C than at 20°C. The amounts of Ca(2+) released and crossbridge cycles performed are consistent with a scheme in which Ca(2+) binding to troponin-C allowed an average of ∼1.7 crossbridge cycles in the two muscles.

Quantifying Ca2+ release and inactivation of Ca2+ release in fast- and slow-twitch muscles

PubMed Central

Barclay, C J

2012-01-01

The aims of this study were to quantify the Ca2+ release underlying twitch contractions of mammalian fast- and slow-twitch muscle and to comprehensively describe the transient inactivation of Ca2+ release following a stimulus. Experiments were performed using bundles of fibres from mouse extensor digitorum longus (EDL) and soleus muscles. Ca2+ release was quantified from the amount of ATP used to remove Ca2+ from the myoplasm following stimulation. ATP turnover by crossbridges was blocked pharmacologically (N-benzyl-p-toluenesulphonamide for EDL, blebbistatin for soleus) and muscle heat production was used as an index of Ca2+ pump ATP turnover. At 20°C, Ca2+ release in response to a single stimulus was 34 and 84 μmol (kg muscle)−1 for soleus and EDL, respectively, and increased with temperature (30°C: soleus, 61 μmol kg−1; EDL, 168 μmol kg−1). Delivery of another stimulus within 100 ms of the first produced a smaller Ca2+ release. The maximum magnitude of the decrease in Ca2+ release was greater in EDL than soleus. Ca2+ release recovered with an exponential time course which was faster in EDL (mean time constant at 20°C, 32.1 ms) than soleus (65.6 ms) and faster at 30°C than at 20°C. The amounts of Ca2+ released and crossbridge cycles performed are consistent with a scheme in which Ca2+ binding to troponin-C allowed an average of ∼1.7 crossbridge cycles in the two muscles. PMID:23027818

Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension

PubMed Central

Manders, Emmy; Bonta, Peter I.; Kloek, Jaap J.; Symersky, Petr; Bogaard, Harm-Jan; Hooijman, Pleuni E.; Jasper, Jeff R.; Malik, Fady I.; Stienen, Ger J. M.; Vonk-Noordegraaf, Anton; de Man, Frances S.

2016-01-01

Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients (N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls (N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast-twitch muscle fibers of CTEPH patients, resulting in a ∼40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 μM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients. PMID:27190061

Incubating Isolated Mouse EDL Muscles with Creatine Improves Force Production and Twitch Kinetics in Fatigue Due to Reduction in Ionic Strength

PubMed Central

Head, Stewart I.; Greenaway, Bronwen; Chan, Stephen

2011-01-01

Background Creatine supplementation can improve performance during high intensity exercise in humans and improve muscle strength in certain myopathies. In this present study, we investigated the direct effects of acute creatine incubation on isolated mouse fast-twitch EDL muscles, and examined how these effects change with fatigue. Methods and Results The extensor digitorum longus muscle from mice aged 12–14 weeks was isolated and stimulated with field electrodes to measure force characteristics in 3 different states: (i) before fatigue; (ii) immediately after a fatigue protocol; and (iii) after recovery. These served as the control measurements for the muscle. The muscle was then incubated in a creatine solution and washed. The measurement of force characteristics in the 3 different states was then repeated. In un-fatigued muscle, creatine incubation increased the maximal tetanic force. In fatigued muscle, creatine treatment increased the force produced at all frequencies of stimulation. Incubation also increased the rate of twitch relaxation and twitch contraction in fatigued muscle. During repetitive fatiguing stimulation, creatine-treated muscles took 55.1±9.5% longer than control muscles to lose half of their original force. Measurement of weight changes showed that creatine incubation increased EDL muscle mass by 7%. Conclusion Acute creatine application improves force production in isolated fast-twitch EDL muscle, and these improvements are particularly apparent when the muscle is fatigued. One likely mechanism for this improvement is an increase in Ca2+ sensitivity of contractile proteins as a result of ionic strength decreases following creatine incubation. PMID:21850234

Caffeine-induced increase in voluntary activation and strength of the quadriceps muscle during isometric, concentric and eccentric contractions

PubMed Central

Behrens, Martin; Mau-Moeller, Anett; Weippert, Matthias; Fuhrmann, Josefin; Wegner, Katharina; Skripitz, Ralf; Bader, Rainer; Bruhn, Sven

2015-01-01

This study investigated effects of caffeine ingestion (8 mg/kg) on maximum voluntary torque (MVT) and voluntary activation of the quadriceps during isometric, concentric and eccentric contractions. Fourteen subjects ingested caffeine and placebo in a randomized, controlled, counterbalanced, double-blind crossover design. Neuromuscular tests were performed before and 1 h after oral caffeine and placebo intake. MVTs were measured and the interpolated twitch technique was applied during isometric, concentric and eccentric contractions to assess voluntary activation. Furthermore, normalized root mean square of the EMG signal was calculated and evoked spinal reflex responses (H-reflex evoked at rest and during weak isometric voluntary contraction) as well as twitch torques were analyzed. Caffeine increased MVT by 26.4 N m (95%CI: 9.3-43.5 N m, P = 0.004), 22.5 N m (95%CI: 3.1-42.0 N m, P = 0.025) and 22.5 N m (95%CI: 2.2-42.7 N m, P = 0.032) for isometric, concentric and eccentric contractions. Strength enhancements were associated with increases in voluntary activation. Explosive voluntary strength and voluntary activation at the onset of contraction were significantly increased following caffeine ingestion. Changes in spinal reflex responses and at the muscle level were not observed. Data suggest that caffeine ingestion induced an acute increase in voluntary activation that was responsible for the increased strength regardless of the contraction mode. PMID:25969895

The assessment of neuromuscular fatigue during 120 min of simulated soccer exercise.

PubMed

Goodall, Stuart; Thomas, Kevin; Harper, Liam David; Hunter, Robert; Parker, Paul; Stevenson, Emma; West, Daniel; Russell, Mark; Howatson, Glyn

2017-04-01

This investigation examined the development of neuromuscular fatigue during a simulated soccer match incorporating a period of extra time (ET) and the reliability of these responses on repeated test occasions. Ten male amateur football players completed a 120 min soccer match simulation (SMS). Before, at half time (HT), full time (FT), and following a period of ET, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation (TMS) were obtained from the knee-extensors to measure neuromuscular fatigue. Within 7 days of the first SMS, a second 120 min SMS was performed by eight of the original ten participants to assess the reliability of the fatigue response. At HT, FT, and ET, reductions in maximal voluntary force (MVC; -11, -20 and -27%, respectively, P ≤ 0.01), potentiated twitch force (-15, -23 and -23%, respectively, P < 0.05), voluntary activation (FT, -15 and ET, -18%, P ≤ 0.01), and voluntary activation measured with TMS (-11, -15 and -17%, respectively, P ≤ 0.01) were evident. The fatigue response was robust across both trials; the change in MVC at each time point demonstrated a good level of reliability (CV range 6-11%; ICC 2,1 0.83-0.94), whilst the responses identified with motor nerve stimulation showed a moderate level of reliability (CV range 5-18%; ICC 2,1 0.63-0.89) and the data obtained with motor cortex stimulation showed an excellent level of reliability (CV range 3-6%; ICC 2,1 0.90-0.98). Simulated soccer exercise induces a significant level of fatigue, which is consistent on repeat tests, and involves both central and peripheral mechanisms.

Intercostal muscle twitching: An unusual manifestation of extracardiac stimulation related to right ventricular outflow tract pacing

PubMed Central

Erdogan, Okan

2007-01-01

The present case report describes a patient who underwent successful dual-chamber pacemaker implantation with active ventricular lead fixation at a high septal region in the right ventricular outflow tract. Unexpectedly, stimulation at a high output in the right ventricular outflow tract caused an unusual extracardiac stimulation, specifically, intercostal muscle twitching. PMID:17703261

An Active Learning Mammalian Skeletal Muscle Lab Demonstrating Contractile and Kinetic Properties of Fast- and Slow-Twitch Muscle

ERIC Educational Resources Information Center

Head, S. I.; Arber, M. B.

2013-01-01

The fact that humans possess fast and slow-twitch muscle in the ratio of approximately 50% has profound implications for designing exercise training strategies for power and endurance activities. With the growth of exercise and sport science courses, we have seen the need to develop an undergraduate student laboratory that demonstrates the basic…

Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension induced disuse

NASA Technical Reports Server (NTRS)

Gupta, R. C.; Misulis, K. E.; Dettbarn, W. D.

1984-01-01

Muscle disused induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) muscle were studied in rats. Rats with hindlimbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase (ChAT) in sciatic nerve (38%), in SOL (108%) and in EDL (67%). Acetylcholinesterase (AChE) activity in SOL increased by 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant changes in activity and molecular forms pattern of AChE were seen in EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of 3H-acetylcholine was increased in both muscles. When measured after 3 weeks of hindlimb suspension the normal distribution of type 1 fibers in SOL was reduced and a corresponding increase in type IIa and IIb fibers is seen. In EDL no significant change in fiber proportion is observed. Muscle activity, such as loadbearing, appears to have a greater controlling influence on the characteristics of the slow twitch SOL muscle than upon the fast twitch EDL muscle.

Emergence of complex behavior in pili-based motility in early stages of P. aeruginosa surface adaptation

NASA Astrophysics Data System (ADS)

Brill-Karniely, Yifat; Jin, Fan; Wong, Gerard C. L.; Frenkel, Daan; Dobnikar, Jure

2017-04-01

Pseudomonas aeruginosa move across surfaces by using multiple Type IV Pili (TFP), motorized appendages capable of force generation via linear extension/retraction cycles, to generate surface motions collectively known as twitching motility. Pseudomonas cells arrive at a surface with low levels of piliation and TFP activity, which both progressively increase as the cells sense the presence of a surface. At present, it is not clear how twitching motility emerges from these initial minimal conditions. Here, we build a simple model for TFP-driven surface motility without complications from viscous and solid friction on surfaces. We discover the unanticipated structural requirement that TFP motors need to have a minimal amount of effective angular rigidity in order for cells to perform the various classes of experimentally-observed motions. Moreover, a surprisingly small number of TFP are needed to recapitulate movement signatures associated with twitching: Two TFP can already produce movements reminiscent of recently observed slingshot type motion. Interestingly, jerky slingshot motions characteristic of twitching motility comprise the transition region between different types of observed crawling behavior in the dynamical phase diagram, such as self-trapped localized motion, 2-D diffusive exploration, and super-diffusive persistent motion.

Postdoctoral Fellowship for Dr. Lindholm, Underwater Physiology and Medicine

DTIC Science & Technology

2008-05-01

St Croix 2000) and/or an increased reliance on fast twitch muscle fibers that are dependent on glycogen and produce La. The changes in muscle and...resistance protocol ( isometric ) increases respiratory muscle strength but not endurance, while, a protocol designed to increase respiratory muscle endurance... muscles (RMT). RMT minimized respiratory muscle fatigue and normalized the ventilatory response to increasing C02 (C02 sensitivity) and blood C02 in C02

Catalase-positive microperoxisomes in rat soleus and extensor digitorum longus muscle fiber types

NASA Technical Reports Server (NTRS)

Riley, Danny A.; Bain, James L. W.; Ellis, Stanley

1988-01-01

The size, distribution, and content of catalase-reactive microperoxisomes were investigated cytochemically in three types of muscle fibers from the soleus and the extensor digitorum longus (EDL) of male rats. Muscle fibers were classified on the basis of the mitochondrial content and distribution, the Z-band widths, and the size and shape of myofibrils as the slow-twitch oxidative (SO), the fast-twitch oxidative glycolytic (FOG), and the fast-twitch glycolytic (FG) fibers. It was found that both the EDL and soleus SO fibers possessed the largest microperoxisomes. A comparison of microperoxisome number per muscle fiber area or the microperoxisome area per fiber area revealed following ranking, starting from the largest number and the area-ratio values: soleus SO, EDL SO, EDL FOG, and EDL FG.

Estimating Isometric Tension of Finger Muscle Using Needle EMG Signals and the Twitch Contraction Model

NASA Astrophysics Data System (ADS)

Tachibana, Hideyuki; Suzuki, Takafumi; Mabuchi, Kunihiko

We address an estimation method of isometric muscle tension of fingers, as fundamental research for a neural signal-based prosthesis of fingers. We utilize needle electromyogram (EMG) signals, which have approximately equivalent information to peripheral neural signals. The estimating algorithm comprised two convolution operations. The first convolution is between normal distribution and a spike array, which is detected by needle EMG signals. The convolution estimates the probability density of spike-invoking time in the muscle. In this convolution, we hypothesize that each motor unit in a muscle activates spikes independently based on a same probability density function. The second convolution is between the result of the previous convolution and isometric twitch, viz., the impulse response of the motor unit. The result of the calculation is the sum of all estimated tensions of whole muscle fibers, i.e., muscle tension. We confirmed that there is good correlation between the estimated tension of the muscle and the actual tension, with >0.9 correlation coefficients at 59%, and >0.8 at 89% of all trials.

Development of standard operating procedures to obtain longitudinal vaginal specimens from nulliparous rabbits as part of HIV vaccine mucosal immunogenicity studies.

PubMed

Gómez Román, Victor Raúl; Vinner, Lasse; Grevstad, Berit; Hansen, Jesper Juhl; Wegmann, Frank; Spetz, Anna-Lena; Fomsgaard, Anders

2010-12-15

The New Zealand white rabbit model (Oryctolagus cuniculus) is widely used to test whether HIV vaccine candidates elicit systemic antibody responses; however, its use in mucosal immunology has not been fully exploited due to the difficulty in collecting mucosal specimens longitudinally and reproducibly. Here we describe feasible and non-feasible methods to collect vaginal and nasal specimens from nulliparous rabbits. Non-feasible methods were those resulting in poor reproducibility and considerable animal twitching during sampling, whereas feasible methods resulted in no animal twitching and potential for sampling reproducibility. Standard operating procedures (SOPs) were implemented to collect vaginal swabs yielding total IgA titres ranging from 12,500 to 312,500. Intranasal immunisation with a naked DNA vaccine encoding HIV gp140 elicited HIV envelope-specific IgA detectable in nasal but not in vaginal secretions. Our methods provide an alternative to reliably assess pre- and post-vaccination mucosal antibody titres longitudinally in rabbits as part of mucosal HIV vaccine immunogenicity studies. Copyright © 2010 Elsevier B.V. All rights reserved.

Skeletal muscle fiber type composition and performance during repeated bouts of maximal, concentric contractions

NASA Technical Reports Server (NTRS)

Colliander, E. B.; Dudley, G. A.; Tesch, P. A.

1988-01-01

Force output and fatigue and recovery patterns were studied during intermittent short-term exercise. 27 men performed three bouts of 30 maximal unilateral knee extensions on 2 different occasions. Blood flow was maintained or occluded during recovery periods (60 s). Blood flow was restricted by inflating a pneumatic cuff placed around the proximal thigh. Muscle biopsies from vastus lateralis were analyzed for identification of fast twitch (FT) and slow twitch (ST) fibers and relative FT area. Peak torque decreased during each bout of exercise and more when blood flow was restricted during recovery. Initial peak torque (IPT) and average peak torque (APT) decreased over the three exercise bouts. This response was 3 fold greater without than with blood flow during recovery. IPT and APT decreased more in individuals with mainly FT fibers than in those with mainly ST fibers. It is suggested that performance during repeated bouts of maximal concentric contractions differs between individuals with different fiber type composition. Specifically, in high intensity, intermittent exercise with emphasis on anaerobic energy release a high FT composition may not necessarily be advantageous for performance.

Octopamine mediated relaxation of maintained and catch tension in locust skeletal muscle.

PubMed

Evans, P D; Siegler, M V

1982-03-01

1. The modulatory actions of an identified octopaminergic neurone (DUMETi) that projects to the extensor-tibiae muscle of the locust hind leg depend upon the frequency of stimulation of the slow motoneurone (SETi) to this muscle. 2. At low frequencies of SETi stimulation (1Hz and below) the predominant modulatory effects are increases in the amplitude and relaxation rate of twitch tension. At higher frequencies, where twitches summate but tetanus is incomplete (up to 20 Hz), the reduction of maintained tension becomes considerably more important. 3. Both octopamine application and DUMETi stimulation reduce the amount of catch tension displayed by the extensor muscle when SETi is fired in a variety of different stimulus patterns. The extensor-tibiae muscle is itself 'pattern sensitive' since is shows a 'positive spacing effect' when SETi is stimulated at an average frequency of 1 Hz. 4. It is suggested that a primary function of DUMETi is to change the response of the muscle from one that favours maintenance of posture to one that favours rapid changes in joint position or force, such as might occur during locomotion.

Octopamine mediated relaxation of maintained and catch tension in locust skeletal muscle.

PubMed Central

Evans, P D; Siegler, M V

1982-01-01

1. The modulatory actions of an identified octopaminergic neurone (DUMETi) that projects to the extensor-tibiae muscle of the locust hind leg depend upon the frequency of stimulation of the slow motoneurone (SETi) to this muscle. 2. At low frequencies of SETi stimulation (1Hz and below) the predominant modulatory effects are increases in the amplitude and relaxation rate of twitch tension. At higher frequencies, where twitches summate but tetanus is incomplete (up to 20 Hz), the reduction of maintained tension becomes considerably more important. 3. Both octopamine application and DUMETi stimulation reduce the amount of catch tension displayed by the extensor muscle when SETi is fired in a variety of different stimulus patterns. The extensor-tibiae muscle is itself 'pattern sensitive' since is shows a 'positive spacing effect' when SETi is stimulated at an average frequency of 1 Hz. 4. It is suggested that a primary function of DUMETi is to change the response of the muscle from one that favours maintenance of posture to one that favours rapid changes in joint position or force, such as might occur during locomotion. PMID:6808122

Neurofibromatosis 1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like symptoms.

PubMed

Waheed, Waqar; Nathan, Muriel H; Allen, Gilman B; Borden, Neil M; Babi, M Ali; Tandan, Rup

2015-11-03

A 37-year-old man with a known history of neurofibromatosis 1 (NF1) presented within 2 days of diarrhoeal illness followed by encephalopathy, facial twitching, hypoglycaemia, hypotension, tachycardia and low-grade fever. Examination showed multiple café-au-lait spots and neurofibromas over the trunk, arms and legs and receptive aphasia with right homonymous hemianopia, which resolved. Workup for cardiac, inflammatory and infectious aetiologies was unrevealing. A brain MRI showed gyral swelling with increased T2 fluid-attenuated inversion recovery signal and diffusion restriction in the left cerebral cortex. Neuroendocrine findings suggested panhypopituitarism with centrally derived adrenal insufficiency. Supportive treatment, hormone supplementation, antibiotics, antivirals and levetiracetam yielded clinical improvement. A follow-up brain MRI showed focal left parieto-occipital atrophy with findings of cortical laminar necrosis. In conclusion, we describe a case of NF1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like findings, hitherto unreported manifestations of NF1. Prompt recognition and treatment of these associated conditions can prevent devastating complications. 2015 BMJ Publishing Group Ltd.

Neurofibromatosis 1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like symptoms

PubMed Central

Waheed, Waqar; Nathan, Muriel H; Allen, Gilman B; Borden, Neil M; Babi, M Ali; Tandan, Rup

2015-01-01

A 37-year-old man with a known history of neurofibromatosis 1 (NF1) presented within 2 days of diarrhoeal illness followed by encephalopathy, facial twitching, hypoglycaemia, hypotension, tachycardia and low-grade fever. Examination showed multiple café-au-lait spots and neurofibromas over the trunk, arms and legs and receptive aphasia with right homonymous hemianopia, which resolved. Workup for cardiac, inflammatory and infectious aetiologies was unrevealing. A brain MRI showed gyral swelling with increased T2 fluid-attenuated inversion recovery signal and diffusion restriction in the left cerebral cortex. Neuroendocrine findings suggested panhypopituitarism with centrally derived adrenal insufficiency. Supportive treatment, hormone supplementation, antibiotics, antivirals and levetiracetam yielded clinical improvement. A follow-up brain MRI showed focal left parieto-occipital atrophy with findings of cortical laminar necrosis. In conclusion, we describe a case of NF1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like findings, hitherto unreported manifestations of NF1. Prompt recognition and treatment of these associated conditions can prevent devastating complications. PMID:26531733

Cardiac troponin T and fast skeletal muscle denervation in ageing.

PubMed

Xu, Zherong; Feng, Xin; Dong, Juan; Wang, Zhong-Min; Lee, Jingyun; Furdui, Cristina; Files, Daniel Clark; Beavers, Kristen M; Kritchevsky, Stephen; Milligan, Carolanne; Jin, Jian-Ping; Delbono, Osvaldo; Zhang, Tan

2017-10-01

Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown. Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real-time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ. Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA) RIα subunit was largely removed from, while PKA RIIα and RIIβ are enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RIα and reduced PKA RIIα at the NMJ; (ii) decreased the levels of gene expression of muscle denervation markers; and (iii) enhanced neurotransmission efficiency at NMJ. Cardiac troponin T at the NMJ region contributes to NMJ functional decline with ageing mainly in the fast-twitch skeletal muscle through interfering with PKA signalling. This knowledge could inform useful targets for prevention and therapy of age-related decline in muscle function. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure

NASA Technical Reports Server (NTRS)

Massie, B. M.; Simonini, A.; Sahgal, P.; Wells, L.; Dudley, G. A.

1996-01-01

OBJECTIVES. The present study was undertaken to further characterize changes in skeletal muscle morphology and histochemistry in congestive heart failure and to determine the relation of these changes to abnormalities of systemic and local muscle exercise capacity. BACKGROUND. Abnormalities of skeletal muscle appear to play a role in the limitation of exercise capacity in congestive heart failure, but information on the changes in muscle morphology and biochemistry and their relation to alterations in muscle function is limited. METHODS. Eighteen men with predominantly mild to moderate congestive heart failure (mean +/- SEM New York Heart Association functional class 2.6 +/- 0.2, ejection fraction 24 +/- 2%) and eight age- and gender-matched sedentary control subjects underwent measurements of peak systemic oxygen consumption (VO2) during cycle ergometry, resistance to fatigue of the quadriceps femoris muscle group and biopsy of the vastus lateralis muscle. RESULTS. Peak VO2 and resistance to fatigue were lower in the patients with heart failure than in control subjects (15.7 +/- 1.2 vs. 25.1 +/- 1.5 ml/min-kg and 63 +/- 2% vs. 85 +/- 3%, respectively, both p < 0.001). Patients had a lower proportion of slow twitch, type I fibers than did control subjects (36 +/- 3% vs. 46 +/- 5%, p = 0.048) and a higher proportion of fast twitch, type IIab fibers (18 +/- 3% vs. 7 +/- 2%, p = 0.004). Fiber cross-sectional area was smaller, and single-fiber succinate dehydrogenase activity, a mitochondrial oxidative marker, was lower in patients (both p < or = 0.034). Likewise, the ratio of average fast twitch to slow twitch fiber cross-sectional area was lower in patients (0.780 +/- 0.06 vs. 1.05 +/- 0.08, p = 0.019). Peak VO2 was strongly related to integrated succinate dehydrogenase activity in patients (r = 0.896, p = 0.001). Peak VO2, resistance to fatigue and strength also correlated significantly with several measures of fiber size, especially of fast twitch fibers, in patients. None of the skeletal muscle characteristics examined correlated with exercise capacity in control subjects. CONCLUSIONS. These results indicate that congestive heart failure is associated with changes in the characteristics of skeletal muscle and local as well as systemic exercise performance. There are fewer slow twitch fibers, smaller fast twitch fibers and lower succinate dehydrogenase activity. The latter finding suggests that mitochondrial content of muscle is reduced in heart failure and that impaired aerobic-oxidative capacity may play a role in the limitation of systemic exercise capacity.

Histamine H2-receptors on guinea-pig ileum myenteric plexus neurons mediate the release of contractile agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barker, L.A.; Ebersole, B.J.

1982-04-01

Dimaprit, a highly selective H2-agonist, caused a multiphasic contraction of guinea-pig ileal segments and ileal myenteric plexus-longitudinal muscle preparations. The initial phase was characterized by a twitch which reached a maximum in 15 to 30 sec and was followed by a partial relaxation. The later phase was variable and consisted of a series of twitch responses or of a slowly developing contracture which sometimes was accompanied by oscillatory changes in tension. dose-response curves were generated for the initial response; for isolated ileal segments the EC50 was 5.1 +/- 1.8 micrometers (mean +/- S.D., N . 7) and the Hill coefficientmore » was 1.1 +/- 0.2 and for longitudinal muscle strips the EC50 was 5.8 +/- 1.2 micrometer and the Hill coefficient was 1.2 +/- 0.1 (N . 7). Both the initial and secondary components of the contractile responses to dimaprit were prevented by 0.2 micron tetrodotoxin or 10 microns mefenamic acid and by the production of tachphylaxis to either substance P or serotonin. Scopolamine, 0.001 to 0.1 micron, insurmountably antagonized only the initial component of the response. Mepyramine (1.0 micrometer), hexamethonium (100 microns), bromolysergic acid (0.25 microns) and p-(imidazol-1-yl)phenyl (10 microns) were without effect on the response to dimaprit. The histamine H2-receptor antagonist, tiotidine, produced parallel dextral shifts in the dose-response curve for dimaprit. The apparent pA2 value for tiotidine was 7.65. The results suggest that dimaprit acts on H2-receptors located on myenteric plexus neurons to cause the release of contractile substances. The mediators of the contractile response are tentatively identified as acetylcholine, substance P, serotonin and a product(s) of the arachadonic acid cascade.« less

Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness.

PubMed

Stuart, Charles A; Lee, Michelle L; South, Mark A; Howell, Mary E A; Cartwright, Brian M; Ramsey, Michael W; Stone, Michael H

2017-03-01

Stuart, CA, Lee, ML, South, MA, Howell, MEA, Cartwright, BM, Ramsey, MW, and Stone, MH. Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798-808, 2017-Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow-twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and glucose transporter type 4 (GLUT4) expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole-body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pretraining baseline.

Muscle Contractile Properties in Severely Burned Rats

DTIC Science & Technology

2010-01-01

slow - twitch muscles such as sloeus (data not shown). In rats, the TA contains predominantly fast ...Hasselgren PO. The molecular regulation of protein breakdown following burn injury is different in fast - and slow - twitch skeletal muscle . Int J Mol Med 1998;1...burn model, it was reported that only fast muscle fibers are affected and slow muscle fibers were mostly preserved [30–32]. We found similar results

Interaction of Mechanical Load with Growth Hormone (GH) and Insulin-Like Growth Factor I (IGF-I) on Slow-Twitch Skeletal Muscle and Bone

NASA Technical Reports Server (NTRS)

Linderman, Jon K.; Gosselink, Kristin L.; Wang, Tommy J.; Mukku, Venkat R.; Grindeland, Richard E.

1994-01-01

Exogenous humoral growth factors, combined with increased mechanical loading, reportedly induce hypertrophy of fast-, but not slow-twitch skeletal muscles, and have little effect in attenuating atrophy of slow-twitch muscle associated with exposure to microgravity in animals with intact neuroendocrine systems. These observations suggest that anabolic adjuvants and muscle tension do not interact to stimulate growth or maintenance of slow-twitch skeletal muscle. The purpose of the present study was to determine whether a chronic increase in mechanical loading (synergistic ablation) or hindlimb unweighting (hindlimb suspension) interact with exogenous GH and IGF-I (Genentech, So San Francisco, CA) in the slow-twitch soleus muscles of female rats (approx. 250 g). Bilateral ablation of the plantaris and gastrocnemius muscles induced 38% and 40% increases in the absolute (mg/pair) and relative (mg/100 g body weight) weights of the soleus, respectively (p less than or = 0.05), in ambulatory rats. GH and IGF-I interacted with chronic loading to increase absolute soleus mass an additional 20% (p less than or = 0.05), and mixed and myofibrillar protein contents an additional 12% and 7%, respectively (NS). In contrast, hindlimb suspension (HLS) resulted in 20% and 18% decreases in the absolute and relative weights of the soleus, respectively (p less than or = 0.05); GH and IGF-I did not spare loss of soleus mass or protein content in HLS rats. HLS decreased tibial plate thickness approx. 11% (p less than or = 0.05), but not weights of the tibia or femus. GH and IGF-I increased tibial plate thickness approx. 30% (p less than or = 0.05), in ambulatory and HLS rats, and increased femur and tibial weights 12% (p less than or = 0.05) and 8% (NS), respectively, in ambulatory rats, but had no effect in HLS rats. Results of the present investigation suggest that GH and IGF-I can stimulate hypertrophy of slow-twitch skeletal muscle when chronically overloaded, but can also stimulate growth of hindlimb bones in the absence of mechanical load.

Differential effects of peroxynitrite on contractile protein properties in fast- and slow-twitch skeletal muscle fibers of rat.

PubMed

Dutka, T L; Mollica, J P; Lamb, G D

2011-03-01

Oxidative modification of contractile proteins is thought to be a key factor in muscle weakness observed in many pathophysiological conditions. In particular, peroxynitrite (ONOO(-)), a potent short-lived oxidant, is a likely candidate responsible for this contractile dysfunction. In this study ONOO(-) or 3-morpholinosydnonimine (Sin-1, a ONOO(-) donor) was applied to rat skinned muscle fibers to characterize the effects on contractile properties. Both ONOO(-) and Sin-1 exposure markedly reduced maximum force in slow-twitch fibers but had much less effect in fast-twitch fibers. The rate of isometric force development was also reduced without change in the number of active cross bridges. Sin-1 exposure caused a disproportionately large decrease in Ca(2+) sensitivity, evidently due to coproduction of superoxide, as it was prevented by Tempol, a superoxide dismutase mimetic. The decline in maximum force with Sin-1 and ONOO(-) treatments could be partially reversed by DTT, provided it was applied before the fiber was activated. Reversal by DTT indicates that the decrease in maximum force was due at least in part to oxidation of cysteine residues. Ascorbate caused similar reversal, further suggesting that the cysteine residues had undergone S-nitrosylation. The reduction in Ca(2+) sensitivity, however, was not reversed by either DTT or ascorbate. Western blot analysis showed cross-linking of myosin heavy chain (MHC) I, appearing as larger protein complexes after ONOO(-) exposure. The findings suggest that ONOO(-) initially decreases maximum force primarily by oxidation of cysteine residues on the myosin heads, and that the accompanying decrease in Ca(2+) sensitivity is likely due to other, less reversible actions of hydroxyl or related radicals.

Hydrogen peroxide modulates Ca2+-activation of single permeabilized fibres from fast- and slow-twitch skeletal muscles of rats.

PubMed

Plant, D R; Lynch, G S; Williams, D A

2000-01-01

We examined the effects of redox modulation on single membrane-permeabilized fibre segments from the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of adult rats to determine whether the contractile apparatus was the redox target responsible for the increased contractility of muscles exposed to low concentrations of H2O2. The effects of H2O2 on maximum Ca2+-activated force were dose-dependent with 30 min exposure to 5 mM H2O2 causing a progressive decrease by 22+/-3 and 13+/-2% in soleus and EDL permeabilized muscle fibres, respectively. Lower concentrations of exogenous H2O2 (100 microM and 1 mM) had no effect on maximum Ca2+-activated force. Subsequent exposure to the reductant dithiothreitol (DTT, 10 mM, 10 min) fully reversed the H2O2-induced depression of force in EDL, but not in soleus muscle fibres. Incubation with DTT alone for 10 min did not alter Ca2+-activated force in either soleus or EDL muscle fibres. The sensitivity of the contractile filaments to Ca2+ (pCa50) was not altered by exposure to any concentration of exogenous H2O2. However, all concentrations of H2O2 diminished the Hill coefficient in permeabilized fibres from the EDL muscle, indicating that the cooperativity of Ca2+ binding to troponin is altered. H2O2 (5 mM) did not affect rigor force, which indicates that the number of crossbridges participating in contraction was not reduced. In conclusion, H2O2 may reduce the maximum Ca2+ activated force production in skinned muscle fibres by decreasing the force per crossbridge.

Cycle Training Increased GLUT4 and Activation of mTOR in Fast Twitch Muscle Fibers

PubMed Central

Stuart, Charles A.; Howell, Mary E.A.; Baker, Jonathan D.; Dykes, Rhesa J.; Duffourc, Michelle M.; Ramsey, Michael W.; Stone, Michael H.

2009-01-01

Purpose To determine if cycle training of sedentary subjects would increase the expression of the principle muscle glucose transporters, six volunteers completed six weeks of progressively increasing intensity stationary cycle cycling. Methods In vastus lateralis muscle biopsies, changes in expression of GLUT1, GLUT4, GLUT5, and GLUT12 were compared using quantitative immunoblots with specific protein standards. Regulatory pathway components were evaluated by immunoblots of muscle homogenates and immunohistochemistry of microscopic sections. Results GLUT1 was unchanged, GLUT4 increased 66%, GLUT12 increased 104%, and GLUT5 decreased 72%. A mitochondrial marker (cytochrome c) and regulators of mitochondrial biogenesis (PGC-1α and phospho-AMPK) were unchanged, but the muscle hypertrophy pathway component, phospho-mTOR increased 83% after the exercise program. In baseline biopsies, GLUT4 by immunohistochemical techniques was 37% greater in Type I (slow twitch, red) muscle fibers, but the exercise training increased GLUT4 expression in Type II (fast twitch, white) fibers by 50%, achieving parity with the Type I fibers. Baseline phospho-mTOR expression was 50% higher in Type II fibers and increased more in Type II fibers (62%) with training, but also increased in Type I fibers (34%). Conclusion Progressive intensity stationary cycle training of previously sedentary subjects increased muscle insulin-responsive glucose transporters (GLUT4 and GLUT12) and decreased the fructose transporter (GLUT5). The increase in GLUT4 occurred primarily in Type II muscle fibers and this coincided with activation of the mTOR muscle hypertrophy pathway. There was little impact on Type I fiber GLUT4 expression and no evidence of change in mitochondrial biogenesis. PMID:20010125

Innervation of the cricothyroid muscle by extralaryngeal branches of the recurrent laryngeal nerve.

PubMed

Miyauchi, Akira; Masuoka, Hiroo; Nakayama, Ayako; Higashiyama, Takuya

2016-05-01

A major concern in thyroid surgery is possible changes in the patient's voice due to dysfunction of the laryngeal muscles. The classical understanding of the anatomy is that the cricothyroid muscle (CTM) is innervated solely by the external branch of the superior laryngeal nerve (EBSLN), and the endolaryngeal muscles are covered only by the recurrent laryngeal nerve (RLN). Meticulous anatomical studies found communication between these nerves. Recent neurophysiological studies revealed cross-innervations among these nerve-muscle sets. Here, we report innervation of the CTM by extralaryngeal branches of the RLN. Clinical observation during thyroid surgery at a hospital center for thyroid diseases. During thyroid cancer surgeries, we encountered four adult Japanese patients who had an extralaryngeal branch of the RLN, the electrical stimulation of which showed contraction of the CTM. The EBSLN and RLN were electrically stimulated. Responses were evaluated by visual observation of contraction of the CTM and palpable laryngeal twitch of the endolaryngeal muscles. Electromyographic studies were also performed in two patients. Five of the seven RLNs examined showed contraction of the CTM on stimulation. Four of these five RLNs had an extralaryngeal branch that showed contraction of the CTM on stimulation. Stimulation of the RLN proximal to the branch yielded contraction of the CTM and laryngeal twitch, whereas stimulation of the RLN distal to the branch yielded only laryngeal twitch. Extralaryngeal branches of the RLN innervated the CTM in four patients. This phenomenon might influence voice changes following thyroid surgery. 4. Laryngoscope, 126:1157-1162, 2016. Laryngoscope published by Wiley on behalf of the American Laryngological, Rhinological and Otological Society, Inc, “The Triological Society” and American Laryngological Association (the “Owner”).

Accumulation of severely atrophic myofibers marks the acceleration of sarcopenia in slow and fast twitch muscles.

PubMed

Rowan, Sharon L; Purves-Smith, Fennigje M; Solbak, Nathan M; Hepple, Russell T

2011-08-01

The age-related decline in muscle mass, known as sarcopenia, exhibits a marked acceleration in advanced age. Although many studies have remarked upon the accumulation of very small myofibers, particularly at advanced stages of sarcopenia, the significance of this phenomenon in the acceleration of sarcopenia has never been examined. Furthermore, although mitochondrial dysfunction characterized by a lack of cytochrome oxidase (COX) activity has been implicated in myofiber atrophy in sarcopenia, the contribution of this phenotype to the accumulation of severely atrophied fibers in aged muscles has never been determined. To this end, we examined the fiber size distribution in the slow twitch soleus (Sol) and fast twitch gastrocnemius (Gas) muscles between young adulthood (YA) and senescence (SEN). We also quantified the abundance of COX deficient myocytes and their size attributes to gain insight into the contribution of this phenotype to myofiber atrophy with aging. Our data showed that the progression of muscle atrophy, particularly its striking acceleration between late middle age and SEN, was paralleled by an accumulation of severely atrophic myofibers (≤ 1000 μm(2) in size) in both Sol and Gas. On the other hand, we observed no COX deficient myofibers in Sol, despite nearly 20% of the myofibers being severely atrophic. Similarly, only 0.17 ± 0.06% of all fibers in Gas were COX deficient, and their size was generally larger (2375 ± 319 μm(2)) than the severely atrophied myofibers noted above. Collectively, our results suggest that similar processes likely contribute to the acceleration of sarcopenia in both slow twitch and fast twitch muscles, and that COX deficiency is not a major contributor to this phenomenon. Copyright © 2011 Elsevier Inc. All rights reserved.

Single muscle fiber adaptations with marathon training.

PubMed

Trappe, Scott; Harber, Matthew; Creer, Andrew; Gallagher, Philip; Slivka, Dustin; Minchev, Kiril; Whitsett, David

2006-09-01

The purpose of this investigation was to characterize the effects of marathon training on single muscle fiber contractile function in a group of recreational runners. Muscle biopsies were obtained from the gastrocnemius muscle of seven individuals (22 +/- 1 yr, 177 +/- 3 cm, and 68 +/- 2 kg) before, after 13 wk of run training, and after 3 wk of taper. Slow-twitch myosin heavy chain [(MHC) I] and fast-twitch (MHC IIa) muscle fibers were analyzed for size, strength (P(o)), speed (V(o)), and power. The run training program led to the successful completion of a marathon (range 3 h 56 min to 5 h 35 min). Oxygen uptake during submaximal running and citrate synthase activity were improved (P < 0.05) with the training program. Muscle fiber size declined (P < 0.05) by approximately 20% in both fiber types after training. P(o) was maintained in both fiber types with training and increased (P < 0.05) by 18% in the MHC IIa fibers after taper. This resulted in >60% increase (P < 0.05) in force per cross-sectional area in both fiber types. Fiber V(o) increased (P < 0.05) by 28% in MHC I fibers with training and was unchanged in MHC IIa fibers. Peak power increased (P < 0.05) in MHC I and IIa fibers after training with a further increase (P < 0.05) in MHC IIa fiber power after taper. These data show that marathon training decreased slow-twitch and fast-twitch muscle fiber size but that it maintained or improved the functional profile of these fibers. A taper period before the marathon further improved the functional profile of the muscle, which was targeted to the fast-twitch muscle fibers.

Effect of Aging on Tongue Protrusion Forces in Rats

PubMed Central

Nagai, Hiromi; Russell, John A.; Jackson, Michelle A.

2010-01-01

The purpose of this study was to ascertain the effect of aging on muscle contractile properties associated with tongue protrusion in a rat model. Fischer 344/Brown Norway hybrid rats, ten young (9 months old) and ten old (32 months old), were used to measure protrusive contractile properties. Results showed a significant reduction in tetanic forces in the old animals. The following measures of muscle contraction were not different between age groups: mean twitch contraction force, twitch contraction time, twitch contraction half-decay time, and a calculated measure of fatigability. In conclusion, aging influenced protrusive tongue muscle contractions in a rat model such that tetanic forces were reduced. The reduction of tetanus force may parallel findings in human subjects relative to isometric tongue force generation and may be associated with age-related disorders of swallowing. PMID:17694408

Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle.

PubMed

Umeki, Daisuke; Ohnuki, Yoshiki; Mototani, Yasumasa; Shiozawa, Kouichi; Fujita, Takayuki; Nakamura, Yoshiki; Saeki, Yasutake; Okumura, Satoshi

2013-01-01

To examine the effects of the Akt/mammalian target of rapamycin (mTOR) pathway on masseter muscle hypertrophy and myosin heavy chain (MHC) transition in response to mechanical overload, we analyzed the effects of bite-opening (BO) on the hypertrophy and MHC composition of masseter muscle of BO-rats treated or not treated with rapamycin (RAPA), a selective mTOR inhibitor. The masseter muscle weight in BO-rats was significantly greater than that in controls, and this increase was attenuated by RAPA treatment. Expression of slow-twitch MHC isoforms was significantly increased in BO-rats with/without RAPA treatment, compared with controls, but the magnitude of the increase was much smaller in RAPA-treated BO-rats. Phosphorylation of p44/42 MAPK (ERK1/2), which preserves fast-twitch MHC isoforms in skeletal muscle, was significantly decreased in BO-rats, but the decrease was abrogated by RAPA treatment. Calcineurin signaling is known to be important for masseter muscle hypertrophy and fast-to-slow MHC isoform transition, but expression of known calcineurin activity modulators was unaffected by RAPA treatment. Taken together, these results indicate that the Akt/mTOR pathway is involved in both development of masseter muscle hypertrophy and fast-to-slow MHC isoform transition in response to mechanical overload with inhibition of the ERK1/2 pathway and operates independently of the calcineurin pathway.

Optimizing patient-reported outcome and risk factor reporting from cancer survivors: a randomized trial of four different survey methods among colorectal cancer survivors.

PubMed

Feigelson, Heather Spencer; McMullen, Carmit K; Madrid, Sarah; Sterrett, Andrew T; Powers, J David; Blum-Barnett, Erica; Pawloski, Pamala A; Ziegenfuss, Jeanette Y; Quinn, Virginia P; Arterburn, David E; Corley, Douglas A

2017-06-01

The goal of this study was to determine response rates and associated costs of different survey methods among colorectal cancer (CRC) survivors. We assembled a cohort of 16,212 individuals diagnosed with CRC (2010-2014) from six health plans, and randomly selected 4000 survivors to test survey response rates across four mixed-mode survey administration protocols (in English and Spanish): arm 1, mailed survey with phone follow-up; arm 2, interactive voice response (IVR) followed by mail; arm 3; email linked to web-based survey with mail follow-up; and arm 4, email linked to web-based survey followed by IVR. Our overall response rate was 50.2%. Arm 1 had the highest response rate (59.9%), followed by arm 3 (51.9%), arm 2 (51.2%), and arm 4 (37.9%). Response rates were higher among non-Hispanic whites in all arms than other racial/ethnic groups (p < 0.001), among English (51.5%) than Spanish speakers (36.4%) (p < 0.001), and among higher (53.7%) than lower (41.4%) socioeconomic status (p < 0.001). Survey arms were roughly comparable in cost, with a difference of only 8% of total costs between the most (arm 2) and least (arm 3) expensive arms. Mailed surveys followed by phone calls achieved the highest response rate; email invitations and online surveys cost less per response. Electronic methods, even among those with email availability, may miss important populations including Hispanics, non-English speakers, and those of lower socioeconomic status. Our results demonstrate effective methods for capturing patient-reported outcomes, inform the relative benefits/disadvantages of the different methods, and identify future research directions.

Muscle atrophy associated with microgravity in rat: Basic data for countermeasures

NASA Astrophysics Data System (ADS)

Falempin, M.; Mounier, Y.

Morphological, contractile properties and myosin heavy chain (MHC) composition of rat soleus muscles were studied after 2 weeks of unloading (HS) and after 2 weeks of HS associated with selective deafferentation (HS + DEAF) at the level L4 and L5. The same significant reductions in muscle mass and tetanic tension were found after HS and HS + DEAF. However, the transformation of the slow-twitch soleus muscle towards a faster type characterized by a decrease in twitch time parameters and an increase in fast-twitch type MHC isoforms in HS did not appear in HS + DEAF conditions. Our results also showed that a pattern similar to firing rate of motoneurones innervating slow-twitch muscles inhibited the slow to fast fiber changes observed during HS. Nevertheless, neither the loss of mass or force output in the HS muscles were prevented by electrostimulation. Immobilization in a stretched position during HS maintained the muscle wet weight, mechanical and electrophoretical characteristics close to control values. We concluded that the decrease in mechanical strains imposed on the muscle during unloading was the main factor for the development of atrophy, while the kinetic changes might be predominantly modulated by the nervous command. These basic data suggested that some experimental conditions such as electrostimulation or stretching, could participate in countermeasure programmes.

Force generation by groups of migrating bacteria

PubMed Central

Koch, Matthias D.; Liu, Guannan; Stone, Howard A.; Shaevitz, Joshua W.

2017-01-01

From colony formation in bacteria to wound healing and embryonic development in multicellular organisms, groups of living cells must often move collectively. Although considerable study has probed the biophysical mechanisms of how eukaryotic cells generate forces during migration, little such study has been devoted to bacteria, in particular with regard to the question of how bacteria generate and coordinate forces during collective motion. This question is addressed here using traction force microscopy. We study two distinct motility mechanisms of Myxococcus xanthus, namely, twitching and gliding. For twitching, powered by type-IV pilus retraction, we find that individual cells exert local traction in small hotspots with forces on the order of 50 pN. Twitching bacterial groups also produce traction hotspots, but with forces around 100 pN that fluctuate rapidly on timescales of <1.5 min. Gliding, the second motility mechanism, is driven by lateral transport of substrate adhesions. When cells are isolated, gliding produces low average traction on the order of 1 Pa. However, traction is amplified approximately fivefold in groups. Advancing protrusions of gliding cells push, on average, in the direction of motion. Together, these results show that the forces generated during twitching and gliding have complementary characters, and both forces have higher values when cells are in groups. PMID:28655845

Force generation by groups of migrating bacteria.

PubMed

Sabass, Benedikt; Koch, Matthias D; Liu, Guannan; Stone, Howard A; Shaevitz, Joshua W

2017-07-11

From colony formation in bacteria to wound healing and embryonic development in multicellular organisms, groups of living cells must often move collectively. Although considerable study has probed the biophysical mechanisms of how eukaryotic cells generate forces during migration, little such study has been devoted to bacteria, in particular with regard to the question of how bacteria generate and coordinate forces during collective motion. This question is addressed here using traction force microscopy. We study two distinct motility mechanisms of Myxococcus xanthus , namely, twitching and gliding. For twitching, powered by type-IV pilus retraction, we find that individual cells exert local traction in small hotspots with forces on the order of 50 pN. Twitching bacterial groups also produce traction hotspots, but with forces around 100 pN that fluctuate rapidly on timescales of <1.5 min. Gliding, the second motility mechanism, is driven by lateral transport of substrate adhesions. When cells are isolated, gliding produces low average traction on the order of 1 Pa. However, traction is amplified approximately fivefold in groups. Advancing protrusions of gliding cells push, on average, in the direction of motion. Together, these results show that the forces generated during twitching and gliding have complementary characters, and both forces have higher values when cells are in groups.

The adequate rocuronium dose required for complete block of the adductor muscles of the thigh.

PubMed

Fujimoto, M; Kawano, K; Yamamoto, T

2018-03-01

Rocuronium can prevent the obturator jerk during transurethral resection of bladder tumors. We investigated the adequate rocuronium dose required for complete block of the thigh adductor muscles, and its correlation with individual responses of the adductor pollicis muscle to rocuronium. Eleven patients scheduled for transurethral resection of bladder tumors under general anesthesia were investigated. After general anesthesia induction, neuromuscular monitoring of the adductor pollicis muscle and ultrasonography-guided stimulation of the obturator nerve was commenced. Rocuronium, 0.15 mg/kg, was repeatedly administered intravenously. The adequate rocuronium dose required for complete block of the thigh muscles, defined as the cumulative dose of rocuronium administered until that time, and its correlation with the first twitch response of the adductor pollicis muscle on train-of-four stimulation after initial rocuronium administration was analyzed. The rocuronium dose found adequate for complete block of the thigh muscles was 0.30 mg/kg in seven patients and 0.45 mg/kg in the remaining four patients, which did not correlate with the first twitch response. At the time of complete block of the thigh muscles, the neuromuscular blockade level of the adductor pollicis muscle varied greatly, although the level was never more profound than a post-tetanic count of 1. Although the response of the adductor pollicis muscle to rocuronium cannot be used to determine the adequate rocuronium dose required for complete block of the thigh muscles, intense blockade, with maintenance of post-tetanic count at ≤ 1 in the adductor pollicis muscle is essential to prevent the obturator jerk. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Reflexive contraction of the levator palpebrae superioris muscle to involuntarily sustain the effective eyelid retraction through the transverse trigeminal proprioceptive nerve on the proximal Mueller's muscle: verification with evoked electromyography.

PubMed

Ban, Ryokuya; Matsuo, Kiyoshi; Osada, Yoshiro; Ban, Midori; Yuzuriha, Shunsuke

2010-01-01

We have proposed a hypothetical mechanism to involuntarily sustain the effective eyelid retraction, which consists of not only voluntary but also reflexive contractions of the levator palpebrae superior muscle (LPSM). Voluntary contraction of fast-twitch fibres of the LPSM stretches the mechanoreceptors in Mueller's muscle to evoke trigeminal proprioception, which induces continuous reflexive contraction of slow-twitch fibres of the LPSM through the trigeminal proprioceptive nerve fibres innervating the mechanoreceptors in Mueller's muscle via the oculomotor neurons, as a tonic trigemino-oculomotor reflex. In the common skeletal mixed muscles, electrical stimulation of the proprioceptive nerve, which apparently connects the mechanoreceptors in muscle spindles to the motoneurons, induces the electromyographic response as the Hoffmann reflex. To verify the presence of the trigemino-oculomotor reflex, we confirmed whether intra-operative electrical simulation of the transverse trigeminal proprioceptive nerve on the proximal Mueller's muscle evokes an electromyographic response in the LPSM under general anaesthesia in 12 patients. An ipsilateral, phasic, short-latency response (latency: 2.8+/-0.3 ms) was induced in the ipsilateral LPSM in 10 of 12 subjects. As successful induction of the short-latency response in the ipsilateral LPSM corresponds to the Hoffmann reflex in the common skeletal mixed muscles, the present study is the first electromyographic verification of the presence of the monosynaptic trigemino-oculomotor reflex to induce reflexive contraction of the LPSM. The presence of the trigemino-oculomotor reflex may elucidate the unexplainable blepharoptosis due to surgery, trauma and tumour, all of which may damage the trigeminal proprioceptive nerve fibres to impair the trigemino-oculomotor reflex. Copyright (c) 2008. Published by Elsevier Ltd.

Glucose stimulates protein synthesis in skeletal muscle of neonatal pigs through an AMPK- and mTOR-independent process.

PubMed

Jeyapalan, Asumthia S; Orellana, Renan A; Suryawan, Agus; O'Connor, Pamela M J; Nguyen, Hanh V; Escobar, Jeffery; Frank, Jason W; Davis, Teresa A

2007-08-01

Skeletal muscle protein synthesis is elevated in neonates in part due to an enhanced response to the rise in insulin and amino acids after eating. In vitro studies suggest that glucose plays a role in protein synthesis regulation. To determine whether glucose, independently of insulin and amino acids, is involved in the postprandial rise in skeletal muscle protein synthesis, pancreatic-substrate clamps were performed in neonatal pigs. Insulin secretion was inhibited with somatostatin and insulin was infused to reproduce fasting or fed levels, while glucose and amino acids were clamped at fasting or fed levels. Fractional protein synthesis rates and translational control mechanisms were examined. Raising glucose alone increased protein synthesis in fast-twitch glycolytic muscles but not in other tissues. The response in muscle was associated with increased phosphorylation of protein kinase B (PKB) and enhanced formation of the active eIF4E.eIF4G complex but no change in phosphorylation of AMP-activated protein kinase (AMPK), tuberous sclerosis complex 2 (TSC2), mammalian target of rapamycin (mTOR), 4E-binding protein-1 (4E-BP1), ribosomal protein S6 kinase (S6K1), or eukaryotic elongation factor 2 (eEF2). Raising glucose, insulin, and amino acids increased protein synthesis in most tissues. The response in muscle was associated with phosphorylation of PKB, mTOR, S6K1, and 4E-BP1 and enhanced eIF4E.eIF4G formation. The results suggest that the postprandial rise in glucose, independently of insulin and amino acids, stimulates protein synthesis in neonates, and this response is specific to fast-twitch glycolytic muscle and occurs by AMPK- and mTOR-independent pathways.

In Vitro and In Vivo Characterization of the Alkaloid Nuciferine.

PubMed

Farrell, Martilias S; McCorvy, John D; Huang, Xi-Ping; Urban, Daniel J; White, Kate L; Giguere, Patrick M; Doak, Allison K; Bernstein, Alison I; Stout, Kristen A; Park, Su Mi; Rodriguiz, Ramona M; Gray, Bradley W; Hyatt, William S; Norwood, Andrew P; Webster, Kevin A; Gannon, Brenda M; Miller, Gary W; Porter, Joseph H; Shoichet, Brian K; Fantegrossi, William E; Wetsel, William C; Roth, Bryan L

2016-01-01

The sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays. Nuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms. Nuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy. The molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions.

Effects of adenosine receptor agonist on the rocuroniuminduced neuromuscular block and sugammadex-induced recovery.

PubMed

Kim, Yong Beom; Lee, Sangseok; Choi, Hey Ran; In, Junyong; Chang, Young Jin; Kim, Ha Jung; Ro, Young Jin; Yang, Hong-Seuk

2018-04-25

Several types of receptors are found at neuromuscular presynaptic membranes. Presynaptic inhibitory A1 and facilitatory A2A receptors mediate different modulatory functions on acetylcholine release. This study investigated whether adenosine A1 receptor agonist contributes to the first twitch tension (T1) of train-of-four (TOF) stimulation depression and TOF fade during rocuronium-induced neuromuscular blockade, and sugammadex-induced recovery. Phrenic nerve-diaphragm tissues were obtained from 30 adult Sprague-Dawley rats. Each tissue specimen was randomly allocated to either control group or 2-chloroadenosine (CADO, 10 μM) group. One hour of reaction time was allowed before initiating main experimental data collection. Loading and boost doses of rocuronium were sequentially administered until > 95% depression of the T1 was achieved. After confirming that there was no T1 twitch tension response, 15 min of resting time was allowed, after which sugammadex was administered. Recovery profiles (T1, TOF ratio [TOFR], and recovery index) were collected for 1 h and compared between groups. There were statistically significant differences on amount of rocuronium (actually used during experiment), TOFR changes during concentration-response of rocuronium (P = 0.04), and recovery profiles (P < 0.01) of CADO group comparing with the control group. However, at the initial phase of this experiment, dose-response of rocuronium in each group demonstrated no statistically significant differences (P = 0.12). The adenosine A1 receptor agonist (CADO) influenced the TOFR and the recovery profile. After activating adenosine receptor, sugammadex-induced recovery from rocuronium-induced neuromuscular block was delayed.

Muscle sarcomere lesions and thrombosis after spaceflight and suspension unloading

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riley, D.A.; Ellis, S.; Giometti, C.S.

1992-08-01

Extended exposure of humans to spaceflight produces a progressive loss of skeletal muscle strength. This process must be understood to design effective countermeasures. The present investigation examined hindlimb muscles from flight rats killed as close to landing as possible. Spaceflight and tail suspension-hindlimb unloading (unloaded) produced significant decreases in fiber cross-sectional areas of the adductor longus (AL), a slow-twitch antigravity muscle. However, the mean wet weight of the flight AL muscles was near normal, whereas that of the suspension unloaded AL muscles was significantly reduced. Interstitial edema within the flight AL, but not in the unloaded AL, appeared to accountmore » for this apparent disagreement.In both conditions, the slow-twitch oxidative fibers atrophied more than the fast-twitch oxidative-glycolytic fibers. Microcirculation was also compromised by spaceflight, such that there was increased formation of thrombi in the postcapillary venules and capillaries.« less

[Neuromuscular blocking and respiratory depressing actions of sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate].

PubMed

Cao, B J; Chen, Z K; Chi, Z Q

1990-05-01

The neuromuscular blocking and respiratory depressing actions of the new insecticide sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate (SCD) were investigated. In peroneal-tibialis anterior nerve-muscle preparations of urethane anesthetized rabbit, SCD 6.5 mg/kg iv completely depressed the indirectly elicited twitch tension but not the directly elicited one. This compound also caused initial potentiation of the indirectly elicited twitch tension. In the partially paralyzed preparations, potentiation of contractions occurred following a brief period of indirectly tetanic stimulation. Nereistoxin but not SCD blocked the indirectly elicited twitch tension of isolated rat diaphragm. The neuromuscular blockade induced by SCD and nereistoxin was antagonized by neostigmine and 4-aminopyridine. SCD and nereistoxin had little or no effect on arterial blood pressure and phrenic nerve discharge of rabbits. The results indicated that SCD-poisoned rabbits died of respiratory paralysis following the neuromuscular blockade.

Morphometric analysis of rat muscle fibers following space flight and hypogravity

NASA Technical Reports Server (NTRS)

Chui, L. A.; Castleman, K. R.

1982-01-01

The effect of hypogravity on striate muscles, containing both fast twitch glycolytic and slow twitch oxidative fibers, was studied in rats aboard two Cosmos biosatellites. Results of a computer-assisted image analysis of extensor digitorum muscles from five rats, exposed to 18.5 days of hypogravity and processed for the alkaline ATPase reaction, showed a reduction of the mean fiber diameter (41.32 + or - 0.55 microns), compared to synchronous (46.32 + or - 0.55 microns) and vivarium (49 + or - 0.5 microns) controls. A further experiment studied the ratio of fast to slow twitch fibers in 25 rats exposed to 18.5 days of hypogravity and analyzed at four different periods of recovery following the space flight. Using the previous techniques, the gastrocnemius muscle showed a reduction of the total muscle fiber area in square microns and a reduction in the percentage of slow fibers of flight animals compared to the control animals.

Differential expression of the skeletal muscle proteome in grazed cattle.

PubMed

Shibata, M; Matsumoto, K; Oe, M; Ohnishi-Kameyama, M; Ojima, K; Nakajima, I; Muroya, S; Chikuni, K

2009-08-01

The objective of this study was to investigate the differences in the muscle proteome of grass-fed and grain-fed cattle. Eight Japanese Black Cattle 10 mo of age were separated randomly into 2 groups: 1) grazing (grass-fed) and 2) concentrate (grain-fed) groups. All cattle were first housed individually in a stall barn and fed a combination of concentrate ad libitum and Italian ryegrass hay until 21 mo of age. After this control period, the 4 grass-fed cattle were placed on outdoor pasture, whereas the other 4 grain-fed cattle continued on the concentrate diet. The cattle were slaughtered at 27 mo of age, and tissues from the semitendinosus muscle were obtained for use in proteome analysis. Differential expression of muscle proteins in the 2 groups was carried out using 2-dimensional gel electrophoresis (2DE) and Western blot analyses, with subsequent mass spectrometry. Approximately 200 individual protein spots were detected and compared in each group using 2DE, of which 20 and 9 spots, respectively, showed differences in the spot intensity for the sarcoplasmic fraction and myofibrillar fraction. In the grazing group, the relative intensity of spots was significantly greater for adenylate kinase 1 and myoglobin in the sarcoplasmic fraction, and for slow-twitch myosin light chain 2 in the myofibrillar fraction (P < 0.05), than the concentrate group. The relative spot intensity of several glycolytic enzymes was significantly greater in the grazing group, such as beta-enolase 3, fructose-1,6-bisphosphate aldolase A, triosephosphate isomerase, and heat shock 27 kDa protein (P < 0.05). Moreover, significantly greater slow twitch of troponin T, troponin I, and myosin heavy chain of semitendinosus muscle was detected in the grazing group than in the concentrate group using Western blot analysis (P < 0.05). Several previous reports have described that the slow-twitch muscle contents affect elements of nutrition, flavor, and food texture of meat. This study revealed muscle fiber type conversion to slow-twitch tissues from fast-twitch tissues occurring with change in the energy metabolic enzyme when cattle were grazed in the latter fattening period. Although analyses of the influence on elements of nutrition, flavor, and food texture were not done for this study, these results show that slow-twitch converted muscle resulting from the grazing of cattle might modify several meat characteristics.

Factors in Maximal Power Production and in Exercise Endurance Relative to Maximal Power

DTIC Science & Technology

1988-10-13

Mechanical efficiency of fast -and slow - twitch muscle fibers in mnan during cycling. J. ADLi Physiol.:Reespirat. Environ. Exercise Physiol. 47: 263- 267...R.S. Hikida, and F.C. Hagerman. Myofibrillar ATPase activity in hu-man muscle fast - twitch subtypes. Histochem. 78: 405-408, 1983. 31. Suzuki, Y...capacity and muscle fibre composition in mnan. J. Physiol (London) 354: 73P, 1984. 21. Margaria, R., P. Aghemo, and E. Rovelli. Measurement of muscular

Conversion of muscle fiber types in regenerating chicken muscles following cross-reinnervation.

PubMed

Kikuchi, T; Akiba, T; Ashmore, C R

1986-01-01

Slow-tonic anterior latissimus dorsi (ALD) and fast-twitch posterior latissimus dorsi (PLD) muscles of 7 to 10-day-old White Leghorn chickens were crushed and allowed to be reinnervated by their own nerve, or crushed and transplanted to the other side and allowed to be reinnervated by the nerve of the side to which they were transplanted. Following transplantation, changes in the weight of the muscle, fiber-type composition and innervation pattern during regeneration were investigated. Normal growth rate of PLD was about twice that of ALD. Regenerating PLD, however, atrophied rapidly after crushing and denervation whether innervated by its own nerve or the other nerve type, whereas ALD reinnervated by its own nerve showed marked hypertrophy. PLD fibers transformed rapidly to fast-twitch alpha or slow-tonic (ST) fibers when they were reinnervated by PLD or ALD nerve, respectively. When ALD fibers were reinnervated by their own nerve, they differentiated into ST fibers that were surrounded by smaller immature fibers. ALD fibers were, however, resistant to complete control by fast-twitch PLD nerve and contained a large number of slow fibers (ST and beta) long after transplantation. Slow fibers in regenerates were initially multiply innervated, but later transformed into fast-twitch alpha fibers that were focally innervated. The mode of differentiation and innervation pattern of different muscle fiber types in regenerating muscles are discussed.

Crystal structure analysis reveals Pseudomonas PilY1 as an essential calcium-dependent regulator of bacterial surface motility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orans, Jillian; Johnson, Michael D.L.; Coggan, Kimberly A.

Several bacterial pathogens require the 'twitching' motility produced by filamentous type IV pili (T4P) to establish and maintain human infections. Two cytoplasmic ATPases function as an oscillatory motor that powers twitching motility via cycles of pilus extension and retraction. The regulation of this motor, however, has remained a mystery. We present the 2.1 {angstrom} resolution crystal structure of the Pseudomonas aeruginosa pilus-biogenesis factor PilY1, and identify a single site on this protein required for bacterial translocation. The structure reveals a modified {beta}-propeller fold and a distinct EF-hand-like calcium-binding site conserved in pathogens with retractile T4P. We show that preventing calciummore » binding by PilY1 using either an exogenous calcium chelator or mutation of a single residue disrupts Pseudomonas twitching motility by eliminating surface pili. In contrast, placing a lysine in this site to mimic the charge of a bound calcium interferes with motility in the opposite manner - by producing an abundance of nonfunctional surface pili. Our data indicate that calcium binding and release by the unique loop identified in the PilY1 crystal structure controls the opposing forces of pilus extension and retraction. Thus, PilY1 is an essential, calcium-dependent regulator of bacterial twitching motility.« less

Electrophysiological, histochemical, and hormonal adaptation of rat muscle after prolonged hindlimb suspension

NASA Astrophysics Data System (ADS)

Kourtidou-Papadeli, Chrysoula; Kyparos, Antonios; Albani, Maria; Frossinis, Athanasios; Papadelis, Christos L.; Bamidis, Panagiotis; Vivas, Ana; Guiba-Tziampiri, Olympia

2004-05-01

The perspective of long-duration flights for future exploration, imply more research in the field of human adaptation. Previous studies in rat muscles hindlimb suspension (HLS), indicated muscle atrophy and a change of fibre composition from slow-to-fast twitch types. However, the contractile responses to long-term unloading is still unclear. Fifteen adult Wistar rats were studied in 45 and 70 days of muscle unweighting and soleus (SOL) muscle as well as extensor digitorum longus (EDL) were prepared for electrophysiological recordings (single, twitch, tetanic contraction and fatigue) and histochemical stainings. The loss of muscle mass observed was greater in the soleus muscle. The analysis of electrophysiological properties of both EDL and SOL showed significant main effects of group, of number of unweighting days and fatigue properties. Single contraction for soleus muscle remained unchanged but there was statistically significant difference for tetanic contraction and fatigue. Fatigue index showed a decrease for the control rats, but increase for the HLS rats. According to the histochemical findings there was a shift from oxidative to glycolytic metabolism during HLS. The data suggested that muscles atrophied, but they presented an adaptation pattern, while their endurance in fatigue was decreased.

A new view of “dream enactment” in REM sleep behavior disorder

PubMed Central

Blumberg, Mark S.; Plumeau, Alan M.

2015-01-01

SUMMARY REM sleep behavior disorder (RBD) is a disorder in which patients exhibit increased muscle tone and exaggerated myoclonic twitching during REM sleep. In addition, violent movements of the limbs, and complex behaviors that can sometimes appear to involve the enactment of dreams, are associated with RBD. These behaviors are widely thought to result from a dysfunction involving atonia-producing neural circuitry in the brainstem, thereby unmasking cortically generated dreams. Here we scrutinize the assumptions that led to this interpretation of RBD. In particular, we challenge the assumption that motor cortex produces twitches during REM sleep, thus calling into question the related assumption that motor cortex is primarily responsible for all of the pathological movements of RBD. Moreover, motor cortex is not even necessary to produce complex behavior; for example, stimulation of some brainstem structures can produce defensive and aggressive behaviors in rats and monkeys that are striking similar to those reported in human patients with RBD. Accordingly, we suggest an interpretation of RBD that focuses increased attention on the brainstem as a source of the pathological movements and that considers sensory feedback from moving limbs as an important influence on the content of dream mentation. PMID:26802823

Hemodynamic responses to etomidate versus ketamine-thiopental sodium combination for anesthetic induction in coronary artery bypass graft surgery patients with low ejection fraction: a double-blind, randomized, clinical trial.

PubMed

Habibi, Mohammad Reza; Baradari, Afshin Gholipour; Soleimani, Aria; Emami Zeydi, Amir; Nia, Hamid Sharif; Habibi, Ali; Onagh, Naser

2014-10-01

During induction of anesthesia and intubation, hemodynamic changes are very important; especially in patients with coronary artery disease (CAD) and left ventricular dysfunction. A little information is available on the hemodynamic effects of a combination of ketamine-thiopental for induction of anesthesia in patients undergoing coronary artery bypass graft (CABG) surgery, with impaired ventricular function. The aim of this study was to compare the hemodynamic responses to etomidate versus ketamine-thiopental sodium combination for anesthetic induction in CABG surgery patients with low ejection fraction (EF<45%). In a double blind randomized clinical trial, a total of 100 patients, scheduled for elective CABG surgery were randomly assigned into two groups. These patients received either etomidate or ketamine-thiopental sodium combination at induction of anesthesia. Hemodynamics variable were measured and recorded at baseline, immediately before and after laryngoscopy and intubation, one, two and three minutes after intubation. Also, muscle twitching incidence among patients in two groups was evaluated. No significant differences between the two groups regarding the changes of hemodynamic variables including systolic and diastolic arterial blood pressure, mean arterial pressure and heart rate, were notice (p>0.05). Muscle twitching was not observed in the two groups. Hemodynamic stability after administration of ketamine-thiopental sodium combination for induction of anesthesia in patients undergoing CABG surgery, with impaired ventricular function, supports the clinical impression that this combination is safe in CABG surgery patients with low EF.

Dysregulated corticostriatal activity in open-field behavior and the head-twitch response induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine.

PubMed

Rangel-Barajas, Claudia; Estrada-Sánchez, Ana María; Barton, Scott J; Luedtke, Robert R; Rebec, George V

2017-02-01

The substituted amphetamine, 2,5-dimethoxy-4-iodoamphetamine (DOI), is a hallucinogen that has been used to model a variety of psychiatric conditions. Here, we studied the effect of DOI on neural activity recorded simultaneously in the primary motor cortex (M1) and dorsal striatum of freely behaving FvB/N mice. DOI significantly decreased the firing rate of individually isolated neurons in M1 and dorsal striatum relative to pre-drug baseline. It also induced a bursting pattern of activity by increasing both the number of spikes within a burst and burst duration. In addition, DOI increased coincident firing between simultaneously recorded neuron pairs within the striatum and between M1 and dorsal striatum. Local field potential (LFP) activity also increased in coherence between M1 and dorsal striatum after DOI in the low frequency gamma band (30-50 Hz), while corticostriatal coherence in delta, theta, alpha, and beta activity decreased. We also assessed corticostriatal LFP activity in relation to the DOI-induced head-twitch response (HTR), a readily identifiable behavior used to assess potential treatments for the conditions it models. The HTR was associated with increased delta and decreased theta power in both M1 and dorsal striatum. Together, our results suggest that DOI dysregulates corticostriatal communication and that the HTR is associated with this dysregulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lactate Accumulation in Muscle and Blood during Submaximal Exercise

DTIC Science & Technology

1981-09-21

exercise, fast and slow twitch fibers Short title: Lactate in muscle and blood P.A. Tesch, W.L. Daniels and D.S. Sharp Exercise Physiology Division, U.S...KIRBY, R.L. & BELCASTRO, A.N. 1978. Relationship between slow - twitch muscle fibres and lactic acid removal. Can J Appl Sports Sci 3:160-162. BRODAL, P...oxygen uptake (Karlsson 1971, Knuttgen & Saltin 1972). It is generally agreed that the main muscle fiber type to be recruited below this level is the slow

Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

PubMed

Guagnini, F; Valenti, M; Mukenge, S; Matias, I; Bianchetti, A; Di Palo, S; Ferla, G; Di Marzo, V; Croci, T

2006-07-01

Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis). The neural contractile response to electrical field stimulation of longitudinal muscle strips from the colon of patients undergoing surgery for colonic cancer or diverticulitis was challenged by different receptor agonists and antagonists. Contractions of colonic strips from healthy controls and diverticulitis specimens were abolished by atropine. The beta adrenergic agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar potency in reducing the electrical twitch response in controls and diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1 receptor, had no intrinsic activity in control preparations but potentiated the neural twitch in diseased tissues by up to 196% in a concentration dependent manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular disease patients. Colonic levels of the endogenous ligand of cannabinoid and vanilloid TRPV1 receptors anandamide were more than twice those of control tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had opposite effects in the two preparations, completely inhibiting the contractions of control strips but potentiating those in diverticular preparations, an effect selectively inhibited by SR140333. Neural control of colon motility is profoundly altered in patients with diverticulitis. Their raised levels of anandamide, apparent desensitisation of the presynaptic neural cannabinoid CB1 receptor, and the SR141716 induced intrinsic response, suggest that endocannabinoids may be involved in the pathophysiology of complications of colonic diverticular disease.

Physiological Responses to Arm Activity in Individuals With Chronic Obstructive Pulmonary Disease Compared With Healthy Controls: A SYSTEMATIC REVIEW.

PubMed

Lima, Vanessa Pereira; Iamonti, Vinicius C; Velloso, Marcelo; Janaudis-Ferreira, Tania

The mechanisms underlying physiological limitations during arm activity in individuals with chronic obstructive pulmonary disease (COPD) are unknown. The objective of this systematic review was to describe cardiorespiratory responses, symptoms, chest wall kinematics, muscle activity, and lung volumes during arm activity in individuals with COPD relative to the responses of healthy controls. Original research articles that compared cardiorespiratory responses, symptoms, muscle activity, chest wall kinematics, and lung function during arm activity between individuals with COPD and healthy controls were identified after searches of 5 electronic databases and reference lists of pertinent articles. Two reviewers performed the electronic and manual searches with 1 screening title and abstracts. Two investigators screened the full texts to determine eligibility for inclusion. One reviewer performed the data extraction and tabulation using a standardized form with a second reviewer double-checking the data extracted. Of the 54 full-text articles assessed for eligibility, 6 met the inclusion criteria. Reduced cardiorespiratory responses during peak arm exercise in individuals with COPD compared with healthy controls were evident. Compared with healthy controls, individuals with COPD had increased dyspnea and hyperinflation during peak arm exercise. Increased effort of the trapezius muscle during arm activities was also found in persons with COPD compared with healthy controls. There is limited evidence describing physiological responses during arm activity in individuals with COPD. Findings of this systematic review suggest that individuals with COPD have decreased cardiorespiratory responses during peak arm exercise compared with controls but increased dyspnea, hyperinflation, and arm muscle effort.

Comparable Neutrophil Responses for Arm and Intensity-matched Leg Exercise.

PubMed

Leicht, Christof A; Goosey-Tolfrey, Victoria L; Bishop, Nicolette C

2017-08-01

Arm exercise is performed at lower absolute intensities than lower body exercise. This may impact on intensity-dependent neutrophil responses, and it is unknown whether individuals restricted to arm exercise experience the same changes in the neutrophil response as found for lower body exercise. Therefore, we aimed to investigate the importance of exercise modality and relative exercise intensity on the neutrophil response. Twelve moderately trained men performed three 45-min constant load exercise trials after determination of peak oxygen uptake for arm exercise (V˙O2peak arms) and cycling (V˙O2peak legs): 1) arm cranking exercise at 60% V˙O2peak arms, 2) moderate cycling at 60% V˙O2peak legs, and 3) easy cycling at 60% V˙O2peak arms. Neutrophil numbers in the circulation increased for all exercise trials, but were significantly lower for easy cycling when compared with arm exercise (P = 0.009), mirroring the blunted increase in HR and epinephrine during easy cycling. For all trials, exercising HR explained some of the variation of the neutrophil number 2 h postexercise (R = 0.51-0.69), epinephrine explaining less of this variation (R = 0.21-0.34). The number of neutrophils expressing CXCR2 decreased in the recovery from exercise in all trials (P < 0.05). Arm and leg exercise elicits the same neutrophil response when performed at the same relative intensity, implying that populations restricted to arm exercise might achieve a similar exercise induced neutrophil response as those performing lower body exercise. A likely explanation for this is the higher sympathetic activation and cardiac output for arm and relative intensity-matched leg exercise when compared with easy cycling, which is partly reflected in HR. This study further shows that the downregulation of CXCR2 may be implicated in exercise-induced neutrophilia.

Gene Regions Responding to Skeletal Muscle Atrophy

NASA Technical Reports Server (NTRS)

Booth, Frank W.

1997-01-01

Our stated specific aims for this project were: 1) Identify the region(s) of the mouse IIb myosin heavy chain (MHC) promoter necessary for in vivo expression in mouse fast-twitch muscle, and 2) Identify the region(s) of the mouse IIb MHC promoter responsive to immobilization in mouse slow-twitch muscle in vivo. We sought to address these specific aims by introducing various MHC IIb promoter/reporter gene constructs directly into the tibialis anterior and gastrocnemius muscles of living mice. Although the method of somatic gene transfer into skeletal muscle by direct injection has been successfully used in our laboratory to study the regulation of the skeletal alpha actin gene in chicken skeletal muscle, we had many difficulties utilizing this procedure in the mouse. Because of the small size of the mouse soleus and the difficulty in obtaining consistent results, we elected not to study this muscle as first proposed. Rather, our MHC IIb promoter deletion experiments were performed in the gastrocnemius. Further, we decided to use hindlimb unloading via tail suspension to induce an upregulation of the MHC IIb gene, rather than immobilization of the hindlimbs via plaster casts. This change was made because tail suspension more closely mimics spaceflight, and this procedure in our lab results in a smaller loss of overall body mass than the mouse hindlimb immobilization procedure. This suggests that the stress level during tail suspension is less than during immobilization. This research has provided an important beginning point towards understanding the molecular regulation of the MHC lIb gene in response to unweighting of skeletal muscle Future work will focus on the regulation of MHC IIb mRNA stability in response to altered loading of skeletal muscle

Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists.

PubMed

Moreno, José L; Holloway, Terrell; Albizu, Laura; Sealfon, Stuart C; González-Maeso, Javier

2011-04-15

Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects the hallucinogen-regulated cellular signaling pathways. Here, we tested the cellular and behavioral effects of hallucinogenic 5-HT2AR agonists in mGluR2 knockout (mGluR2-KO) mice. Mice were intraperitoneally injected with the hallucinogens DOI (2 mg/kg) and LSD (0.24 mg/kg), or vehicle. Head-twitch behavioral response, expression of c-fos, which is induced by all 5-HT2AR agonists, and expression of egr-2, which is hallucinogen-specific, were determined in wild type and mGluR2-KO mice. [(3)H]Ketanserin binding displacement curves by DOI were performed in mouse frontal cortex membrane preparations. Head twitch behavior was abolished in mGluR2-KO mice. The high-affinity binding site of DOI was undetected in mGluR2-KO mice. The hallucinogen DOI induced c-fos in both wild type and mGluR2-KO mice. However, the induction of egr-2 by DOI was eliminated in mGlu2-KO mice. These findings suggest that the 5-HT2AR-mGluR2 complex is necessary for the neuropsychological responses induced by hallucinogens. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists

PubMed Central

Moreno, José L.; Holloway, Terrell; Albizu, Laura; Sealfon, Stuart C.; González-Maeso, Javier

2011-01-01

Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects the hallucinogen-regulated cellular signaling pathways. Here, we tested the cellular and behavioral effects of hallucinogenic 5-HT2AR agonists in mGluR2 knockout (mGluR2-KO) mice. Mice were intraperitoneally injected with the hallucinogens DOI (2 mg/kg) and LSD (0.24 mg/kg), or vehicle. Head-twitch behavioral response, expression of c-fos, which is induced by all 5-HT2AR agonists, and expression of egr-2, which is hallucinogen-specific, were determined in wild type and mGluR2-KO mice. [3H]Ketanserin binding displacement curves by DOI were performed in mouse frontal cortex membrane preparations. Head twitch behavior was abolished in mGluR2-KO mice. The high-affinity binding site of DOI was undetected in mGluR2-KO mice. The hallucinogen DOI induced c-fos in both wild type and mGluR2-KO mice. However, the induction of egr-2 by DOI was eliminated in mGlu2-KO mice. These findings suggest that the 5-HT2AR-mGluR2 complex is necessary for the neuropsychological responses induced by hallucinogens. PMID:21276828

Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice

PubMed Central

Moreno, José L.; Holloway, Terrell; Umali, Adrienne; Rayannavar, Vinayak; Sealfon, Stuart C.

2013-01-01

Rationale In schizophrenia patients, optimal treatment with antipsychotics requires weeks to months of sustained drug therapy. However, single administration of antipsychotic drugs can reverse schizophrenia-like behavioral alterations in rodent models of psychosis. This raises questions about the physiological relevance of such antipsychotic-like activity. Objective This study evaluates the effects of chronic treatment with clozapine on the cellular and behavioral responses induced by the hallucinogenic serotonin 5-HT2A receptor agonist lysergic acid diethylamide (LSD) as a mouse model of psychosis. Method Mice were treated chronically (21 days) with 25 mg/kg/day clozapine. Experiments were conducted 1, 7, 14, and 21 days after the last clozapine administration. [3H]Ketanserin binding and 5-HT2A mRNA expression were determined in mouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT2A agonists, and expression of egr-1 and egr-2, which are LSD-like specific, were assayed. Results Head-twitch response was decreased and [3H]ketanserin binding was downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2A mRNA was reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, was rescued 7 days after chronic clozapine. These effects were not observed after short treatment (2 days) with clozapine or chronic haloperidol (1 mg/kg/day). Conclusion Our findings provide a murine model of chronic atypical antipsychotic drug action and suggest downregulation of the 5-HT2A receptor as a potential mechanism involved in these persistent therapeutic-like effects. PMID:22842765

Recovery of skeletal muscle after 3 mo of hindlimb immobilization in rats

NASA Technical Reports Server (NTRS)

Booth, F. W.; Seider, M. J.

1979-01-01

During immobilization, skeletal muscle undergoes decreases in size and strength with concomitant atrophic and degenerative changes in slow-twitch muscle fibers. Currently there are no objective data in slow-twitch muscle demonstrating recovery of biochemical or physiological indices following termination of immobilization. The purpose of this study was to determine whether the soleus, a slow-twitch muscle, could recover normal biochemical or physiological levels following termination of immobilization. Adenosine triphosphate, glycogen, and protein concentration (mg/g wet wt) all significantly decreased following 90 days of hindlimb immobilization, but these three values returned to control levels by the 60th recovery day. Similarly, soleus muscle wet weight and protein content (mg protein/muscle) returned to control levels by the 14th recovery day. In contrast, maximal isometric tension did not return to normal until the 120th day. These results indicate that following muscular atrophy, which was achieved through 90 days of hindlimb immobilization, several biochemical and physiological values in skeletal muscle are recovered at various times after the end of immobilization.

Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles.

PubMed

Dufresne, Sébastien S; Dumont, Nicolas A; Boulanger-Piette, Antoine; Fajardo, Val A; Gamu, Daniel; Kake-Guena, Sandrine-Aurélie; David, Rares Ovidiu; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M; Pape, Paul C; Tupling, A Russell; Frenette, Jérôme

2016-04-15

Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca(2+)sensor, and altered activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) modulating Ca(2+)storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca(2+)storage and SERCA activity, ultimately affecting denervated skeletal muscle function. Copyright © 2016 the American Physiological Society.

Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles

PubMed Central

Dufresne, Sébastien S.; Dumont, Nicolas A.; Boulanger-Piette, Antoine; Fajardo, Val A.; Gamu, Daniel; Kake-Guena, Sandrine-Aurélie; David, Rares Ovidiu; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M.; Pape, Paul C.; Tupling, A. Russell

2016-01-01

Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca2+ sensor, and altered activity of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) modulating Ca2+ storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca2+ storage and SERCA activity, ultimately affecting denervated skeletal muscle function. PMID:26825123

Visualization of the diaphragm muscle with ultrasound improves diagnostic accuracy of phrenic nerve conduction studies.

PubMed

Johnson, Nicholas E; Utz, Michael; Patrick, Erica; Rheinwald, Nicole; Downs, Marlene; Dilek, Nuran; Dogra, Vikram; Logigian, Eric L

2014-05-01

Evaluation of phrenic neuropathy (PN) with phrenic nerve conduction studies (PNCS) is associated with false negatives. Visualization of diaphragmatic muscle twitch with diaphragm ultrasound (DUS) when performing PNCS may help to solve this problem. We performed bilateral, simultaneous DUS-PNCS in 10 healthy adults and 12 patients with PN. The amplitude of the diaphragm compound muscle action potential (CMAP) (on PNCS) and twitch (on DUS) was calculated. Control subjects had <38% side-to-side asymmetry in twitch amplitude (on DUS) and 53% asymmetry in phrenic CMAP (on PCNS). In the 12 patients with PN, 12 phrenic neuropathies were detected. Three of these patients had either significant side-to-side asymmetry or absolute reduction in diaphragm movement that was not detected with PNCS. There were no cases in which the PNCS showed an abnormality but the DUS did not. The addition of DUS to PNCS enhances diagnostic accuracy in PN. Copyright © 2013 Wiley Periodicals, Inc.

Fiber specific changes in sphingolipid metabolism in skeletal muscles of hyperthyroid rats.

PubMed

Chabowski, A; Zendzian-Piotrowska, M; Mikłosz, A; Łukaszuk, B; Kurek, K; Górski, J

2013-07-01

Thyroid hormones (T3, T4) are well known modulators of different cellular signals including the sphingomyelin pathway. However, studies regarding downstream effects of T3 on sphingolipid metabolism in skeletal muscle are scarce. In the present work we sought to investigate the effects of hyperthyroidism on the activity of the key enzymes of ceramide metabolism as well as the content of fundamental sphingolipids. Based on fiber/metabolic differences, we chose three different skeletal muscles, with diverse fiber compositions: soleus (slow-twitch oxidative), red (fast-twitch oxidative-glycolytic) and white (fast-twitch glycolytic) section of gastrocnemius. We demonstrated that T3 induced accumulation of sphinganine, ceramide, sphingosine, as well as sphingomyelin, mostly in soleus and in red, but not white section of gastrocnemius. Concomitantly, the activity of serine palmitoyltransferase and acid/neutral ceramidase was increased in more oxidative muscles. In conclusion, hyperthyroidism induced fiber specific changes in the content of sphingolipids that were relatively more related to de novo synthesis of ceramide rather than to its generation via hydrolysis of sphingomyelin.

Meat from wild boar (Sus scrofa L.): a review.

PubMed

Sales, James; Kotrba, Radim

2013-06-01

Wild boar is a species that is utilised for food and sport hunting throughout the world. Recent increases in natural populations and the potential of farming wild boars have stimulated interest in this species as a meat producer. Compared to domestic pigs, wild boars present a higher degree of carcass fatness and larger loin areas, more slow-twitch oxidative (I) and fast-twitch oxidative glycolytic (IIA) and less fast-twitch glycolytic (IIB) muscle fibres, and darker, less tender and leaner meat. Differences in diets might contribute to differences in cooked meat flavour and fatty acid composition between wild boars and domestic pigs. Higher α-tocopherol concentrations in wild boar might extend its meat shelf-life. Mechanical massaging of muscles, vacuum package ageing and addition of marinates have been attempted to tenderise wild boar meat. Further research on hunting protocols for wild boar, and value-added products from its meat, are needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Interleaved neuromuscular electrical stimulation: Motor unit recruitment overlap.

PubMed

Wiest, Matheus J; Bergquist, Austin J; Schimidt, Helen L; Jones, Kelvin E; Collins, David F

2017-04-01

In this study, we quantified the "overlap" between motor units recruited by single pulses of neuromuscular electrical stimulation (NMES) delivered over the tibialis anterior muscle (mNMES) and the common peroneal nerve (nNMES). We then quantified the torque produced when pulses were alternated between the mNMES and nNMES sites at 40 Hz ("interleaved" NMES; iNMES). Overlap was assessed by comparing torque produced by twitches evoked by mNMES, nNMES, and both delivered together, over a range of stimulus intensities. Trains of iNMES were delivered at the intensity that produced the lowest overlap. Overlap was lowest (5%) when twitches evoked by both mNMES and nNMES produced 10% peak twitch torque. iNMES delivered at this intensity generated 25% of maximal voluntary dorsiflexion torque (11 Nm). Low intensity iNMES leads to low overlap and produces torque that is functionally relevant to evoke dorsiflexion during walking. Muscle Nerve 55: 490-499, 2017. © 2016 Wiley Periodicals, Inc.

Spatial distribution of motor units recruited during electrical stimulation of the quadriceps muscle versus the femoral nerve.

PubMed

Rodriguez-Falces, Javier; Maffiuletti, Nicola A; Place, Nicolas

2013-11-01

In this study we investigated differences in the spatial recruitment of motor units (MUs) in the quadriceps when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. M-waves and mechanical twitches were evoked using over-the-quadriceps and femoral nerve stimulation of gradually increasing intensity from 22 young, healthy subjects. Spatial recruitment was investigated using recruitment curves of M-waves recorded from the vastus medialis (VM) and vastus lateralis (VL) and of twitches recorded from the quadriceps. At maximal stimulation intensity (Imax), no differences were found between nerve and over-the-quadriceps stimulation. At submaximal intensities, VL M-wave amplitude was higher for over-the-quadriceps stimulation at 40% Imax, and peak twitch force was greater for nerve stimulation at 60% and 80% Imax. For the VM, MU spatial recruitment during nerve and over-the-quadriceps stimulation of increasing intensity occurred in a similar manner, whereas significant differences were observed for the VL. Copyright © 2013 Wiley Periodicals, Inc.

Size and metabolic properties of single muscle fibers in rat soleus after hindlimb suspension

NASA Technical Reports Server (NTRS)

Hauschka, Edward O.; Roy, Roland R.; Edgerton, V. Reggie

1987-01-01

The effect of 28-day-long hind-limb suspension (HS) combined with 10 daily forceful lengthening contractions of the limb on the morphological and metabolic properties of individual fibers of the soleus was studied in rats, using quantitative histochemical techniques. Compared with nonsuspended controls (CON), soleus wet weights of HS rats were decreased by 49 percent; the fibers staining lightly for myosin ATPase ('light-ATPase' fibers) atrophied more than the 'dark-ATPase' fibers. Single-fiber alpha-glycerophosphate dehydrogenase (GPD) and succinate dehydrogenase (SDH) activities were higher in HS than in CON rats. Daily forceful lengthening contractions did not prevent the HS-induced changes. The results support the view that the soleus fibers can change from a slow-twitch oxidative to a fast-twitch oxidative-glycolytic profile, but rarely to a fast-twitch glycolytic one, and that the SDH and GPD activities per volume of tissue can be increased even when there are severe losses of contractile proteins.

In vivo determination of the direction of rotation and moment-angle relationship of individual elbow muscles.

PubMed

Zhang, L; Butler, J; Nishida, T; Nuber, G; Huang, H; Rymer, W Z

1998-10-01

The direction of rotation (DOR) of individual elbow muscles, defined as the direction in which a muscle rotates the forearm relative to the upper arm in three-dimensional space, was studied in vivo as a function of elbow flexion and forearm rotation. Electrical stimulation was used to activate an individual muscle selectively, and the resultant flexion-extension, supination-pronation, and varus-valgus moments were used to determine the DOR. Furthermore, multi-axis moment-angle relationships of individual muscles were determined by stimulating the muscle at a constant submaximal level across different joint positions, which was assumed to result in a constant level of muscle activation. The muscles generate significant moments about axes other than flexion-extension, which is potentially important for actively controlling joint movement and maintaining stability about all axes. Both the muscle DOR and the multi axis moments vary with the joint position systematically. Variations of the DOR and moment-angle relationship across muscle twitches of different amplitudes in a subject were small, while there were considerable variations between subjects.

Increased susceptibility to fatigue of slow- and fast-twitch muscles from mice lacking the MG29 gene.

PubMed

Nagaraj, R Y; Nosek, C M; Brotto, M A; Nishi, M; Takeshima, H; Nosek, T M; Ma, J

2000-11-09

Mitsugumin 29 (MG29), a major protein component of the triad junction in skeletal muscle, has been identified to play roles in the formation of precise junctional membrane structures important for efficient signal conversion in excitation-contraction (E-C) coupling. We carried out several experiments to not only study the role of MG29 in normal muscle contraction but also to determine its role in muscle fatigue. We compared the in vitro contractile properties of three muscles types, extensor digitorum longus (EDL) (fast-twitch muscle), soleus (SOL) (slow-twitch muscle), and diaphragm (DPH) (mixed-fiber muscle), isolated from mice lacking the MG29 gene and wild-type mice prior to and after fatigue. Our results indicate that the mutant EDL and SOL muscles, but not DPH, are more susceptible to fatigue than the wild-type muscles. The mutant muscles not only fatigued to a greater extent but also recovered significantly less than the wild-type muscles. Following fatigue, the mutant EDL and SOL muscles produced lower twitch forces than the wild-type muscles; in addition, fatiguing produced a downward shift in the force-frequency relationship in the mutant mice compared with the wild-type controls. Our results indicate that fatiguing affects the E-C components of the mutant EDL and SOL muscles, and the effect of fatigue in these mutant muscles could be primarily due to an alteration in the intracellular Ca homeostasis.

Divergence of a strain of Pseudomonas aeruginosa during an outbreak of ovine mastitis.

PubMed

Wright, Elli A; Di Lorenzo, Valeria; Trappetti, Claudia; Liciardi, Manuele; Orru, Germano; Viti, Carlo; Bronowski, Christina; Hall, Amanda J; Darby, Alistair C; Oggioni, Marco R; Winstanley, Craig

2015-01-30

Bacterial infections causing mastitis in sheep can result in severe economic losses for farmers. A large survey of milk samples from ewes with mastitis in Sardinia, Italy, indicated an increasing prevalence of Pseudomonas aeruginosa infections. It has been shown previously that during chronic, biofilm-associated infections P. aeruginosa populations diversify. We report the phenotypic and genomic characterisation of two clonal P. aeruginosa isolates (PSE305 and PSE306) from a mastitis infection outbreak, representing distinct colony morphology variants. In addition to pigment production, PSE305 and PSE306 differed in phenotypic characteristics including biofilm formation, utilisation of various carbon and nitrogen sources, twitching motility. We found higher levels of expression of genes associated with biofilm formation (pelB) and twitching motility (flgD) in PSE305, compared to the biofilm and twitching-defective PSE306. Comparative genomics analysis revealed single nucleotide polymorphisms (SNPs) and minor insertion/deletion variations between PSE305 and PSE306, including a SNP mutation in the pilP gene of PSE306. By introducing a wild-type pilP gene we were able to partially complement the defective twitching motility of PSE306. There were also three larger regions of difference between the two genomes, indicating genomic instability. Hence, we have demonstrated that P. aeruginosa population divergence can occur during an outbreak of mastitis, leading to significant variations in phenotype and genotype, and resembling the behaviour of P. aeruginosa during chronic biofilm-associated infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Cognitive-behavioral therapy as continuation treatment to sustain response after electroconvulsive therapy in depression: a randomized controlled trial.

PubMed

Brakemeier, Eva-Lotta; Merkl, Angela; Wilbertz, Gregor; Quante, Arnim; Regen, Francesca; Bührsch, Nicole; van Hall, Franziska; Kischkel, Eva; Danker-Hopfe, Heidi; Anghelescu, Ion; Heuser, Isabella; Kathmann, Norbert; Bajbouj, Malek

2014-08-01

Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response. In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months. Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm. These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Neuromuscular blockade of slow twitch muscle fibres elevates muscle oxygen uptake and energy turnover during submaximal exercise in humans.

PubMed

Krustrup, Peter; Secher, Niels H; Relu, Mihai U; Hellsten, Ylva; Söderlund, Karin; Bangsbo, Jens

2008-12-15

We tested the hypothesis that a greater activation of fast-twitch (FT) fibres during dynamic exercise leads to a higher muscle oxygen uptake (VO2 ) and energy turnover as well as a slower muscle on-kinetics. Subjects performed one-legged knee-extensor exercise for 10 min at an intensity of 30 W without (CON) and with (CUR) arterial injections of the non-depolarizing neuromuscular blocking agent cisatracurium. In CUR, creatine phosphate (CP) was unaltered in slow twitch (ST) fibres and decreased (P < 0.05) by 28% in FT fibres, whereas in CON, CP decreased (P < 0.05) by 33% and 23% in ST and FT fibres, respectively. From 127 s of exercise, muscle VO2 was higher (P < 0.05) in CUR compared to CON (425 +/- 25 (+/- S.E.M.) versus 332 +/- 30 ml min(-1)) and remained higher (P < 0.05) throughout exercise. Using monoexponential fitting, the time constant of the exercise-induced muscle VO2 response was slower (P < 0.05) in CUR than in CON (55 +/- 6 versus 33 +/- 5 s). During CUR and CON, muscle homogenate CP was lowered (P < 0.05) by 32 and 35%, respectively, and also muscle lactate production was similar in CUR and CON (37.8 +/- 4.1 versus 35.2 +/- 6.2 mmol). Estimated total muscle ATP turnover was 19% higher (P < 0.05) in CUR than in CON (1196 +/- 90 versus 1011 +/- 59 mmol) and true mechanical efficiency was lower (P < 0.05) in CUR than in CON (26.2 +/- 2.0 versus 30.9 +/- 1.5%). In conclusion, the present findings provide evidence that FT fibres are less efficient than ST fibres in vivo at a contraction frequency of 1 Hz, and that the muscle VO2 kinetics is slowed by FT fibre activation.

Comparison of phonomyography with balloon pressure mechanomyography to measure contractile force at the corrugator supercilii muscle.

PubMed

Hemmerling, Thomas M; Michaud, Guillaume; Babin, Denis; Trager, Guillaume; Donati, François

2004-02-01

Phonomyography is based on the creation of low frequency sounds during muscle contraction, which can be recorded and used for neuromuscular monitoring. In this study, balloon pressure mechanomyography, a novel method to measure the force of contraction via pressure changes in an air-filled balloon, was compared with phonomyography to determine neuromuscular blockade at the corrugator supercilii muscle. After approval of the Ethics Committee and informed consent, 15 patients were studied. A small condenser microphone was taped to the area just above the eyebrow for phonomyography; an air-filled balloon was taped to the area just above the opposite eyebrow. After induction of anesthesia using remifentanil and propofol, a laryngeal mask airway was inserted without the aid of neuromuscular blocking agents. The facial nerve was stimulated supramaximally with single-twitch stimulation (0.1 Hz) using superficial electrodes placed on both temporal areas for onset and train-of-four stimulation every 12 sec during offset of neuromuscular blockade produced by mivacurium 0.1 mg.kg(-1). Onset and recovery measured by the two methods were compared using the t test and agreement between phonomyography and balloon pressure mechanomyography was examined using the Bland-Altman method. Onset, peak effect, and time to reach 25%, 75%, and 90% of control twitch response for phonomyography vs balloon pressure method were 83 +/- 16 sec vs 81 +/- 15 sec, 80 +/- 15% vs 82 +/- 17%, 7.7 +/- 2.3 min vs 7.5 +/- 2.4 min, 9.9 +/- 4.1 min vs 10.5 +/- 4 min, and 12.6 +/- 4.3 min vs 13.1 +/- 4.5 min respectively without being significantly different. Mean bias was 1% with limits of agreement of -9 and +9% of twitch height (T1). We applied a balloon pressure method to measure the force at the corrugator supercilii. Phonomyography at the corrugator supercilii shows good agreement with this modified version of mechanomyography.

Measurement and simulation of myoplasmic calcium transients in mouse slow-twitch muscle fibres.

PubMed

Hollingworth, Stephen; Kim, Michele M; Baylor, Stephen M

2012-02-01

Bundles of intact fibres from soleus muscles of adult mice were isolated by dissection and one fibre within a bundle was micro-injected with either furaptra or mag-fluo-4, two low-affinity rapidly responding Ca(2+) indicators. Fibres were activated by action potentials to elicit changes in indicator fluorescence (ΔF), a monitor of the myoplasmic free Ca(2+) transient ([Ca(2+)]), and changes in fibre tension. All injected fibres appeared to be slow-twitch (type I) fibres as inferred from the time course of their tension responses. The full-duration at half-maximum (FDHM) of ΔF was found to be essentially identical with the two indicators; the mean value was 8.4 ± 0.3 ms (±SEM) at 16°C and 5.1 ± 0.3 ms at 22°C. The value at 22°C is about one-third that reported previously in enzyme-dissociated slow-twitch fibres that had been AM-loaded with mag-fluo-4: 12.4 ± 0.8 ms and 17.2 ± 1.7 ms. We attribute the larger FDHM in enzyme-dissociated fibres either to an alteration of fibre properties due to the enzyme treatment or to some error in the measurement of ΔF associated with AM loading. ΔF in intact fibres was simulated with a multi-compartment reaction-diffusion model that permitted estimation of the amount and time course of Ca(2+) release from the sarcoplasmic reticulum (SR), the binding and diffusion of Ca(2+) in the myoplasm, the re-uptake of Ca(2+) by the SR Ca(2+) pump, and Δ[Ca(2+)] itself. In response to one action potential at 16°C, the following estimates were obtained: 107 μm for the amount of Ca(2+) release; 1.7 ms for the FDHM of the release flux; 7.6 μm and 4.9 ms for the peak and FDHM of spatially averaged Δ[Ca(2+)]. With five action potentials at 67 Hz, the estimated amount of Ca(2+) release is 186 μm. Two important unknown model parameters are the on- and off-rate constants of the reaction between Ca(2+) and the regulatory sites on troponin; values of 0.4 × 10(8) m(-1) s(-1) and 26 s(-1), respectively, were found to be consistent with the ΔF measurements.

Functional properties of slow and fast gastrocnemius muscle fibers after a 17-day spaceflight

NASA Technical Reports Server (NTRS)

Widrick, J. J.; Romatowski, J. G.; Norenberg, K. M.; Knuth, S. T.; Bain, J. L.; Riley, D. A.; Trappe, S. W.; Trappe, T. A.; Costill, D. L.; Fitts, R. H.

2001-01-01

The purpose of this investigation was to study the effects of a 17-day spaceflight on the contractile properties of individual fast- and slow-twitch fibers isolated from biopsies of the fast-twitch gastrocnemius muscle of four male astronauts. Single chemically skinned fibers were studied during maximal Ca2+-activated contractions with fiber myosin heavy chain (MHC) isoform expression subsequently determined by SDS gel electrophoresis. Spaceflight had no significant effect on the mean diameter or specific force of single fibers expressing type I, IIa, or IIa/IIx MHC, although a small reduction in average absolute force (P(o)) was observed for the type I fibers (0.68 +/- 0.02 vs. 0.64 +/- 0.02 mN, P < 0.05). Subject-by-flight interactions indicated significant intersubject variation in response to the flight, as postflight fiber diameter and P(o) where significantly reduced for the type I and IIa fibers obtained from one astronaut and for the type IIa fibers from another astronaut. Average unloaded shortening velocity [V(o), in fiber lengths (FL)/s] was greater after the flight for both type I (0.60 +/- 0.03 vs. 0.76 +/- 0.02 FL/s) and IIa fibers (2.33 +/- 0.25 vs. 3.10 +/- 0.16 FL/s). Postflight peak power of the type I and IIa fibers was significantly reduced only for the astronaut experiencing the greatest fiber atrophy and loss of P(o). These results demonstrate that 1) slow and fast gastrocnemius fibers show little atrophy and loss of P(o) but increased V(o) after a typical 17-day spaceflight, 2) there is, however, considerable intersubject variation in these responses, possibly due to intersubject differences in in-flight physical activity, and 3) in these four astronauts, fiber atrophy and reductions in P(o) were less for slow and fast fibers obtained from the phasic fast-twitch gastrocnemius muscle compared with slow and fast fibers obtained from the slow antigravity soleus [J. J. Widrick, S. K. Knuth, K. M. Norenberg, J. G. Romatowski, J. L. W. Bain, D. A. Riley, M. Karhanek, S. W. Trappe, T. A. Trappe, D. L. Costill, and R. H. Fitts. J Physiol (Lond) 516: 915-930, 1999].

Brain activation underlying threat detection to targets of different races.

PubMed

Senholzi, Keith B; Depue, Brendan E; Correll, Joshua; Banich, Marie T; Ito, Tiffany A

2015-01-01

The current study examined blood oxygen level-dependent signal underlying racial differences in threat detection. During functional magnetic resonance imaging, participants determined whether pictures of Black or White individuals held weapons. They were instructed to make shoot responses when the picture showed armed individuals but don't shoot responses to unarmed individuals, with the cost of not shooting armed individuals being greater than that of shooting unarmed individuals. Participants were faster to shoot armed Blacks than Whites, but faster in making don't shoot responses to unarmed Whites than Blacks. Brain activity differed to armed versus unarmed targets depending on target race, suggesting different mechanisms underlying threat versus safety decisions. Anterior cingulate cortex was preferentially engaged for unarmed Whites than Blacks. Parietal and visual cortical regions exhibited greater activity for armed Blacks than Whites. Seed-based functional connectivity of the amygdala revealed greater coherence with parietal and visual cortices for armed Blacks than Whites. Furthermore, greater implicit Black-danger associations were associated with increased amygdala activation to armed Blacks, compared to armed Whites. Our results suggest that different neural mechanisms may underlie racial differences in responses to armed versus unarmed targets.

Skeletal muscle response to spaceflight, whole body suspension, and recovery in rats

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Steffen, J. M.; Fell, R. D.; Dombrowski, M. J.

1990-01-01

The effects of a 7-day spaceflight (SF), 7- and 14-day-long whole body suspension (WBS), and 7-day-long recovery on the muscle weight and the morphology of the soleus and the extensor digitorum longus (EDL) of rats were investigated. It was found that the effect of 7-day-long SF and WBS were highly comparable for both the soleus and the EDL, although the soleus muscle from SF rats showed greater cross-sectional area reduction than that from WBS rats. With a longer duration of WBS, there was a continued reduction in cross-sectional fast-twitch fiber area. Muscle plasticity, in terms of fiber and capillary responses, showed differences in responses of the two types of muscles, indicating that antigravity posture muscles are highly susceptible to unloading.

Effect of dolutegravir functional monotherapy on HIV-1 virological response in integrase strand transfer inhibitor resistant patients.

PubMed

Naeger, Lisa K; Harrington, Patrick; Komatsu, Takashi; Deming, Damon

2016-01-01

VIKING-4 assessed the safety and efficacy of dolutegravir in heavily antiretroviral treatment-experienced patients who had documented integrase strand transfer inhibitor (INSTI) resistance-associated substitutions in their HIV. VIKING-4 had a placebo-controlled 7-day dolutegravir functional monotherapy phase followed by dolutegravir plus an optimized background regimen for 48 weeks. Independent resistance analyses evaluated week 48 virological responses in the VIKING-4 trial based on the presence of baseline INSTI resistance-associated substitutions and baseline dolutegravir phenotypic susceptibility. Response rates at week 48 based on baseline dolutegravir resistance subgroups were compared for the 7-day dolutegravir functional monotherapy arm and placebo-control arm. Additionally, genotypic and phenotypic resistance at day 8 and time of failure was analysed for the virological failures from both arms. Week 48 response rates for VIKING-4 were 23% (3/13) in the 7-day dolutegravir functional monotherapy arm compared with 60% (9/15) in the 7-day placebo arm. Response rates were consistently lower in the dolutegravir functional monotherapy arm across baseline INSTI genotypic and phenotypic subgroups. There was a higher proportion of virological failures in the 7-day dolutegravir functional monotherapy arm (n=6/13; 46%) compared with the 7-day placebo arm (n=3/15; 20%). Additionally, five virological failures in the dolutegravir arm had virus expressing emergent INSTI resistance-associated substitutions compared with two in the placebo arm. Analysis of response rates and resistance emergence in VIKING-4 suggests careful consideration should be given to the duration of functional monotherapy in future studies of highly treatment-experienced patients to reduce the risk of resistance and virological failure.

Slow-tonic muscle fibers and their potential innervation in the turtle, Pseudemys (Trachemys) scripta elegans.

PubMed

Callister, Robert J; Pierce, Patricia A; McDonagh, Jennifer C; Stuart, Douglas G

2005-04-01

A description is provided of the ratio of slow-tonic vs. slow- and fast-twitch fibers for five muscles in the adult turtle, Pseudemys (Trachemys) scripta elegans. The cross-sectional area of each fiber type and an estimation of the relative (weighted) cross-sectional area occupied by the different fiber types are also provided. Two hindlimb muscles (flexor digitorum longus, FDL; external gastrocnemius, EG) were selected on the basis of their suitability for future motor-unit studies. Three neck muscles (the fourth head of testo-cervicis, TeC4; the fourth head of retrahens capitus collique, RCCQ4; transversalis cervicis, TrC) were chosen for their progressively decreasing oxidative capacity. Serial sections were stained for myosin adenosine triphosphatase (ATPase), NADH-diaphorase, and alpha-glycerophosphate dehydrogenase (alpha-GPDH). Conventional fiber-type classification was then performed using indirect markers for contraction speed and oxidative (aerobic) vs. glycolytic (anaerobic) metabolism: i.e., slow oxidative (SO, including slow-twitch and possibly slow-tonic fibers), fast-twitch, oxidative-glycolytic (FOG), and fast-twitch glycolytic (Fg) fibers. Slow-tonic fibers in the SO class were then revealed by directing the monoclonal antibody, ALD-58 (raised against the slow-tonic fiber myosin heavy chain of chicken anterior latissimus dorsi), to additional muscle cross sections. All five of the tested muscles contained the four fiber types, with the ATPase-stained fibers including both slow-tonic and slow-twitch fibers. The extreme distributions of SO fibers were in the predominately glycolytic TrC vs. the predominately oxidative TeC4 muscle (TrC-SO, 9%; FOG, 20%; Fg, 71% vs. TeC4-SO, 58%: FOG, 16%; Fg, 25%). Across the five muscles, the relative prevalence of slow-tonic fibers (4-47%) paralleled that of the SO fibers (9-58%). TeC4 had the highest prevalence of slow-tonic fibers (47%). The test muscles exhibited varying degrees of regional concentration of each fiber type, with the distribution of slow-tonic fibers paralleling that of the SO fibers. In the five test muscles, fiber cross-sectional area was usually ranked Fg > FOG > SO, and slow-twitch always > slow-tonic. In terms of weighted cross-sectional area, which provides a coarse-grain measure of each fiber type's potential contribution to whole muscle force, all five muscles exhibited a higher Fg and lower SO contribution to cross-sectional area than suggested by their corresponding fiber-type prevalence. This was also the case for the slow-twitch vs. slow-tonic fibers. We conclude that slow-tonic fibers are widespread in turtle muscle. The weighted cross-sectional area evidence suggested, however, that their contribution to force generation is minor except in highly oxidative muscles, with a special functional role, like TeC4. There is discussion of: 1) the relationship between the present results and previous work on homologous neck and hindlimb muscles in other nonmammalian species, and 2) the potential motoneuronal innervation of slow-tonic fibers in turtle hindlimb muscles. Copyright 2005 Wiley-Liss, Inc.

Effect of altered thyroid state on the in situ mechanical properties of adult cat soleus

NASA Technical Reports Server (NTRS)

Roy, R. R.; Zhong, H.; Hodgson, J. A.; Grossman, E. J.; Edgerton, V. R.

2003-01-01

To determine the responsiveness of cat hindlimb muscles to thyroid manipulation, adult female cats were made hypothyroid (thyroidectomy plus tapazole treatment), hyperthyroid (synthroid pellets), or maintained euthyroid. After 4 months, the hypothyroid soleus had slower time-to-peak (TPT, 80%) and half-relaxation (HRT) times, whereas the hyperthyroid soleus had faster TPT (20%) and HRT than euthyroid cats. The tension at low stimulation frequencies (5-15 Hz) was higher in hypothyroid and lower in hyperthyroid cats compared to euthyroid cats. Muscle weight, maximum twitch and tetanic (Po) tensions, and maximum rates of shortening (Vmax) were similar across groups. The soleus of hypothyroid cats was more fatigable than normal. The myosin heavy chain (MHC) composition, based on gel electrophoresis, was unaffected by thyroid hormone manipulation. Based on the reaction of monoclonal antibodies for specific MHCs, some fast fibers in the hypothyroid cats coexpressed developmental MHC. These data indicate that 4 months of an altered thyroid state result in changes in the isometric twitch speed properties of the cat soleus, but not the tension-related or isotonic properties. Further, a chronic decrease in thyroid hormone had a greater impact than a chronic increase in thyroid hormone on the mechanical properties of the adult cat soleus. Copyright 2003 S. Karger AG, Basel.

Effect of spaceflight on the functional, biochemical, and metabolic properties of skeletal muscle

NASA Technical Reports Server (NTRS)

Baldwin, K. M.

1996-01-01

This paper summarizes the effects of spaceflight on the functional, morphological, and biochemical properties of human and rodent skeletal muscle. The findings suggest that following as little as 5-6 in space there are deficits in both human and rodent motor capacity, strength, and endurance properties of skeletal muscle. The reduced strength is associated, in part, with a reduction in muscle mass as reflected in smaller cross-sectional areas of both fast- and slow-twitch fibers. Available evidence in animal models suggests that slow-twitch fibers are more sensitive to the atrophying process. Accompanying the atrophy is a transformation of slow to fast protein phenotype involving myosin heavy chain and sarcoplasmic reticulum protein isoforms. These transformations appear to be regulated, in part, by pretranslational processes. Data on the oxidative capacity of rodent skeletal muscle suggest a bias toward preferential utilization of carbohydrate as the primary substrate. These collective findings suggest that skeletal muscles comprised chiefly of slow fibers are highly dependent on gravity for the normal expression of protein mass and slow phenotype. Future studies need to focus on elucidating the mechanisms associated with the atrophy response, as well as identifying suitable exercise and other countermeasures capable of preserving the structural and functional integrity of skeletal muscle.

Dimethylarginine Dimethylaminohydrolase Overexpression enhances Insulin Sensitivity

PubMed Central

Sydow, Karsten; Mondon, Carl E.; Schrader, Joerg; Konishi, Hakuoh; Cooke, John P.

2011-01-01

Objective Previous studies suggest that nitric oxide (NO) may modulate insulin-induced uptake of glucose in insulin-sensitive tissues. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS). We hypothesized that a reduction in endogenous ADMA would increase NO synthesis and thereby enhance insulin sensitivity. Methods and Results To test this hypothesis we employed a transgenic mouse in which we overexpressed human dimethylarginine dimethylaminohydrolase (DDAH-I). The DDAH-I mice had lower plasma ADMA at all ages (22–70 weeks) by comparison to wild-type (WT) littermates. With a glucose challenge, WT mice showed a prompt increase in ADMA, whereas DDAH-I mice had a blunted response. Furthermore, DDAH-I mice had a blunted increase in plasma insulin and glucose levels after glucose challenge, with a 50% reduction in the insulin resistence index, consistent with enhanced sensitivity to insulin. In liver, we observed an increased Akt phosphorylation in the DDAH-I mice after i.p. glucose challenge. Incubation of skeletal muscle from WT mice ex vivo with ADMA (2μM) markedly suppressed insulin-induced glycogen synthesis in fast-twitch but not slow-twitch muscle. Conclusions These findings suggest that the endogenous NOS inhibitor ADMA reduces insulin sensitivity, consistent with previous observations that NO plays a role in insulin sensitivity. PMID:18239148

Effect of ageing on the myosin heavy chain composition of the human sternocleidomastoid muscle.

PubMed

Meznaric, M; Eržen, I; Karen, P; Cvetko, E

2018-03-01

The myosin heavy chain (MyHC) composition of ageing limb muscles is transformed into a slower phenotype and expresses fast-twitch fibre type atrophy, presumably due to age-related motor unit remodelling and a change in the patterns of physical activity. It is not known if ageing affects the sternocleidomastoid muscle (SCM) in a similar way. The goal of the study was to analyze the MyHC composition and the size of muscle fibres in the ageing SCM by immunohistochemical methods and quantitative analysis and stereology using our own software for morphometry. We hypothesize that with ageing the MyHC composition of SCM transforms similarly as in ageing limb muscles, but the size of the muscle fibres is less effected as in limb muscles. The study was performed on the autopsy samples of the SCM in 12 older males. The results were compared with those published in our previous study on 15 young adult males. An ageing SCM transforms into a slower MyHC profile: the percentage of slow-twitch fibres is enhanced (numerical proportion 44.6 vs. 31.5%, P<0.05; area proportion 57.2 vs. 38.4%, P<0.05). The share of hybrid 2a/2x fibres is diminished (numerical proportion 14.1 vs. 26.8%, P<0.05), the area proportion of all fast-twitch fibres expressing MyHC-2a and 2x is smaller (50.6 vs. 63.5%, P<0.05), and the area proportion of fibres expressing the fastest myosin isoform MyHC-2x is smaller too (19.0 vs. 34.5%, P<0.05). The slower phenotype with the preferential reduction of the fibres expressing the fastest MyHC-2x provide circumstantial evidence for: (i) more fast-twitch than slow-twitch motor units being lost; and (ii) reinnervation by the surviving motor units. There appears to be no significant influence on muscle fibre size, which is congruent with relatively unchanged SCM activity during life. Copyright © 2017 Elsevier GmbH. All rights reserved.

Effects of thyroid hormone on fast- and slow-twitch skeletal muscles in young and old rats.

PubMed Central

Larsson, L; Li, X; Teresi, A; Salviati, G

1994-01-01

1. The effects of 4 weeks of thyroid hormone treatment on contractile, enzyme-histochemical and morphometric properties and on the myosin isoform composition were compared in the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscle in young (3-6 months) and old (20-24 months) male rats. 2. In the soleus of untreated controls, contraction and half-relaxation times of the isometric twitch increased by 19-32% with age. The change in contractile properties was paralleled by an age-related increase in the proportions of type I fibres and type I myosin heavy chain (MHC) and slow myosin light chain (MLC) isoforms. 3. In the EDL of controls, contraction and half-relaxation times were significantly prolonged (21-38%) in the post-tetanus twitch in the old animals. No significant age-related changes were observed in enzyme-histochemical fibre-type proportions, although the number of fibres expressing both type IIA and IIB MHCs and of fibres expressing slow MLC isoforms was increased in the old animals. 4. Serum 3,5,3',5'-tetraiodothyronine (T4) levels were lower (34%) in the old animals, but the primary byproduct of T4, 3,5,3'-triiodothyronine (T3), did not differ between young and old animals. 5. The effects of 4 weeks of thyroid hormone treatment were highly muscle specific, and were more pronounced in soleus than in EDL, irrespective of animal age. In the soleus, this treatment shortened the contraction and half-relaxation times by 35-57% and decreased the number of type I fibres by 66-77% in both young and old animals. In EDL, thyroid hormone treatment significantly shortened the contraction time by 24%, but the change was restricted to the old animals. 6. In conclusion, the ability of skeletal muscle to respond to thyroid hormone treatment was not impaired in old age and the age-related changes in speed of contraction and enzyme-histochemical properties and myosin isoform compositions were diminished after thyroid hormone treatment in both the soleus and EDL. Images Figure 3 Figure 4 PMID:7853237

Interaction of antibiotics on pipecuronium-induced neuromuscular blockade.

PubMed

de Gouw, N E; Crul, J F; Vandermeersch, E; Mulier, J P; van Egmond, J; Van Aken, H

1993-01-01

To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug). Prospective, randomized, placebo-controlled study. Inpatient gynecologic and gastroenterologic service at a university medical center. Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia. Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen. Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response. At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo. The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist. RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test. Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin. When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.

Skeletal muscle fiber size and fiber type distribution in human cancer: Effects of weight loss and relationship to physical function.

PubMed

Toth, Michael J; Callahan, Damien M; Miller, Mark S; Tourville, Timothy W; Hackett, Sarah B; Couch, Marion E; Dittus, Kim

2016-12-01

Cancer patients frequently experience weight loss, with negative consequences for functionality and prognosis. The extent to which muscle atrophy contributes to weight loss, however, is not clear, as few studies have directly measured muscle fiber morphology in cancer patients. Whole body and regional tissue composition were measured, along with the cross-sectional area (CSA) and fiber type of mechanically-isolated, single muscle fibers, in 19 cancer patients (8 with a history of weight loss, 11 weight-stable) and 15 non-diseased controls. Whole body fat mass was reduced in cancer patients with a history of weight loss, but no differences in whole body or leg fat-free mass were apparent. In contrast, reductions (∼20%) in single muscle fiber CSA were found in both slow-twitch, myosin heavy chain (MHC) I and fast-twitch, MHC IIA fibers in both weight-stable patients and those with a history of weight loss. Fiber type distribution showed a shift towards a fast-twitch phenotype compared to controls, which may preserve muscle function in cancer patients despite atrophy, as positive relationships were found between the fractions of hybrid MHC IIAX and I/IIA fibers and 6-min walk performance. Our results suggest that, although not apparent from whole body or regional measurements, cancer is associated with reduced skeletal muscle fiber size independent of weight loss history and a shift towards fast-twitch fibers, phenotypes that resemble adaptations to muscle disuse. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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

PubMed

Bunda, Jordan; Gittings, William; Vandenboom, Rene

2018-01-30

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

Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

DOE PAGES

Rice, Kevin M.; Manne, Nandini D. P. K.; Gadde, Murali K.; ...

2015-03-28

Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fast- and slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD × Brown Norway/BiNiamore » (F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of α-fodrin protein were regulated differently between muscles. As a result, These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.« less

Neuromuscular fatigue and recovery dynamics following prolonged continuous run at anaerobic threshold.

PubMed

Skof, B; Strojnik, V

2006-03-01

The aim of this study was to determine the influence of intensive aerobic running on some muscle contractile characteristics and the dynamics of their recovery during a 2 hour period afterwards. Seven well trained runners performed a 6 km run at anaerobic threshold (V(OBLA)). Knee torque during single twitch, low and high frequency electrical stimulation (ES), maximum voluntary knee extension, and muscle activation level test of the quadriceps femoris muscles were measured before and immediately after the run, and at several time points during a 120 minute interval that followed the run. After exercise, the mean (SE) maximum twitch torque (T(TW)) and torque at ES with 20 Hz (low frequency ES; T(F20)) dropped by 14.1 (5.1)% (p<0.05) and 20.6 (7.9)% (p<0.05) respectively, while torque at stimulation with 100 Hz (high frequency ES; T(F100)), maximum isometric knee extension torque (maximum voluntary contraction torque; T(MVC)), and activation level did not change significantly. Twitch contraction time was shortened by 8 (2)% (p<0.05). Ten minutes after the run, T(TW) was 40% higher than immediately after the run and 10% (p<0.05) higher than before the run. T(F20), T(F100), and T(MVC) remained lower for 60 minutes (p<0.05) than before the run. A 6 km continuous run at V(OBLA) caused peripheral fatigue by impairing excitation-contraction coupling. Twitch torque recovered very quickly. However, the process of torque restoration at maximum isometric knee extension torque and at high and low frequency ES took much longer.

Desensitization of the Mechanoreceptors in Müller's Muscle Reduces the Increased Reflex Contraction of the Orbicularis Oculi Slow-Twitch Fibers in Blepharospasm.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya; Ban, Midori

2014-01-01

Although the mixed orbicularis oculi muscle lacks the muscle spindles required to induce reflex contraction of its slow-twitch fibers, the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction. We hypothesize that strong stretching of these mechanoreceptors increases reflex contraction of the orbicularis oculi slow-twitch muscle fibers, resulting in blepharospasm. We examined a 71-year-old man with right blepharospasm and bilateral aponeurosis-disinserted blepharoptosis to determine whether the patient's blepharospasm was worsened by increased trigeminal proprioceptive evocation via stretching of the mechanoreceptors in Müller's muscle owing to a 60° upward gaze and serrated eyelid closure, and whether local anesthesia of the mechanoreceptors via lidocaine administration to the upper fornix as well as surgical disinsertion of Müller's muscle from the tarsus and fixation of the disinserted aponeurosis to the tarsus decreased trigeminal proprioceptive evocation and improved patient's blepharospasm. Before pharmacological desensitization, 60° upward gaze and serrated eyelid closure exacerbated the patient's blepharospasm. In contrast, these maneuvers did not worsen his blepharospasm following lidocaine administration. One year after surgical desensitization, the blepharospasm had disappeared and a 60° upward gaze did not induce blepharospasm. Strong stretching of the mechanoreceptors in Müller's muscle appeared to increase reflex contraction of the orbicularis oculi slow-twitch muscle fibers, resulting in blepharospasm. In addition to botulinum neurotoxin injections into the involuntarily contracted orbicularis oculi muscle and myectomy, surgical desensitization of the mechanoreceptors in Müller's muscle may represent an additional procedure to reduce blepharospasm.

Desensitization of the Mechanoreceptors in Müller's Muscle Reduces the Increased Reflex Contraction of the Orbicularis Oculi Slow-Twitch Fibers in Blepharospasm

PubMed Central

Ban, Ryokuya; Ban, Midori

2014-01-01

Objective: Although the mixed orbicularis oculi muscle lacks the muscle spindles required to induce reflex contraction of its slow-twitch fibers, the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction. We hypothesize that strong stretching of these mechanoreceptors increases reflex contraction of the orbicularis oculi slow-twitch muscle fibers, resulting in blepharospasm. Methods: We examined a 71-year-old man with right blepharospasm and bilateral aponeurosis-disinserted blepharoptosis to determine whether the patient's blepharospasm was worsened by increased trigeminal proprioceptive evocation via stretching of the mechanoreceptors in Müller's muscle owing to a 60° upward gaze and serrated eyelid closure, and whether local anesthesia of the mechanoreceptors via lidocaine administration to the upper fornix as well as surgical disinsertion of Müller's muscle from the tarsus and fixation of the disinserted aponeurosis to the tarsus decreased trigeminal proprioceptive evocation and improved patient's blepharospasm. Results: Before pharmacological desensitization, 60° upward gaze and serrated eyelid closure exacerbated the patient's blepharospasm. In contrast, these maneuvers did not worsen his blepharospasm following lidocaine administration. One year after surgical desensitization, the blepharospasm had disappeared and a 60° upward gaze did not induce blepharospasm. Conclusions: Strong stretching of the mechanoreceptors in Müller's muscle appeared to increase reflex contraction of the orbicularis oculi slow-twitch muscle fibers, resulting in blepharospasm. In addition to botulinum neurotoxin injections into the involuntarily contracted orbicularis oculi muscle and myectomy, surgical desensitization of the mechanoreceptors in Müller's muscle may represent an additional procedure to reduce blepharospasm. PMID:25328566

Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rice, Kevin M.; Manne, Nandini D. P. K.; Gadde, Murali K.

Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fast- and slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD × Brown Norway/BiNiamore » (F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of α-fodrin protein were regulated differently between muscles. As a result, These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.« less

Recruitment order of quadriceps motor units: femoral nerve vs. direct quadriceps stimulation.

PubMed

Rodriguez-Falces, Javier; Place, Nicolas

2013-12-01

To investigate potential differences in the recruitment order of motor units (MUs) in the quadriceps femoris when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. M-waves and mechanical twitches were evoked using femoral nerve stimulation and direct quadriceps stimulation of gradually increasing intensity from 20 young, healthy subjects. Recruitment order was investigated by analysing the time-to-peak twitch and the time interval from the stimulus artefact to the M-wave positive peak (M-wave latency) for the vastus medialis (VM) and vastus lateralis (VL) muscles. During femoral nerve stimulation, time-to-peak twitch and M-wave latency decreased consistently (P < 0.05) with increasing stimulus intensity, whereas, during graded direct quadriceps stimulation, time-to-peak twitch and VL M-wave latency did not show a clear trend (P > 0.05). For the VM muscle, M-wave latency decreased with increasing stimulation level for both femoral nerve and direct quadriceps stimulation, whereas, for the VL muscle, the variation of M-wave latency with stimulus intensity was different for the two stimulation geometries (P < 0.05). Femoral nerve stimulation activated MUs according to the size principle, whereas the recruitment order during direct quadriceps stimulation was more complex, depending ultimately on the architecture of the peripheral nerve and its terminal branches below the stimulating electrodes for each muscle. For the VM, MUs were orderly recruited for both stimulation geometries, whereas, for the VL muscle, MUs were orderly recruited for femoral nerve stimulation, but followed no particular order for direct quadriceps stimulation.

Induction of a pathological complete response by four courses of neoadjuvant chemotherapy for gastric cancer: early results of the randomized phase II COMPASS trial.

PubMed

Yoshikawa, Takaki; Tanabe, Kazuaki; Nishikawa, Kazuhiro; Ito, Yuichi; Matsui, Takanori; Kimura, Yutaka; Hirabayashi, Naoki; Mikata, Shoki; Iwahashi, Makoto; Fukushima, Ryoji; Takiguchi, Nobuhiro; Miyashiro, Isao; Morita, Satoshi; Miyashita, Yumi; Tsuburaya, Aakira; Sakamoto, Junichi

2014-01-01

The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results. Patients received S-1 (80 mg/m(2) for 21 days with 1 week's rest)/cisplatin (60 mg/m(2) at day 8) or paclitaxel/cisplatin (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week's rest) as neoadjuvant chemotherapy. Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms. Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.

The slow component of O(2) uptake is not accompanied by changes in muscle EMG during repeated bouts of heavy exercise in humans.

PubMed

Scheuermann, B W; Hoelting, B D; Noble, M L; Barstow, T J

2001-02-15

1. We hypothesized that either the recruitment of additional muscle motor units and/or the progressive recruitment of less efficient fast-twitch muscle fibres was the predominant contributor to the additional oxygen uptake (VO2) observed during heavy exercise. Using surface electromyographic (EMG) techniques, we compared the VO2 response with the integrated EMG (iEMG) and mean power frequency (MPF) response of the vastus lateralis with the VO2 response during repeated bouts of moderate (below the lactate threshold, < LT) and heavy (above the lactate threshold, > LT) intensity cycle ergometer exercise. 2. Seven male subjects (age 29 +/- 7 years, mean +/- S.D.) performed three transitions to a work rate (WR) corresponding to 90 % LT and two transitions to a work rate that would elicit a VO2 corresponding to 50 % of the difference between peak VO2 and the LT (i.e. Delta50 %, > LT1 and > LT2). 3. The VO2 slow component was significantly reduced by prior heavy intensity exercise (> LT1, 410 +/- 196 ml min(-1); > LT2, 230 +/- 191 ml min-1). The time constant (tau), amplitude (A) and gain (DeltaVO2/DeltaWR) of the primary VO2 response (phase II) were not affected by prior heavy exercise when a three-component, exponential model was used to describe the V2 response. 4. Integrated EMG and MPF remained relatively constant and at the same level throughout both > LT1 and > LT2 exercise and therefore were not associated with the VO2 slow component. 5. These data are consistent with the view that the increased O2 cost (i.e. VO2 slow component) associated with performing heavy exercise is coupled with a progressive increase in ATP requirements of the already recruited motor units rather than to changes in the recruitment pattern of slow versus fast-twitch motor units. Further, the lack of speeding of the kinetics of the primary VO2 component with prior heavy exercise, thought to represent the initial muscle VO2 response, are inconsistent with O2 delivery being the limiting factor in V > O2 kinetics during heavy exercise.

The immunological and clinical effects of mutated ras peptide vaccine in combination with IL-2, GM-CSF, or both in patients with solid tumors.

PubMed

Rahma, Osama E; Hamilton, J Michael; Wojtowicz, Malgorzata; Dakheel, Omar; Bernstein, Sarah; Liewehr, David J; Steinberg, Seth M; Khleif, Samir N

2014-02-24

Mutant Ras oncogenes produce proteins that are unique to cancer cells and represent attractive targets for vaccine therapy. We have shown previously that vaccinating cancer patients with mutant ras peptides is feasible and capable of inducing a specific immune response against the relevant mutant proteins. Here, we tested the mutant ras peptide vaccine administered in combination with low dose interleukin-2 (IL-2) or/and granulocyte-macrophage colony-stimulating factor (GM-CSF) in order to enhance the vaccine immune response. 5000 μg of the corresponding mutant ras peptide was given subcutaneously (SQ) along with IL-2 (Arm A), GM-CSF (Arm B) or both (Arm C). IL-2 was given SQ at 6.0 million IU/m²/day starting at day 5, 5 days/week for 2 weeks. GM-CSF was given SQ in a dose of 100 μg/day one day prior to each ras peptide vaccination for 4 days. Vaccines were repeated every 5 weeks on arm A and C, and every 4 weeks on arm B, for a maximum of 15 cycles or until disease progression. We treated 53 advanced cancer patients (38 with colorectal, 11 with pancreatic, 1 with common bile duct and 3 with lung) on 3 different arms (16 on arm A, 18 on arm B, and 19 on arm C). The median progression free survival (PFS) and overall survival (OS) was 3.6 and 16.9 months, respectively, for all patients evaluable for clinical response (n = 48). There was no difference in PFS or OS between the three arms (P = 0.73 and 0.99, respectively). Most adverse events were grade 1-2 toxicities and resolved spontaneously. The vaccine induced an immune response to the relevant ras peptide in a total of 20 out of 37 evaluable patients (54%) by ELISPOT, proliferative assay, or both. While 92.3% of patients on arm B had a positive immune response, only 31% of patients on arm A and 36% of patients on arm C had positive immune responses (P = 0.003, Fisher's exact test). The reported data showed that IL-2 might have a negative effect on the specific immune response induced by the relevant mutant ras vaccine in patients with advanced cancer. This observation deserves further investigations. NCI97C0141.

Up-regulation of MHC class I in transgenic mice results in reduced force-generating capacity in slow-twitch muscle

PubMed Central

Salomonsson, Stina; Grundtman, Cecilia; Zhang, Shi-Jin; Lanner, Johanna T.; Li, Charles; Katz, Abram; Wedderburn, Lucy R.; Nagaraju, Kanneboyina; Lundberg, Ingrid E.; Westerblad, Håkan

2008-01-01

Expression of major histocompatibility complex (MHC) class I in skeletal muscle fibers is an early and consistent finding in inflammatory myopathies. To test if MHC class I has a primary role in muscle impairment; we used transgenic mice with inducible over-expression of MHC class I in their skeletal muscle cells. Contractile function was studied in isolated extensor digitorum longus (EDL, fast-twitch) and soleus (slow-twitch) muscles. We found that EDL was smaller, whereas soleus muscle was slightly larger. Both muscles generated less absolute force in myopathic compared to control mice, however when force was expressed per cross-sectional area, only soleus muscle generated less force. Inflammation was markedly increased, but no changes were found in the activities of key mitochondrial and glycogenolytic enzymes in myopathic mice. The induction of MHC class I results in muscle atrophy and an intrinsic decrease in force-generation capacity. These observations may have important implications for our understanding of the pathophysiological processes of muscle weakness seen in inflammatory myopathies. PMID:19229963

Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue

PubMed Central

Sanchez, B; Li, J; Bragos, R; Rutkove, S B

2014-01-01

Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial content than fast-twitch (type 2) fibers. Accordingly, we sought to determine whether the dielectric properties of these two fiber types differed, consistent with their distinct intracellular morphologies. The longitudinal and transverse dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were measured in the 1 kHz–10 MHz frequency range and modeled to a resistivity Cole–Cole function. Major differences were especially apparent in the dielectric spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a well-defined, higher center frequency than the soleus muscle, whereas the soleus muscle showed a greater difference in the modeled zero and infinite resistivities than the gastrocnemius. These findings are consistent with the fact that soleus tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation of tissue at high frequency could provide a novel approach for assessing intracellular structure in health and disease. PMID:24743385

Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue

NASA Astrophysics Data System (ADS)

Sanchez, B.; Li, J.; Bragos, R.; Rutkove, S. B.

2014-05-01

Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial content than fast-twitch (type 2) fibers. Accordingly, we sought to determine whether the dielectric properties of these two fiber types differed, consistent with their distinct intracellular morphologies. The longitudinal and transverse dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were measured in the 1 kHz-10 MHz frequency range and modeled to a resistivity Cole-Cole function. Major differences were especially apparent in the dielectric spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a well-defined, higher center frequency than the soleus muscle, whereas the soleus muscle showed a greater difference in the modeled zero and infinite resistivities than the gastrocnemius. These findings are consistent with the fact that soleus tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation of tissue at high frequency could provide a novel approach for assessing intracellular structure in health and disease.

"Bird in the hand" cash was more effective than prize draws in increasing physician questionnaire response.

PubMed

Drummond, Frances J; O'Leary, Eamonn; O'Neill, Ciaran; Burns, Richeal; Sharp, Linda

2014-02-01

To investigate the effects of two monetary incentives on response rates to postal questionnaires from primary care physicians (PCPs). The PCPs were randomized into three arms (n=550 per arm), namely (1) €5 sent with the questionnaire (cash); (2) entry into a draw on return of completed questionnaire (prize); or (3) no incentive. Effects of incentives on response rates and item nonresponse were examined, as was cost-effectiveness. Response rates were significantly higher in the cash (66.1%; 95% confidence interval [CI]: 61.9, 70.4%) and prize arms (44.8%; 95% CI: 40.1, 49.3%) compared with the no-incentive arm (39.9%; 95% CI: 35.4, 44.3%). Adjusted relative risk of response was 1.17 (95% CI: 1.02, 1.35) and 1.68 (95% CI: 1.48, 1.91) in the prize and cash arms, respectively, compared with the no-incentive group. Costs per completed questionnaire were €9.85, €11.15, and €6.31 for the cash, prize, and no-incentive arms, respectively. Compared with the no-incentive arm, costs per additional questionnaire returned in the cash and prize arms were €14.72 and €37.20, respectively. Both a modest cash incentive and entry into a prize draw were effective in increasing response rates. The cash incentive was most effective and the most cost-effective. Where it is important to maximize response, a modest cash incentive may be cost-effective. Copyright © 2014 Elsevier Inc. All rights reserved.

Experiment K-7-21: Effect of Microgravity on 1: Metabolic Enzymes of Type 1 and Type 2 Muscle Fibers, and on 2: Metabolic Enzymes, Neurotransmitter Amino Acids, and Neurotransmitter Associated Enzymes in Selected Regions of the Central Nervous System. Part 1; Metabolic Enzymes of Individual Muscle Fibers

NASA Technical Reports Server (NTRS)

Lowry, O. H.; Ilyina-Kakueva, E. I.; Krasnov, I. B.; Carter, J. G.; Chi, M. M.-Y.; Choksi, R.; Manchester, J. K.; McDougal, D. B.; Nemeth, P. M.; Pusateri, M. E.

1994-01-01

Individual fibers of any given muscle vary widely in enzyme composition, a fact obscured when enzyme levels of whole muscle are measured. Therefore, the purpose of this part of the study was to assess the effects of microgravity and hind limb suspension on the enzyme patterns within a slow twitch muscle (soleus) and a fast twitch muscle (tibialis anterior).

Quantification of Bacterial Twitching Motility in Dense Colonies Using Transmitted Light Microscopy and Computational Image Analysis.

PubMed

Smith, Benjamin; Li, Jianfang; Metruccio, Matteo; Wan, Stephanie; Evans, David; Fleiszig, Suzanne

2018-04-20

A method was developed to allow the quantification and mapping of relative bacterial twitching motility in dense samples, where tracking of individual bacteria was not feasible. In this approach, movies of bacterial films were acquired using differential interference contrast microscopy (DIC), and bacterial motility was then indirectly quantified by the degree to which the bacteria modulated the intensity of light in the field-of-view over time. This allowed the mapping of areas of relatively high and low motility within a single field-of-view, and comparison of the total distribution of motility between samples.

Continuous Low-Dose Oral Cyclophosphamide and Methotrexate as Maintenance Therapy in Patients With Advanced Ovarian Carcinoma After Complete Clinical Response to Platinum and Paclitaxel Chemotherapy.

PubMed

El-Husseiny, Khalid; Motawei, Helmy; Ali, Mohamad Sayed

2016-03-01

The aim of this study was to evaluate efficacy and safety of continuous, low dose of oral, metronomic chemotherapy as maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy. In this nonrandomized study, patients older than 18 years, with Eastern Cooperative Oncology Group performance status less than 2, with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy were enrolled in 2 arms--arm A (maintenance arm), treated with continuous low-dose oral cyclophosphamide 50 mg and methotrexate 2.5 mg, and arm B (observation arm). Both arms were followed up for progression-free survival and toxicity. Thirty patients were accrued in each arm from January 2009 to December 2010 in Ain Shams University Hospitals, where they received the treatment and followed up for disease progression and toxicity. Patients had a median age of 53 years in maintenance arm and 52.5 years in the observational arm, respectively. Over 80% had papillary serous adenocarcinoma, and over 40% of them had a stage IV disease in both arms. After median follow-up of 27 months, patients achieved median progression-free survival of 18 months in maintenance arm (A) and 15.5 months in observational arm (B), respectively. Toxicity profile was excellent with no grade 3 or 4 toxicity reported. Current study may provide an evidence of efficacy and tolerability of continuous low-dose oral cyclophosphamide and methotrexate as a maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy.

Study of design and control of remote manipulators. Modeling manipulator arms with distributed flexibility for design and control

NASA Technical Reports Server (NTRS)

Book, W. J.

1974-01-01

The interactions of control system and distributed flexible structural dynamics is explored for mechanical arms. A modeling process using 4 x 4 transfer matrices is described which permits the closed loop response of many current arm configurations to be evaluated. Root locus, frequency response, modal shapes, and time impulse response have all been obtained from the digital computer implementation of this model, which is oriented to arm design and allows for easy variation of the arm configuration through data cards. The model corresponds with experimentally observed natural frequencies with an average error of less than 5% in the first three flexible modes in the seven cases considered. The model was used to explore the limits imposed by structural flexibility on a nondimensionalized two link arm with one and two joints for planar motion.

Lottery ticket was more effective than a prize draw in increasing questionnaire response among cancer survivors.

PubMed

Drummond, Frances J; O'Leary, Eamonn; Sharp, Linda

2015-07-01

Compare the effect of financial incentives on response to a cancer survivors' postal questionnaire. Prostate cancer survivors in Ireland, 1.5-18 years after diagnosis, were randomized to the (1) "lottery" arm [a € 1 lottery scratch card sent with the questionnaire (n = 2,413)] or (2) "prize" arm [entry into a draw on return of a completed questionnaire (n = 2,407)]. Impact of interventions on response overall and by survival period ("short term": < 5 years after diagnosis; "long term": ≥ 5 years after diagnosis) was compared as was cost-effectiveness. Adjusted response rate was 54.4%. Response was higher among younger men (P < 0.001) and those with earlier stage disease (P = 0.002). A modest 2.6% higher response rate was observed in the lottery compared with the prize arm [multivariate relative risk (RR) = 1.06; 95% confidence interval (CI): 1.00, 1.11]. When stratified by survival period, higher response in the lottery arm was only observed among long-term survivors (multivariate RR = 1.10; 95% CI: 1.02, 1.19; short-term survivors: RR = 1.01; 95% CI: 0.94, 1.09). Costs per completed questionnaire were € 4.54 and € 3.57 for the lottery and prize arms, respectively. Compared with the prize arm, cost per additional questionnaire returned in the lottery arm was € 25.65. Although more expensive, to optimize response to postal questionnaires among cancer survivors, researchers might consider inclusion of a lottery scratch card. Copyright © 2015 Elsevier Inc. All rights reserved.

In situ hybridisation of a large repertoire of muscle-specific transcripts in fish larvae: the new superficial slow-twitch fibres exhibit characteristics of fast-twitch differentiation.

PubMed

Chauvigné, F; Ralliere, C; Cauty, C; Rescan, P Y

2006-01-01

Much of the present information on muscle differentiation in fish concerns the early embryonic stages. To learn more about the maturation and the diversification of the fish myotomal fibres in later stages of ontogeny, we investigated, by means of in situ hybridisation, the developmental expression of a large repertoire of muscle-specific genes in trout larvae from hatching to yolk resorption. At hatching, transcripts for fast and slow muscle protein isoforms, namely myosins, tropomyosins, troponins and myosin binding protein C were present in the deep fast and the superficial slow areas of the myotome, respectively. During myotome expansion that follows hatching, the expression of fast isoforms became progressively confined to the borders of the fast muscle mass, whereas, in contrast, slow muscle isoform transcripts were uniformly expressed in all the slow fibres. Transcripts for several enzymes involved in oxidative metabolism such as citrate synthase, cytochrome oxidase component IV and succinate dehydrogenase, were present throughout the whole myotome of hatching embryos but in later stages became concentrated in slow fibre as well as in lateral fast fibres. Surprisingly, the slow fibres that are added externally to the single superficial layer of the embryonic (original) slow muscle fibres expressed not only slow twitch muscle isoforms but also, transiently, a subset of fast twitch muscle isoforms including MyLC1, MyLC3, MyHC and myosin binding protein C. Taken together these observations show that the growth of the myotome of the fish larvae is associated with complex patterns of muscular gene expression and demonstrate the unexpected presence of fast muscle isoform-expressing fibres in the most superficial part of the slow muscle.

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain.

PubMed

Rukhadze, I; Kamani, H; Kubin, L

2011-12-01

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.

Effects of dantrolene and its derivatives on Ca2+ release from the sarcoplasmic reticulum of mouse skeletal muscle fibres

PubMed Central

Ikemoto, Takaaki; Hosoya, Takamitsu; Aoyama, Hiroshi; Kihara, Yasutaka; Suzuki, Masaaki; Endo, Makoto

2001-01-01

We analysed the effect of dantrolene (Dan) and five newly synthesized derivatives (GIFs) on Ca2+ release from the sarcoplasmic reticulum (SR) of mouse skeletal muscle.In intact muscles, GIF-0185 reduced the size of twitch contraction induced by electrical stimulation to the same extent as Dan. GIF-0082, an azido-functionalized Dan derivative, also inhibited twitch contraction, although the extent of inhibition was less than that of Dan and of GIF-0185.In skinned fibres, Dan inhibited Ca2+-induced Ca2+ release (CICR) under Mg2+-free conditions at room temperature. In contrast, GIF-0082 and GIF-0185 showed no inhibitory effect on CICR under the same conditions.Dan-induced inhibition of CICR was not affected by the presence of GIF-0082, whereas it was diminished in the presence of GIF-0185.GIF-0082 and GIF-0185 significantly inhibited clofibric acid (Clof)-induced Ca2+ release, as did Dan.Several Dan derivatives other than GIF-0082 and GIF-0185 showed an inhibitory effect on twitch tension but not on the CICR mechanism. All of these derivatives inhibited Clof-induced Ca2+ release.The magnitudes of inhibition of Clof-induced Ca2+ release by all Dan derivatives were well correlated with those of twitch inhibition. This supports the notion that the mode of Clof-induced opening of the RyR-Ca2+ release channel may be similar to that of physiological Ca2+ release (PCR).These results indicate that the difference in opening modes of the RyR-Ca2+ release channel is recognized by certain Dan derivatives. PMID:11606312

Androgen Action via the Androgen Receptor in Neurons Within the Brain Positively Regulates Muscle Mass in Male Mice.

PubMed

Davey, Rachel A; Clarke, Michele V; Russell, Patricia K; Rana, Kesha; Seto, Jane; Roeszler, Kelly N; How, Jackie M Y; Chia, Ling Yeong; North, Kathryn; Zajac, Jeffrey D

2017-10-01

Although it is well established that exogenous androgens have anabolic effects on skeletal muscle mass in humans and mice, data from muscle-specific androgen receptor (AR) knockout (ARKO) mice indicate that myocytic expression of the AR is dispensable for hind-limb muscle mass accrual in males. To identify possible indirect actions of androgens via the AR in neurons to regulate muscle, we generated neuron-ARKO mice in which the dominant DNA binding-dependent actions of the AR are deleted in neurons of the cortex, forebrain, hypothalamus, and olfactory bulb. Serum testosterone and luteinizing hormone levels were elevated twofold in neuron-ARKO males compared with wild-type littermates due to disruption of negative feedback to the hypothalamic-pituitary-gonadal axis. Despite this increase in serum testosterone levels, which was expected to increase muscle mass, the mass of the mixed-fiber gastrocnemius (Gast) and the fast-twitch fiber extensor digitorum longus hind-limb muscles was decreased by 10% in neuron-ARKOs at 12 weeks of age, whereas muscle strength and fatigue of the Gast were unaffected. The mass of the soleus muscle, however, which consists of a high proportion of slow-twitch fibers, was unaffected in neuron-ARKOs, demonstrating a stimulatory action of androgens via the AR in neurons to increase the mass of fast-twitch hind-limb muscles. Furthermore, neuron-ARKOs displayed reductions in voluntary and involuntary physical activity by up to 60%. These data provide evidence for a role of androgens via the AR in neurons to positively regulate fast-twitch hind-limb muscle mass and physical activity in male mice. Copyright © 2017 Endocrine Society.

Microvascular oxygen pressures in muscles comprised of different fiber types: Impact of dietary nitrate supplementation

PubMed Central

Ferguson, Scott K.; Holdsworth, Clark T.; Wright, Jennifer L.; Fees, Alex J.; Allen, Jason D.; Jones, Andrew M.; Musch, Timothy I.; Poole, David C.

2014-01-01

Nitrate (NO3−) supplementation via beetroot juice (BR) preferentially improves vascular conductance and O2 delivery to contracting skeletal muscles comprised predominantly of type IIb + d/x (i.e. highly glycolytic) fibers following its reduction to nitrite and nitric oxide (NO). To address the mechanistic basis for NO3− to improve metabolic control we tested the hypothesis that increased NO bioavailability via BR supplementation would elevate microvascular PO2 (PO2mv) in fast twitch but not slow twitch muscle. Twelve young adult male Sprague-Dawley rats were administered BR ([NO3−] 1 mmol/kg/day, n=6) or water (control, n=6) for 5 days. PO2mv (phosphorescence quenching) was measured at rest and during 180s of electrically induced 1-Hz twitch contractions (6–8 V) of the soleus (9% type IIb +d/x) and mixed portion of the gastrocnemius (MG, 91% type IIb + d/x) muscles. In the MG, but not the soleus, BR elevated contracting steady state PO2mv by ~43% (control: 13.7 ± 0.5, BR: 19 ± 1.6 mmHg, (P<0.05). This higher PO2mv represents a greater blood-myocyte O2 driving force during muscle contractions thus providing a potential mechanism by which NO3− supplementation via BR improves metabolic control in fast twitch muscle. Recruitment of higher order type II muscle fibers is thought to play a role in the development of the V.O2 slow component which is inextricably linked to the fatigue process. These data therefore provide a putative mechanism for the BR-induced improvements in high-intensity exercise performance seen in humans. PMID:25280991

Functional pools of fast and slow twitch fibers observed by /sup 31/P-NMR during exercise of flexor wrist muscles in man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J.H.; Park, C.R.; Brown, R.L.

Functional compartments of fast and slow twitch fibers have been observed by /sup 31/P-NMR spectroscopy during exercise of the wrist flexor muscles in a sedentary, young male subject. Values of Pi, phosphocreatine (PCr) and adenine nucleotides were determined at rest and during an exercise protocol. The subject flexed his wrist muscles at 20% of maximum strength every 5 sec for 6 min and then increased his effort in the next two 6 min intervals to 40% and 60% of maximum. With exercise, the Pi/PCr rose rapidly to the exceptionally high value of 2.2 at 60% effort. As the Pi increased,more » the initial single peak (pH 7.0-6.9) split into two distinct components with pH values of 6.8 and 6.3. Quantitatively, distribution of the Pi was 40% in the pH 6.8 peak and 60% in the pH 6.3 peak as determined by area estimation following curve fitting. This presumably reflects two pools of Pi corresponding to the oxidative (slow twitch, high pH) and glycolytic (fast twitch, low pH) fibers. In the second identical exercise sequence which followed immediately, only one Pi peak (pH 6.8-6.9) appeared. This suggested that the glycolytic contribution to energy production was largely exhausted and the residual energy was derived from oxidative metabolism. During exercise at high levels, total phosphate decreased due primarily to loss of NMR visible adenine nucleotides. Similar phenomena have been observed in three other sedentary individuals, but not in trained athletes.« less

Changes in force and calcium sensitivity in the developing avian heart.

PubMed

Godt, R E; Fogaça, R T; Nosek, T M

1991-11-01

The aim of this study was to characterize the development of the contractile properties of intact and chemically skinned muscle from chicken heart and to compare these characteristics with those of developing mammalian heart reported by others. Small trabeculae were dissected from left ventricles of Arbor Acre chickens between embryonic day 7 and young adulthood (7 weeks post-hatching). At all ages, increasing extracellular calcium (0.45-3.6 mM) progressively increased twitch force of electrically stimulated trabeculae. Twitch force at 1.8 mM extracellular calcium, normalized to cross-sectional area, increased to a maximum at 1 day post-hatching, remained constant through 3 weeks post-hatching, but then decreased at 7 weeks post-hatching. The maximal calcium-activated force of trabeculae chemically skinned with Triton X-100 detergent increased to a maximum 2 days before the time of hatching and was not significantly changed up to 7 weeks post-hatching. Over the ages studied, average twitch force in 1.8 mM calcium was between 26 and 66% of maximal calcium-activated force after skinning, suggesting that the contractile apparatus is not fully activated during the twitch in normal Ringer. In skinned trabeculae, the calcium sensitivity of the contractile apparatus was higher in the embryo than in the young adult. These age-dependent changes in calcium sensitivity are correlated with isoform switching in troponin T. A decrease in pH from 7.0 to 6.5 decreased the calcium sensitivity of the contractile apparatus to a greater degree in skinned trabeculae from young adult hearts than in those from embryonic hearts. This change in susceptibility to acidosis is temporally associated with isoform switching in troponin I.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuro-muscular fatigue and recovery dynamics following anaerobic interval workload.

PubMed

Skof, B; Strojnik, V

2006-03-01

The aim of this study was to determine the influence of anaerobic running on muscle contractile characteristics and voluntary muscle activation level during MVC as well as the dynamics of their recovery during a 2-hour period. Seven well-trained runners performed 5 x 300 m at submaximal velocity with a 1-minute active recovery interval between the runs. The average run velocity was 6.69 m.s(-1), which represented 77 % of their top velocity. Contractile characteristics of the vastus lateralis and activation level of quadriceps femoris muscles were measured before and immediately after the runs and within the 120-minute time interval that followed the workload. To do this we used: single twitch, low- and high-frequency electrical stimulation, maximal voluntary knee extension test, and muscle activation level test. After the exercise the maximal twitch torque (T(TW)) decreased for 28 +/- 3.7 % (p < 0.001) and torque at stimulation with 20 Hz and 100 Hz were 19.2 +/- 4.6 % (p < 0.01) and 7.5 +/- 2.3 % (p < 0.05) lower, respectively, while MVC torque and activation level remained unchanged. Subjects with higher blood lactate accumulation level showed significant decrease in the torque at low frequency stimulation (T(F20)) (r = - 0.80; p < 0.01) and T(TW) (r = - 0.92; p < 0.01). The restoration of twitch torque took a short time despite the fact that blood lactate concentration remained high. Ten minutes after the last interval run the twitch torque exceeded the pre-workload value by 11 % (p < 0.01). Potentiation lasted until the 40th min. It was concluded that fatigue after the anaerobic interval workload was peripheral in character and caused by contractile mechanisms disturbances.

Microvascular oxygen pressures in muscles comprised of different fiber types: Impact of dietary nitrate supplementation.

PubMed

Ferguson, Scott K; Holdsworth, Clark T; Wright, Jennifer L; Fees, Alex J; Allen, Jason D; Jones, Andrew M; Musch, Timothy I; Poole, David C

2015-08-01

Nitrate (NO3(-)) supplementation via beetroot juice (BR) preferentially improves vascular conductance and O2 delivery to contracting skeletal muscles comprised predominantly of type IIb + d/x (i.e. highly glycolytic) fibers following its reduction to nitrite and nitric oxide (NO). To address the mechanistic basis for NO3(-) to improve metabolic control we tested the hypothesis that BR supplementation would elevate microvascular PO2 (PO2mv) in fast twitch but not slow twitch muscle. Twelve young adult male Sprague-Dawley rats were administered BR ([NO3(-)] 1 mmol/kg/day, n = 6) or water (control, n = 6) for 5 days. PO2mv (phosphorescence quenching) was measured at rest and during 180 s of electrically-induced 1-Hz twitch contractions (6-8 V) of the soleus (9% type IIb +d/x) and mixed portion of the gastrocnemius (MG, 91% type IIb + d/x) muscles. In the MG, but not the soleus, BR elevated contracting steady state PO2mv by ~43% (control: 14 ± 1, BR: 19 ± 2 mmHg (P < 0.05)). This higher PO2mv represents a greater blood-myocyte O2 driving force during muscle contractions thus providing a potential mechanism by which NO3(-) supplementation via BR improves metabolic control in fast twitch muscle. Recruitment of higher order type II muscle fibers is thought to play a role in the development of the VO2 slow component which is inextricably linked to the fatigue process. These data therefore provide a putative mechanism for the BR-induced improvements in high-intensity exercise performance seen in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of dominant and non-dominant passive arm manoeuvres on the neurovascular coupling response.

PubMed

Llwyd, Osian; Panerai, Ronney B; Robinson, Thompson G

2017-11-01

Models designed to study neurovascular coupling (NVC) describe a possible cerebral hemisphere dominance dependent on task completed and preference in handedness. We investigated whether passive arm manoeuvre performed with dominant (Dom-Arm) or non-dominant arm (ND-Arm) stimulated haemodynamic differences in either contralateral (Cont-H) or ipsilateral (Ipsil-H) cerebral hemisphere. Healthy individuals lying in supine position, had measurements of beat-to-beat blood pressure (BP, mmHg), electrocardiogram (HR, bpm), end-tidal CO 2 (etCO 2 , mmHg), and bilateral insonation of the middle cerebral arteries (MCA, cm s -1 ). Arm movement was performed for 60 s with passive flexion and extension of the elbow (1 Hz), before manoeuvre was repeated on other arm. Data were normalised and effect of treatment was analysed for differences between manoeuvres and within each time period. Seventeen (eight males) healthy volunteers, aged 56 ± 7 years, were studied. Dom-Arm and ND-Arm manoeuvres stimulated a comparable temporal response in peripheral and cerebral haemodynamic parameters between Cont-H and Ipsil-H. Both manoeuvres can be used to evoke similar bilateral MCA responses in assessing NVC. This finding should lead to more efficient protocols when using passive arm movement for NVC studies in healthy subjects.

The neuromuscular activity of Bothriopsis bilineata smaragdina (forest viper) venom and its toxin Bbil-TX (Asp49 phospholipase A2) on isolated mouse nerve-muscle preparations.

PubMed

Floriano, Rafael Stuani; Rocha, Thalita; Carregari, Victor Corasolla; Marangoni, Sergio; da Cruz-Höfling, Maria Alice; Hyslop, Stephen; Rodrigues-Simioni, Léa; Rowan, Edward G

2015-03-01

The presynaptic action of Bothriopsis bilineata smaragdina (forest viper) venom and Bbil-TX, an Asp49 PLA2 from this venom, was examined in detail in mouse phrenic nerve-muscle (PND) preparations in vitro and in a neuroblastoma cell line (SK-N-SH) in order to gain a better insight into the mechanism of action of the venom and associated Asp49 PLA2. In low Ca(2+) solution, venom (3μg/ml) caused a quadriphasic response in PND twitch height whilst at 10μg/ml the venom additionally induced an abrupt and marked initial contracture followed by neuromuscular facilitation, rhythmic oscillations of nerve-evoked twitches, alterations in baseline and progressive blockade. The venom slowed the relaxation phase of muscle twitches. In low Ca(2+), Bbil-TX [210nM (3μg/ml)] caused a progressive increase in PND twitch amplitude but no change in the decay time constant. Venom (10μg/ml) and Bbil-TX (210nM) caused minor changes in the compound action potential (CAP) amplitude recorded from sciatic nerve preparations, with no significant effect on rise time and latency; tetrodotoxin (3.1nM) blocked the CAP at the end of the experiments. In mouse triangularis sterni nerve-muscle (TSn-m) preparations, venom (10μg/ml) and Bbil-TX (210nM) significantly reduced the perineural waveform associated with the outward K(+) current while the amplitude of the inward Na(+) current was not significantly affected. Bbil-TX (210nM) caused a progressive increase in the quantal content of TSn-m preparations maintained in low Ca(2+) solution. Venom (3μg/ml) and toxin (210nM) increased the calcium fluorescence in SK-N-SH neuroblastoma cells loaded with Fluo3 AM and maintained in low or normal Ca(2+) solution. In normal Ca(2+), the increase in fluorescence amplitude was accompanied by irregular and frequent calcium transients. In TSn-m preparations loaded with Fluo4 AM, venom (10μg/ml) caused an immediate increase in intracellular Ca(2+) followed by oscillations in fluorescence and muscle contracture; Bbil-TX did not change the calcium fluorescence in TSn-m preparations. Immunohistochemical analysis of toxin-treated PND preparations revealed labeling of junctional ACh receptors but a loss of the presynaptic proteins synaptophysin and SNAP25. Together, these data confirm the presynaptic action of Bbil-TX and show that it involves modulation of K(+) channel activity and presynaptic protein expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma.

PubMed

Weber, Jeffrey S; Zarour, Hassan; Redman, Bruce; Trefzer, Uwe; O'Day, Steven; van den Eertwegh, Alfons J M; Marshall, Ernest; Wagner, Stefan

2009-09-01

The primary objective of this phase 2 study was to assess the objective response rate (complete response [CR] + partial responses [PR]), by Response Evaluation Criteria in Solid Tumors, of PF-3512676, a CpG oligodeoxynucleotide, alone in 2 doses or in combination with dacarbazine (DTIC) in patients with unresectable stage IIIB/C or stage IV malignant melanoma, with the aim of selecting an arm to take forward to a phase 3 portion of the study. A total of 184 patients were randomized to 1 of 4 treatments: PF-3512676 10 mg (low dose), at 40 mg (high dose), 40 mg plus DTIC (850 mg/m(2)), or DTIC (850 mg/m(2)) alone. Patients received PF-3512676 subcutaneously weekly in a 3-week cycle and received DTIC intravenously on the first week of the cycle. The objective response rate (PR or CR, confirmed or unconfirmed) in the 40 mg + DTIC arm was 16% (7 patients) compared with 8% (3 patients) with DTIC alone. One (2%) patient in the 10-mg and 0 patients in the 40-mg arms achieved an objective response. Best response of CR or PR or stable disease (SD), with no minimum duration defined for SD, was achieved by 15 (33%) patients in the 40 mg + DTIC arm, 15 (38%) patients in the DTIC-only arm, 8 (17%) patients in the 10-mg arm, and 9 (20%) patients in the 40-mg arm. The most frequently reported adverse events were classified as local injection site reactions or systemic flu-like symptoms, specifically fatigue, rigors, and pyrexia. PF-3512676 at the doses used was generally well tolerated. The modest objective response rates observed in all arms did not warrant continuation to the phase 3 portion of the study.

Efficacy of tandospirone in patients with irritable bowel syndrome-diarrhea and anxiety

PubMed Central

Lan, Ling; Chen, Yu-Long; Zhang, Hao; Jia, Bai-Ling; Chu, Yan-Jun; Wang, Jin; Tang, Shi-Xiao; Xia, Guo-Dong

2014-01-01

AIM: To investigate the efficacy of tandospirone in patients with irritable bowel syndrome-diarrhea (IBS-D) and anxiety in a prospective, randomized, controlled study. METHODS: Two hundred patients with IBS-D and moderate anxiety were randomized to receive pinaverium and tandospirone (arm A) or pinaverium and placebo (arm B). Tandospirone or placebo was given thrice daily at a fixed dose of 10 mg and pinaverium was given thrice daily at a fixed dose of 50 mg. The duration of treatment was 8 wk. Patients were assessed for abdominal pain and diarrhea. Anxiety was evaluated using the Hamilton Rating Scale for Anxiety (HAM-A). The primary study endpoints were response rates for abdominal pain and diarrhea. The secondary study endpoints were response rates for anxiety. Adverse events were also evaluated. RESULTS: One hundred and seventy of 200 patients (82 patients in arm A and 88 patients in arm B) completed the study. Demographic and baseline characteristics of the 200 participants were comparable in the two arms. At week 8, the overall response rate for abdominal pain and diarrhea was 52.0% for arm A and 37.0% for arm B (P < 0.05). The HAM-A score showed that the response rate was 61.0% for arm A and 21.0% for arm B (P < 0.01). The treatments were well tolerated and no significant adverse events were reported. CONCLUSION: Tandospirone is effective and can be combined with pinaverium in IBS-D patients with anxiety. PMID:25170231

Upper motor neurone modulation of the structure of the terminal cisternae in rat skeletal muscle fibres.

PubMed

Dulhunty, A F; Gage, P W; Valois, A A

1981-12-23

There are fewer indentations on the flat surfaces of terminal cisternae in soleus (slow-twitch) than in extensor digitorum longus (EDL, fast-twitch) muscle fibres of rats. Following mid-thoracic spinal cord transection, there is an increase in the number of indentations in soleus fibres but no change in EDL fibres. The increase in the numbers of indentations after spinal cord transections is correlated with changes in the contractile and charge movement properties of the soleus fibres so that they resemble normal EDL fibres. The indentations appear to have an important role in excitation-contraction coupling.

Changes of muscle function and size with bedrest

NASA Technical Reports Server (NTRS)

Dudley, Gary A.; Gollnick, Philip D.; Convertino, Victor A.; Buchanan, Paul

1989-01-01

The impact of a short-term head-down bedrest on the skeletal-muscle function of humans was investigated in healthy males subjected (after five days of control period) to 30-day 6-deg head-down bed rest (BR) followed by a five-day recovery period. It was found that the head-down BR led to a decrease in force developed by the knee extensor muscle group during maximal voluntary efforts, with the average reduction of 21 percent across the speeds of concentric and eccentric muscle action. Significant decreases were also found in the cross-sectional areas of slow-twitch and fast-twitch muscle fibers of the vastus lateralis.

Effects of an acute bout of resistance exercise on fiber-type specific to GLUT4 and IGF-1R expression.

PubMed

Gallagher, Philip M; Touchberry, Chad D; Teson, Kelli; McCabe, Everlee; Tehel, Michelle; Wacker, Michael J

2013-05-01

The effects of resistance exercise on fiber-type-specific expression of insulin-like growth factor I receptor (IGF-1R) and glucose transporter 4 (GLUT4) was determined in 6 healthy males. The expression of both genes increased in Type I fibers (p < 0.05), but only GLUT4 increased (p < 0.05) in Type II fibers. These data demonstrates that an acute bout of resistance exercise can up-regulate mechanisms of glucose uptake in slow and fast-twitch fibers, but the IGF signaling axis may not be as effective in fast-twitch fibers.

Multiple roles of Pseudomonas aeruginosa TBCF10839 PilY1 in motility, transport and infection

PubMed Central

Bohn, Yu-Sing Tammy; Brandes, Gudrun; Rakhimova, Elza; Horatzek, Sonja; Salunkhe, Prabhakar; Munder, Antje; van Barneveld, Andrea; Jordan, Doris; Bredenbruch, Florian; Häußler, Susanne; Riedel, Kathrin; Eberl, Leo; Jensen, Peter Østrup; Bjarnsholt, Thomas; Moser, Claus; Hoiby, Niels; Tümmler, Burkhard; Wiehlmann, Lutz

2008-01-01

Polymorphonuclear neutrophils are the most important mammalian host defence cells against infections with Pseudomonas aeruginosa. Screening of a signature tagged mutagenesis library of the non-piliated P. aeruginosa strain TBCF10839 uncovered that transposon inactivation of its pilY1 gene rendered the bacterium more resistant against killing by neutrophils than the wild type and any other of the more than 3000 tested mutants. Inactivation of pilY1 led to the loss of twitching motility in twitching-proficient wild-type PA14 and PAO1 strains, predisposed to autolysis and impaired the secretion of quinolones and pyocyanin, but on the other hand promoted growth in stationary phase and bacterial survival in murine airway infection models. The PilY1 population consisted of a major full-length and a minor shorter PilY1* isoform. PilY1* was detectable in small extracellular quinolone-positive aggregates, but not in the pilus. P. aeruginosa PilY1 is not an adhesin on the pilus tip, but assists in pilus biogenesis, twitching motility, secretion of secondary metabolites and in the control of cell density in the bacterial population. PMID:19054330

The Major Outer Membrane Protein MopB Is Required for Twitching Movement and Affects Biofilm Formation and Virulence in Two Xylella fastidiosa strains.

PubMed

Chen, Hongyu; Kandel, Prem P; Cruz, Luisa F; Cobine, Paul A; De La Fuente, Leonardo

2017-11-01

MopB is a major outer membrane protein (OMP) in Xylella fastidiosa, a bacterial plant pathogen that causes losses on many economically important crops. Based on in silico analysis, the uncharacterized MopB protein of X. fastidiosa contains a β-barrel structure with an OmpA-like domain and a predicted calcium-binding motif. Here, MopB function was studied by mutational analysis taking advantage of the natural competence of X. fastidiosa. Mutants of mopB were constructed in two different X. fastidiosa strains, the type strain Temecula and the more virulent WM1-1. Deletion of the mopB gene impaired cell-to-cell aggregation, surface attachment, and biofilm formation in both strains. Interestingly, mopB deletion completely abolished twitching motility. Electron microscopy of the bacterial cell surface revealed that mopB deletion eliminated type IV and type I pili formation, potentially caused by destabilization of the outer membrane. Both mopB mutants showed reduced virulence using tobacco (Nicotiana tabacum) as a host under greenhouse conditions. These results suggest that MopB has pleiotropic functions in biofilm formation and twitching motility and is important for virulence of X. fastidiosa.

Gene expression levels of heat shock proteins in the soleus and plantaris muscles of rats after hindlimb suspension or spaceflight.

PubMed

Ishihara, Akihiko; Fujino, Hidemi; Nagatomo, Fumiko; Takeda, Isao; Ohira, Yoshinobu

2008-12-01

Gene expression levels of heat shock proteins (HSPs) in the slow-twitch soleus and fast-twitch plantaris muscles of rats were determined after hindlimb suspension or spaceflight. Male rats were hindlimb-suspended for 14 d or exposed to microgravity for 9 d. The mRNA expression levels of HSP27, HSP70, and HSP84 in the hindlimb-suspended and microgravity-exposed groups were compared with those in the controls. The mRNA expression levels of the 3 HSPs in the soleus muscle under normal conditions were higher compared with those in the plantaris muscle. The mRNA expression levels of the 3 HSPs in the soleus muscle were inhibited by hindlimb suspension and spaceflight. The mRNA expression levels of the 3 HSPs in the plantaris muscle did not change after hindlimb suspension. It is suggested that the mRNA expression levels of the 3 HSPs are regulated by the mechanical and neural activity levels, and therefore the decreased mRNA expression levels of HSPs in the slow-twitch muscle following hindlimb suspension and spaceflight are related to a reduction in the mechanical and neural activity levels.

Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice.

PubMed

Egawa, Tatsuro; Goto, Ayumi; Ohno, Yoshitaka; Yokoyama, Shingo; Ikuta, Akihiro; Suzuki, Miho; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Hayashi, Tatsuya; Goto, Katsumasa

2015-10-01

AMPK is considered to have a role in regulating skeletal muscle mass. However, there are no studies investigating the function of AMPK in modulating skeletal muscle mass during atrophic conditions. In the present study, we investigated the difference in unloading-associated muscle atrophy and molecular functions in response to 2-wk hindlimb suspension between transgenic mice overexpressing the dominant-negative mutant of AMPK (AMPK-DN) and their wild-type (WT) littermates. Male WT (n = 24) and AMPK-DN (n = 24) mice were randomly divided into two groups: an untreated preexperimental control group (n = 12 in each group) and an unloading (n = 12 in each group) group. The relative soleus muscle weight and fiber cross-sectional area to body weight were decreased by ∼30% in WT mice by hindlimb unloading and by ∼20% in AMPK-DN mice. There were no changes in puromycin-labeled protein or Akt/70-kDa ribosomal S6 kinase signaling, the indicators of protein synthesis. The expressions of ubiquitinated proteins and muscle RING finger 1 mRNA and protein, markers of the ubiquitin-proteasome system, were increased by hindlimb unloading in WT mice but not in AMPK-DN mice. The expressions of molecules related to the protein degradation system, phosphorylated forkhead box class O3a, inhibitor of κBα, microRNA (miR)-1, and miR-23a, were decreased only in WT mice in response to hindlimb unloading, and 72-kDa heat shock protein expression was higher in AMPK-DN mice than in WT mice. These results imply that AMPK partially regulates unloading-induced atrophy of slow-twitch muscle possibly through modulation of the protein degradation system, especially the ubiquitin-proteasome system. Copyright © 2015 the American Physiological Society.

Skeletal muscle responses to unloading with special reference to man

NASA Technical Reports Server (NTRS)

Dudley, G. A.; Hather, B. M.; Buchanan, P.

1992-01-01

The limited space flight data suggest that exposure to microgravity decreases muscle strength in humans and muscle mass in lower mammals. Several earth-based models have been used to address the effect of unloading on the human neuromuscular system due to the limited access of biological research to long-term space flight. Bedrest eliminates body weight bearing of both lower limbs. Unilateral lower limb suspension (ULLS), where all ambulatory activity is performed on crutches with an elevated sole on the shoe of one foot, has recently been used to unload one lower limb. The results from studies using these two models support their efficacy. The decrease in strength of m. quadriceps femoris, for example, after four to six weeks of bedrest, ULLS or space flight is 20 to 25 percent. The results from the earth-based studies show that this response can be attributed in part to a decrease in the cross-sectional area of the KE which reflects muscle fiber atrophy. The results from the ground based studies also support the limited flight data and show that reductions in strength are larger in lower than upper limbs and in extensor than flexor muscle groups. They also raise issue with the generally held concept that postural muscle is most affected by unweighting. Slow-twitch fibers in lower limb muscles of mixed fiber type composition and muscle composed mainly of slow-twitch fibers do not preferentially atrophy after bedrest or ULLS. Taken together, the data suggest that unloading causes remarkable adaptations in the neuromuscular system of humans. It should be appreciated, however, that this area of research is in its infancy.

Hand-transmitted vibration and biodynamic response of the human hand-arm: a critical review.

PubMed

Dong, R G; Rakheja, S; Schopper, A W; Han, B; Smutz, W P

2001-01-01

Hand-arm vibration syndrome (HAVS) has been associated with prolonged exposure to vibration transmitted to the human hand-arm system from hand-held power tools, vibrating machines, or hand-held vibrating workpieces. The biodynamic response of the human hand and arm to hand transmitted vibration (HTV) forms an essential basis for effective evaluations of exposures, vibration-attenuation mechanisms, and potential injury mechanisms. The biodynamic response to HTV and its relationship to HAVS are critically reviewed and discussed to highlight the advances and the need for further research. In view of its strong dependence on the nature of HTV and the lack of general agreement on the characteristics of HTV, the reported studies are first reviewed to enhance an understanding of HTV and related issues. The characteristics of HTV and relevant unresolved issues are discussed on the basis of measured data, proposed standards, and measurement methods, while the need for further developments in measurement systems is emphasized. The studies on biodynamic response and their findings are grouped into four categories based on the methodology used and the objective. These include studies on (1) through-the-hand-arm response, expressed in terms of vibration transmissibility; (2) to-the-hand response, expressed in terms of the force-motion relationship of the hand-arm system; (3) to-the-hand biodynamic response function, expressed in terms of vibration energy absorption; and (4) computer modeling of the biodynamic response characteristics.

Primary reaction control system/remote manipulator system interaction with loaded arm. Space shuttle engineering and operations support

NASA Technical Reports Server (NTRS)

Taylor, E. C.; Davis, J. D.

1978-01-01

A study of the interaction between the orbiter primary reaction control system (PRCS) and the remote manipulator system (RMS) with a loaded arm is documented. This analysis was performed with the Payload Deployment and Retrieval Systems Simulation (PDRSS) program with the passive arm bending option. The passive-arm model simulates the arm as massless elastic links with locked joints. The study was divided into two parts. The first part was the evaluation of the response of the arm to step inputs (i.e. constant jet torques) about each of the orbiter body axes. The second part of the study was the evaluation of the response of the arm to minimum impulse primary RCS jet firings with both single pulse and pulse train inputs.

Impact of weightlessness on muscle function

NASA Technical Reports Server (NTRS)

Tischler, M. E.; Slentz, M.

1995-01-01

The most studied skeletal muscles which depend on gravity, "antigravity" muscles, are located in the posterior portion of the legs. Antigravity muscles are characterized generally by a different fiber type composition than those which are considered nonpostural. The gravity-dependent function of the antigravity muscles makes them particularly sensitive to weightlessness (unweighting) resulting in a substantial loss of muscle protein, with a relatively greater loss of myofibrillar (structural) proteins. Accordingly alpha-actin mRNA decreases in muscle of rats exposed to microgravity. In the legs, the soleus seems particularly responsive to the lack of weight-bearing associated with space flight. The loss of muscle protein leads to a decreased cross-sectional area of muscle fibers, particularly of the slow-twitch, oxidative (SO) ones compared to fast-twitch glycolytic (FG) or oxidative-glycolytic (FOG) fibers. In some muscles, a shift in fiber composition from SO to FOG has been reported in the adaptation to spaceflight. Changes in muscle composition with spaceflight have been associated with decreased maximal isometric tension (Po) and increased maximal shortening velocity. In terms of fuel metabolism, results varied depending on the pathway considered. Glucose uptake, in the presence of insulin, and activities of glycolytic enzymes are increased by space flight. In contrast, oxidation of fatty acids may be diminished. Oxidation of pyruvate, activity of the citric acid cycle, and ketone metabolism in muscle seem to be unaffected by microgravity.

Nootropic activity of tuber extract of Pueraria tuberosa (Roxb).

PubMed

Rao, N Venkata; Pujar, Basavaraj; Nimbal, S K; Shantakumar, S M; Satyanarayana, S

2008-08-01

Nootropic effect of alcoholic (ALE; 50, 75, 100 mg/kg) and aqueous (AQE; 100, 200, 400 mg/kg) extracts of P. tuberosa was evaluated by using Elevated Plus Maze (EPM), scopolamine-induced amnesia (SIA), diazepam-induced amnesia (DIA), clonidine-induced (NA-mediated) hypothermia (CIH), lithium-induced (5-HT mediated) head twitches (LIH) and haloperidol-induced (DA- mediated) catalepsy (HIC) models. Piracetam was used as the standard drug. A significant increase in inflexion ratio (IR) was recorded in EPM, SIA and DIA models. A significant reversal effect was observed on rectal temperature in CIH model, reduction of head twitches in LIH models. However no significant reduction in catalepsy scores in HIC models were observed with test extracts and standard piracetam. The results indicate that nootropic activity observed with ALE and AQE of tuber extracts of P. tuberosa could be through improved learning and memory either by augmenting the noradrenaline (NA) transmission or by interfering with 5-hydroxytryptamine (5-HT) release. Further, the extracts neither facilitated nor blocked release of the dopamine (DA). Thus ALE and AQE elicited significant nootropic effect in mice and rats by interacting with cholinergic, GABAnergic, adrenergic and serotonergic systems. Phytoconstituents like flavonoids have been reported for their nootropic effect and these are present in both ALE and AQE extracts of tubers of P. tuberosa (Roxb) and these active principles may be responsible for nootropic activity.

Rocuronium versus vecuronium during fentanyl induction in patients undergoing coronary artery surgery.

PubMed

Smith, C E; Botero, C; Holbrook, C; Pinchak, A C; Hagen, J F

1999-10-01

To evaluate the neuromuscular, ventilatory, and cardiovascular effects of rocuronium and vecuronium. Randomized, prospective, blinded study. Tertiary care teaching center, single institution. Patients undergoing elective coronary artery bypass graft procedure. Patients received rocuronium, 1.0 mg/kg (n = 17), or vecuronium, 0.15 mg/kg (n = 15), during fentanyl induction of anesthesia. Measures consisted of time to visual loss of orbicularis oculi twitches in response to facial nerve stimulation, ease of mask ventilation, hemodynamics, need for vasoactive drugs, and tracheal intubating conditions. Median time to twitch loss was faster (p < 0.05) after rocuronium (60 s) than after vecuronium (>84 s). Within 45 seconds, only 3 of 17 patients in the rocuronium group had moderate-to-severe difficulty with mask ventilation versus 12 of 15 patients in the vecuronium group (p < 0.05). Tracheal intubating conditions were excellent in all patients after rocuronium. In the vecuronium group, intubating conditions were excellent in 46%, good in 27%, and poor in 27% (p < 0.05 vrocuronium). Patients receiving vecuronium were more likely to require ephedrine and phenylephrine for hypotension (10/15 patients v 5/17 patients for rocuronium, p < 0.05). There were no clinically important differences in hemodynamic variables, oxygen metabolism, or myocardial ischemia between groups. During narcotic induction of anesthesia, rocuronium was associated with lower requirement for vasopressors, faster onset of neuromuscular blockade, and better conditions for mask ventilation and tracheal intubation compared with vecuronium.

Is the notion of central fatigue based on a solid foundation?

PubMed

Contessa, Paola; Puleo, Alessio; De Luca, Carlo J

2016-02-01

Exercise-induced muscle fatigue has been shown to be the consequence of peripheral factors that impair muscle fiber contractile mechanisms. Central factors arising within the central nervous system have also been hypothesized to induce muscle fatigue, but no direct empirical evidence that is causally associated to reduction of muscle force-generating capability has yet been reported. We developed a simulation model to investigate whether peripheral factors of muscle fatigue are sufficient to explain the muscle force behavior observed during empirical studies of fatiguing voluntary contractions, which is commonly attributed to central factors. Peripheral factors of muscle fatigue were included in the model as a time-dependent decrease in the amplitude of the motor unit force twitches. Our simulation study indicated that the force behavior commonly attributed to central fatigue could be explained solely by peripheral factors during simulated fatiguing submaximal voluntary contractions. It also revealed important flaws regarding the use of the interpolated twitch response from electrical stimulation of the muscle as a means for assessing central fatigue. Our analysis does not directly refute the concept of central fatigue. However, it raises important concerns about the manner in which it is measured and about the interpretation of the commonly accepted causes of central fatigue and questions the very need for the existence of central fatigue. Copyright © 2016 the American Physiological Society.

Inorganic Nitrate Mimics Exercise-Stimulated Muscular Fiber-Type Switching and Myokine and γ-Aminobutyric Acid Release.

PubMed

Roberts, Lee D; Ashmore, Tom; McNally, Ben D; Murfitt, Steven A; Fernandez, Bernadette O; Feelisch, Martin; Lindsay, Ross; Siervo, Mario; Williams, Elizabeth A; Murray, Andrew J; Griffin, Julian L

2017-03-01

Exercise is an effective intervention for the prevention and treatment of type 2 diabetes. Skeletal muscle combines multiple signals that contribute to the beneficial effects of exercise on cardiometabolic health. Inorganic nitrate increases exercise efficiency, tolerance, and performance. The transcriptional regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) coordinates the exercise-stimulated skeletal muscle fiber-type switch from glycolytic fast-twitch (type IIb) to oxidative slow-twitch (type I) and intermediate (type IIa) fibers, an effect reversed in insulin resistance and diabetes. We found that nitrate induces PGC1α expression and a switch toward type I and IIa fibers in rat muscle and myotubes in vitro. Nitrate induces the release of exercise/PGC1α-dependent myokine FNDC5/irisin and β-aminoisobutyric acid from myotubes and muscle in rats and humans. Both exercise and nitrate stimulated PGC1α-mediated γ-aminobutyric acid (GABA) secretion from muscle. Circulating GABA concentrations were increased in exercising mice and nitrate-treated rats and humans; thus, GABA may function as an exercise/PGC1α-mediated myokine-like small molecule. Moreover, nitrate increased circulating growth hormone levels in humans and rodents. Nitrate induces physiological responses that mimic exercise training and may underlie the beneficial effects of this metabolite on exercise and cardiometabolic health. © 2017 by the American Diabetes Association.

Muscle Contractile Properties in Severely Burned Rats

PubMed Central

Wu, Xiaowu; Wolf, Steven E.; Walters, Thomas J.

2010-01-01

Burn induces a sustained catabolic response which causes massive loss of muscle mass after injury. A better understanding of the dynamics of muscle wasting and its impact on muscle function is necessary for the development of effective treatments. Male Sprague-Dawley rats underwent either a 40% total body surface area (TBSA) scald burn or sham burn, and were further assigned to subgroups at four time points after injury (days 3, 7, 14 and 21). In situ isometric contractile properties were measured including twitch tension (Pt), tetanic tension (Po) and fatigue properties. Body weight decreased in burn and sham groups through day 3, however, body weight in the sham groups recovered and increased over time compared to burned groups, which progressively decreased until day 21 after injury. Significant differences in muscle wet weight and protein weight were found between sham and burn. Significant differences in muscle contractile properties were found at day 14 with lower absolute Po as well as specific Po in burned rats compared to sham. After burn, the muscle twitch tension was significantly higher than the sham at day 21. No significant difference in fatigue properties was found between the groups. This study demonstrates dynamics of muscle atrophy and muscle contractile properties after severe burn; this understanding will aid in the development of approaches designed to reduce the rate and extent of burn induced muscle loss and function. PMID:20381255

Hierarchical control of motor units in voluntary contractions.

PubMed

De Luca, Carlo J; Contessa, Paola

2012-01-01

For the past five decades there has been wide acceptance of a relationship between the firing rate of motor units and the afterhyperpolarization of motoneurons. It has been promulgated that the higher-threshold, larger-soma, motoneurons fire faster than the lower-threshold, smaller-soma, motor units. This relationship was based on studies on anesthetized cats with electrically stimulated motoneurons. We questioned its applicability to motor unit control during voluntary contractions in humans. We found that during linearly force-increasing contractions, firing rates increased as exponential functions. At any time and force level, including at recruitment, the firing rate values were inversely related to the recruitment threshold of the motor unit. The time constants of the exponential functions were directly related to the recruitment threshold. From the Henneman size principle it follows that the characteristics of the firing rates are also related to the size of the soma. The "firing rate spectrum" presents a beautifully simple control scheme in which, at any given time or force, the firing rate value of earlier-recruited motor units is greater than that of later-recruited motor units. This hierarchical control scheme describes a mechanism that provides an effective economy of force generation for the earlier-recruited lower force-twitch motor units, and reduces the fatigue of later-recruited higher force-twitch motor units-both characteristics being well suited for generating and sustaining force during the fight-or-flight response.

Hierarchical control of motor units in voluntary contractions

PubMed Central

Contessa, Paola

2012-01-01

For the past five decades there has been wide acceptance of a relationship between the firing rate of motor units and the afterhyperpolarization of motoneurons. It has been promulgated that the higher-threshold, larger-soma, motoneurons fire faster than the lower-threshold, smaller-soma, motor units. This relationship was based on studies on anesthetized cats with electrically stimulated motoneurons. We questioned its applicability to motor unit control during voluntary contractions in humans. We found that during linearly force-increasing contractions, firing rates increased as exponential functions. At any time and force level, including at recruitment, the firing rate values were inversely related to the recruitment threshold of the motor unit. The time constants of the exponential functions were directly related to the recruitment threshold. From the Henneman size principle it follows that the characteristics of the firing rates are also related to the size of the soma. The “firing rate spectrum” presents a beautifully simple control scheme in which, at any given time or force, the firing rate value of earlier-recruited motor units is greater than that of later-recruited motor units. This hierarchical control scheme describes a mechanism that provides an effective economy of force generation for the earlier-recruited lower force-twitch motor units, and reduces the fatigue of later-recruited higher force-twitch motor units—both characteristics being well suited for generating and sustaining force during the fight-or-flight response. PMID:21975447

US conventional arms transfer policy. Strategy research project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langhorst, R.H.

1996-04-15

Millions of people around the world have been killed by conventional arms since the end of World War II. If increasing access to conventional arms is partly responsible for political and military aggression in post-Cold War Europe, what should be the United States` response. This study explores the new US Conventional Arms Transfer Policy of February 1995 in terms of ends1 ways and means and its linkages to US National Security and National Military Strategies. Analysis focuses mainly on post- Cold War Europe, providing examples of multilateral arms control successes and recommendations for US policy implementation.

Pharmacological modulation of abnormal involuntary DOI-induced head twitch response movements in male DBA/2J mice: II. Effects of D3 dopamine receptor selective compounds.

PubMed

Rangel-Barajas, Claudia; Malik, Maninder; Mach, Robert H; Luedtke, Robert R

2015-06-01

We recently reported on the characterization of the hallucinogen 2,5-dimethoxy-4-methylamphetamine's (DOI) ability to elicit a head twitch response (HTR) in DBA/2J mice and the ability of D2 vs. D3 dopamine receptor selective compounds to modulate that response. For these studies, the ability of D3 vs. D2 dopamine receptor selective compounds to attenuate the DOI-dependent HTR was examined. WC 10, a D3 dopamine receptor weak partial agonist with 40-fold binding selectivity for D3 vs. D2 dopamine receptors, produced a dose-dependent decrease in the DOI-induced HTR (IC50 = 3.7 mg/kg). WC 44, a D3 receptor selective full agonist, also inhibited the DOI-induced HTR (IC50 = 5.1 mg/kg). The effect of two D3 receptor selective partial agonists, LAX-4-136 and WW-III-55, were also evaluated. These analogs exhibit 150-fold and 800-fold D3 vs. D2 binding selectivity, respectively. Both compounds inhibited the HTR with similar potency but with different maximum efficacies. At 10 mg/kg WW-III-55 inhibited the HTR by 95%, while LAX-4-136 administration resulted in a 50% reduction. In addition, DOI (5 mg/kg) was administered at various times after LAX-4-136 or WW-III-55 administration to compare the duration of action. The homopiperazine analog LAX-4-136 exhibited greater stability. An assessment of our test compounds on motor performance and coordination was performed using a rotarod test. None of the D3 dopamine receptor selective compounds significantly altered latency to fall, suggesting that these compounds a) did not attenuate the DOI-dependent HTR due to sedative or adverse motor effects and b) may have antipsychotic/antihallucinogenic activity. Copyright © 2015. Published by Elsevier Ltd.

A simple integrated ratiometric wavelength monitor based on multimode interference structure

NASA Astrophysics Data System (ADS)

Hatta, Agus Muhamad; Farrell, Gerald; Wang, Qian

2008-09-01

Wavelength measurement or monitoring can be implemented using a ratiometric power measurement technique. A ratiometric wavelength monitor normally consists of a Y-branch splitter with two arms: an edge filter arm with a well defined spectral response and a reference arm or alternatively, two edge filters arms with opposite slope spectral responses. In this paper, a simple configuration for an integrated ratiometric wavelength monitor based on a single multimode interference structure is proposed. By optimizing the length of the MMI and the two output port positions, opposite spectral responses for the two output ports can be achieved. The designed structure demonstrates a spectral response suitable for wavelength measurement with potentially a 10 pm resolution over a 100 nm wavelength range.

Effects of presynaptic muscarinic cholinoreceptor blockade on neuromuscular transmission as assessed by the train-of-four and the tetanic fade response to rocuronium.

PubMed

Kim, Yong Beom; Lee, Sangseok; Lee, Kyeong Chun; Kim, Ha Jung; Ro, Young Jin; Yang, Hong-Seuk

2017-07-01

This study investigated the effect of muscarinic M 1 and M 2 receptor antagonists on the rocuronium-induced train of four (TOF) fade and tetanic fade, respectively. Ex-vivo phrenic nerves and diaphragms were obtained from adult Sprague-Dawley rats and stabilized in Krebs buffer; the nerve-stimulated muscle TOF fade was observed at 20 s intervals. For the TOF study, phrenic nerves and diaphragms were incubated with pirenzepine (an M 1 blocker) at concentrations of 0 nmol L -1 (control), 10 nmol L -1 (PZP10), or 100 nmol L -1 (PZP100). Rocuronium was then administered incrementally until the first twitch tension had depressed by >95% during TOF stimulation. The mean TOF ratios were compared when the first twitch tensions were depressed by 40%-50%. For the tetanic fade study, 50 Hz/5 s tetani was applied initially, 30 min after the administration of a loading dose of rocuronium and methoctramine (an M 2 receptor blocker, loaded at 0 μmol L -1 [control], 1 μmol L -1 [MET1], or 10 μmol L -1 [MET10]). The EC 95 of rocuronium was significantly lower in the PZP10 group than in the control group. In the PZP10 group, the TOF ratios at 50% and first twitch tension depression were significantly lower than those in the control group (P=.02). During tetanic stimulation, the tetanic fade was significantly enhanced in the MET10 group compared to the other groups. This study shows that antagonists of muscarinic M 1 and M 2 receptors affect the rocuronium-induced neuromuscular block as demonstrated by the reduced EC 95 and TOF ratios (M 1 antagonist, pirenzepine) or the enhanced 50-Hz tetanic fade (M 2 antagonist, methoctramine). © 2017 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

MicroRNA-206: A Potential Circulating Biomarker Candidate for Amyotrophic Lateral Sclerosis

PubMed Central

Toivonen, Janne M.; Manzano, Raquel; Oliván, Sara; Zaragoza, Pilar; García-Redondo, Alberto; Osta, Rosario

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease that progressively debilitates neuronal cells that control voluntary muscle activity. Biomarkers are urgently needed to facilitate ALS diagnosis and prognosis, and as indicators of therapeutic response in clinical trials. microRNAs (miRNAs), small posttranscriptional modifiers of gene expression, are frequently altered in disease conditions. Besides their important regulatory role in variety of biological processes, miRNAs can also be released into the circulation by pathologically affected tissues and display remarkable stability in body fluids. In a mouse model of ALS that expresses mutated human superoxide dismutase 1 (SOD1-G93A) skeletal muscle is one of the tissues affected early by mutant SOD1 toxicity. To find biomarkers for ALS, we studied miRNA alterations from skeletal muscle and plasma of SOD1-G93A mice, and subsequently tested the levels of the affected miRNAs in the serum from human ALS patients. Fast-twitch and slow-twitch muscles from symptomatic SOD1-G93A mice (age 90 days) and their control littermates were first studied using miRNA microarrays and then evaluated with quantitative PCR from five age groups from neonatal to the terminal disease stage (10–120 days). Among those miRNA changed in various age/gender/muscle groups (miR-206, -1, -133a, -133b, -145, -21, -24), miR-206 was the only one consistently altered during the course of the disease pathology. In both sexes, mature miR-206 was increased in fast-twitch muscles preferably affected in the SOD1-G93A model, with highest expression towards the most severely affected animals. Importantly, miR-206 was also increased in the circulation of symptomatic animals and in a group of 12 definite ALS patients tested. We conclude that miR-206 is elevated in the circulation of symptomatic SOD1-G93A mice and possibly in human ALS patients. Although larger scale studies on ALS patients are warranted, miR-206 is a promising candidate biomarker for this motor neuron disease. PMID:24586506

ATP utilization for calcium uptake and force production in skinned muscle fibres of Xenopus laevis.

PubMed Central

Stienen, G J; Zaremba, R; Elzinga, G

1995-01-01

1. A method has been developed to discriminate between the rate of ATP hydrolysis associated with calcium uptake into the sarcoplasmic reticulum (SR) and force development of the contractile apparatus in mechanically or saponin-skinned skeletal muscle fibres. The rate of ATP hydrolysis was determined in fibres of different types from the iliofibularis muscle of Xenopus laevis by enzymatic coupling of ATP re-synthesis to the oxidation of NADH. 2. The ATPase activity was determined before and after exposure of the preparations for 30 min to a solution containing 0.5% Triton X-100, which effectively abolishes the SR ATPase activity. The fibres were activated in a solution containing 5 mM caffeine to ensure that calcium uptake into the SR was maximal. 3. At saturating Ca2+ concentrations the actomyosin (AM) and SR ATPase activities in fast-twitch fibres, at 4.3 degrees C, amounted to 1.52 +/- 0.07 and 0.58 +/- 0.10 mumol s-1 (g dry wt)-1, respectively (means +/- S.E.M.; n = 25). The SR ATPase activity was 25% of the total ATPase activity. At submaximal calcium concentrations the AM ATPase activity varied in proportion to the isometric force. 4. The calcium sensitivity of the SR ATPase was larger than that of the AM ATPase and its dependence on [Ca2+] was less steep. The AM ATPase activity was half-maximal at a pCa of 6.11 (pCa = -log [Ca2+]) whereas the SR ATPase activity was half-maximal at a pCa of 6.62. 5. In Triton X-100-treated fibres, at different 2,3-butanedione monoxime (BDM) concentrations, the AM ATPase activity and isometric force varied proportionally. The SR ATPase activity determined by extrapolation of the total ATPase activity in mechanically skinned or saponin-treated fibres to zero force, was independent of the BDM concentration in the range studied (0-20 mM). The values obtained for the SR ATPase activity in this way were similar to those obtained with Triton X-100 treatment. 6. The AM ATPase activity in slow-twitch fibres amounted to 0.74 +/- 0.13 mumol s-1 (g dry wt)-1, i.e. about a factor of two smaller than in fast-twitch fibres. The SR ATPase activity amounted to 0.47 +/- 0.07 mumol s-1 (g dry wt)-1, i.e. rather similar to the value in fast-twitch fibres. The proportion of the total ATPase activity that was due to SR ATPase (40%) was larger than in fast-twitch fibres. 7. The temperature dependence of the AM and SR ATPase activities in fast-twitch fibres differed. In the temperature range 5-10 degrees C, the relative changes in AM and SR ATPase activities for a 10 degrees C temperature change (Q10) were 3.9 +/- 0.3 and 7.2 +/- 1.5, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7730976

Occupant thorax response variations due to arm position and restraint systems in side impact crash scenarios.

PubMed

Gierczycka, Donata; Cronin, Duane S

2017-09-01

Recent epidemiological studies have identified that thoracic side airbags may vary in efficacy to reduce injury severity in side impact crash scenarios, while previous experimental and epidemiological studies have presented contrasting results. This study aimed to quantify the variations in occupant response in side impact conditions using a human body computational model integrated with a full vehicle model. The model was analyzed for a Moving Deformable Barrier side impact at 61km/h to assess two pre-crash arm positions, the incorporation of a seatbelt, and a thorax air bag on thorax response. The occupant response was evaluated using chest compression, the viscous criterion and thoracic spinal curvature. The arm position accounted for largest changes in the thorax response (106%) compared to the presence of the airbag and seatbelt systems (75%). It was also noted that the results were dependant on the method and location of thorax response measurement and this should be investigated further. Assessment using lateral displacement of the thoracic spine correlated positively with chest compression and Viscous Criterion, with the benefit of evaluating whole thorax response and provides a useful metric to compare occupant response for different side impact safety systems. The thoracic side airbag was found to increase the chest compression for the driving arm position (+70%), and reduced the injury metrics for the vertical arm position (-17%). This study demonstrated the importance of occupant arm position on variability in thoracic response, and provides insight for future design and optimization of side impact safety systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

The RAndomized Placebo Phase Study Of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)

PubMed Central

Ilowite, Norman T.; Prather, Kristi; Lokhnygina, Yuliya; Schanberg, Laura E.; Elder, Melissa; Milojevic, Diana; Verbsky, James W.; Spalding, Steven J.; Kimura, Yukiko; Imundo, Lisa F.; Punaro, Marilynn G.; Sherry, David D.; Tarvin, Stacey E.; Zemel, Lawrence S.; Birmingham, James D.; Gottlieb, Beth S.; Miller, Michael L.; O'Neil, Kathleen; Ruth, Natasha M.; Wallace, Carol A.; Singer, Nora G.; Sandborg, Christy I.

2015-01-01

Background Interleukin-1 plays a pivotal role in in the pathogenesis of systemic juvenile idiopathic arthritis (sJIA). We assessed the efficacy and safety of rilonacept (IL-1 trap), an IL-1 inhibitor, in a randomized, double-blind, placebo-controlled trial. Methods An initial 4-week double-blind placebo phase was incorporated into a 24-week randomized multi-center design, followed by an open label phase. We randomized 71 children with at least 2 active joints 1:1 to 2 arms of the study. Patients in the rilonacept arm received rilonacept (4.4mg/kg loading dose followed by 2.2mg/kg weekly, subcutaneously) from day 0; patients in the placebo arm received placebo for 4 weeks followed by a loading dose of rilonacept at week 4 followed by weekly maintenance doses. The primary endpoint was time to response, using adapted JIA ACR30 response criteria coupled with absence of fever and taper of systemic corticosteroids using pre-specified criteria. Results Time to response was shorter in the rilonacept arm than in the placebo arm (Chi-square 7.235, P=.007). Secondary analysis showed 20/35 (57%) of patients in the rilonacept arm responded at week 4 compared to 9/33 (27%) in the placebo arm (P=.016) using the same response criteria. Exacerbation of sJIA (4) was the most common SAE. More patients in the rilonacept arm had elevated liver transaminases, including more than three times the upper limits of normal, as compared to those in the placebo arm. Adverse events were similar in the two arms of the study. Conclusions Rilonacept was generally well tolerated and demonstrated efficacy in active sJIA. PMID:24839206

Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

PubMed

González-Martín, A J; Calvo, E; Bover, I; Rubio, M J; Arcusa, A; Casado, A; Ojeda, B; Balañá, C; Martínez, E; Herrero, A; Pardo, B; Adrover, E; Rifá, J; Godes, M J; Moyano, A; Cervantes, A

2005-05-01

The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

The apparent mass and mechanical impedance of the hand and the transmission of vibration to the fingers, hand, and arm

NASA Astrophysics Data System (ADS)

Concettoni, Enrico; Griffin, Michael

2009-08-01

Although hand-transmitted vibration causes injury and disease, most often evident in the fingers, the biodynamic responses of the fingers, hand, and arm are not yet well understood. A method of investigating the motion of the entire finger-hand-arm system, based on the simultaneous measurement of the biodynamic response at the driving point and the transmissibility to many points on the finger-hand-arm system, is illustrated. Fourteen male subjects participated in an experiment in which they pushed down on a vertically vibrating metal plate with their right forearm pronated and their elbow bent at 90°. The apparent mass and mechanical impedance of the finger-hand-arm system were measured for each of seven different contact conditions between the plate and the fingers and hand. Simultaneously, the vibration of the fingers, hand, and arm was measured at 41 locations using a scanning laser Doppler vibrometer. Transmissibilities showed how the vibration was transmitted along the arm and allowed the construction of spectral operating deflection shapes showing the vibration pattern of the fingers, hand, and arm for each of the seven contact conditions. The vibration patterns at critical frequencies for each contact condition have been used to explain features in the driving point biodynamic responses and the vibration behaviour of the hand-arm system. Spectral operating deflection shapes for the upper limb assist the interpretation of driving point biodynamic responses and help to advance understanding required to predict, explain, and control the various effects of hand-transmitted vibration.

Evidence-based narratives to improve recall of opioid prescribing guidelines: a randomized experiment.

PubMed

Kilaru, Austin S; Perrone, Jeanmarie; Auriemma, Catherine L; Shofer, Frances S; Barg, Frances K; Meisel, Zachary F

2014-03-01

Physicians adopt evidence-based guidelines with variable consistency. Narratives, or stories, offer a novel dissemination strategy for clinical recommendations. The study objective was to compare whether evidence-based narrative versus traditional summary improved recall of opioid prescribing guidelines from the American College of Emergency Physicians (ACEP). This was a prospective, randomized controlled experiment to compare whether narrative versus summary promoted short-term recall of six themes contained in the ACEP opioid guideline. The experiment was modeled after the free-recall test, an established technique in studies of memory. At a regional conference, emergency physicians (EPs) were randomized to read either a summary of the guideline (control) or a narrative (intervention). The fictional narrative was constructed to match the summary in content and length. One hour after reading the text, participants listed all content that they could recall. Two reviewers independently scored the responses to assess recall of the six themes. The primary outcome was the total number of themes recalled per participant. Secondary outcomes included the proportion of responses in each study arm that recalled individual themes and the proportion of responses in each arm that contained falsely recalled or extraneous information. Ninety-five physicians were randomized. Eighty-two physicians completed the experiment, for a response rate of 86%. The mean of the total number of themes recalled per participant was 3.1 in the narrative arm versus 2.0 in the summary arm (difference = 1.1, 95% confidence interval [CI] = 0.6 to 1.7). For three themes, the proportion of responses that recalled the theme was significantly greater in the narrative arm compared to the summary arm, with the differences ranging from 20% to 51%. For one theme, recall was significantly greater in the summary arm. For two themes, there was no statistically significant difference in recall between the arms. In the summary arm, 54% of responses were found to contain falsely recalled or extraneous information versus 21% of responses in the narrative arm (difference = 33%, 95% CI = 14% to 53%). Physicians exposed to a narrative about opioid guidelines were more likely to recall guideline content at 1 hour than those exposed to a summary of the guidelines. Future studies should examine whether the incorporation of narratives in dissemination campaigns improves guideline adoption and changes clinical practice

Evidence-based Narratives to Improve Recall of Opioid Prescribing Guidelines: A Randomized Experiment

PubMed Central

Kilaru, Austin S.; Perrone, Jeanmarie; Auriemma, Catherine L.; Shofer, Frances S.; Barg, Frances K.; Meisel, Zachary F.

2014-01-01

Objectives Physicians adopt evidence-based guidelines with variable consistency. Narratives, or stories, offer a novel dissemination strategy for clinical recommendations. The study objective was to compare whether evidence-based narrative versus traditional summary improved recall of opioid prescribing guidelines from the American College of Emergency Physicians (ACEP). Methods This was a prospective, randomized controlled experiment to compare whether narrative versus summary promoted short-term recall of six themes contained in the ACEP opioid guideline. The experiment was modeled after the free-recall test, an established technique in studies of memory. At a regional conference, emergency physicians were randomized to read either a summary of the guideline (control) or a narrative (intervention). The fictional narrative was constructed to match the summary in content and length. One hour after reading the text, participants listed all content that they could recall. Two reviewers independently scored the responses to assess recall of the six themes. The primary outcome was the total number of themes recalled per participant. Secondary outcomes included the proportion of responses in each study arm that recalled individual themes and the proportion of responses in each arm that contained falsely recalled or extraneous information. Results Ninety-five physicians were randomized. Eighty-two physicians completed the experiment, for a response rate of 86%. The mean of the total number of themes recalled per participant was 3.1 in the narrative arm versus 2.0 in the summary arm (difference = 1.1, 95% confidence interval [CI] = 0.6 to 1.7). For three themes, the proportion of responses that recalled the theme was significantly greater in the narrative arm compared to the summary arm, with the differences ranging from 20% to 51%. For one theme, recall was significantly greater in the summary arm. For two themes, there was no statistically significant difference in recall between the arms. In the summary arm, 54% of responses were found to contain falsely recalled or extraneous information versus 21% of responses in the narrative arm (difference = 33%, 95% CI = 14% to 53%). Conclusions Physicians exposed to a narrative about opioid guidelines were more likely to recall guideline content at 1 hour than those exposed to a summary of the guidelines. Future studies should examine whether the incorporation of narratives in dissemination campaigns improves guideline adoption and changes clinical practice. PMID:24761456

Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release.

PubMed

Yun, Jaesuk

2014-05-15

Methamphetamine is a psychomotor stimulant that produces hyperlocomotion in rodents. Limonene (a cyclic terpene from citrus essential oils) has been reported to induce sedative effects. In this study, we demonstrated that limonene administration significantly inhibited serotonin (5-hydroxytryptamine, 5-HT)-induced head twitch response in mice. In rats, pretreatment with limonene decreased hyperlocomotion induced by methamphetamine injection. In addition, limonene reversed the increase in dopamine levels in the nucleus accumbens of rats given methamphetamine. These results suggest that limonene may inhibit stimulant-induced behavioral changes via regulating dopamine levels and 5-HT receptor function. Copyright © 2013 Elsevier GmbH. All rights reserved.

Colonoscopy screening for colorectal cancer: the outcomes of two recruitment methods.

PubMed

Corbett, Mike; Chambers, Sharon L; Shadbolt, Bruce; Hillman, Lybus C; Taupin, Doug

2004-10-18

To determine the response to colorectal cancer (CRC) screening by colonoscopy, through direct invitation or through invitation by general practitioners. Two-way comparison of randomised population sampling versus cluster sampling of a representative general practice population in the Australian Capital Territory, May 2002 to January 2004. Invitation to screen, assessment for eligibility, interview, and colonoscopy. 881 subjects aged 55-74 years were invited to screen: 520 from the electoral roll (ER) sample and 361 from the general practice (GP) cluster sample. Response rate, participation rate, and rate of adenomatous polyps in the screened group. Participation was similar in the ER arm (35.1%; 95% CI, 30.2%-40.3%) and the GP arm (40.1%; 95% CI, 29.2%-51.0%) after correcting for ineligibility, which was higher in the ER arm. Superior eligibility in the GP arm was offset by the labour of manual record review. Response rates after two invitations were similar for the two groups (ER arm: 78.8%; 95% CI, 75.1%-82.1%; GP arm: 81.7%; 95% CI, 73.8%-89.6%). Overall, 53.4% ineligibility arose from having a colonoscopy in the past 10 years (ER arm, 98/178; GP arm, 42/84). Of 231 colonoscopies performed, 229 were complete, with 32% of subjects screened having adenomatous polyps. Colonoscopy-based CRC screening yields similar response and participation rates with either random population sampling or general practice cluster sampling, with population sampling through the electoral roll providing greater ease of recruitment.

Response functions of free mass gravitational wave antennas

NASA Technical Reports Server (NTRS)

Estabrook, F. B.

1985-01-01

The work of Gursel, Linsay, Spero, Saulson, Whitcomb and Weiss (1984) on the response of a free-mass interferometric antenna is extended. Starting from first principles, the earlier work derived the response of a 2-arm gravitational wave antenna to plane polarized gravitational waves. Equivalent formulas (generalized slightly to allow for arbitrary elliptical polarization) are obtained by a simple differencing of the '3-pulse' Doppler response functions of two 1-arm antennas. A '4-pulse' response function is found, with quite complicated angular dependences for arbitrary incident polarization. The differencing method can as readily be used to write exact response functions ('3n+1 pulse') for antennas having multiple passes or more arms.

Cardio-Respiratory and Perceived Exertion Responses to Different Cranking Rates during Maximal Arm Ergometry.

ERIC Educational Resources Information Center

Israel, Richard G.; And Others

This study compared cardio-respiratory and perceived exertion responses for four cranking rates (50, 60, 70 and 80 rpm) during a continuous maximal arm ergometry protocol in order to determine the most efficient cranking rate for maximal testing. Fifteen male volunteers from 18-30 years of age performed a continuous arm ergometry stress test in…

Experiment K-308: Automatic analysis of muscle fibers from rats subjected to spaceflight

NASA Technical Reports Server (NTRS)

Castleman, K. R.; Chui, L. A.; Vandermeullen, J. P.

1981-01-01

The morphology of histochemically prepared muscle sections from the gastrocnemius and plantaris muscles of flight and vivarium control rats was studied quantitatively. Both fast-twitch and slow-twitch fibers were significantly smaller in flight groups than in control groups. Fibers in group 4F were somewhat larger than in 1F, presumably due to growth after recovery. Fibers in 4V were slightly larger than in 1V, presumably due to age. The slow fibers showed more spaceflight induced size loss than fast fibers, suggesting they suffered more from hypogravity. The proportion of slow fibers was also lower in the flight groups, suggesting spaceflight induced fiber type conversion from slow to fast.

Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, Anna W.; Satyshur, Kenneth A.; Moreno Morales, Neydis

2016-02-01

ABSTRACT Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulatormore » (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR mon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems. IMPORTANCEBphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of these proteins, rather than on signal transduction or the resultant phenotypes. To begin to address this knowledge gap, we solved the crystal structures of two single-domain response regulators encoded by a region immediately downstream of that encoding BphPs. We observed a previously unknown arm-in-arm dimer linkage. Monomerization via deletion of the C-terminal dimerization motif had an inhibitory effect on net response regulator phosphorylation, underlining the importance of these unusual dimers for signal transduction.« less

Aminophylline overdose

MedlinePlus

... MUSCLES AND JOINTS Muscle twitching and cramping NERVOUS SYSTEM Confusion , hallucination Convulsions Dizziness Fever Headache Irritability, restlessness Confused thinking, poor judgment and agitation (psychosis) Sweating Trouble sleeping ...

Main outcomes of an RCT to pilot test reporting and feedback to foster research integrity climates in the VA.

PubMed

Martinson, Brian C; Mohr, David C; Charns, Martin P; Nelson, David; Hagel-Campbell, Emily; Bangerter, Ann; Bloomfield, Hanna E; Owen, Richard; Thrush, Carol R

2017-01-01

Assessing the integrity of research climates and sharing such information with research leaders may support research best practices. We report here results of a pilot trial testing the effectiveness of a reporting and feedback intervention using the Survey of Organizational Research Climate (SOuRCe). We randomized 41 Veterans Health Administration (VA) facilities to a phone-based intervention designed to help research leaders understand their survey results (enhanced arm) or to an intervention in which results were simply distributed to research leaders (basic arm). Primary outcomes were (1) whether leaders took action, (2) whether actions taken were consistent with the feedback received, and (3) whether responses differed by receptivity to quality improvement input. Research leaders from 25 of 42 (59%) VA facilities consented to participate in the study intervention and follow-up, of which 14 were at facilities randomized to the enhanced arm. We completed follow-up interviews with 21 of the 25 leaders (88%), 12 from enhanced arm facilities. While not statistically significant, the proportion of leaders reporting taking some action in response to the feedback was twice as high in the enhanced arm than in the basic arm (67% vs. 33%, p = .20). While also not statistically significant, a higher proportion of actions taken among facilities in the enhanced arm were responsive to the survey results than in the basic arm (42% vs. 22%, p = .64). Enhanced feedback of survey results appears to be a promising intervention that may increase the likelihood of responsive action to improve organizational climates. Due to the small sample size of this pilot study, even large percentage-point differences between study arms are not statistically distinguishable. This hypothesis should be tested in a larger trial.

GLUT-3 expression in human skeletal muscle

NASA Technical Reports Server (NTRS)

Stuart, C. A.; Wen, G.; Peng, B. H.; Popov, V. L.; Hudnall, S. D.; Campbell, G. A.

2000-01-01

Muscle biopsy homogenates contain GLUT-3 mRNA and protein. Before these studies, it was unclear where GLUT-3 was located in muscle tissue. In situ hybridization using a midmolecule probe demonstrated GLUT-3 within all muscle fibers. Fluorescent-tagged antibody reacting with affinity-purified antibody directed at the carboxy-terminus demonstrated GLUT-3 protein in all fibers. Slow-twitch muscle fibers, identified by NADH-tetrazolium reductase staining, possessed more GLUT-3 protein than fast-twitch fibers. Electron microscopy using affinity-purified primary antibody and gold particle-tagged second antibody showed that the majority of GLUT-3 was in association with triads and transverse tubules inside the fiber. Strong GLUT-3 signals were seen in association with the few nerves that traversed muscle sections. Electron microscopic evaluation of human peripheral nerve demonstrated GLUT-3 within the axon, with many of the particles related to mitochondria. GLUT-3 protein was found in myelin but not in Schwann cells. GLUT-1 protein was not present in nerve cells, axons, myelin, or Schwann cells but was seen at the surface of the peripheral nerve in the perineurium. These studies demonstrated that GLUT-3 mRNA and protein are expressed throughout normal human skeletal muscle, but the protein is predominantly found in the triads of slow-twitch muscle fibers.

BRANCHED FIBERS FROM OLD FAST-TWITCH DYSTROPHIC MUSCLES ARE THE SITES OF TERMINAL DAMAGE IN MUSCULAR DYSTROPHY.

PubMed

Kiriaev, Leonit; Kueh, Sindy; Morley, John W; North, Kathryn N; Houweling, Peter J; Head, Stewart I

2018-02-07

A striking pathological feature of dystrophinopathies is the presence of morphologically abnormal branched skeletal muscle fibers. The deterioration of muscle contractile function in Duchenne muscular dystrophy is accompanied by both an increase in number and complexity of these branched fibers. We propose that when number and complexity of branched fibers reaches a critical threshold, "tipping point" the branches in and of themselves are the site of contraction-induced rupture. In the present study, we use the dystrophic mdx mouse and littermate controls to study the pre-diseased dystrophic fast-twitch EDL muscle at 2-3-weeks, the peak myonecrotic phase at 6-9 weeks and finally "old" at 58-112 weeks. Using a combination of isolated muscle function contractile measurements coupled with single fiber imaging and confocal microscope imaging of cleared whole muscles we identified a distinct pathophysiology; acute fiber rupture at branch nodes, which occurs in "old" fast-twitch EDL muscle approaching the end stage of the dystrophinopathy muscle disease, where the EDL muscles are entirely composed of complexed branched fibers. This evidence supports our concept of "tipping point" where the number and extent of fiber branching reaches a level where the branching itself terminally compromises muscle function, irrespective of the absence of dystrophin.

Classification of involuntary movements in dogs: Tremors and twitches.

PubMed

Lowrie, Mark; Garosi, Laurent

2016-08-01

This review focuses on important new findings in the field of involuntary movements (IM) in dogs and illustrates the importance of developing a clear classification tool for diagnosing tremor and twitches. Developments over the last decade have changed our understanding of IM and highlight several caveats in the current tremor classification. Given the ambiguous association between tremor phenomenology and tremor aetiology, a more cautious definition of tremors based on clinical assessment is required. An algorithm for the characterisation of tremors is presented herein. The classification of tremors is based on the distinction between tremors that occur at rest and tremors that are action-related; tremors associated with action are divided into postural or kinetic. Controversial issues are outlined and thus reflect the open questions that are yet to be answered from an evidence base of peer-reviewed published literature. Peripheral nerve hyper-excitability (PNH; cramps and twitches) may manifest as fasciculations, myokymia, neuromyotonia, cramps, tetany and tetanus. It is anticipated that as we learn more about the aetiology and pathogenesis of IMs, future revisions to the classification will be needed. It is therefore the intent of this work to stimulate discussions and thus contribute to the development of IM research. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

cAMP levels in fast- and slow-twitch skeletal muscle after an acute bout of aerobic exercise

NASA Technical Reports Server (NTRS)

Sheldon, A.; Booth, F. W.; Kirby, C. R.

1993-01-01

The present study examined whether exercise duration was associated with elevated and/or sustained elevations of postexercise adenosine 3',5'-cyclic monophosphate (cAMP) by measuring cAMP levels in skeletal muscle for up to 4 h after acute exercise bouts of durations that are known to either produce (60 min) or not produce (10 min) mitochondrial proliferation after chronic training. Treadmill-acclimatized, but untrained, rats were run at 22 m/min for 0 (control), 10, or 60 min and were killed at various postexercise (0, 0.5, 1, 2, and 4 h) time points. Fast-twitch white and red (quadriceps) and slow-twitch (soleus) muscles were quickly excised, frozen in liquid nitrogen, and assayed for cAMP with a commercial kit. Unexpectedly, cAMP contents in all three muscles were similar to control (nonexercise) at most (21 of 30) time points after a single 10- or 60-min run. Values at 9 of 30 time points were significantly different from control (P < 0.05); i.e., 3 time points were significantly higher than control and 6 were significantly less than control. These data suggest that the cAMP concentration of untrained skeletal muscle after a single bout of endurance-type exercise is not, by itself, associated with exercise duration.

Effects of fish size and temperature on weakfish disturbance calls: implications for the mechanism of sound generation.

PubMed

Connaughton, M A; Taylor, M H; Fine, M L

2000-05-01

To categorize variation in disturbance calls of the weakfish Cynoscion regalis and to understand their generation, we recorded sounds produced by different-sized fish, and by similar-sized fish at different temperatures, as well as muscle electromyograms. Single, simultaneous twitches of the bilateral sonic muscles produce a single sound pulse consisting of a two- to three-cycle acoustic waveform. Typical disturbance calls at 18 degrees C consist of trains of 2-15 pulses with a sound pressure level (SPL) of 74 dB re 20 microPa at 10 cm, a peak frequency of 540 Hz, a repetition rate of 20 Hz and a pulse duration of 3.5 ms. The pulse duration suggests an incredibly short twitch time. Sound pressure level (SPL) and pulse duration increase and dominant frequency decreases in larger fish, whereas SPL, repetition rate and dominant frequency increase and pulse duration decreases with increasing temperature. The dominant frequency is inversely related to pulse duration and appears to be determined by the duration of muscle contraction. We suggest that the lower dominant frequency of larger fish is caused by a longer pulse (=longer muscle twitch) and not by the lower resonant frequency of a larger swimbladder.

Arm and Intensity-Matched Leg Exercise Induce Similar Inflammatory Responses.

PubMed

Leicht, Christof A; Paulson, Thomas A W; Goosey-Tolfrey, Victoria L; Bishop, Nicolette C

2016-06-01

The amount of active muscle mass can influence the acute inflammatory response to exercise, associated with reduced risk for chronic disease. This may affect those restricted to upper body exercise, for example, due to injury or disability. The purpose of this study was to compare the inflammatory responses for arm exercise and intensity-matched leg exercise. Twelve male individuals performed three 45-min constant load exercise trials after determination of peak oxygen uptake for arm exercise (V˙O2peak A) and cycling (V˙O2peak C): 1) arm cranking exercise at 60% V˙O2peak A, 2) moderate cycling at 60% V˙O2peak C, and 3) easy cycling at 60% V˙O2peak A. Cytokine, adrenaline, and flow cytometric analysis of monocyte subsets were performed before and up to 4 h postexercise. Plasma IL-6 increased from resting concentrations in all trials; however, postexercise concentrations were higher for arm exercise (1.73 ± 1.04 pg·mL) and moderate cycling (1.73 ± 0.95 pg·mL) compared with easy cycling (0.87 ± 0.41 pg·mL; P < 0.04). Similarly, the plasma IL-1ra concentration in the recovery period was higher for arm exercise (325 ± 139 pg·mL) and moderate cycling (316 ± 128 pg·mL) when compared with easy cycling (245 ± 77 pg·mL, P < 0.04). Arm exercise and moderate cycling induced larger increases in monocyte numbers and larger increases of the classical monocyte subset in the recovery period than easy cycling (P < 0.05). The postexercise adrenaline concentration was lowest for easy cycling (P = 0.04). Arm exercise and cycling at the same relative exercise intensity induces a comparable acute inflammatory response; however, cycling at the same absolute oxygen uptake as arm exercise results in a blunted cytokine, monocyte, and adrenaline response. Relative exercise intensity appears to be more important to the acute inflammatory response than modality, which is of major relevance for populations restricted to upper body exercise.

Onset and effectiveness of rocuronium for rapid onset of paralysis in patients with major burns: priming or large bolus

PubMed Central

Han, T.-H.; Martyn, J. A. J.

2009-01-01

Background Burn injury leads to resistance to the effects of non-depolarizing muscle relaxants. We tested the hypothesis that a larger bolus dose is as effective as priming for rapid onset of paralysis after burns. Methods Ninety adults, aged 18–59 yr with 40 (2)% [mean (se)] burn and 30 (2) days after injury, received rocuronium as a priming dose followed by bolus (0.06+0.94 mg kg−1), or single bolus of either 1.0 or 1.5 mg kg−1. Sixty-one non-burned, receiving 1.0 mg kg−1 as a primed (0.06+0.94 mg kg−1) or full bolus dose, served as controls. Acceleromyography measured the onset times. Results Priming when compared with 1.0 mg kg−1 bolus in burned patients shortened the time to first appearance of twitch depression (30 vs 45 s, P<0.05) and time to maximum twitch inhibition (135 vs 210 s, P<0.05). The onset times between priming and higher bolus dose (1.5 mg kg−1) were not different (30 vs 30 s for first twitch depression and 135 vs 135 s for maximal depression, respectively). The onset times in controls, however, were significantly (P<0.05) faster than burns both for priming and for full bolus (15 and 15 s, respectively, for first twitch depression and 75 and 75 s for maximal depression). Priming caused respiratory distress in 10% of patients in both groups. Intubating conditions in burns were significantly better with 1.5 mg kg−1 than with priming or full 1.0 mg kg−1 bolus. Conclusions A dose of 1.5 mg kg−1 not only produces an initial onset of paralysis as early as 30 s, which we speculate could be a reasonable onset time for relief of laryngospasm, but also has an onset as fast as priming with superior intubating conditions and no respiratory side-effects. PMID:19029093

Reinnervation of the lateral gastrocnemius and soleus muscles in the rat by their common nerve.

PubMed Central

Gillespie, M J; Gordon, T; Murphy, P R

1986-01-01

To determine whether there is any specificity of regenerating nerves for their original muscles, the common lateral gastrocnemius soleus nerve (l.g.s.) innervating the fast-twitch lateral gastrocnemius (l.g.) and slow-twitch soleus muscles was sectioned in the hind limb of twenty adult rats. The proximal nerve stump was sutured to the dorsal surface of the l.g. muscle and 4-14 months later, the contractile properties of the reinnervated l.g. and soleus muscles and their single motor units were studied by dissection and stimulation of the ventral root filaments. Contractile properties of normal contralateral muscles were examined for comparison and motor units were isolated in l.g. and soleus muscles for study in a group of untreated animals. Measurement of time and rate parameters of maximal twitch and tetanic contractions showed that the rate of development of force increased significantly in reinnervated soleus muscles and approached the speed of l.g. muscles but rate of relaxation did not change appreciably. In reinnervated l.g. muscles, contraction speed was similar to normal l.g. muscles but relaxation rate declined toward the rates of relaxation in control soleus muscles. After reinnervation by the common l.g.s. nerve, the proportion of slow motor units in l.g. increased from 10 to 31% and decreased in soleus from 80 to 31%. The relative proportions of fast and slow motor units in each muscle were the same as the proportions of fast and slow units in the normal l.g. and soleus muscles combined. It was concluded that fast and slow muscles do not show any preference for their former nerves and that the change in the force profile of the reinnervated muscles is indicative of the relative proportions of fast and slow motor units: fast units dominate the contraction phase and slow units the relaxation phase of twitch and tetanic contractions of the muscle. PMID:3723414

Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain

PubMed Central

RUKHADZE, I.; KAMANI, H.; KUBIN, L.

2017-01-01

In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N > GH > GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I > GH > N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70–120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes. PMID:22205596

Release of prostaglandins from the isolated frog ventricle and associated changes in endogenous cyclic nucleotide levels.

PubMed Central

Flitney, F W; Singh, J

1980-01-01

1. A study has been made of the decline in contractility and some associated metabolic changes which occur in the isolated frog ventricle during the development of hypodynamic depression. 2. The release of two identified prostaglandins (PG), E1 and E2, together with several as yet unknown prostaglandin-related substances (PRS), accompanies the development of hypodynamic depression. There is a close correlation between the extent to which the isometric twitch is depressed and the quantity of prostaglandin released into the superfusate. 3. Fractionation of extracts of 'used' superfusates, using preparative-scale thin-layer chromatography, revealed the presence of six major components, four of which (PGE1 and PGE2 and two unidentified components) were found to be cardioactive and potentiated contraction when tested subsequently on hypodynamic preparations. 4. Two agents which influence prostaglandin biosynthesis, arachidonic acid and indomethacin, are found to affect both the rate at which the hypodynamic state develops and the extent to which the 'steady-state' twitch tension is depressed, in a dose-dependent manner. Indomethacin, a PG-synthetase inhibitor, accelerates the decay and depresses the final 'steady-state' tension attained, whereas arachidonic acid, the principal precursor for prostaglandin biosynthesis, has the converse effects. 5. Measurements of endogenous 3'5'-cyclic nucleotide levels reveal a time-dependent decrease in intracellular adenosine 3'5'-cyclic monophosphate (3'5'-cyclic AMP) and a concomitant increase in guanosine 3'5' cyclic monophosphate (3'5'-cyclic GMP). The decline in isometric twitch tension is paralleled almost exactly by an equivalent reduction in the ratio 3'5'-cyclic AMP: 3'5'-cyclic GMP. 6. Superfusion of isolated ventricles with Ringer solution containing exogenous, lipid-soluble derivatives of 3'5'-cyclic AMP and 3'5'-cyclic GMP affects both the rate of decline of the isometric twitch and the steady-state tension ultimately reached: thus, 8-bromo-3'5'-cyclic GMP accelerates the decline in contractility and depresses the steady-state level, whereas dibutyryl 3'5'-cyclic AMP delays the development of hypodynamic depression, and elevates the final twitch tension. The effects of both 3'5' cyclic nucleotide derivatives are dose-dependent. 7. The possible involvement of prostaglandins and 3'5'-cyclic nucleotides as causal agents in the mechanism of hypodynamic depression is discussed. The biochemical basis for the implied antangonistic effects of 3'5'-cyclic AMP and 3'5'-cyclic GMP in regulating ventricular contractility is considered in the following paper (Flitney & Singh, 1980). PMID:6255139

A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck.

PubMed

de Souza, Jonas A; Davis, Darren W; Zhang, Yujian; Khattri, Arun; Seiwert, Tanguy Y; Aktolga, Serdal; Wong, Stuart J; Kozloff, Mark F; Nattam, Sreenivasa; Lingen, Mark W; Kunnavakkam, Rangesh; Stenson, Kerstin M; Blair, Elizabeth A; Bozeman, Jeffrey; Dancey, Janet E; Vokes, Everett E; Cohen, Ezra E W

2012-04-15

This study sought to determine the efficacy and safety profile of lapatinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). This phase II multiinstitutional study enrolled patients with recurrent/metastatic SCCHN into two cohorts: those without (arm A) and those with (arm B) before exposure to an epidermal growth factor receptor (EGFR) inhibitor. All subjects were treated with lapatinib 1,500 mg daily. Primary endpoints were response rate (arm A) and progression-free survival (PFS; arm B). The biologic effects of lapatinib on tumor growth and survival pathways were assessed in paired tumor biopsies obtained before and after therapy. Forty-five patients were enrolled, 27 in arm A and 18 in arm B. Diarrhea was the most frequent toxicity occurring in 49% of patients. Seven patients experienced related grade 3 toxicity (3 fatigue, 2 hyponatremia, 1 vomiting, and 1 diarrhea). In an intent-to-treat analysis, no complete or partial responses were observed, and stable disease was the best response observed in 41% of arm A (median duration, 50 days, range, 34-159) and 17% of arm B subjects (median, 163 days, range, 135-195). Median PFS was 52 days in both arms. Median OS was 288 (95% CI, 62-374) and 155 (95% CI, 75-242) days for arms A and B, respectively. Correlative analyses revealed an absence of EGFR inhibition in tumor tissue. Lapatinib as a single agent in recurrent/metastatic SCCHN, although well tolerated, appears to be inactive in either EGFR inhibitor naive or refractory subjects. ©2012 AACR.

Myosin Binding Protein-C Slow Phosphorylation is Altered in Duchenne Dystrophy and Arthrogryposis Myopathy in Fast-Twitch Skeletal Muscles.

PubMed

Ackermann, Maegen A; Ward, Christopher W; Gurnett, Christina; Kontrogianni-Konstantopoulos, Aikaterini

2015-08-19

Myosin Binding Protein-C slow (sMyBP-C), encoded by MYBPC1, comprises a family of regulatory proteins of skeletal muscles that are phosphorylated by PKA and PKC. MYBPC1 missense mutations are linked to the development of Distal Arthrogryposis-1 (DA-1). Although structure-function details for this myopathy are evolving, function is undoubtedly driven by sequence variations and post-translational modifications in sMyBP-C. Herein, we examined the phosphorylation profile of sMyBP-C in mouse and human fast-twitch skeletal muscles. We used Flexor Digitorum Brevis (FDB) isolated from young (~2-months old) and old (~14-months old) wild type and mdx mice, and human Abductor Hallucis (AH) and gastrocnemious muscles carrying the DA-1 mutations. Our results indicate both constitutive and differential phosphorylation of sMyBP-C in aged and diseased muscles. We report a 7-35% reduction in the phosphorylation levels of select sites in old wild type and young or old mdx FDB mouse muscles, compared to young wild type tissue. Similarly, we observe a 30-70% decrease in the phosphorylation levels of all PKA and PKC phospho-sites in the DA-1 AH, but not gastrocnemius, muscle. Overall, our studies show that the phosphorylation pattern of sMyBP-C is differentially regulated in response to age and disease, suggesting that phosphorylation plays important roles in these processes.

Muscle-specific gene expression is underscored by differential stressor responses and coexpression changes.

PubMed

Moreno-Sánchez, Natalia; Rueda, Julia; Reverter, Antonio; Carabaño, María Jesús; Díaz, Clara

2012-03-01

Variations on the transcriptome from one skeletal muscle type to another still remain unknown. The reliable identification of stable gene coexpression networks is essential to unravel gene functions and define biological processes. The differential expression of two distinct muscles, M. flexor digitorum (FD) and M. psoas major (PM), was studied using microarrays in cattle to illustrate muscle-specific transcription patterns and to quantify changes in connectivity regarding the expected gene coexpression pattern. A total of 206 genes were differentially expressed (DE), 94 upregulated in PM and 112 in FD. The distribution of DE genes in pathways and biological functions was explored in the context of system biology. Global interactomes for genes of interest were predicted. Fast/slow twitch genes, genes coding for extracellular matrix, ribosomal and heat shock proteins, and fatty acid uptake centred the specific gene expression patterns per muscle. Genes involved in repairing mechanisms, such as ribosomal and heat shock proteins, suggested a differential ability of muscles to react to similar stressing factors, acting preferentially in slow twitch muscles. Muscle attributes do not seem to be completely explained by the muscle fibre composition. Changes in connectivity accounted for 24% of significant correlations between DE genes. Genes changing their connectivity mostly seem to contribute to the main differential attributes that characterize each specific muscle type. These results underscore the unique flexibility of skeletal muscle where a substantial set of genes are able to change their behavior depending on the circumstances.

Immunohistochemical evidence for expression of fast-twitch type sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) in German shepherd dogs with dilated cardiomyopathy myocardium.

PubMed

Summerfield, Nuala; Peters, Mary E; Hercock, Carol A; Mobasheri, Ali; Young, Iain S

2010-04-01

Dilated cardiomyopathy (DCM) is one of the most common acquired canine heart diseases. It is particularly common in large and giant breed dogs. Although a great deal is known about the clinical progression and manifestations of the disease, the underlying cellular and molecular mechanisms remain poorly understood. One widely held belief is that calcium-handling abnormalities are critically involved in the disease process. This study investigates the changes in expression of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) isoforms in DCM myocardium from German shepherd dogs. Affected tissue samples were obtained from German shepherd dogs with DCM, euthanized for intractable congestive heart failure while normal myocardial tissue samples were obtained from German shepherd dogs, euthanized for non-cardiovascular reasons. Tissue microarrays containing normal and DCM myocardium samples were prepared, immunostained with SERCA1 and SERCA2 antibodies and analyzed. We were able to demonstrate, for the first time, that while there is little change in the expression of the cardiac isoform (SERCA2), there is clear expression of the fast-twitch skeletal muscle isoform SERCA1 in the myocardium of dogs diagnosed with DCM. We propose that SERCA1 expression is evidence of a natural adaptive response to the impaired Ca2+ handling thought to occur in German shepherd dogs with DCM and heart failure. Copyright 2010 Elsevier B.V. All rights reserved.

Armed conflict: a model for understanding and intervention.

PubMed

2013-01-01

Acts of deadly violence give rise to powerful emotions and trigger pre-programmed responses that often cause affected persons, including leaders, media, armed forces, and the general public, to act in ways that aggravate the situation and feed into cycles of violence. In this article, a model of the cycle of violence is presented that facilitates logical analysis and response. Starting from an act of deadly violence this model traces a series of interacting factors that can lead to armed conflict. These include distortions of perception and response that impact the public and their leaders. Negative codes, prejudices, and myths feed fear and grief which may then escalate and lead to violent retaliation thereby triggering a similar response. Those professionals who care for bereaved individuals and families are familiar with these emotions and responses and are well qualified to analyze, explain, and support people affected by armed conflict. We suggest that they could also play educational and other important roles in reducing escalation and breaking the cycle of violence.

Contractile properties of rat fast-twitch skeletal muscle during reinnervation - Effects of testosterone and castration

NASA Technical Reports Server (NTRS)

Yeagle, S. P.; Mayer, R. F.; Max, S. R.

1983-01-01

The peroneal nerve of subject rats were crushed 1 cm from the muscle in order to examine the isometric contractile properties of skeletal muscle in the recovery sequency during reinnervation of normal, castrated, and testosterone-treated rats. The particular muscle studied was the extensor digitorum longus, with functional reinnervation first observed 8-9 days after nerve crush. No evidence was found that either castration or testosterone injections altered the process of reinnervation after the nerve crush, with the conclusion being valid at the 0.05 p level. The most reliable index of reinnervation was found to be the twitch:tetanus ratio, a factor of use in future studies of the reinnervation of skeletal muscle.

Cosmos 2044

NASA Technical Reports Server (NTRS)

Lowry, Oliver H.; Krasnov, Igor; Kakueva, E. Ilyina; Nemeth, Patti M.; Mcdougal, David B., Jr.; Choksi, Rati; Carter, Joyce G.; Chi, Maggie M. Y.; Manchester, Jill K.; Pusateri, Mary Ellen

1990-01-01

The effects of microgravity and hind limb suspension on the enzyme patterns are assessed within a slow twitch muscle (soleus) and a fast twitch muscle (tibialis anterior). Studies were made on 95 soleus fibers and about 300 tibialis anterior (TA) fibers. Over 2200 individual enzyme measurements were made. Six key metabolic enzymes (hexokinase, pyruvate kinease, citrate kinase, beta-hydroxyacyl CoA dehydrogenase, glucose-6-P dehydrogenase, and aspartate aminotransferase) plus glutaminase and glutamate decarboxylase, as well as glutamate, aspartate, and GABA, were measured in 11 regions of the hippocampal formation of synchronous, flight, and tail suspension rats. Major differences were observed in the normal distribution of each enzyme and amine acid, but no substantive effects of either microgravity or tail suspension on these patterns were clearly demonstrated.

39 CFR 235.1 - Postal Service to the Armed Forces.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Postal Service to the Armed Forces. 235.1 Section... LIAISON § 235.1 Postal Service to the Armed Forces. (a) Publication 38, Postal Agreement with the... Armed Forces. (b) The Chief Inspector is responsible for military liaison. (c) Postal inspectors provide...

Does metabosensitive afferent fibers activity differ from slow- and fast-twitch muscles?

PubMed

Caron, Guillaume; Decherchi, Patrick; Marqueste, Tanguy

2015-09-01

This study was designed to investigate the metabosensitive afferent response evoked by electrically induced fatigue (EIF), lactic acid (LA) and potassium chloride (KCl) in three muscle types. We recorded the activity of groups III-IV afferents originating from soleus, gastrocnemius and tibialis anterior muscles. Our data showed a same pattern of response in the three muscles after chemical injections, i.e., a bell curve with maximal discharge rate at 1 mM for LA injections and a linear relationship between KCl concentrations and the afferent discharge rate. Furthermore, a stronger response was recorded after EIF in the gastrocnemius muscle compared to the two other muscles. The change in afferent discharge after 1 mM LA injection was higher for the gastrocnemius muscle compared to the response obtained with the corresponding concentration applied in the two other muscles, whereas changes to KCl injections did not dramatically differ between the three muscles. We conclude that anatomical (mass, phenotype, vascularization, receptor and afferent density…) and functional (flexor vs. extensor) differences between muscles could explain the amplitude of these responses.

Establishment of one-axis vibration test system for measurement of biodynamic response of human hand-arm system.

PubMed

Shibata, Nobuyuki; Hosoya, Naoki; Maeda, Setsuo

2008-12-01

Prolonged exposure to hand-arm vibration (HAV) due to use of hand-held power tools leads to an increased occurrence of symptoms of disorders in the vascular, neurological, and osteo-articular systems of the upper limbs called hand-arm vibration syndrome (HAVS). Biodynamic responses of the hand-arm system to vibration can be suggestive parameters that give us better assessment of exposure to HAV and fundamental data for design of low-vibration-exposure power tools. Recently, a single axis hand-arm vibration system has been installed in the Japan National Institute of Occupational Safety and Health (NIOSH). The aims of this study were to obtain the fundamental dynamic characteristics of an instrumented handle and to validate the performance and measurement accuracy of the system applied to dynamic response measurement. A pseudo-random vibration signal with a frequency range of 5-1,250 Hz and a power spectrum density of 1.0 (m/s2)2/Hz was used in this study. First the dynamic response of the instrumented handle without any weight was measured. After this measurement, the dynamic response measurement of the handle with weights mounted on the handle was performed. The apparent mass of a weight itself was obtained by using the mass cancellation method. The mass of the measuring cap on the instrumented handle was well compensated by using the mass cancellation method. Based on the 10% error tolerance, this handle can reliably measure the dynamic response represented by an apparent mass with a minimum weight of 2.0 g in a frequency range of 10.0 to 1,000 Hz. A marked increase in the AM magnitude of the weights of 15 g and 20 g in frequency ranges greater than 800 Hz is attributed not to the fundamental resonance frequency of the handle with weights, but to the fixation of the weight to the measuring cap. In this aspect, the peak of the AM magnitude can be reduced and hence should not be an obstacle to the biodynamic response measurement of the human hand-arm system. On the basis of the results obtained in this study, we conclude that this hand-arm vibration test system can be used to measure biodynamic response parameters of the human hand-arm system.

Temperature-dependent changes in the viscoelasticity of intact resting mammalian (rat) fast- and slow-twitch muscle fibres.

PubMed

Mutungi, G; Ranatunga, K W

1998-04-01

1. The tension and sarcomere length responses induced by ramp stretches (at amplitudes of 1-3 % fibre length (Lo) and speeds of 0.01-12 Lo s-1) were examined at different temperatures (range, 10-35 degrees C) in resting intact muscle fibre bundles isolated from the soleus (a slow-twitch muscle) and extensor digitorum longus (a fast-twitch muscle) of the rat. Some observations are also presented on the effects of chemical skinning on passive viscoelasticity at 10 degrees C. 2. As previously reported, the tension response to a ramp stretch, in different preparations and under various conditions, could be resolved into a viscous (P1), a viscoelastic (P2) and an elastic (P3) component and showed characteristic differences between slow and fast muscle fibres. 3. Chemical skinning of the muscle fibres led to a decrease in the amplitude of all three tension components. However, the fast-slow fibre differences remained after skinning. For example, the viscosity coefficient derived from P1 tension data decreased from 0.84 +/- 0.06 before skinning to 0.44 +/- 0.06 kN s m-2 after skinning in fast fibres; the corresponding values in slow fibres were 2.1 +/- 0.08 and 0.87 +/- 0.09 kN s m-2, respectively. 4. Increasing the experimental temperature from 10 to 35 degrees C led to a decrease in all the tension components in both fast and slow muscle fibre bundles. The decrease of P1 (viscous) tension was such that the viscosity coefficient calculated using P1 data was reduced from 0.84 +/- 0.1 to 0.43 +/- 0.05 kN s m-2 in fast fibres and from 2.0 +/- 0.1 to 1.0 +/- 0.1 kN s m-2 in slow fibres (Q10 of approximately 1.3 in both). 5. In both fast and slow muscle fibre preparations, the plateau tension of the viscoelastic component (P2) decreased by 60-80 % as the temperature was increased from 10 to 35 degrees C giving P2 tension a Q10 of approximately 1.4 in slow fibres and approximately 1.7 in the fast fibres. Additionally, the relaxation time of the viscoelasticity decreased from 11.9 +/- 1 ms (fast) and 43.1 +/- 1 ms (slow) at 10 degrees C to 3 +/- 0.5 ms (fast) at 25 C degrees and 8. 7 +/- 0.6 ms (slow) at 35 degrees C (Q10 of approximately 2.0 in slow and approximately 2.5 in fast fibres). 6. The fast-slow fibre differences in passive viscoelasticity remained at the high physiological temperatures. The physiological significance of such fibre-type differences and their possible underlying mechanisms are discussed.

Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma.

PubMed

Gan, Hui K; Reardon, David A; Lassman, Andrew B; Merrell, Ryan; van den Bent, Martin; Butowski, Nicholas; Lwin, Zarnie; Wheeler, Helen; Fichtel, Lisa; Scott, Andrew M; Gomez, Erica J; Fischer, JuDee; Mandich, Helen; Xiong, Hao; Lee, Ho-Jin; Munasinghe, Wijith P; Roberts-Rapp, Lisa A; Ansell, Peter J; Holen, Kyle D; Kumthekar, Priya

2018-05-18

We recently reported an acceptable safety and pharmacokinetic profile of depatuxizumab mafodotin (depatux-m), formerly called ABT-414, plus radiation and temozolomide in newly diagnosed glioblastoma (arm A). The purpose of this study was to evaluate the safety and pharmacokinetics of depatux-m, either in combination with temozolomide in newly diagnosed or recurrent glioblastoma (arm B) or as monotherapy in recurrent glioblastoma (arm C). In this multicenter phase I dose escalation study, patients received depatux-m (0.5-1.5 mg/kg in arm B, 1.25 mg/kg in arm C) every 2 weeks by intravenous infusion. Maximum tolerated dose (MTD), recommended phase II dose (RP2D), and preliminary efficacy were also determined. Thirty-eight patients were enrolled as of March 1, 2016. The most frequent toxicities were ocular, occurring in 35/38 (92%) patients. Keratitis was the most common grade 3 adverse event observed in 6/38 (16%) patients; thrombocytopenia was the most common grade 4 event seen in 5/38 (13%) patients. The MTD was set at 1.5 mg/kg in arm B and was not reached in arm C. RP2D was declared as 1.25 mg/kg for both arms. Depatux-m demonstrated a linear pharmacokinetic profile. In recurrent glioblastoma patients, the progression-free survival (PFS) rate at 6 months was 30.8% and the median overall survival was 10.7 months. Best Response Assessment in Neuro-Oncology responses were 1 complete and 2 partial responses. Depatux-m alone or in combination with temozolomide demonstrated an acceptable safety and pharmacokinetic profile in glioblastoma. Further studies are currently under way to evaluate its efficacy in newly diagnosed (NCT02573324) and recurrent glioblastoma (NCT02343406).

Mechanical impedance and absorbed power of hand-arm under x(h)-axis vibration and role of hand forces and posture.

PubMed

Aldien, Yasser; Marcotte, Pierre; Rakheja, Subhash; Boileau, Paul-Emile

2005-07-01

The biodynamic responses of the hand-arm system under x(h)-axis vibration are investigated in terms of the driving point mechanical impedance (DPMI) and absorbed power in a laboratory study. For this purpose, seven healthy male subjects are exposed to two levels of random vibration in the 8-1,000 Hz frequency range, using three instrumented cylindrical handles of different diameters (30, 40 and 50 mm), and different combinations of grip (10, 30 and 50 N) and push (0, 25 and 50 N) forces. The experiments involve grasping the handle while adopting two different postures, involving elbow flexion of 90 degrees and 180 degrees, with wrist in the neutral position for both postures. The analyses of the results revealed peak DPMI magnitude and absorbed power responses near 25 Hz and 150 Hz, for majority of the test conditions considered. The frequency corresponding to the peak response increased with increasing hand forces. Unlike the absorbed power, the DPMI response was mostly observed to be insensitive to variations in the excitation magnitude. The handle diameter revealed obvious effects on the DPMI magnitude, specifically at frequencies above 250 Hz, which was not evident in the absorbed power due to relatively low velocity at higher frequencies. The influence of hand forces was also evident on the DPMI magnitude response particularly at frequencies. above 100 Hz, while the effect of hand-arm posture on the DPMI magnitude was nearly negligible. The magnitude of power absorbed within the hand and arm was observed to be strongly dependent upon the excitation level over the entire frequency range, while the influence of hand-arm posture on the total absorbed power was observed to be important. The effect of variations in the hand forces on the absorbed power was relatively small for the bent elbow posture, while an increase in either the grip or the push force coupled with the extended arm posture resulted in considerably higher energy absorption. The results suggested that the handle size, hand-arm posture and hand forces, produce coupled effect on the biodynamic response of the hand-arm system.

Mechanisms underlying hypothermia-induced cardiac contractile dysfunction.

PubMed

Han, Young-Soo; Tveita, Torkjel; Prakash, Y S; Sieck, Gary C

2010-03-01

Rewarming patients after profound hypothermia may result in acute heart failure and high mortality (50-80%). However, the underlying pathophysiological mechanisms are largely unknown. We characterized cardiac contractile function in the temperature range of 15-30 degrees C by measuring the intracellular Ca(2+) concentration ([Ca(2+)](i)) and twitch force in intact left ventricular rat papillary muscles. Muscle preparations were loaded with fura-2 AM and electrically stimulated during cooling at 15 degrees C for 1.5 h before being rewarmed to the baseline temperature of 30 degrees C. After hypothermia/rewarming, peak twitch force decreased by 30-40%, but [Ca(2+)](i) was not significantly altered. In addition, we assessed the maximal Ca(2+)-activated force (F(max)) and Ca(2+) sensitivity of force in skinned papillary muscle fibers. F(max) was decreased by approximately 30%, whereas the pCa required for 50% of F(max) was reduced by approximately 0.14. In rewarmed papillary muscle, both total cardiac troponin I (cTnI) phosphorylation and PKA-mediated cTnI phosphorylation at Ser23/24 were significantly increased compared with controls. We conclude that after hypothermia/rewarming, myocardial contractility is significantly reduced, as evidenced by reduced twitch force and F(max). The reduced myocardial contractility is attributed to decreased Ca(2+) sensitivity of force rather than [Ca(2+)](i) itself, resulting from increased cTnI phosphorylation.

Biophysical, histopathological and pharmacological characterization of crotamine isoforms F22 and F32.

PubMed

Toyama, Marcos H; Marangoni, Sérgio; Novello, José C; Leite, Gildo B; Prado-Franceschi, Julia; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

2003-03-01

Two major crotamine isoforms (F22 and F32) were obtained after three chromatographic steps and were assayed in mouse phrenic nerve-diaphragm preparations. F32 and F22 (0.5 microg/ml, n=4) produced a facilitatory effect, which increased isometric twitch-tension by 300 and 230%, respectively, after a 120 min incubation. At a concentration of 0.1 microg/ml, both isoforms increased the twitch-tension by about 160%. However, when the isoforms were co-incubated (final concentration, 0.5 microg/ml) for 30 min prior to testing, they did not cause the facilitation seen with > or =0.1 microg/ml of each isoform alone. Histologically, F32 and F22 at 0.5 and 1 microg/ml were quantitatively alike in inducing tissue myonecrosis. However, a mixture of the two isoforms (final concentration, 0.5 microg/ml) significantly attenuated the damage seen with either toxin alone. Mass spectrometry analysis showed that the isoforms had the same molecular mass (4.8 kDa) and that they existed as monomers with a highly stable structure. These results indicate that F22 and F32 acted on muscle cells of the mouse phrenic-nerve diaphragm preparation through similar mechanisms. Since the isoforms did not produce the expected summation in the increase in muscle twitch-tension, it is possible that they may have different affinities for the sodium channel subunits.

Changes in oxygenation and phosphocreatine during exercise and recovery in relation to fiber types and capillary supply in human skeletal muscle

NASA Astrophysics Data System (ADS)

Hamaoka, Takatumi; Mizuno, Masano; Osada, Takuya; Ratkevicius, Aivaras; Nielsen, Alexander N.; Nakagawa, Yoshinao; Katsumura, Toshihito; Shimomitsu, Teruichi; Quistorff, Bjorn

1998-01-01

The purpose of this study was to examine the relationship between histochemical characteristics obtained from the gastrocnemius and changes in muscle energetics. Muscle oxygenation was determined by near infrared spectroscopy, and phosphocreatine (PCr) by 31-phosphorus magnetic resonance spectroscopy (31P-MRS) during a submaximal plantar flexion exercise and recovery. The relative occurrence (%) of slow-twitch fibers (ST), fast-twitch oxidative fibers (FTa), fast-twitch glycolytic fibers (FTb), and the number of capillaries per fiber (Cap/Fiber) were also determined. The sum of %ST and %FTa (%ST + %FTa) was 85.8 +/- 8.74% (mean +/- SD), while the number of Cap/Fiber was 2.52 +/- 0.63. The initial rate of deoxygenation (Ratedeoxy) at the beginning of the exercise was 2.43 +/- 0.95 %(DOT)sec-1. The time constants (Tc) for the recovery of PCr and muscle oxygenation after exercise were 22.1 +/- 6.3 sec. and 20.3 +/- 13.6 sec., respectively. The %ST + FTa, and the number of Cap/Fiber were each positively correlated to the Ratedeoxy (P < 0.05). The %ST + %FTa, and the number of Cap/Fiber were negatively correlated to the Tc for PCr recovery (P < 0.05), but not correlated to that for muscle oxygenation recovery. In conclusion, the Ratedeoxy during localized submaximal exercise, and the Tc for PCr recovery are indicators of the muscle's oxidative capacity.

Changes in oxygenation and phosphocreatine during exercise and recovery in relation to fiber types and capillary supply in human skeletal muscle

NASA Astrophysics Data System (ADS)

Hamaoka, Takatumi; Mizuno, Masano; Osada, Takuya; Ratkevicius, Aivaras; Nielsen, Alexander N.; Nakagawa, Yoshinao; Katsumura, Toshihito; Shimomitsu, Teruichi; Quistorff, Bjorn

1997-12-01

The purpose of this study was to examine the relationship between histochemical characteristics obtained from the gastrocnemius and changes in muscle energetics. Muscle oxygenation was determined by near infrared spectroscopy, and phosphocreatine (PCr) by 31-phosphorus magnetic resonance spectroscopy (31P-MRS) during a submaximal plantar flexion exercise and recovery. The relative occurrence (%) of slow-twitch fibers (ST), fast-twitch oxidative fibers (FTa), fast-twitch glycolytic fibers (FTb), and the number of capillaries per fiber (Cap/Fiber) were also determined. The sum of %ST and %FTa (%ST + %FTa) was 85.8 +/- 8.74% (mean +/- SD), while the number of Cap/Fiber was 2.52 +/- 0.63. The initial rate of deoxygenation (Ratedeoxy) at the beginning of the exercise was 2.43 +/- 0.95 %(DOT)sec-1. The time constants (Tc) for the recovery of PCr and muscle oxygenation after exercise were 22.1 +/- 6.3 sec. and 20.3 +/- 13.6 sec., respectively. The %ST + FTa, and the number of Cap/Fiber were each positively correlated to the Ratedeoxy (P < 0.05). The %ST + %FTa, and the number of Cap/Fiber were negatively correlated to the Tc for PCr recovery (P < 0.05), but not correlated to that for muscle oxygenation recovery. In conclusion, the Ratedeoxy during localized submaximal exercise, and the Tc for PCr recovery are indicators of the muscle's oxidative capacity.

A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse.

PubMed

Wright, Craig Robert; Allsopp, Giselle Larissa; Addinsall, Alex Bernard; McRae, Natasha Lee; Andrikopoulos, Sofianos; Stupka, Nicole

2017-01-01

Excessive inflammation is a hallmark of muscle myopathies, including Duchenne muscular dystrophy (DMD). There is interest in characterising novel genes that regulate inflammation due to their potential to modify disease progression. Gene polymorphisms in Selenoprotein S ( Seps1 ) are associated with elevated proinflammatory cytokines, and in vitro SEPS1 is protective against inflammatory stress. Given that SEPS1 is highly expressed in skeletal muscle, we investigated whether the genetic reduction of Seps1 exacerbated inflammation in the mdx mouse. F1 male mdx mice with a heterozygous Seps1 deletion ( mdx : Seps1 -/+ ) were generated. The mdx:Seps1 -/+ mice had a 50% reduction in SEPS1 protein expression in hindlimb muscles. In the extensor digitorum longus (EDL) muscles, mRNA expression of monocyte chemoattractant protein 1 ( Mcp-1 ) ( P = 0.034), macrophage marker F4/80 ( P = 0.030), and transforming growth factor-β1 ( Tgf-β1 ) ( P = 0.056) were increased in mdx:Seps1 -/+ mice. This was associated with a reduction in muscle fibre size; however, ex vivo EDL muscle strength and endurance were unaltered. In dystrophic slow twitch soleus muscles, SEPS1 reduction had no effect on the inflammatory profile nor function. In conclusion, the genetic reduction of Seps1 appears to specifically exacerbate the inflammatory profile of fast-twitch muscle fibres, which are typically more vulnerable to degeneration in dystrophy.

Anatomy and histochemistry of hindlimb flight posture in birds. I. The extended hindlimb posture of shorebirds.

PubMed

McFarland, Joshua C; Meyers, Ron A

2008-08-01

Birds utilize one of two hindlimb postures during flight: an extended posture (with the hip and knee joints flexed, while the ankle joint is extended caudally) or a flexed posture (with the hip, knee, and ankle joints flexed beneath the body). American Avocets (Recurvirostra americana) and Black-necked Stilts (Himantopus mexicanus) extend their legs caudally during flight and support them for extended periods. Slow tonic and slow twitch muscle fibers are typically found in muscles functioning in postural support due to the fatigue resistance of these fibers. We hypothesized that a set of small muscles composed of high percentages of slow fibers and thus dedicated to postural support would function in securing the legs in the extended posture during flight. This study examined the anatomy and histochemical profile of eleven hindlimb muscles to gain insight into their functional roles during flight. Contrary to our hypothesis, all muscles possessed both fast twitch and slow twitch or slow tonic fibers. We believe this finding is due to the versatility of dynamic and postural functions the leg muscles must facilitate, including standing, walking, running, swimming, and hindlimb support during flight. Whether birds use an extended or flexed hindlimb flight posture may be related to the aerodynamic effect of leg position or may reflect evolutionary history. (c) 2008 Wiley-Liss, Inc.

Anabolic steroid and gender-dependent modulation of cytosolic HSP70s in fast- and slow-twitch skeletal muscle.

PubMed

González, B; Hernando, R; Manso, R

2000-09-01

Besides their clinical uses, anabolic steroids (AASs) are self-administered by athletes to improve muscle mass and sports performance. The biological basis for their presumed effectiveness at suprapharmacological doses, however, remains uncertain. Since the expression of high levels of some stress proteins (HSPs) has been associated with an increased tolerance to stress and chronic exercise up-regulates HSP72 in skeletal muscle, this investigation was aimed at testing whether the administration of suprapharmacological doses of AASs, either alone or in conjunction with chronic exercise, induced changes in HSP72. Nandrolone decanoate (ND), an estrene derivative, but not stanozolol (ST), a derivative of the androstane series, up-regulated the levels of HSP72 and changed the proportions of various charge variants of the cytosolic HSP70s in sedentary and exercise-trained rats, exclusively in fast-twitch fibres. Since the expression of HSP73-levels in skeletal muscle was dependent on gender but not on muscle type, and that of HSP72-levels was muscle type specific but gender-independent, ND effects on cytosolic HSP70s could not be explained solely by a functional relationship with sex steroids. The reported results indicate that, by up-regulating the expression levels of HSP72 in fast-twitch fibres, nandrolone decanoate could contribute to improving the tolerance of skeletal muscle to high-intensity training.

Cloning of a neonatal calcium atpase isoform (SERCA 1B) from extraocular muscle of adult blue marlin (Makaira nigricans).

PubMed

Londraville, R L; Cramer, T D; Franck, J P; Tullis, A; Block, B A

2000-10-01

Complete cDNAs for the fast-twitch Ca2+ -ATPase isoform (SERCA 1) were cloned and sequenced from blue marlin (Makaira nigricans) extraocular muscle (EOM). Complete cDNAs for SERCA 1 were also cloned from fast-twitch skeletal muscle of the same species. The two sequences are identical over the coding region except for the last five codons on the carboxyl end; EOM SERCA 1 cDNA codes for 996 amino acids and the fast-twitch cDNAs code for 991 aa. Phylogenetic analysis revealed that EOM SERCA 1 clusters with an isoform of Ca2+ -ATPase normally expressed in early development of mammals (SERCA 1B). This is the first report of SERCA 1B in an adult vertebrate. RNA hybridization assays indicate that 1B expression is limited to extraocular muscles. Because EOM gives rise to the thermogenic heater organ in marlin, we investigated whether SERCA 1B may play a role in heat generation, or if 1B expression is common in EOM among vertebrates. Chicken also expresses SERCA 1B in EOM, but rat expresses SERCA 1A; because SERCA 1B is not specific to heater tissue we conclude it is unlikely that it plays a specific role in intracellular heat production. Comparative sequence analysis does reveal, however, several sites that may be the source of functional differences between fish and mammalian SERCAs.

Fatigue and Muscle Strength Involving Walking Speed in Parkinson's Disease: Insights for Developing Rehabilitation Strategy for PD.

PubMed

Huang, Ying-Zu; Chang, Fang-Yu; Liu, Wei-Chia; Chuang, Yu-Fen; Chuang, Li-Ling; Chang, Ya-Ju

2017-01-01

Background . Problems with gait in Parkinson's disease (PD) are a challenge in neurorehabilitation, partly because the mechanisms causing the walking disability are unclear. Weakness and fatigue, which may significantly influence gait, are commonly reported by patients with PD. Hence, the aim of this study was to investigate the association between weakness and fatigue and walking ability in patients with PD. Methods . We recruited 25 patients with idiopathic PD and 25 age-matched healthy adults. The maximum voluntary contraction (MVC), twitch force, and voluntary activation levels were measured before and after a knee fatigue exercise. General fatigue, central fatigue, and peripheral fatigue were quantified by exercise-induced changes in MVC, twitch force, and activation level. In addition, subjective fatigue was measured using the Multidimensional Fatigue Inventory (MFI) and Fatigue Severity Scale (FSS). Results . The patients with PD had lower activation levels, more central fatigue, and more subjective fatigue than the healthy controls. There were no significant differences in twitch force or peripheral fatigue index between the two groups. The reduction in walking speed was related to the loss of peripheral strength and PD itself. Conclusion . Fatigue and weakness of central origin were related to PD, while peripheral strength was important for walking ability. The results suggest that rehabilitation programs for PD should focus on improving both central and peripheral components of force.

Cardio-Respiratory Responses to Maximal Work During Arm and Bicycle Ergometry.

ERIC Educational Resources Information Center

Israel, Richard G.; Hardison, George T.

This study compared cardio-respiratory responses during maximal arm work using a Monarch Model 880 Rehab Trainer to cardio-respiratory responses during maximal leg work on a Monarch Model 850 Bicycle Ergometer. Subjects for the investigation were 17 male university students ranging from 18 to 28 years of age. The specific variables compared…

Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III.

PubMed

Udina, Esther; Putman, Charles T; Harris, Luke R; Tyreman, Neil; Cook, Victoria E; Gordon, Tessa

2017-03-01

Smn +/- transgenic mouse is a model of the mildest form of spinal muscular atrophy. Although there is a loss of spinal motoneurons in 11-month-old animals, muscular force is maintained. This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons. The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity. We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die-back. Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn +/- transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die-back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at 11 months of age, with a significant loss of 19% at 7 months. Motor axon die-back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast-twitch and one slow-twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn +/- transgenic mouse increases their susceptibility to cell death demonstrated that all the motoneurons survived and they sustained their capacity to regenerate their nerve fibres. It is concluded the systematic die-back of motoneurons that innervate both fast- and slow-twitch muscle fibres is not related to immaturity of the neuromuscular system in SMA. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Muscle and bone follow similar temporal patterns of recovery from muscle-induced disuse due to botulinum toxin injection.

PubMed

Manske, Sarah L; Boyd, Steven K; Zernicke, Ronald F

2010-01-01

If muscle force is a primary source for triggering bone adaptation, with disuse and reloading, bone changes should follow muscle changes. We examined the timing and magnitude of changes in muscle cross-sectional area (MCSA) and bone architecture in response to muscle inactivity following botulinum toxin (BTX) injection. We hypothesized that MCSA would return to baseline levels sooner than bone properties following BTX injection. Female BALB mice (15 weeks old) were injected with 20 muL of BTX (1 U/100 g body mass, n=18) or saline (SAL, n=18) into the posterior calf musculature of one limb. The contralateral limb (CON) served as an internal control. MCSA and bone properties were assessed at baseline, 2, 4, 8, 12, and 16 weeks post-injection using in vivo micro-CT at the tibia proximal metaphysis (bone only) and diaphysis. Muscles were dissected and weighed after sacrifice. Significant GroupxLegxTime interactions indicated that the maximal decrease in MCSA (56%), proximal metaphyseal BV/TV (38%) and proximal diaphyseal Ct.Ar (7%) occurred 4 weeks after injection. There was no delay prior to bone recovery as both muscle and bone properties began to recover after this time, but MCSA and BV/TV remained 15% and 20% lower, respectively, in the BTX-injected leg than the BTX-CON leg 16 weeks post-injection. Gastrocnemius mass (primarily fast-twitch) was 14% lower in the BTX-injected leg than the SAL-injected leg, while soleus mass (primarily slow-twitch) was 15% greater in the BTX group than the SAL group. Our finding that muscle size and bone began to recover at similar times after BTX injection was unexpected. This suggested that partial weight-bearing and/or return of slow-twitch muscle activity in the BTX leg may have been sufficient to stimulate bone recovery. Alternatively, muscle function may have recovered sooner than MCSA. Our results indicated that muscle cross-sectional area, while important, may not be the primary factor associated with bone loss and recovery when muscle atrophy is induced through BTX injection. To understand the nature of the interaction between muscle and bone, future work should focus on the functional recovery of individual muscles in relation to bone. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Paroxetine

MedlinePlus

... sleepiness or feeling ''drugged'' nausea vomiting diarrhea constipation gas stomach pain heartburn changes in ability to taste ... symptoms yellowing of the skin and eyes aggressive behavior muscle pain, stiffness, or weakness sudden muscle twitching ...

Recent Advances in the Neuropsychopharmacology of Serotonergic Hallucinogens

PubMed Central

Halberstadt, Adam L.

2014-01-01

Serotonergic hallucinogens, such as (+)-lysergic acid diethylamide, psilocybin, and mescaline, are somewhat enigmatic substances. Although these drugs are derived from multiple chemical families, they all produce remarkably similar effects in animals and humans, and they show cross-tolerance. This article reviews the evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action. The 5-HT2A receptor is responsible for mediating the effects of hallucinogens in human subjects, as well as in animal behavioral paradigms such as drug discrimination, head twitch response, prepulse inhibition of startle, exploratory behavior, and interval timing. Many recent clinical trials have yielded important new findings regarding the psychopharmacology of these substances. Furthermore, the use of modern imaging and electrophysiological techniques is beginning to help unravel how hallucinogens work in the brain. Evidence is also emerging that hallucinogens may possess therapeutic efficacy. PMID:25036425

Recent advances in the neuropsychopharmacology of serotonergic hallucinogens.

PubMed

Halberstadt, Adam L

2015-01-15

Serotonergic hallucinogens, such as (+)-lysergic acid diethylamide, psilocybin, and mescaline, are somewhat enigmatic substances. Although these drugs are derived from multiple chemical families, they all produce remarkably similar effects in animals and humans, and they show cross-tolerance. This article reviews the evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action. The 5-HT2A receptor is responsible for mediating the effects of hallucinogens in human subjects, as well as in animal behavioral paradigms such as drug discrimination, head twitch response, prepulse inhibition of startle, exploratory behavior, and interval timing. Many recent clinical trials have yielded important new findings regarding the psychopharmacology of these substances. Furthermore, the use of modern imaging and electrophysiological techniques is beginning to help unravel how hallucinogens work in the brain. Evidence is also emerging that hallucinogens may possess therapeutic efficacy. Copyright © 2014 Elsevier B.V. All rights reserved.

Advanced colorectal carcinoma. A prospective randomized trial of sequential methotrexate, 5-fluorouracil, and leucovorin versus 5-fluorouracil alone.

PubMed

Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Bianco, A; Pérez, J E; Rodríguez, R; Cuevas, M A; Alvarez, L A

1991-06-01

One hundred and twenty-five previously untreated patients bearing metastatic or advanced recurrent (inoperable) colorectal carcinoma and measurable disease were prospectively randomized. Those in arm A received 5-fluorouracil (5-FU), 1,200 mg/m2 i.v. infusion over 2 h, while those in arm B received methotrexate (MTX), 200 mg/m2 i.v. (push injection), followed 20 h later by 5-FU, 1,200 mg/m2 i.v. infusion over 2 h, plus calcium leucovorin (LV), 25 mg i.m. every 6 h for eight doses beginning 24 h after MTX administration. Cycles were repeated every 15 days. All patients receiving treatment were evaluable for toxicity and survival, and 118 patients were evaluable for response. The objective regression rate (complete plus partial response) was 12% (7 of 58) in arm A and 28% (17 of 60) in arm B (p = 0.049). No change was observed in 24% (14 of 58) in arm A and in 35% (21 of 60) in arm B (p = 0.28), while progressive disease was registered in 64% (37 of 58) and 37% (22 of 60) in arms A and B, respectively (p = 0.006). Median duration of response was 3 months in arm A and 5 months in arm B (p = 0.39). The median survival was 8.3 months in arm A and 11.2 months in arm B (p = 0.25). No statistically significant differences were found when objective regression and survival were related to site of primary tumor, performance status, and number of involved organs. There were two drug-related deaths in arm B due to severe myelosuppression followed by mucositis and sepsis. Of nonhematologic toxicities, diarrhea was more frequently observed in arm B, as were mucositis and infectious complications. Our results indicate that the sequential schedule MTX-5-FU-LV with 20-h intervals between MTX and 5-FU is superior in terms of objective regression to 5-FU alone given at the dose and schedule used in the present study. However, MTX-5-FU-LV did not have a significant impact on survival.

Morphine Rectal

MedlinePlus

... of lung function) or other breathing problems; prostatic hypertrophy (enlargement of a male reproductive gland); urethral stricture ( ... exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, ...

Redox responses are preserved across muscle fibres with differential susceptibility to aging.

PubMed

Smith, Neil T; Soriano-Arroquia, Ana; Goljanek-Whysall, Katarzyna; Jackson, Malcolm J; McDonagh, Brian

2018-04-15

Age-related loss of muscle mass and function is associated with increased frailty and loss of independence. The mechanisms underlying the susceptibility of different muscle types to age-related atrophy are not fully understood. Reactive oxygen species (ROS) are recognised as important signalling molecules in healthy muscle and redox sensitive proteins can respond to intracellular changes in ROS concentrations modifying reactive thiol groups on Cysteine (Cys) residues. Conserved Cys residues tend to occur in functionally important locations and can have a direct impact on protein function through modifications at the active site or determining protein conformation. The aim of this work was to determine age-related changes in the redox proteome of two metabolically distinct murine skeletal muscles, the quadriceps a predominantly glycolytic muscle and the soleus which contains a higher proportion of mitochondria. To examine the effects of aging on the global proteome and the oxidation state of individual redox sensitive Cys residues, we employed a label free proteomics approach including a differential labelling of reduced and reversibly oxidised Cys residues. Our results indicate the proteomic response to aging is dependent on muscle type but redox changes that occur primarily in metabolic and cytoskeletal proteins are generally preserved between metabolically distinct tissues. Skeletal muscle containing fast twitch glycolytic fibres are more susceptible to age related atrophy compared to muscles with higher proportions of oxidative slow twitch fibres. Contracting skeletal muscle generates reactive oxygen species that are required for correct signalling and adaptation to exercise and it is also known that the intracellular redox environment changes with age. To identify potential mechanisms for the distinct response to age, this article combines a global proteomic approach and a differential labelling of reduced and reversibly oxidised Cysteine residues in two metabolically distinct skeletal muscles, quadriceps and soleus, from adult and old mice. Our results indicate that the global proteomic changes with age in skeletal muscles are dependent on fibre type. However, redox specific changes are preserved across muscle types and accompanied with a reduction in the number of redox sensitive Cysteine residues. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

A survey on some biochemical and pharmacological activities of venom from two Colombian colubrid snakes, Erythrolamprus bizona (Double-banded coral snake mimic) and Pseudoboa neuwiedii (Neuwied's false boa).

PubMed

Torres-Bonilla, Kristian A; Floriano, Rafael S; Schezaro-Ramos, Raphael; Rodrigues-Simioni, Léa; da Cruz-Höfling, Maria Alice

2017-06-01

Colombian colubrid snake venoms have been poorly studied. They represent a great resource of biological, ecological, toxinological and pharmacological research. We assessed some enzymatic properties and neuromuscular effects of Erythrolamprus bizona and Pseudoboa neuwiedii venoms from Colombia. Proteolytic, amidolytic and phospholipase A 2 (PLA 2 ) activities were analyzed using colorimetric assays and the neuromuscular activity was analyzed in chick biventer cervicis (BC) preparations. The venom of both species showed very low PLA 2 and amidolytic activities; however, both exhibited high proteolytic activity, which in E. bizona venom surpassed that of P. neuwiedii venom. E. bizona and P. neuwiedii venoms provoked partial neuromuscular blockade, which was more prominent in P. neuwiedii venom. E. bizona venom (30 μg/ml) induced a significant potentiation of the contracture response to exogenous ACh (110 μM), which was not accompanied by twitch height alteration, whereas the highest venom concentration (100 μg/ml) inhibited contracture responses to both ACh and KCl (40 mM). In contrast, P. neuwiedii venom (30 and 100 μg/ml) caused significant reduction in the contracture responses to exogenous ACh and KCl. The morphological analyses showed high myotoxic effects in the muscle fibers of BC incubated with either venoms; however, they are more prominent in the P. neuwiedii venom. Our results suggest that the myotoxicity of the venom of the two Colombian species can be ascribed to their high proteolytic activity. An interesting data was the potentiation of the ACh-induced contracture, but not the twitch height, caused by E. bizona venom, at a concentration that is harmless to muscle fibers integrity. This phenomenon remains to be further elucidated, and suggest that a possible involvement of post-synaptic receptors cannot be discarded. This work is a contribution to expand the knowledge on colubrid venoms; it allows envisaging that the two venoms offer the potential to go further in the identification of their components and biological targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modelling the Active Hearing Process in Mosquitoes

NASA Astrophysics Data System (ADS)

Avitabile, Daniele; Homer, Martin; Jackson, Joe; Robert, Daniel; Champneys, Alan

2011-11-01

A simple microscopic mechanistic model is described of the active amplification within the Johnston's organ of the mosquito species Toxorhynchites brevipalpis. The model is based on the description of the antenna as a forced-damped oscillator coupled to a set of active threads (ensembles of scolopidia) that provide an impulsive force when they twitch. This twitching is in turn controlled by channels that are opened and closed if the antennal oscillation reaches a critical amplitude. The model matches both qualitatively and quantitatively with recent experiments. New results are presented using mathematical homogenization techniques to derive a mesoscopic model as a simple oscillator with nonlinear force and damping characteristics. It is shown how the results from this new model closely resemble those from the microscopic model as the number of threads approach physiologically correct values.

Synthesis of 2,4-dihydroxychalcone derivatives as potential antidepressant effect.

PubMed

Guan, L-P; Zhao, D-H; Chang, Y; Wen, Z-S; Tang, L-M; Huang, F-F

2013-01-01

In this study, twelve 2,4-dihydroxychalcone derivatives were synthesized and evaluated for antidepressant activities using the forced swimming test (FST). The pharmacological test showed that 6 compounds significantly reduced the immobility times in the FST at a dose of 10 mg/kg, indicative of antidepressant activity. Among the derivatives, compounds designated 3d and 3 h exhibited the best antidepressant activity, with reduced immobility time by 32.05% and 34.33%, respectively. In the 5-hydroxytryptophan-induced head-twitch test and yohimbine-induced mortality test, compounds 3d and 3 h increased head-twitch and increased the mortality rate. The mechanisms of the antidepressant effects of compounds 3d and 3 h may be related with the 5-HTP and NE nervous system. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of hindlimb immobilization on the fatigability of skeletal muscle

NASA Technical Reports Server (NTRS)

Witzmann, F. A.; Kim, D. H.; Fitts, R. H.

1983-01-01

The effect of 6 weeks of disuse atrophy produced by hindlimb immobilization was studied in situ (33.5 C) in the soleus and extensor digitorum longus muscles of rats. The results indicate that disuse causes preferential alterations in the isometric contractile properties of slow-twitch, as opposed to fast-twitch, skeletal muscles. During continuous contractile activity, atrophied muscles were found to have lower ATP levels and an apparent increase in their dependence on anaerobic metabolism, as reflected by the more extensive depletion of glycogen and enhanced lactate formation. Although the atrophied muscles were determined to have fewer cross bridges and thus generated lower tension, the pattern of decline in active cross-bridge formation and tetanic tension during contractile activity was found to proceed in a manner similar to controls.

Effect of inactivity and passive stretch on protein turnover in phasic and postural rat muscles

NASA Technical Reports Server (NTRS)

Loughna, P.; Goldspink, G.; Goldspink, D. F.

1986-01-01

Muscle atrophy in humans can occur during prolonged bed rest, plaster cast immobilization, and space flight. In the present study, the suspension model used by Musacchia et al. (1983) is employed to investigate changes in protein synthesis and degradation in fast-twitch phasic (extensor digitorum longus) and slow-twitch postural (soleus) muscles in the rat, following hypokinesia and hypodynamia. In addition, the use of passive stretch was examined as a means of preventing atrophy. The obtained results suggest that the mechanisms controlling the processes of protein synthesis and protein breakdown during muscle disuse atrophy may be independent of each other. It appears, however, that the muscle atrophy due to hypokinesia and hypodynamia can be temporarily prevented by passively stretching a muscle.

Phase-dependent organization of postural adjustments associated with arm movements while walking.

PubMed

Nashner, L M; Forssberg, H

1986-06-01

This study examines the interactions between anteroposterior postural responses and the control of walking in human subjects. In the experimental paradigm, subjects walked upon a treadmill, gripping a rigid handle with one hand. Postural responses at different phases of stepping were elicited by rapid arm pulls or pushes against the handle. During arm movements, EMG's recorded the activity of representative arm, ankle, and thigh segment muscles. Strain gauges in the handle measured the force of the arm movement. A Selspot II system measured kinematics of the stepping movements. The duration of support and swing phases were marked by heel and toe switches in the soles of the subjects' shoes. In the first experiment, subjects were instructed to pull on the handle at their own pace. In these trials all subjects preferred to initiate pulls near heel strikes. Next, when instructed to pull as rapidly as possible in response to tone stimuli, reaction times were similar for all phases of the step cycle. Leg muscle responses associated with arm pulls and pushes, referred to as "postural activations," were directionally specific and preceded arm muscle activity. The temporal order and spatial distribution of postural activations in the muscles of the support leg were similar when arm pull movements occurred while the subject was standing in place and after heel strike while walking. Activations began in the ankle and radiated proximally to the thigh and then the arm. Activations of swing leg muscles were also directionally specific and involved flexion and forward or backward thrust of the limb. When arm movements were initiated during transitions from support by one leg to the other, patterns of postural activations were altered. Alterations usually occurred 10-20 ms before hell strikes and involved changes in the timing and sometimes the spatial structure of postural activations. Postural activation patterns are similar during in-place standing and during the support phase of locomotion. Walking and posture control appear to be separately organized but interrelated activities. Our results also suggest that the stepping generators, not peripheral feedback time locked to heel strikes, modulate postural activation patterns.

A Phase 2 Randomized Study of Ramucirumab (IMC-1121B) with or without Dacarbazine in Patients with Metastatic Melanoma

PubMed Central

Carvajal, Richard D.; Wong, Michael K.; Thompson, John A.; Gordon, Michael S.; Lewis, Karl D.; Pavlick, Anna C.; Wolchok, Jedd D.; Rojas, Patrick B.; Schwartz, Jonathan D.; Bedikian, Agop Y.

2017-01-01

SUMMARY Background To evaluate the efficacy and safety of ramucirumab (IMC-1121B; LY3009806), a fully human monoclonal antibody targeting the vascular endothelial growth factor receptor-2, alone and in combination with dacarbazine in chemotherapy-naïve patients with metastatic melanoma (MM). Methods Eligible patients received ramucirumab (10 mg/kg) + dacarbazine (1000 mg/m2) (Arm A) or ramucirumab only (10 mg/kg) (Arm B) every 3 weeks. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response, and safety. Findings Of 106 randomized patients, 102 received study treatment (Arm A, N = 52; Arm B, N = 50). Baseline characteristics were similar in both arms. Median PFS was 2·6 months (Arm A) and 1·7 months (Arm B); median 6-month PFS rates were 30·7% and 17·9% and 12-month PFS rates were 23·7% and 15·6%, respectively. In Arm A, 9 (17·3%) patients had partial response (PR) and 19 (36·5%), stable disease (SD); PR and SD in Arm B were 2 (4·0%) and 21 (42·0%), respectively. Median OS was 8·7 months in Arm A and 11·1 months in Arm B. Patients in both arms tolerated the treatment with limited grade 3/4 toxicities. Interpretation Ramucirumab alone or in combination with dacarbazine was associated with an acceptable safety profile in patients with MM. Although the study was not powered for comparison between treatment arms, PFS appeared greater with combination therapy. Sustained disease control was observed on both study arm Funding Funded by ImClone Systems LLC, a wholly-owned subsidiary of Eli Lilly and Company, Bridgewater, NJ PMID:24930625

Proprioceptive role for palisade endings in extraocular muscles: evidence from the Jendrassik Maneuver.

PubMed

Niechwiej-Szwedo, E; González, E; Bega, S; Verrier, M C; Wong, A M; Steinbach, M J

2006-07-01

A proprioceptive hypothesis for the control of eye movements has been recently proposed based on neuroanatomical tracing studies. It has been suggested that the non-twitch motoneurons could be involved in modulating the gain of sensory feedback from the eye muscles analogous to the gamma (gamma) motoneurons which control the gain of proprioceptive feedback in skeletal muscles. We conducted behavioral and psychophysical experiments to test the above hypothesis using the Jendrassik Maneuver (JM) to alter the activity of gamma motoneurons. It was hypothesized that the JM would alter the proprioceptive feedback from the eye muscles which would result in misregistration of eye position and mislocalization of targets. In the first experiment, vergence eye movements and pointing responses were examined. Data showed that the JM affected the localization responses but not the actual eye position. Perceptual judgments were tested in the second experiment, and the results showed that targets were perceived as farther when the afferent feedback was altered by the JM. Overall, the results from the two experiments showed that eye position was perceived as more divergent with the JM, but the actual eye movements were not affected. We tested this further in Experiment 3 by examining the effect of JM on the amplitude and velocity of saccadic eye movements. As expected, there were no significant differences in saccadic parameters between the control and experimental conditions. Overall, the present study provides novel insight into the mechanism which may be involved in the use of sensory feedback from the eye muscles. Data from the first two experiments support the hypothesis that the JM alters the registered eye position, as evidenced by the localization errors. We propose that the altered eye position signal is due to the effect of the JM which changes the gain of the sensory feedback from the eye muscles, possibly via the activity of non-twitch motoneurons.

Hyperpolarized functional magnetic resonance of murine skeletal muscle enabled by multiple tracer-paradigm synchronizations.

PubMed

Leftin, Avigdor; Roussel, Tangi; Frydman, Lucio

2014-01-01

Measuring metabolism's time- and space-dependent responses upon stimulation lies at the core of functional magnetic resonance imaging. While focusing on water's sole resonance, further insight could arise from monitoring the temporal responses arising from the metabolites themselves, in what is known as functional magnetic resonance spectroscopy. Performing these measurements in real time, however, is severely challenged by the short functional timescales and low concentrations of natural metabolites. Dissolution dynamic nuclear polarization is an emerging technique that can potentially alleviate this, as it provides a massive sensitivity enhancement allowing one to probe low-concentration tracers and products in a single-scan. Still, conventional implementations of this hyperpolarization approach are not immediately amenable to the repeated acquisitions needed in real-time functional settings. This work proposes a strategy for functional magnetic resonance of hyperpolarized metabolites that bypasses this limitation, and enables the observation of real-time metabolic changes through the synchronization of stimuli-triggered, multiple-bolus injections of the metabolic tracer 13C1-pyruvate. This new approach is demonstrated with paradigms tailored to reveal in vivo thresholds of murine hind-limb skeletal muscle activation, involving the conversion of 13C1-pyruvate to 13C1-lactate and 13C1-alanine. These functional hind-limb studies revealed that graded skeletal muscle stimulation causes commensurate increases in glycolytic metabolism in a frequency- and amplitude-dependent fashion, that can be monitored on the seconds/minutes timescale using dissolution dynamic nuclear polarization. Spectroscopic imaging further allowed the in vivo visualization of uptake, transformation and distribution of the tracer and products, in fast-twitch glycolytic and in slow-twitch oxidative muscle fiber groups. While these studies open vistas in time and sensitivity for metabolic functional magnetic resonance studies in muscle, the simplicity of our approach makes this technique amenable to a wide range of functional metabolic tracer studies.

The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice.

PubMed

Malik, Maninder; Rangel-Barajas, Claudia; Mach, Robert H; Luedtke, Robert R

2016-09-01

Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds. Copyright © 2016. Published by Elsevier Inc.

Pharmacological modulation of abnormal involuntary DOI-induced head twitch response in male DBA/2J mice: I. Effects of D2/D3 and D2 dopamine receptor selective compounds.

PubMed

Rangel-Barajas, Claudia; Malik, Maninder; Vangveravong, Suwanna; Mach, Robert H; Luedtke, Robert R

2014-08-01

Because of the complexity and heterogeneity of human neuropsychiatric disorders, it has been difficult to identify animal models that mimic the symptoms of these neuropathologies and can be used to screen for antipsychotic agents. For this study we selected the murine 5HT2A/2C receptor agonist-induced head twitch response (HTR) induced by the administration of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), which has been proposed as an animal model of symptoms associated with a variety of behavioral and psychiatric conditions. We investigated the DOI-induced HTR in male DBA/2J mice using a panel of D2-like (D2, D3 and D4) and D2 dopamine receptor selective compounds. When DBA/2J mice were administered a daily dose of DOI (5 mg/kg), tolerance to the DOI occurs. However, administrations of the same dose of DOI every other day (48 h) or on a weekly basis did not lead to tolerance and the ability to induce tolerance after daily administration of DOI remains intact after repeated weekly administration of DOI. Subsequently, a panel of D2-like dopamine receptor antagonists was found to effectively inhibit the DOI-induced HTR in DBA/2J mice. However, the benzamide eticlopride, which is a high affinity D2-like antagonist, was a notable exception. SV 293, SV-III-130s and N-methylbenperidol, which exhibit a high affinity for D2 versus the D3 dopamine receptor subtypes (60- to 100-fold binding selectivity), were also found to inhibit the HTR in DBA/2J mice. This observation suggests a functional interaction between dopaminergic and serotonergic systems through D2 dopamine receptors and the 5-HT2A serotonin receptors in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats.

PubMed

Noworyta-Sokołowska, Karolina; Kamińska, Katarzyna; Kreiner, Grzegorz; Rogóż, Zofia; Gołembiowska, Krystyna

2016-11-01

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, 'foxy') is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors. In this study, using microdialysis in freely moving rats, we examined the effect of 5-MeO-DIPT on dopamine (DA), serotonin (5-HT), and glutamate release in the rat striatum, nucleus accumbens, and frontal cortex. In search of a possible neurotoxic effect of 5-MeO-DIPT, we measured DA and 5-HT tissue content in the above rat brain regions and also determined the oxidative DNA damage with the comet assay. Moreover, we tested drug-elicited head-twitch response and a forepaw treading induced by 8-OH-DPAT. 5-MeO-DIPT at doses of 5, 10, and 20 mg/kg increased extracellular DA, 5-HT, and glutamate level but the differences in the potency were found between brain regions. 5-MeO-DIPT increased 5-HT and decreased 5-HIAA tissue content which seems to result from SERT inhibition. On the other hand, a decrease in DA, DOPAC, and HVA tissue contents suggests possible adaptive changes in DA turnover or damage of DA terminals by 5-MeO-DIPT. DNA single and double-strand breaks persisted up to 60 days after the treatment, indicating marked neurotoxicity of 5-MeO-DIPT. The induction of head-twitch response and potentiation of forepaw treading induced by 8-OH-DPAT indicate that hallucinogenic activity seems to be mediated through the stimulation of 5-HT2A and 5-HT1A receptors by 5-MeO-DIPT.

A quantitative description of tubular system Ca(2+) handling in fast- and slow-twitch muscle fibres.

PubMed

Cully, Tanya R; Edwards, Joshua N; Murphy, Robyn M; Launikonis, Bradley S

2016-06-01

Current methods do not allow a quantitative description of Ca(2+) movements across the tubular (t-) system membrane without isolating the membranes from their native skeletal muscle fibre. Here we present a fluorescence-based method that allows determination of the t-system [Ca(2+) ] transients and derivation of t-system Ca(2+) fluxes in mechanically skinned skeletal muscle fibres. Differences in t-system Ca(2+) -handling properties between fast- and slow-twitch fibres from rat muscle are resolved for the first time using this new technique. The method can be used to study Ca(2+) handling of the t-system and allows direct comparisons of t-system Ca(2+) transients and Ca(2+) fluxes between groups of fibres and fibres from different strains of animals. The tubular (t-) system of skeletal muscle is an internalization of the plasma membrane that maintains a large Ca(2+) gradient and exchanges Ca(2+) between the extracellular and intracellular environments. Little is known of the Ca(2+) -handling properties of the t-system as the small Ca(2+) fluxes conducted are difficult to resolve with conventional methods. To advance knowledge in this area we calibrated t-system-trapped rhod-5N inside skinned fibres from rat and [Ca(2+) ]t-sys , allowing confocal measurements of Ca(2+) -dependent changes in rhod-5N fluorescence during rapid changes in the intracellular ionic environment to be converted to [Ca(2+) ] transients in the t-system ([Ca(2+) ]t-sys (t)). Furthermore, t-system Ca(2+) -buffering power was determined so that t-system Ca(2+) fluxes could be derived from [Ca(2+) ]t-sys (t). With this new approach, we show that rapid depletion of sarcoplasmic reticulum (SR) Ca(2+) induced a robust store-operated Ca(2+) entry (SOCE) in fast- and slow-twitch fibres, reducing [Ca(2+) ]t-sys to < 0.1 mm. The rapid activation of SOCE upon Ca(2+) release was consistent with the presence of STIM1L in both fibre types. Abruptly introducing internal solutions with 1 mm Mg(2+) and [Ca(2+) ]cyto (28 nm-1.3 μm) to Ca(2+) -depleted fibres generated t-system Ca(2+) uptake rates dependent on [Ca(2+) ]cyto with [Ca(2+) ]t-sys reaching final plateaus in the millimolar range. For the same [Ca(2+) ]cyto , t-system Ca(2+) fluxes of fast-twitch fibres were greater than that in slow-twitch fibres. In addition, simultaneous imaging of t-system and SR Ca(2+) signals indicated that both membrane compartments accumulated Ca(2+) at similar rates and that SOCE was activated early during SR Ca(2+) depletion. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

A quantitative description of tubular system Ca2+ handling in fast‐ and slow‐twitch muscle fibres

PubMed Central

Cully, Tanya R.; Edwards, Joshua N.; Murphy, Robyn M.

2016-01-01

Key points Current methods do not allow a quantitative description of Ca2+ movements across the tubular (t‐) system membrane without isolating the membranes from their native skeletal muscle fibre.Here we present a fluorescence‐based method that allows determination of the t‐system [Ca2+] transients and derivation of t‐system Ca2+ fluxes in mechanically skinned skeletal muscle fibres. Differences in t‐system Ca2+‐handling properties between fast‐ and slow‐twitch fibres from rat muscle are resolved for the first time using this new technique.The method can be used to study Ca2+ handling of the t‐system and allows direct comparisons of t‐system Ca2+ transients and Ca2+ fluxes between groups of fibres and fibres from different strains of animals. Abstract The tubular (t‐) system of skeletal muscle is an internalization of the plasma membrane that maintains a large Ca2+ gradient and exchanges Ca2+ between the extracellular and intracellular environments. Little is known of the Ca2+‐handling properties of the t‐system as the small Ca2+ fluxes conducted are difficult to resolve with conventional methods. To advance knowledge in this area we calibrated t‐system‐trapped rhod‐5N inside skinned fibres from rat and [Ca2+]t‐sys, allowing confocal measurements of Ca2+‐dependent changes in rhod‐5N fluorescence during rapid changes in the intracellular ionic environment to be converted to [Ca2+] transients in the t‐system ([Ca2+]t‐sys (t)). Furthermore, t‐system Ca2+‐buffering power was determined so that t‐system Ca2+ fluxes could be derived from [Ca2+]t‐sys (t). With this new approach, we show that rapid depletion of sarcoplasmic reticulum (SR) Ca2+ induced a robust store‐operated Ca2+ entry (SOCE) in fast‐ and slow‐twitch fibres, reducing [Ca2+]t‐sys to < 0.1 mm. The rapid activation of SOCE upon Ca2+ release was consistent with the presence of STIM1L in both fibre types. Abruptly introducing internal solutions with 1 mm Mg2+ and [Ca2+]cyto (28 nm–1.3 μm) to Ca2+‐depleted fibres generated t‐system Ca2+ uptake rates dependent on [Ca2+]cyto with [Ca2+]t‐sys reaching final plateaus in the millimolar range. For the same [Ca2+]cyto, t‐system Ca2+ fluxes of fast‐twitch fibres were greater than that in slow‐twitch fibres. In addition, simultaneous imaging of t‐system and SR Ca2+ signals indicated that both membrane compartments accumulated Ca2+ at similar rates and that SOCE was activated early during SR Ca2+ depletion. PMID:26775687

Role of contralesional hemisphere in paretic arm reaching in patients with severe arm paresis due to stroke: A preliminary report.

PubMed

Mohapatra, Sambit; Harrington, Rachael; Chan, Evan; Dromerick, Alexander W; Breceda, Erika Y; Harris-Love, Michelle

2016-03-23

Stroke is highly prevalent and a leading cause of serious, long-term disability among American adults. Impaired movement (i.e. paresis) of the stroke-affected arm is a major contributor to post-stroke disability, yet the mechanisms of upper extremity motor recovery are poorly understood, particularly in severely impaired patients who lack hand function. To address this problem, we examined the functional relevance of the contralesional hemisphere in paretic arm motor performance in individuals with severe arm paresis. Twelve individuals with severe stroke-induced arm paresis (Upper Extremity Fugl-Meyer Assessment=17.1 ± 8.5; maximum score=66) participated in the study. Participants performed a reaching response time task with their paretic arm. At varying time intervals following a 'Go' cue, a pair of transcranial magnetic stimulation (TMS) pulses were delivered to contralesional hemisphere primary motor (M1) or dorsal pre-motor cortex (PMd) to momentarily disrupt the pattern of neural firing. Response time components and hand-path characteristics were compared across the 2 sites for trials with and without TMS disruption. There was no significant effect of TMS disruption on overall Response time or Reaction time, but Movement time was significantly longer (i.e. slower) with disruption of the contralesional hemisphere (p=0.015), regardless of which area was stimulated. Peak hand-path velocity and hand-path smoothness were also significantly lower (p=0.005 and p<0.0001, respectively) with TMS disruption of the contralesional hemisphere. The data from this study provide evidence supporting a functionally relevant role of contralesional hemisphere motor areas in paretic arm reaching movements in individuals with severe post-stroke arm impairment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Responses of Myosin Heavy Chain Phenotypes and Gene Expressions in Neck Muscle to Micro- an Hyper-Gravity in Mice

NASA Astrophysics Data System (ADS)

Ohira, Tomotaka; Ohira, Takashi; Kawano, F.; Shibaguchi, T.; Okabe, H.; Ohno, Y.; Nakai, N.; Ochiai, T.; Goto, K.; Ohira, Y.

2013-02-01

Neck muscles are known to play important roles in the maintenance of head posture against gravity. However, it is not known how the properties of neck muscle are influenced by gravity. Therefore, the current study was performed to investigate the responses of neck muscle (rhomboideus capitis) in mice to inhibition of gravity and/or increase to 2-G for 3 months to test the hypothesis that the properties of neck muscles are regulated in response to the level of mechanical load applied by the gravitational load. Three male wild type C57BL/10J mice (8 weeks old) were launched by space shuttle Discovery (STS-128) and housed in Japanese Experimental Module “KIBO” on the International Space Station in mouse drawer system (MDS) project, which was organized by Italian Space Agency. Only 1 mouse returned to the Earth alive after 3 months by space shuttle Atlantis (STS-129). Neck muscles were sampled from both sides within 3 hours after landing. Cage and laboratory control experiments were also performed on the ground. Further, 3-month ground-based control experiments were performed with 6 groups, i.e. pre-experiment, 3-month hindlimb suspension, 2-G exposure by using animal centrifuge, and vivarium control (n=5 each group). Five mice were allowed to recover from hindlimb suspension (including 5 cage control) for 3 months in the cage. Neck muscles were sampled bilaterally before and after 3-month suspension and 2-G exposure, and at the end of 3-month ambulation recovery. Spaceflight-associated shift of myosin heavy chain phenotype from type I to II and atrophy of type I fibers were observed. In response to spaceflight, 17 genes were up-regulated and 13 genes were down-regulated vs. those in the laboratory control. Expression of 6 genes were up-regulated and that of 88 genes were down-regulated by 3-month exposure to 2-G vs. the age-matched cage control. In response to chronic hindlimb suspension, 4 and 20 genes were up- or down-regulated. Further, 98 genes responded significantly to both hindlimb unloading and exposure to 2-G. Thirteen genes were up-regulated and 85 were down-regulated. In conclusion, long-term gravitational unloading of mouse caused shift of fiber phenotype toward fast-twitch type and atrophy of slow-twitch fibers in neck muscle. These responses were closely related to the up- or down-regulation of genes, suggesting that oxidative muscular metabolism may be inhibited in microgravity environment.

Physiological and Emotional Reactivity to Learning and Frustration

ERIC Educational Resources Information Center

Lewis, Michael; Hitchcock, Daniel F. A.; Sullivan, Margaret Wolan

2004-01-01

This study examined the behavioral (arm, facial) and autonomic (heart rate, respiratory sinus arrhythmia [RSA], and adrenocortical axis) reactivity of 56 4-month-old infants in response to contingency learning and extinction-induced frustration. During learning, infants displayed increases in operant arm response and positive emotional…

Arm posture-dependent changes in corticospinal excitability are largely spinal in origin.

PubMed

Nuzzo, James L; Trajano, Gabriel S; Barry, Benjamin K; Gandevia, Simon C; Taylor, Janet L

2016-04-01

Biceps brachii motor evoked potentials (MEPs) from cortical stimulation are influenced by arm posture. We used subcortical stimulation of corticospinal axons to determine whether this postural effect is spinal in origin. While seated at rest, 12 subjects assumed several static arm postures, which varied in upper-arm (shoulder flexed, shoulder abducted, arm hanging to side) and forearm orientation (pronated, neutral, supinated). Transcranial magnetic stimulation over the contralateral motor cortex elicited MEPs in resting biceps and triceps brachii, and electrical stimulation of corticospinal tract axons at the cervicomedullary junction elicited cervicomedullary motor evoked potentials (CMEPs). MEPs and CMEPs were normalized to the maximal compound muscle action potential (Mmax). Responses in biceps were influenced by upper-arm and forearm orientation. For upper-arm orientation, biceps CMEPs were 68% smaller (P= 0.001), and biceps MEPs 31% smaller (P= 0.012), with the arm hanging to the side compared with when the shoulder was flexed. For forearm orientation, both biceps CMEPs and MEPs were 34% smaller (both P< 0.046) in pronation compared with supination. Responses in triceps were influenced by upper-arm, but not forearm, orientation. Triceps CMEPs were 46% smaller (P= 0.007) with the arm hanging to the side compared with when the shoulder was flexed. Triceps MEPs and biceps and triceps MEP/CMEP ratios were unaffected by arm posture. The novel finding is that arm posture-dependent changes in corticospinal excitability in humans are largely spinal in origin. An interplay of multiple reflex inputs to motoneurons likely explains the results. Copyright © 2016 the American Physiological Society.

Arm posture-dependent changes in corticospinal excitability are largely spinal in origin

PubMed Central

Nuzzo, James L.; Trajano, Gabriel S.; Barry, Benjamin K.; Gandevia, Simon C.

2016-01-01

Biceps brachii motor evoked potentials (MEPs) from cortical stimulation are influenced by arm posture. We used subcortical stimulation of corticospinal axons to determine whether this postural effect is spinal in origin. While seated at rest, 12 subjects assumed several static arm postures, which varied in upper-arm (shoulder flexed, shoulder abducted, arm hanging to side) and forearm orientation (pronated, neutral, supinated). Transcranial magnetic stimulation over the contralateral motor cortex elicited MEPs in resting biceps and triceps brachii, and electrical stimulation of corticospinal tract axons at the cervicomedullary junction elicited cervicomedullary motor evoked potentials (CMEPs). MEPs and CMEPs were normalized to the maximal compound muscle action potential (Mmax). Responses in biceps were influenced by upper-arm and forearm orientation. For upper-arm orientation, biceps CMEPs were 68% smaller (P = 0.001), and biceps MEPs 31% smaller (P = 0.012), with the arm hanging to the side compared with when the shoulder was flexed. For forearm orientation, both biceps CMEPs and MEPs were 34% smaller (both P < 0.046) in pronation compared with supination. Responses in triceps were influenced by upper-arm, but not forearm, orientation. Triceps CMEPs were 46% smaller (P = 0.007) with the arm hanging to the side compared with when the shoulder was flexed. Triceps MEPs and biceps and triceps MEP/CMEP ratios were unaffected by arm posture. The novel finding is that arm posture-dependent changes in corticospinal excitability in humans are largely spinal in origin. An interplay of multiple reflex inputs to motoneurons likely explains the results. PMID:26864764

Tics

MedlinePlus

... Staying Safe Videos for Educators Search English Español Tics KidsHealth / For Teens / Tics What's in this article? ... tic, such as a nose twitch. What's a Tic? A tic is an uncontrolled sudden, repetitive movement ...

S-nitrosylation and S-glutathionylation of Cys134 on troponin I have opposing competitive actions on Ca2+ sensitivity in rat fast-twitch muscle fibers.

PubMed

Dutka, T L; Mollica, J P; Lamboley, C R; Weerakkody, V C; Greening, D W; Posterino, G S; Murphy, R M; Lamb, G D

2017-03-01

Nitric oxide is generated in skeletal muscle with activity and decreases Ca 2+ sensitivity of the contractile apparatus, putatively by S- nitrosylation of an unidentified protein. We investigated the mechanistic basis of this effect and its relationship to the oxidation-induced increase in Ca 2+ sensitivity in mammalian fast-twitch (FT) fibers mediated by S- glutathionylation of Cys134 on fast troponin I (TnI f ). Force-[Ca 2+ ] characteristics of the contractile apparatus in mechanically skinned fibers were assessed by direct activation with heavily Ca 2+ -buffered solutions. Treatment with S- nitrosylating agents, S- nitrosoglutathione (GSNO) or S- nitroso- N -acetyl-penicillamine (SNAP), decreased pCa 50 ( = -log 10 [Ca 2+ ] at half-maximal activation) by ~-0.07 pCa units in rat and human FT fibers without affecting maximum force, but had no effect on rat and human slow-twitch fibers or toad or chicken FT fibers, which all lack Cys134. The Ca 2+ sensitivity decrease was 1 ) fully reversed with dithiothreitol or reduced glutathione, 2 ) at least partially reversed with ascorbate, indicative of involvement of S-nitrosylation, and 3 ) irreversibly blocked by low concentration of the alkylating agent, N -ethylmaleimide (NEM). The biotin-switch assay showed that both GSNO and SNAP treatments caused S- nitrosylation of TnI f S- glutathionylation pretreatment blocked the effects of S- nitrosylation on Ca 2+ sensitivity, and vice-versa. S- nitrosylation pretreatment prevented NEM from irreversibly blocking S- glutathionylation of TnI f and its effects on Ca 2+ sensitivity, and likewise S- glutathionylation pretreatment prevented NEM block of S- nitrosylation. Following substitution of TnI f into rat slow-twitch fibers, S- nitrosylation treatment caused decreased Ca 2+ sensitivity. These findings demonstrate that S- nitrosylation and S- glutathionylation exert opposing effects on Ca 2+ sensitivity in mammalian FT muscle fibers, mediated by competitive actions on Cys134 of TnI f . Copyright © 2017 the American Physiological Society.

Carbonic Anhydrase III Is Expressed in Mouse Skeletal Muscles Independent of Fiber Type-Specific Myofilament Protein Isoforms and Plays a Role in Fatigue Resistance

PubMed Central

Feng, Han-Zhong; Jin, J.-P.

2016-01-01

Carbonic anhydrase III (CAIII) is a metabolic enzyme and a regulator for intracellular pH. CAIII has been reported with high level expression in slow twitch skeletal muscles. Here we demonstrate that CAIII is expressed in multiple slow and fast twitch muscles of adult mouse independent of the expression of myosin isoforms. Expressing similar fast type of myofilament proteins, CAIII-positive tibial anterior (TA) muscle exhibits higher tolerance to fatigue than that of CAIII-negative fast twitch extensor digitorum longus (EDL) muscle in in situ contractility studies. We further studied the muscles of CAIII knockout (Car3-KO) mice. The loss of CAIII in soleus and TA muscles in Car3-KO mice did not change muscle mass, sarcomere protein isoform contents, and the baseline twitch and tetanic contractility as compared with age-matched wild type (WT) controls. On the other hand, Car3-KO TA muscle showed faster force reduction at the beginning but higher resistance at the end during a fatigue test, followed by slower post fatigue recovery than that of WT TA muscle. Superfused Car3-KO soleus muscle also had faster total force reduction during fatigue test than that of WT soleus. However, it showed a less elevation of resting tension followed by a better post fatigue recovery under acidotic stress. CAIII was detected in neonatal TA and EDL muscle, downregulated during development, and then re-expressed in adult TA but not EDL muscles. The expression of CAIII in Tnnt1-KO myopathy mouse soleus muscle that has diminished slow fiber contents due to the loss of slow troponin T remained high. Car3-KO EDL, TA, and soleus muscles showed no change in the expression of mitochondria biomarker proteins. The data suggest a fiber type independent expression of CAIII with a role in the regulation of intracellular pH in skeletal muscle and may be explored as a target for improving fatigue resistance and for the treatment of TNNT1 myopathies. PMID:28018233

Voluntary activation failure is detectable in some myositis patients with persisting quadriceps femoris weakness: an observational study

PubMed Central

Molloy, Catherine B; Al-Omar, Ahmed O; Edge, Kathryn T; Cooper, Robert G

2006-01-01

This cross-sectional, observational study was undertaken to examine whether voluntary activation failure could contribute to the persisting weakness observed in some patients with treated idiopathic inflammatory myositis. In 20 patients with myositis of more than six months' duration (5 males, 15 females; mean [± 1 SD] age 53 [11] years) and 102 normal subjects (44 males, 58 females; mean age 32 [8] years), isometric maximum voluntary contractions (MVCs) of the dominant quadriceps femoris (QF) were quantified. Absolute MVC results of normal subjects and patients were then normalised with respect to lean body mass (force per units of lean body mass), giving a result in Newtons per kilogram. Based on mass-normalised force data of normal subjects, patients were arbitrarily stratified into "weak" and "not weak" subgroups. During further MVC attempts, the "twitch interpolation" technique was used to assess whether the QF voluntary activation of patients was complete. This technique relies on the fact that, because muscle activation is incomplete during submaximal voluntary contractions, electrical stimulation of the muscle can induce force increments superimposed on the submaximal voluntary force being generated. No between-gender differences were seen in the mass-normalised MVC results of healthy subjects, so the gender-combined results of 6.6 (1.5) N/kg were used for patient stratification. No between-gender difference was found for mass-normalised MVCs in patients: males 5.4 (3.2) and females 3.0 (1.7) N/kg (p > 0.05). Mass-normalised MVCs of male patients were as great as those of normal subjects (p > 0.05), but mass-normalised MVCs of female patients were significantly smaller than those of the normal subjects (p < 0.001). Only one of the six "not weak" patients exhibited interpolated twitches during electrical stimulation, but six of the 14 "weak" patients did, the biggest twitches being seen in the weakest patient. That interpolated twitches can be induced in some myositis patients with ongoing QF weakness during supposed MVCs clearly suggests that voluntary activation failure does contribute to QF weakness in those patients. PMID:16606441

Carbonic Anhydrase III Is Expressed in Mouse Skeletal Muscles Independent of Fiber Type-Specific Myofilament Protein Isoforms and Plays a Role in Fatigue Resistance.

PubMed

Feng, Han-Zhong; Jin, J-P

2016-01-01

Carbonic anhydrase III (CAIII) is a metabolic enzyme and a regulator for intracellular pH. CAIII has been reported with high level expression in slow twitch skeletal muscles. Here we demonstrate that CAIII is expressed in multiple slow and fast twitch muscles of adult mouse independent of the expression of myosin isoforms. Expressing similar fast type of myofilament proteins, CAIII-positive tibial anterior (TA) muscle exhibits higher tolerance to fatigue than that of CAIII-negative fast twitch extensor digitorum longus (EDL) muscle in in situ contractility studies. We further studied the muscles of CAIII knockout ( Car3 -KO) mice. The loss of CAIII in soleus and TA muscles in Car3 -KO mice did not change muscle mass, sarcomere protein isoform contents, and the baseline twitch and tetanic contractility as compared with age-matched wild type (WT) controls. On the other hand, Car3 -KO TA muscle showed faster force reduction at the beginning but higher resistance at the end during a fatigue test, followed by slower post fatigue recovery than that of WT TA muscle. Superfused Car3 -KO soleus muscle also had faster total force reduction during fatigue test than that of WT soleus. However, it showed a less elevation of resting tension followed by a better post fatigue recovery under acidotic stress. CAIII was detected in neonatal TA and EDL muscle, downregulated during development, and then re-expressed in adult TA but not EDL muscles. The expression of CAIII in Tnnt1 -KO myopathy mouse soleus muscle that has diminished slow fiber contents due to the loss of slow troponin T remained high. Car3 -KO EDL, TA, and soleus muscles showed no change in the expression of mitochondria biomarker proteins. The data suggest a fiber type independent expression of CAIII with a role in the regulation of intracellular pH in skeletal muscle and may be explored as a target for improving fatigue resistance and for the treatment of TNNT1 myopathies.

Comparison of myoplasmic calcium movements during excitation–contraction coupling in frog twitch and mouse fast-twitch muscle fibers

PubMed Central

Hollingworth, Stephen

2013-01-01

Single twitch fibers from frog leg muscles were isolated by dissection and micro-injected with furaptra, a rapidly responding fluorescent Ca2+ indicator. Indicator resting fluorescence (FR) and the change evoked by an action potential (ΔF) were measured at long sarcomere length (16°C); ΔF/FR was scaled to units of ΔfCaD, the change in fraction of the indicator in the Ca2+-bound form. ΔfCaD was simulated with a multicompartment model of the underlying myoplasmic Ca2+ movements, and the results were compared with previous measurements and analyses in mouse fast-twitch fibers. In frog fibers, sarcoplasmic reticulum (SR) Ca2+ release evoked by an action potential appears to be the sum of two components. The time course of the first component is similar to that of the entire Ca2+ release waveform in mouse fibers, whereas that of the second component is severalfold slower; the fractional release amounts are ∼0.8 (first component) and ∼0.2 (second component). Similar results were obtained in frog simulations with a modified model that permitted competition between Mg2+ and Ca2+ for occupancy of the regulatory sites on troponin. An anatomical basis for two release components in frog fibers is the presence of both junctional and parajunctional SR Ca2+ release channels (ryanodine receptors [RyRs]), whereas mouse fibers (usually) have only junctional RyRs. Also, frog fibers have two RyR isoforms, RyRα and RyRβ, whereas the mouse fibers (usually) have only one, RyR1. Our simulations suggest that the second release component in frog fibers functions to supply extra Ca2+ to activate troponin, which, in mouse fibers, is not needed because of the more favorable location of their triadic junctions (near the middle of the thin filament). We speculate that, in general, parajunctional RyRs permit increased myofilament activation in fibers whose triadic junctions are located at the z-line. PMID:23630340

Metabolic adaptation of skeletal muscles to gravitational unloading

NASA Astrophysics Data System (ADS)

Ohira, Y.; Yasui, W.; Kariya, F.; Wakatsuki, T.; Nakamura, K.; Asakura, T.; Edgerton, V. R.

Responses of high-energy phosphates and metabolic properties to hindlimb suspension were studied in adult rats. The relative content of phosphocreatine (PCr) in the calf muscles was significantly higher in rats suspended for 10 days than in age-matched cage controls. The Pi/PCr ratio, where Pi is inorganic phosphate, in suspended muscles was less than controls. The absolute weights of soleus and medial gastrocnemius (MG) were approximately 40% less than controls. Although the % fiber distribution in MG was unchanged, the % slow fibers decreased and the % fibers which were classified as both slow and fast was increased in soleus. The activities (per unit weight or protein) of succinate dehydrogenase and lactate dehydrogenase in soleus were unchanged but those of cytochrome oxidase, β-hydroxyacyl CoA dehydrogenase, and citrate synthase were decreased following unloading. None of these enzyme activities in MG changed. However, the total levels of all enzymes in whole muscles decreased by suspension. It is suggested that shift of slow muscle toward fast type by unloading is associated with a decrease in mitochondrial biogenesis. Further, gravitational unloading affected the levels of muscle proteins differently even in the same mitochondrial enzymes. Unloading-related atrophy is prominent in red muscle or slow-twitch fiber 1, 2. Such atrophy is accompanied by a shift of contractile properties toward fast-twitch type 2-9. Further, inhibition of mitochondrial metabolism in these muscles is also reported by some studies 10-14 suggesting a lowered mitochondrial biogenesis, although results from some studies do not necessarily agree 1, 7, 15. However, the precise mechanism responsible for such alterations of muscle properties in response to gravitational unloading is unclear. On the contrary, mitochondrial biogenesis, suggested by mitochondrial enzyme activities and/or mass, is stimulated in muscles with depleted high-energy phosphates by cold exposure 16 and/or by feeding creatine analogue β-guanidinopropionic acid 17-19. Tension production may be inhibited in unloaded antigravity muscles 20, although the muscular activity detected by electromyography is not necessarily decreased 21. Thus, the contents of high-energy phosphates or turnover rate of adenosine triphosphate (ATP), which then affect the mitochondrial energy metabolism, may be altered. Therefore, the responses of high-energy phosphates and metabolic properties of rat hindlimb muscles to gravitational unloading were investigated.

Interactions between the S-domain receptor kinases and AtPUB-ARM E3 ubiquitin ligases suggest a conserved signaling pathway in Arabidopsis.

PubMed

Samuel, Marcus A; Mudgil, Yashwanti; Salt, Jennifer N; Delmas, Frédéric; Ramachandran, Shaliny; Chilelli, Andrea; Goring, Daphne R

2008-08-01

The Arabidopsis (Arabidopsis thaliana) genome encompasses multiple receptor kinase families with highly variable extracellular domains. Despite their large numbers, the various ligands and the downstream interacting partners for these kinases have been deciphered only for a few members. One such member, the S-receptor kinase, is known to mediate the self-incompatibility (SI) response in Brassica. S-receptor kinase has been shown to interact and phosphorylate a U-box/ARM-repeat-containing E3 ligase, ARC1, which, in turn, acts as a positive regulator of the SI response. In an effort to identify conserved signaling pathways in Arabidopsis, we performed yeast two-hybrid analyses of various S-domain receptor kinase family members with representative Arabidopsis plant U-box/ARM-repeat (AtPUB-ARM) E3 ligases. The kinase domains from S-domain receptor kinases were found to interact with ARM-repeat domains from AtPUB-ARM proteins. These kinase domains, along with M-locus protein kinase, a positive regulator of SI response, were also able to phosphorylate the ARM-repeat domains in in vitro phosphorylation assays. Subcellular localization patterns were investigated using transient expression assays in tobacco (Nicotiana tabacum) BY-2 cells and changes were detected in the presence of interacting kinases. Finally, potential links to the involvement of these interacting modules to the hormone abscisic acid (ABA) were investigated. Interestingly, AtPUB9 displayed redistribution to the plasma membrane of BY-2 cells when either treated with ABA or coexpressed with the active kinase domain of ARK1. As well, T-DNA insertion mutants for ARK1 and AtPUB9 lines were altered in their ABA sensitivity during germination and acted at or upstream of ABI3, indicating potential involvement of these proteins in ABA responses.

Rigor force responses of permeabilized fibres from fast and slow skeletal muscles of aged rats.

PubMed

Plant, D R; Lynch, G S

2001-09-01

1. Ageing is generally associated with a decline in skeletal muscle mass and strength and a slowing of muscle contraction, factors that impact upon the quality of life for the elderly. The mechanisms underlying this age-related muscle weakness have not been fully resolved. The purpose of the present study was to determine whether the decrease in muscle force as a consequence of age could be attributed partly to a decrease in the number of cross-bridges participating during contraction. 2. Given that the rigor force is proportional to the approximate total number of interacting sites between the actin and myosin filaments, we tested the null hypothesis that the rigor force of permeabilized muscle fibres from young and old rats would not be different. 3. Permeabilized fibres from the extensor digitorum longus (fast-twitch; EDL) and soleus (predominantly slow-twitch) muscles of young (6 months of age) and old (27 months of age) male F344 rats were activated in Ca2+-buffered solutions to determine force-pCa characteristics (where pCa = -log(10)[Ca2+]) and then in solutions lacking ATP and Ca2+ to determine rigor force levels. 4. The rigor forces for EDL and soleus muscle fibres were not different between young and old rats, indicating that the approximate total number of cross-bridges that can be formed between filaments did not decline with age. We conclude that the age-related decrease in force output is more likely attributed to a decrease in the force per cross-bridge and/or decreases in the efficiency of excitation-contraction coupling.

Voluntary resistance running with short distance enhances spatial memory related to hippocampal BDNF signaling.

PubMed

Lee, Min Chul; Okamoto, Masahiro; Liu, Yu Fan; Inoue, Koshiro; Matsui, Takashi; Nogami, Haruo; Soya, Hideaki

2012-10-15

Although voluntary running has beneficial effects on hippocampal cognitive functions if done abundantly, it is still uncertain whether resistance running would be the same. For this purpose, voluntary resistance wheel running (RWR) with a load is a suitable model, since it allows increased work levels and resultant muscular adaptation in fast-twitch muscle. Here, we examined whether RWR would have potential effects on hippocampal cognitive functions with enhanced hippocampal brain-derived neurotrophic factor (BDNF), as does wheel running without a load (WR). Ten-week-old male Wistar rats were assigned randomly to sedentary (Sed), WR, and RWR (to a maximum load of 30% of body weight) groups for 4 wk. We found that in RWR, work levels increased with load, but running distance decreased by about half, which elicited muscular adaptation for fast-twitch plantaris muscle without causing any negative stress effects. Both RWR and WR led to improved spatial learning and memory as well as gene expressions of hippocampal BDNF signaling-related molecules. RWR increased hippocampal BDNF, tyrosine-related kinase B (TrkB), and cAMP response element-binding (CREB) protein levels, whereas WR increased only BDNF. With both exercise groups, there were correlations between spatial memory and BDNF protein (r = 0.41), p-CREB protein (r = 0.44), and work levels (r = 0.77). These results suggest that RWR plays a beneficial role in hippocampus-related cognitive functions associated with hippocampal BDNF signaling, even with short distances, and that work levels rather than running distance are more determinant of exercise-induced beneficial effects in wheel running with and without a load.

Relationship between first-twitch depression and train-of-four ratio during sugammadex reversal of rocuronium-induced neuromuscular blockade.

PubMed

Kim, Kyo Sang; Oh, You Na; Kim, Tae Yeon; Oh, Song Yee; Sin, Yeong Hun

2016-06-01

The primary outcome of sugammadex reversal for rocuronium-induced neuromuscular block (NMB) is a train-of-four ratio (TOFR) of 0.9, not first twitch (T1) height. We investigated whether the recovery of TOFR or T1 differs based on the reversal of NMB with neostigmine or sugammadex. The acceleromyographic responses from 0.6 mg/kg of rocuronium were monitored supramaximally in 80 patients after induction of anesthesia. The TOFR and T1 height were recorded, and saved in a personal computer using TOF-Watch SX Monitor software in all patients. Patients were randomly assigned to 2 groups to receive either neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg (neostigmine group, n = 40) or sugammadex 2.0 mg/kg (sugammadex group, n = 40). The primary objective was to determine the difference of recovery time between TOFR to 0.9 and T1 to 0.9 after sugammadex or neostigmine administration during moderate rocuronium-induced NMB. The recovery pattern of the TOFR 2 min after sugammadex administration was 1.0 or more, but that of T1 was less than 90% (T1 / control value) up to 6 min after drug was injected. The recovery pattern of TOFR and T1 was similar during the 20 min after reversal with neostigmine. If you have not performed the T1 monitoring, both TOFR and T1 should be considered to confirm suitable recovery during the 6 min after reversal with sugammadex during rocuronium-induced moderate NMB.

Connexin 39.9 Protein Is Necessary for Coordinated Activation of Slow-twitch Muscle and Normal Behavior in Zebrafish*

PubMed Central

Hirata, Hiromi; Wen, Hua; Kawakami, Yu; Naganawa, Yuriko; Ogino, Kazutoyo; Yamada, Kenta; Saint-Amant, Louis; Low, Sean E.; Cui, Wilson W.; Zhou, Weibin; Sprague, Shawn M.; Asakawa, Kazuhide; Muto, Akira; Kawakami, Koichi; Kuwada, John Y.

2012-01-01

In many tissues and organs, connexin proteins assemble between neighboring cells to form gap junctions. These gap junctions facilitate direct intercellular communication between adjoining cells, allowing for the transmission of both chemical and electrical signals. In rodents, gap junctions are found in differentiating myoblasts and are important for myogenesis. Although gap junctions were once believed to be absent from differentiated skeletal muscle in mammals, recent studies in teleosts revealed that differentiated muscle does express connexins and is electrically coupled, at least at the larval stage. These findings raised questions regarding the functional significance of gap junctions in differentiated muscle. Our analysis of gap junctions in muscle began with the isolation of a zebrafish motor mutant that displayed weak coiling at day 1 of development, a behavior known to be driven by slow-twitch muscle (slow muscle). We identified a missense mutation in the gene encoding Connexin 39.9. In situ hybridization found connexin 39.9 to be expressed by slow muscle. Paired muscle recordings uncovered that wild-type slow muscles are electrically coupled, whereas mutant slow muscles are not. The further examination of cellular activity revealed aberrant, arrhythmic touch-evoked Ca2+ transients in mutant slow muscle and a reduction in the number of muscle fibers contracting in response to touch in mutants. These results indicate that Connexin 39.9 facilitates the spreading of neuronal inputs, which is irregular during motor development, beyond the muscle cells and that gap junctions play an essential role in the efficient recruitment of slow muscle fibers. PMID:22075003

Hypericum grandifolium Choisy: a species native to Macaronesian Region with antidepressant effect.

PubMed

Sánchez-Mateo, C C; Bonkanka, C X; Rabanal, R M

2009-01-21

Various species of Hypericum genus have been used in the Canary Islands as sedative, diuretic, vermifuge, wound healing, antihysteric and antidepressant agent. Studies have shown that methanol extract of Hypericum grandifolium Choisy is active in tetrabenazine-induced ptosis and forced swimming tests. In the current study, the aqueous, butanol and chloroform fractions obtained from the methanol extract as well as three sub-fractions derived from the chloroform fraction were evaluated for their central nervous effects in mice, particularly their antidepressant activity. The central nervous effect of different fractions and sub-fractions of Hypericum grandifolium was evaluated in mice using various behavioural models including locomotor and muscle relaxant activity, forced swimming test, effect on normal body temperature, barbiturate-induced sleep, tetrabenazine-induced syndrome and 5-hydroxytryptohan-induced head twitches and syndrome. We found that the butanol and chloroform fractions and all sub-fractions showed an antidepressant effect in the forced swimming test, the chloroform fraction being the most active. They produced no effects or only a slight depression of locomotor activity. Chloroform fraction significantly increased the pentobarbital-induced sleeping time, produced a slight but significant hypothermia and antagonized tetrabenazine-induced ptosis, whereas the butanol fraction produced a slight potentiation of 5-HTP-induced head twitches and syndrome. The present results, together with previous pharmacological and phytochemical data, indicated that Hypericum grandifolium possess antidepressant-like effects in mice and that different constituents, such as the flavonoids and the benzophenone derivatives, could be responsible at least in part for the antidepressant effects observed for this species.

In vivo stimulation of oestrogen receptor α increases insulin-stimulated skeletal muscle glucose uptake

PubMed Central

Gorres, Brittany K; Bomhoff, Gregory L; Morris, Jill K; Geiger, Paige C

2011-01-01

Abstract Previous studies suggest oestrogen receptor α (ERα) is involved in oestrogen-mediated regulation of glucose metabolism and is critical for maintenance of whole body insulin action. Despite this, the effect of direct ERα modulation in insulin-responsive tissues is unknown. The purpose of the current study was to determine the impact of ERα activation, using the ER subtype-selective ligand propylpyrazoletriyl (PPT), on skeletal muscle glucose uptake. Two-month-old female Sprague–Dawley rats, ovariectomized for 1 week, were given subcutaneous injections of PPT (10 mg kg−1), oestradiol benzoate (EB; 20 μg kg−1), the ERβ agonist diarylpropionitrile (DPN, 10 mg kg−1) or vehicle every 24 h for 3 days. On the fourth day, insulin-stimulated skeletal muscle glucose uptake was measured in vitro and insulin signalling intermediates were assessed via Western blotting. Activation of ERα with PPT resulted in increased insulin-stimulated glucose uptake into the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles, activation of insulin signalling intermediates (as measured by phospho-Akt (pAkt) and pAkt substrate (PAS)) and phosphorylation of AMP-activated protein kinase (AMPK). GLUT4 protein was increased only in the EDL muscle. Rats treated with EB or DPN for 3 days did not show an increase in insulin-stimulated skeletal muscle glucose uptake compared to vehicle-treated animals. These new findings reveal that direct activation of ERα positively mediates glucose uptake and insulin action in skeletal muscle. Evidence that oestrogens and ERα stimulate glucose uptake has important implications for understanding mechanisms of glucose homeostasis, particularly in postmenopausal women. PMID:21486807

Central excitability contributes to supramaximal volitional contractions in human incomplete spinal cord injury

PubMed Central

Thompson, Christopher K; Lewek, Michael D; Jayaraman, Arun; Hornby, T George

2011-01-01

Abstract Despite greater muscle fatigue in individuals with spinal cord injury (SCI) when compared to neurologically intact subjects using neuromuscular electrical stimulation (NMES) protocols, few studies have investigated the extent of volitional fatigue in motor incomplete SCI. Using an established protocol of 20 repeated, intermittent, maximal volitional effort (MVE) contractions, we previously demonstrated that subjects with incomplete SCI unexpectedly demonstrated a 15% increase in peak knee extensor torques within the first five MVEs with minimal evidence of fatigue after 20 contraction. In the present study, we investigated potential segmental mechanisms underlying this supramaximal torque generation. Changes in twitch properties and maximum compound muscle action potentials (M-waves) were assessed prior to and following one, three and five MVEs, revealing a significant 17% increase only in maximum twitch torques after a single MVE. Despite this post-activation potentiation of the muscle, use of conventional NMES protocols to elicit repeated muscular contractions resulted in a significant decrease in evoked torque generation, suggesting limited the muscular contributions to the observed phenomenon. To evaluate potential central mechanisms underlying the augmented torques, non-linear responses to wide-pulse width (1 ms), low-intensity, variable-frequency (25–100 Hz) NMES were also tested prior to and following repeated MVEs. When variable-frequency NMES was applied following the repeated MVEs, augmented and prolonged torques were observed and accompanied by sustained quadriceps electromyographic activity often lasting >2s after stimulus termination. Such data suggest a potential contribution of elevated spinal excitability to the reserve in volitional force generation in incomplete SCI. PMID:21610138

Influence of Upper-Body Exercise on the Fatigability of Human Respiratory Muscles

PubMed Central

TILLER, NICHOLAS B.; CAMPBELL, IAN G.; ROMER, LEE M.

2017-01-01

ABSTRACT Purpose Diaphragm and abdominal muscles are susceptible to contractile fatigue in response to high-intensity, whole-body exercise. This study assessed whether the ventilatory and mechanical loads imposed by high-intensity, upper-body exercise would be sufficient to elicit respiratory muscle fatigue. Methods Seven healthy men (mean ± SD; age = 24 ± 4 yr, peak O2 uptake [V˙O2peak] = 31.9 ± 5.3 mL·kg−1·min−1) performed asynchronous arm-crank exercise to exhaustion at work rates equivalent to 30% (heavy) and 60% (severe) of the difference between gas exchange threshold and V˙O2peak. Contractile fatigue of the diaphragm and abdominal muscles was assessed by measuring pre- to postexercise changes in potentiated transdiaphragmatic and gastric twitch pressures (Pdi,tw and Pga,tw) evoked by supramaximal magnetic stimulation of the cervical and thoracic nerves, respectively. Results Exercise time was 24.5 ± 5.8 min for heavy exercise and 9.8 ± 1.8 min for severe exercise. Ventilation over the final minute of heavy exercise was 73 ± 20 L·min−1 (39% ± 11% maximum voluntary ventilation) and 99 ± 19 L·min−1 (53% ± 11% maximum voluntary ventilation) for severe exercise. Mean Pdi,tw did not differ pre- to postexercise at either intensity (P > 0.05). Immediately (5–15 min) after severe exercise, mean Pga,tw was significantly lower than pre-exercise values (41 ± 13 vs 53 ± 15 cm H2O, P < 0.05), with the difference no longer significant after 25–35 min. Abdominal muscle fatigue (defined as ≥15% reduction in Pga,tw) occurred in 1/7 subjects after heavy exercise and 5/7 subjects after severe exercise. Conclusions High-intensity, upper-body exercise elicits significant abdominal, but not diaphragm, muscle fatigue in healthy men. The increased magnitude and prevalence of fatigue during severe-intensity exercise is likely due to additional (nonrespiratory) loading of the thorax. PMID:28288012

Influence of Upper-Body Exercise on the Fatigability of Human Respiratory Muscles.

PubMed

Tiller, Nicholas B; Campbell, Ian G; Romer, Lee M

2017-07-01

Diaphragm and abdominal muscles are susceptible to contractile fatigue in response to high-intensity, whole-body exercise. This study assessed whether the ventilatory and mechanical loads imposed by high-intensity, upper-body exercise would be sufficient to elicit respiratory muscle fatigue. Seven healthy men (mean ± SD; age = 24 ± 4 yr, peak O2 uptake [V˙O2peak] = 31.9 ± 5.3 mL·kg·min) performed asynchronous arm-crank exercise to exhaustion at work rates equivalent to 30% (heavy) and 60% (severe) of the difference between gas exchange threshold and V˙O2peak. Contractile fatigue of the diaphragm and abdominal muscles was assessed by measuring pre- to postexercise changes in potentiated transdiaphragmatic and gastric twitch pressures (Pdi,tw and Pga,tw) evoked by supramaximal magnetic stimulation of the cervical and thoracic nerves, respectively. Exercise time was 24.5 ± 5.8 min for heavy exercise and 9.8 ± 1.8 min for severe exercise. Ventilation over the final minute of heavy exercise was 73 ± 20 L·min (39% ± 11% maximum voluntary ventilation) and 99 ± 19 L·min (53% ± 11% maximum voluntary ventilation) for severe exercise. Mean Pdi,tw did not differ pre- to postexercise at either intensity (P > 0.05). Immediately (5-15 min) after severe exercise, mean Pga,tw was significantly lower than pre-exercise values (41 ± 13 vs 53 ± 15 cm H2O, P < 0.05), with the difference no longer significant after 25-35 min. Abdominal muscle fatigue (defined as ≥15% reduction in Pga,tw) occurred in 1/7 subjects after heavy exercise and 5/7 subjects after severe exercise. High-intensity, upper-body exercise elicits significant abdominal, but not diaphragm, muscle fatigue in healthy men. The increased magnitude and prevalence of fatigue during severe-intensity exercise is likely due to additional (nonrespiratory) loading of the thorax.

Report: Basic Facts About Military Service.

ERIC Educational Resources Information Center

High School News Service (DOD), Great Lakes, IL.

The purpose of the report is to inform students, through counselors and advisers, of opportunities and responsibilities in the Armed Forces. The topics covered are: missions of the Armed Forces, the selective service system, enlistment programs, reserve components, commissioning programs, auxiliary benefits, women in the Armed Forces, and basic…

Feedforward responses of transversus abdominis are directionally specific and act asymmetrically: implications for core stability theories.

PubMed

Allison, Garry T; Morris, Sue L; Lay, Brendan

2008-05-01

Experimental laboratory study supplemented with a repeated case study. To examine bilateral muscle activity of the deep abdominals in response to rapid arm raising, specifically to examine the laterality and directional specificity of feedforward responses of the transversus abdominis (TrA). Based on the feedforward responses of trunk muscles during rapid arm movements, authors have concluded that the deep trunk muscles have different control mechanisms compared to the more superficial muscles. It has been proposed that deep trunk muscles such as TrA contribute substantially to the stability of the lumbar spine and that this is achieved through simultaneous bilateral feedforward activation. These inferences are based on unilateral fine-wire electromyographic (EMG) data and there are limited investigations of bilateral responses of the TrA during unilateral arm raising. Bilateral fine-wire and surface EMG data from the anterior deltoid, TrA, obliquus internus (OI), obliquus externus, biceps femoris, erector spinae, and rectus abdominis during repeated arm raises were recorded at 2 kHz. EMG signal linear envelopes were synchronized to the onset of the anterior deltoid. A feedforward window was defined as the period up to 50 ms after the onset of the anterior deltoid, and paired onsets for bilateral muscles were plotted for both left and right arm movements. Trunk muscles from the group data demonstrated differences between sides (laterality), which were systematically altered when alternate arms were raised (directional specificity). This was clearly evident for the TrA but less obvious for the erector spinae. The ipsilateral biceps femoris and obliquus externus, and contralateral OI and TrA, were activated earlier than the alternate side for both right and left arm movements. This was a consistent pattern over a 7-year period for the case study. Data for the rectus abdominis derived from the case study demonstrated little laterality or directionally specific response. This is the first study to show that the feedforward activity of the TrA is specific to the direction of arm movement and not bilaterally symmetrical. The asymmetry of TrA activity during arm raising suggests that the interpretation of the role of TrA as a bilateral stabilizer during anticipatory postural adjustments needs to be revised. Future research needs to examine muscle synergies associated with the asymmetrical function of the TrA and the underlying mechanism associated with low-load stability training. Therapy, level 5.

Fatigability and Recovery of Arm Muscles with Advanced Age for Dynamic and Isometric Contractions

PubMed Central

Yoon, Tejin; Schlinder-Delap, Bonnie; Hunter, Sandra K.

2012-01-01

This study determined whether age-related mechanisms can increase fatigue of arm muscles during maximal velocity dynamic contractions, as occurs in the lower limb. We compared elbow flexor fatigue of young (n=10, 20.8 ± 2.7 years) and old men (n=16, 73.8 ± 6.1 years) during and in recovery from a dynamic and an isometric postural fatiguing task. Each task was maintained until failure while supporting a load equivalent to 20% of maximal voluntary isometric contraction (MVIC) torque. Transcranial magnetic stimulation (TMS) was used to assess supraspinal fatigue (superimposed twitch, SIT) and muscle relaxation. Time to failure was longer for old men than young for the isometric task (9.5±3.1 vs. 17.2±7.0 min, P=0.01) but similar for the dynamic task (6.3±2.4 min vs. 6.0±2.0 min, P = 0.73). Initial peak rate of relaxation was slower for the old men than young, and associated with a longer time to failure for both tasks (P<0.05). Low initial power during elbow flexion was associated with the greatest difference (reduction) in time to failure between the isometric task and dynamic task (r =−0.54, P=0.015). SIT declined after both fatigue tasks similarly with age, although recovery of SIT was associated with MVIC recovery for the old (both sessions) but not the young. Biceps brachii and brachioradialis EMG activity (%MVIC) of old men were greater than young during the dynamic fatiguing task (P<0.05), but similar during the isometric task. Muscular mechanisms and greater relative muscle activity (EMG activity) explain the greater fatigue during dynamic task for the old men compared with young in elbow flexor muscles. Recovery of MVC torque however relies more on recovery of supraspinal fatigue among older men than the young men. PMID:23103238

Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndrome and anorectal malformations with sacral hypodevelopment.

PubMed

Seri, M; Martucciello, G; Paleari, L; Bolino, A; Priolo, M; Salemi, G; Forabosco, P; Caroli, F; Cusano, R; Tocco, T; Lerone, M; Cama, A; Torre, M; Guys, J M; Romeo, G; Jasonni, V

1999-01-01

Anorectal malformations (ARMs) are common congenital anomalies that account for 1:4 digestive malformations. ARM patients show different degrees of sacral hypodevelopment while the hemisacrum is characteristic of the Currarino syndrome (CS). Cases of CS present an association of ARM, hemisacrum and presacral mass. A gene responsible for CS has recently been mapped in 7q36. Among the genes localized in this critical region, sonic hedgehog (SHH) was thought to represent a candidate gene for CS as well as for ARM with different levels of sacral hypodevelopment according to its role in the differentiation of midline mesoderm. By linkage analysis we confirmed the critical region in one large family with recurrence of CS. In addition, the screening of SHH in 7 CS and in 15 sporadic ARM patients with sacral hypodevelopment allowed us to exclude its role in the pathogenesis of these disorders.

Myoneural necrosis following high-frequency electrical stimulation of the cast-immobilized rabbit hindlimb

NASA Technical Reports Server (NTRS)

Friden, J.; Lieber, R. L.; Myers, R. R.; Powell, H. C.; Hargens, A. R.

1989-01-01

The morphological and physiological effects of 4 weeks of high-frequency electrical stimulation (1 h/day, 5 days/week) on cast-immobilized rabbit hindlimbs were investigated in the tibialis anterior muscle and peroneal nerve. In 2 out of 6 animals, high-frequency stimulation with immobilization caused muscle fiber death, internalization of muscle fiber nuclei, connective tissue proliferation, inflammatory response, altered fiber size distribution and variable staining intensities. The fast-twitch fibers were predominantly affected. Two of six peripheral nerves subjected to immobilization and stimulation showed severe damage. Tetanic forces were significantly reduced in the affected muscles. Therefore, the immobilization and high-frequency stimulation may be detrimental to myoneural structure and function and, thus, this combination of therapies should be applied conservatively.

Targeting myofascial taut bands by ultrasound.

PubMed

Thomas, Kisha; Shankar, Hariharan

2013-07-01

Myofascial pain syndrome (MPS) is a frequent diagnosis in chronic pain and is characterized by tender, taut bands known as trigger points. The trigger points are painful areas in skeletal muscle that are associated with a palpable nodule within a taut band of muscle fibers. Despite the prevalence of myofascial pain syndrome, diagnosis is based on clinical criteria alone. A growing body of evidence that suggests that taut bands are readily visualized under ultrasound-guided exam, especially when results are correlated with elastography, multidimensional imaging, and physical exam findings such as local twitch response. The actual image characteristic in B mode appears to be controversial. Ultrasonography provides an objective modality to assist with diagnosis and treatment of trigger points in the future.

Genetics Home Reference: dystonia 6

MedlinePlus

... neck, causing problems with speaking (dysarthria) and eating (dysphagia). Eyelid twitching (blepharospasm) may also occur. Involvement of ... dystonia, DYT6 type The Bachmann-Strauss Dystonia and Parkinson Foundation: What Is Dystonia? Patient Support and Advocacy ...

Prediction of Recovery from Coma After CPR

MedlinePlus

... to pain. There is good evidence* that myoclonus status epilepticus within the first day after CPR accurately predicts poor recovery from coma. Myoclonus status epilepticus is a constant twitching of muscles, including the ...

Genetics Home Reference: ataxia with oculomotor apraxia

MedlinePlus

... muscle twitches (myoclonus), and disturbances in nerve function (neuropathy). In type 1, ataxia beings around age 4; ... all individuals with ataxia with oculomotor apraxia develop neuropathy, which leads to absent reflexes and weakness. Neuropathy ...

Visualizing Calcium Flux in Freely Moving Nematode Embryos.

PubMed

Ardiel, Evan L; Kumar, Abhishek; Marbach, Joseph; Christensen, Ryan; Gupta, Rishi; Duncan, William; Daniels, Jonathan S; Stuurman, Nico; Colón-Ramos, Daniel; Shroff, Hari

2017-05-09

The lack of physiological recordings from Caenorhabditis elegans embryos stands in stark contrast to the comprehensive anatomical and gene expression datasets already available. Using light-sheet fluorescence microscopy to address the challenges associated with functional imaging at this developmental stage, we recorded calcium dynamics in muscles and neurons and developed analysis strategies to relate activity and movement. In muscles, we found that the initiation of twitching was associated with a spreading calcium wave in a dorsal muscle bundle. Correlated activity in muscle bundles was linked with early twitching and eventual coordinated movement. To identify neuronal correlates of behavior, we monitored brainwide activity with subcellular resolution and identified a particularly active cell associated with muscle contractions. Finally, imaging neurons of a well-defined adult motor circuit, we found that reversals in the eggshell correlated with calcium transients in AVA interneurons. Published by Elsevier Inc.

Effect of hindlimb suspension and clenbuterol treatment on polyamine levels in skeletal muscle

NASA Technical Reports Server (NTRS)

Abukhalaf, Imad K.; von Deutsch, Daniel A.; Wineski, Lawrence E.; Silvestrov, Natalia A.; Abera, Saare A.; Sahlu, Sinafikish W.; Potter, David E.; Thierry-Palmer, M. (Principal Investigator)

2002-01-01

Polyamines are unbiquitous, naturally occurring small aliphatic, polycationic, endogenous compounds. They are involved in many cellular processes and may serve as secondary or tertiary messengers to hormonal regulation. The relationship of polyamines and skeletal muscle mass of adductor longus, extensor digitorum longus, and gastrocnemius under unloading (hindlimb suspension) conditions was investigated. Unloading significantly affected skeletal muscle polyamine levels in a fiber-type-specific fashion. Under loading conditions, clenbuterol treatment increased all polyamine levels, whereas under unloading conditions, only the spermidine levels were consistently increased. Unloading attenuated the anabolic effects of clenbuterol in predominately slow-twitch muscles (adductor longus), but had little impact on clenbuterol's action as a countermeasure in fast- twitch muscles such as the extensor digitorum longus. Spermidine appeared to be the primary polyamine involved in skeletal muscle atrophy/hypertrophy. Copyright 2002 S. Karger AG, Basel.

Phantom Limbs, Neuroprosthetics, and the Developmental Origins of Embodiment.

PubMed

Blumberg, Mark S; Dooley, James C

2017-10-01

Amputees who wish to rid themselves of a phantom limb must weaken the neural representation of the absent limb. Conversely, amputees who wish to replace a lost limb must assimilate a neuroprosthetic with the existing neural representation. Whether we wish to remove a phantom limb or assimilate a synthetic one, we will benefit from knowing more about the developmental process that enables embodiment. A potentially critical contributor to that process is the spontaneous activity - in the form of limb twitches - that occurs exclusively and abundantly during active (REM) sleep, a particularly prominent state in early development. The sensorimotor circuits activated by twitching limbs, and the developmental context in which activation occurs, could provide a roadmap for creating neuroprosthetics that feel as if they are part of the body. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disuse atrophy, plasma corticosterone, and muscle glucocorticoid receptor levels

NASA Technical Reports Server (NTRS)

Steffen, J. M.; Musacchia, X. J.

1987-01-01

The effect of whole-body suspension on the time course and the extent of plasma corticosterone changes and the tissue sensitivity to glucocorticoids were investigated in rats subjected to seven days of whole-body suspension. Plasma corticosterone increased significantly on the first and the third days of suspension, but returned to control levels by day seven. Muscle glucocorticoid receptors exhibited a characteristic hormonal specificity (evaluated in competitive-displacement experiments). In controls, receptor site concentration in the slow-twitch soleus was comparable to that in the fast-twitch gastrocnemius and plantaris, but was significantly less than in the extensor; seven days of suspension resulted in significant differential effects on muscle receptor levels. The largest increase in receptor concentration was observed in the soleus in which it remained elevated after the receptor levels in other muscles returned to normal.

The Middle Cambrian fossil Pikaia and the evolution of chordate swimming.

PubMed

Lacalli, Thurston

2012-07-06

Conway Morris and Caron (2012) have recently published an account of virtually all the available information on Pikaia gracilens, a well-known Cambrian fossil and supposed basal chordate, and propose on this basis some new ideas about Pikaia's anatomy and evolutionary significance. Chief among its chordate-like features are the putative myomeres, a regular series of vertical bands that extends the length of the body. These differ from the myomeres of living chordates in that boundaries between them (the myosepta) are gently curved, with minimal overlap, whereas amphioxus and vertebrates have strongly overlapping V- and W-shaped myomeres. The implication, on biomechanical grounds, is that myomeres in Pikaia exerted much less tension on the myosepta, so the animal would have been incapable of swimming as rapidly as living chordates operating in the fast-twitch mode used for escape and attack. Pikaia either lacked the fast-twitch fibers necessary for such speeds, having instead only slow-twitch fibers, or it had an ancestral fiber type with functional capabilities more like modern slow fibers than fast ones. The first option is supported by the sequence of development in zebrafish, where both myoseptum formation and fast fiber deployment show a dependence on slow fibers, which develop first. For Pikaia, the absence of fast fibers has both behavioral and anatomical implications, which are discussed. Among the latter is the possibility that a notochord may not have been needed as a primary stiffening device if other structures (for example, the dorsal organ) could perform that role.

Influence of fast and slow alkali myosin light chain isoforms on the kinetics of stretch-induced force transients of fast-twitch type IIA fibres of rat.

PubMed

Andruchov, Oleg; Galler, Stefan

2008-03-01

This study contributes to understand the physiological role of slow myosin light chain isoforms in fast-twitch type IIA fibres of skeletal muscle. These isoforms are often attached to the myosin necks of rat type IIA fibres, whereby the slow alkali myosin light chain isoform MLC1s is much more frequent and abundant than the slow regulatory myosin light chain isoform MLC2s. In the present study, single-skinned rat type IIA fibres were maximally Ca(2+) activated and subjected to stepwise stretches for causing a perturbation of myosin head pulling cycles. From the time course of the resulting force transients, myosin head kinetics was deduced. Fibres containing MLC1s exhibited slower kinetics independently of the presence or absence of MLC2s. At the maximal MLC1s concentration of about 75%, the slowing was about 40%. The slowing effect of MLC1s is possibly due to differences in the myosin heavy chain binding sites of the fast and slow alkali MLC isoforms, which changes the rigidity of the myosin neck. Compared with the impact of myosin heavy chain isoforms in various fast-twitch fibre types, the influence of MLC1s on myosin head kinetics of type IIA fibres is much smaller. In conclusion, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the myosin head kinetics.

Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres.

PubMed

Lin, Jiandie; Wu, Hai; Tarr, Paul T; Zhang, Chen-Yu; Wu, Zhidan; Boss, Olivier; Michael, Laura F; Puigserver, Pere; Isotani, Eiji; Olson, Eric N; Lowell, Bradford B; Bassel-Duby, Rhonda; Spiegelman, Bruce M

2002-08-15

The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1 alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We show here that PGC-1 alpha is expressed preferentially in muscle enriched in type I fibres. When PGC-1 alpha is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1 alpha transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1 alpha activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination.

The age related slow and fast contributions to the overall changes in tibialis anterior contractile features disclosed by maximal single twitch scan.

PubMed

Orizio, Claudio; Cogliati, Marta; Bissolotti, Luciano; Diemont, Bertrand; Gobbo, Massimiliano; Celichowski, Jan

2016-01-01

This work aimed to verify if maximal electrically evoked single twitch (STmax) scan discloses the relative functional weight of fast and slow small bundles of fibres (SBF) in determining the contractile features of tibialis anterior (TA) with ageing. SBFs were recruited by TA main motor point stimulation through 60 increasing levels of stimulation (LS): 20 stimuli at 2Hz for each LS. The lowest and highest LS provided the least ST and STmax, respectively. The scanned STmax was decomposed into individual SBF STs. They were identified when twitches from adjacent LS were significantly different and then subtracted from each other. Nine young (Y) and eleven old (O) subjects were investigated. Contraction time (CT) and STarea/STpeak (A/PT) were calculated per each SBF ST. 143 and 155 SBF STs were obtained in Y and O, respectively. Y: CT and A/PT range: 45-105ms and 67-183mNs/mN, respectively. Literature data set TA fast fibres at 34% so, from the arrays of CT and A/PT, 65ms and 100mNs/mN were identified as the upper limit for SBF fast ST classification. O: no SBF ST could be classified as fast. STmax scan reveals age-related changes in the relative contribution of fast and slow SBFs to the overall muscle mechanics. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Top-Down Targeted Proteomics Reveals Decrease in Myosin Regulatory Light-Chain Phosphorylation That Contributes to Sarcopenic Muscle Dysfunction.

PubMed

Gregorich, Zachery R; Peng, Ying; Cai, Wenxuan; Jin, Yutong; Wei, Liming; Chen, Albert J; McKiernan, Susan H; Aiken, Judd M; Moss, Richard L; Diffee, Gary M; Ge, Ying

2016-08-05

Sarcopenia, the loss of skeletal muscle mass and function with advancing age, is a significant cause of disability and loss of independence in the elderly and thus, represents a formidable challenge for the aging population. Nevertheless, the molecular mechanism(s) underlying sarcopenia-associated muscle dysfunction remain poorly understood. In this study, we employed an integrated approach combining top-down targeted proteomics with mechanical measurements to dissect the molecular mechanism(s) in age-related muscle dysfunction. Top-down targeted proteomic analysis uncovered a progressive age-related decline in the phosphorylation of myosin regulatory light chain (RLC), a critical protein involved in the modulation of muscle contractility, in the skeletal muscle of aging rats. Top-down tandem mass spectrometry analysis identified a previously unreported bis-phosphorylated proteoform of fast skeletal RLC and localized the sites of decreasing phosphorylation to Ser14/15. Of these sites, Ser14 phosphorylation represents a previously unidentified site of phosphorylation in RLC from fast-twitch skeletal muscle. Subsequent mechanical analysis of single fast-twitch fibers isolated from the muscles of rats of different ages revealed that the observed decline in RLC phosphorylation can account for age-related decreases in the contractile properties of sarcopenic fast-twitch muscles. These results strongly support a role for decreasing RLC phosphorylation in sarcopenia-associated muscle dysfunction and suggest that therapeutic modulation of RLC phosphorylation may represent a new avenue for the treatment of sarcopenia.

Delayed diaphragm injury and diaphragm force production.

PubMed

Jiang, T X; Reid, W D; Road, J D

1998-03-01

The present study was designed to examine the effect of delayed diaphragm injury produced by inspiratory resistive loading (IRL) on diaphragm force production. On Day 1, three groups of anesthetized and intubated NZW rabbits (n = 7 in each group) were subjected to moderate IRL (Pao approximately 30 cm H2O), high IRL (Pao approximately 45 cm H2O), or no load for 1.5 h. On Day 3, the baseline twitch transdiaphragmatic pressure (Pdi) and Pdi at 10 to 80 Hz were measured during bilateral phrenic stimulation and these measurements were repeated after another IRL (high level) in all three groups. Diaphragm injury was assessed by the point-counting technique. Marked diaphragm injury was observed in the high-IRL group (p < 0.01), but no significant diaphragm injury was observed in the moderate-IRL or control groups. The baseline twitch Pdi was maintained in both IRL groups, whereas the baseline Pdi-frequency values in the high-IRL group were significantly reduced at most frequencies (p < 0.05). The decreases in twitch and Pdi at different frequencies were more pronounced after the IRL on Day 3 in the high-IRL group compared with controls. Moderate IRL did not decrease diaphragm force either before or after the high IRL on Day 3. We conclude that the diaphragm injury induced by high IRL has a significant impact on diaphragm force production and the attendant force loss produced by IRL is dependent on the intensity of inspiratory loading.

The IGF-1/Akt/S6 pathway and expressions of glycolytic myosin heavy chain isoforms are upregulated in chicken skeletal muscle during the first week after hatching.

PubMed

Saneyasu, Takaoki; Tsuchihashi, Tatsuya; Kitashiro, Ayana; Tsuchii, Nami; Kimura, Sayaka; Honda, Kazuhisa; Kamisoyama, Hiroshi

2017-11-01

Skeletal muscle mass is an important trait in the animal industry. We previously reported an age-dependent downregulation of the insulin-like growth factor 1 (IGF-1)/Akt/S6 pathway, major protein synthesis pathway, in chicken breast muscle after 1 week of age, despite a continuous increase of breast muscle weight. Myosin heavy chain (HC), a major protein in muscle fiber, has several isoforms depending on chicken skeletal muscle types. HC I (fast-twitch glycolytic type) is known to be expressed in adult chicken breast muscle. However, little is known about the changes in the expression levels of protein synthesis-related factors and HC isoforms in perihatching chicken muscle. In the present study, protein synthesis-related factors, such as IGF-1 messenger RNA (mRNA) levels, phosphorylation of Akt, and phosphorylated S6 content, increased in an age-dependent manner after post-hatch day (D) 0. The mRNA levels of HC I, III and V (fast-twitch glycolytic type) dramatically increased after D0. The increase ratio of breast muscle weight was approximately 1100% from D0 to D7. To our knowledge, these findings provide the first evidence that upregulation of protein synthesis pathway and transcription of fast twitch glycolytic HC isoforms play critical roles in the increase of chicken breast muscle weight during the first week after hatching. © 2017 Japanese Society of Animal Science.

Bion 11 Spaceflight Project: Effect of Weightlessness on Single Muscle Fiber Function in Rhesus Monkeys

NASA Technical Reports Server (NTRS)

Fitts, Robert H.; Romatowski, Janell G.; Widrick, Jeffrey J.; DeLaCruz, Lourdes

1999-01-01

Although it is well known that microgravity induces considerable limb muscle atrophy, little is known about how weightlessness alters cell function. In this study, we investigated how weightlessness altered the functional properties of single fast and slow striated muscle fibers. Physiological studies were carried out to test the hypothesis that microgravity causes fiber atrophy, a decreased peak force (Newtons), tension (Newtons/cross-sectional area) and power, an elevated peak rate of tension development (dp/dt), and an increased maximal shortening velocity (V(sub o)) in the slow type I fiber, while changes in the fast-twitch fiber are restricted to atrophy and a reduced peak force. For each fiber, we determined the peak force (P(sub o)), V(sub o), dp/dt, the force-velocity relationship, peak power, the power-force relationship, the force-pCa relationship, and fiber stiffness. Biochemical studies were carried out to assess the effects of weightlessness on the enzyme and substrate profile of the fast- and slow-twitch fibers. We predicted that microgravity would increase resting muscle glycogen and glycolytic metabolism in the slow fiber type, while the fast-twitch fiber enzyme profile would be unaltered. The increased muscle glycogen would in part result from an elevated hexokinase and glycogen synthase. The enzymes selected for study represent markers for mitochondrial function (citrate synthase and 0-hydroxyacyl-CoA dehydrogenase), glycolysis (Phosphofructokinase and lactate dehydrogenase), and fatty acid transport (Carnitine acetyl transferase). The substrates analyzed will include glycogen, lactate, adenosine triphosphate, and phosphocreatine.

Development of a parent‐reported questionnaire evaluating upper limb activity limitation in children with cerebral palsy

PubMed Central

Preston, N.; Levesley, M.; Mon‐Williams, M.; O'Connor, R.J.

2017-01-01

Abstract Background and purpose Upper limb activity measures for children with cerebral palsy have a number of limitations, for example, lack of validity and poor responsiveness. To overcome these limitations, we developed the Children's Arm Rehabilitation Measure (ChARM), a parent‐reported questionnaire validated for children with cerebral palsy aged 5–16 years. This paper describes both the development of the ChARM items and response categories and its psychometric testing and further refinement using the Rasch measurement model. Methods To generate valid items for the ChARM, we collected goals of therapy specifically developed by therapists, children with cerebral palsy, and their parents for improving activity limitation of the upper limb. The activities, which were the focus of these goals, formed the basis for the items. Therapists typically break an activity into natural stages for the purpose of improving activity performance, and these natural orders of achievement formed each item's response options. Items underwent face validity testing with health care professionals, parents of children with cerebral palsy, academics, and lay persons. A Rasch analysis was performed on ChARM questionnaires completed by the parents of 170 children with cerebral palsy from 12 hospital paediatric services. The ChARM was amended, and the procedure repeated on 148 ChARMs (from children's mean age: 10 years and 1 month; range: 4 years and 8 months to 16 years and 11 months; 85 males; Manual Ability Classification System Levels I = 9, II = 26, III = 48, IV = 45, and V = 18). Results The final 19‐item unidimensional questionnaire displayed fit to the Rasch model (chi‐square p = .18), excellent reliability (person separation index = 0.95, α = 0.95), and no floor or ceiling effects. Items showed no response bias for gender, distribution of impairment, age, or learning disability. Discussion The ChARM is a psychometrically sound measure of upper limb activity validated for children with cerebral palsy aged 5–16 years. The ChARM is freely available for use to clinicians and nonprofit organisations. PMID:28112465

Application of response surface methodology (RSM) and genetic algorithm in minimizing warpage on side arm

NASA Astrophysics Data System (ADS)

Raimee, N. A.; Fathullah, M.; Shayfull, Z.; Nasir, S. M.; Hazwan, M. H. M.

2017-09-01

The plastic injection moulding process produces large numbers of parts of high quality with great accuracy and quickly. It has widely used for production of plastic part with various shapes and geometries. Side arm is one of the product using injection moulding to manufacture it. However, there are some difficulties in adjusting the parameter variables which are mould temperature, melt temperature, packing pressure, packing time and cooling time as there are warpage happen at the tip part of side arm. Therefore, the work reported herein is about minimizing warpage on side arm product by optimizing the process parameter using Response Surface Methodology (RSM) and with additional artificial intelligence (AI) method which is Genetic Algorithm (GA).

Feasibility of a Short-Arm Centrifuge for Mouse Hypergravity Experiments.

PubMed

Morita, Hironobu; Obata, Koji; Abe, Chikara; Shiba, Dai; Shirakawa, Masaki; Kudo, Takashi; Takahashi, Satoru

2015-01-01

To elucidate the pure impact of microgravity on small mammals despite uncontrolled factors that exist in the International Space Station, it is necessary to construct a 1 g environment in space. The Japan Aerospace Exploration Agency has developed a novel mouse habitat cage unit that can be installed in the Cell Biology Experiment Facility in the Kibo module of the International Space Station. The Cell Biology Experiment Facility has a short-arm centrifuge to produce artificial 1 g gravity in space for mouse experiments. However, the gravitational gradient formed inside the rearing cage is larger when the radius of gyration is shorter; this may have some impact on mice. Accordingly, biological responses to hypergravity induced by a short-arm centrifuge were examined and compared with those induced by a long-arm centrifuge. Hypergravity induced a significant Fos expression in the central nervous system, a suppression of body mass growth, an acute and transient reduction in food intake, and impaired vestibulomotor coordination. There was no difference in these responses between mice raised in a short-arm centrifuge and those in a long-arm centrifuge. These results demonstrate the feasibility of using a short-arm centrifuge for mouse experiments.

Feasibility of a Short-Arm Centrifuge for Mouse Hypergravity Experiments

PubMed Central

Morita, Hironobu; Obata, Koji; Abe, Chikara; Shiba, Dai; Shirakawa, Masaki; Kudo, Takashi; Takahashi, Satoru

2015-01-01

To elucidate the pure impact of microgravity on small mammals despite uncontrolled factors that exist in the International Space Station, it is necessary to construct a 1 g environment in space. The Japan Aerospace Exploration Agency has developed a novel mouse habitat cage unit that can be installed in the Cell Biology Experiment Facility in the Kibo module of the International Space Station. The Cell Biology Experiment Facility has a short-arm centrifuge to produce artificial 1 g gravity in space for mouse experiments. However, the gravitational gradient formed inside the rearing cage is larger when the radius of gyration is shorter; this may have some impact on mice. Accordingly, biological responses to hypergravity induced by a short-arm centrifuge were examined and compared with those induced by a long-arm centrifuge. Hypergravity induced a significant Fos expression in the central nervous system, a suppression of body mass growth, an acute and transient reduction in food intake, and impaired vestibulomotor coordination. There was no difference in these responses between mice raised in a short-arm centrifuge and those in a long-arm centrifuge. These results demonstrate the feasibility of using a short-arm centrifuge for mouse experiments. PMID:26221724

RANDOMIZED TRIAL OF PEGYLATED LIPOSOMAL DOXORUBICIN (PLD) PLUS CARBOPLATIN VERSUS CARBOPLATIN IN PLATINUM-SENSITIVE (PS) PATIENTS WITH RECURRENT EPITHELIAL OVARIAN OR PERITONEAL CARCINOMA AFTER FAILURE OF INITIAL PLATINUM-BASED CHEMOTHERAPY (SOUTH WEST ONCOLOGY GROUP PROTOCOL S0200)

PubMed Central

Alberts, David S.; Liu, P. Y.; Wilczynski, Sharon P.; Clouser, Mary C.; Lopez, Ana Maria; Michelin, David P.; Lanzotti, Victor J.; Markman, Maurie

2008-01-01

Objective Because debate continues over the role of combination, platinum-based chemotherapy for platinum sensitive (PS), recurrent ovarian cancer (OC), we compared overall survival (OS), progression-free survival (PFS), confirmed complete response rate and time to treatment failure in this population. Methods Patients with recurrent stage III or IV OC, a progression-free and platinum-free interval of 6- 24 months after first-line platinum-based chemotherapy and up to 12 courses of a non-platinum containing consolidation treatment were eligible. Patients were randomized to IV pegylated liposomal doxorubicin (PLD) (30 mg/m2) plus IV carboplatin (AUC=5 mg/mL × min) once every 4 weeks (PLD arm) or IV carboplatin alone (AUC=5mg/mL × min) once every 4 weeks. Results The PLD arm enrolled 31 patients and the carboplatin alone arm 30 for a total of 61 patients out of 900 planned. Response rates were 67% for the PLD arm and 32% for the carboplatin only arm (Fisher’s exact p=0.02). The estimated median PFS was 12 and 8 months for PLD versus carboplatin alone. The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm (p=0.02). Twenty-six percent of the patients on the PLD arm reported grade 4 toxicities, all hematological in nature. Conclusion This study was closed early because of slow patient accrual. The response rate, median PFS and OS results are intriguing. These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS, recurrent OC. The regimen should be further tested. PMID:17949799

Form of the compensatory stepping response to repeated laterally directed postural disturbances.

PubMed

Hurt, Christopher P; Rosenblatt, Noah J; Grabiner, Mark D

2011-10-01

A compensatory stepping response (CSR) is a common strategy to restore dynamic stability in response to a postural disturbance. Currently, few studies have investigated the CSR to laterally directed disturbances delivered to subjects during quiet standing. The purpose of this study was to characterize the CSR of younger adults following exposure to a series of similar laterally directed disturbances for which no instructions were given with regard to the recovery response. We hypothesized that in the absence of externally applied constraints to the recovery response, subjects would be equally as likely to perform a crossover step as a sidestep sequence (SSS). We further hypothesized that there would be an asymmetry in arm abduction that would be dependent on the disturbance direction. Finally, we were interested in characterizing the effect of practice on the CSR to repeated disturbances. Ten younger adults were exposed to thirty laterally directed platform disturbances that forced a stepping response. Subjects responded by primarily utilizing a SSS that differs from previously reported results. Further, five of the ten subjects utilized a different recovery response that was dependent on the direction of the disturbance (i.e., left or right). Greater arm abduction was characterized for the arm in the direction of the external disturbance in comparison with the contralateral arm. Lastly, subjects modified their recovery response to this task within 12 disturbances. Taken together, these results suggest that recovery responses to laterally directed disturbances can be quickly modified but can be quite variable between and within subjects.

Kinematic equations for resolved-rate control of an industrial robot arm

NASA Technical Reports Server (NTRS)

Barker, L. K.

1983-01-01

An operator can use kinematic, resolved-rate equations to dynamically control a robot arm by watching its response to commanded inputs. Known resolved-rate equations for the control of a particular six-degree-of-freedom industrial robot arm and proceeds to simplify the equations for faster computations are derived. Methods for controlling the robot arm in regions which normally cause mathematical singularities in the resolved-rate equations are discussed.

Restless Legs Syndrome

MedlinePlus

... Legs Syndrome Condition Restless Legs Syndrome Share Print Table of Contents1. Overview2. Symptoms3. Diagnosis4. Treatment5. Questions Overview ... twitch when you try and sleep (also called periodic limb movements of sleep or PLMS). Diagnosis How ...

Muscle twitching

MedlinePlus

... Some are common and normal. Others are signs of a nervous system disorder. Causes Causes may include: Autoimmune disorders , such ... muscle Spinal muscular atrophy Weak muscles (myopathy) Symptoms of a nervous system disorder include: Loss of, or change in, sensation ...

Sarcomere mechanics in uniform and non-uniform cardiac muscle: a link between pump function and arrhythmias.

PubMed

ter Keurs, Henk E D J; Shinozaki, Tsuyoshi; Zhang, Ying Ming; Zhang, Mei Luo; Wakayama, Yuji; Sugai, Yoshinao; Kagaya, Yutaka; Miura, Masahito; Boyden, Penelope A; Stuyvers, Bruno D M; Landesberg, Amir

2008-01-01

Starling's Law and the well-known end-systolic pressure-volume relationship (ESPVR) of the left ventricle reflect the effect of sarcomere length (SL) on stress (sigma) development and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL-[Ca2+]free relationships (sigma-SL-CaR) at submaximal [Ca2+] in intact and skinned trabeculae were similar, albeit that the sensitivity for Ca2+ of intact muscle was higher. We analyzed the mechanisms underlying the sigma-SL-CaR using a kinetic model where we assumed that the rates of Ca2+ binding by Troponin-C (Tn-C) and/or cross-bridge (XB) cycling are determined by SL, [Ca2+] or stress. We analyzed the correlation between the model results and steady state stress measurements at varied SL and [Ca2+] from skinned rat cardiac trabeculae to test the hypotheses that: (i) the dominant feedback mechanism is SL, stress or [Ca2+]-dependent; and (ii) the feedback mechanism regulates: Tn-C-Ca2+ affinity, XB kinetics or, unitary XB-force. The analysis strongly suggests that feedback of the number of strong XBs to cardiac Tn-C-Ca2+ affinity is the dominant mechanism that regulates XB recruitment. Application of this concept in a mathematical model of twitch-stress accurately reproduced the sigma-SL-CaR and the time course of twitch-stress as well as the time course of intracellular [Ca2+]i. Modeling of the response of the cardiac twitch to rapid stress changes using the above feedback model uniquely predicted the occurrence of [Ca2+]i transients as a result of accelerated Ca2+ dissociation from Tn-C. The above concept has important repercussions for the non-uniformly contracting heart in which arrhythmogenic Ca2+ waves arise from weakened areas in cardiac muscle. These Ca2+ waves can reversibly be induced in muscle with non-uniform excitation contraction coupling (ECC) by the cycle of stretch and release in the border zone between the damaged and intact regions. Stimulus trains induced propagating Ca2+ waves and reversibly induced arrhythmias. We hypothesize that rapid force loss by sarcomeres in the border zone during relaxation causes Ca2+ release from Tn-C and initiates Ca2+ waves propagated by the sarcoplasmic reticulum (SR). These observations suggest the unifying hypothesis that force feedback to Ca2+ binding by Tn-C is responsible for Starling's Law and the ESPVR in uniform myocardium and leads in non-uniform myocardium to a surge of Ca2+ released by the myofilaments during relaxation, which initiates arrhythmogenic propagating Ca2+ release by the SR.

Age-dependent variations in the directional sensitivity of balance corrections and compensatory arm movements in man

PubMed Central

Allum, J H J; Carpenter, M G; Honegger, F; Adkin, A L; Bloem, B R

2002-01-01

We investigated the effects of ageing on balance corrections induced by sudden stance perturbations in different directions. Effects were examined in biomechanical and electromyographic (EMG) recordings from a total of 36 healthy subjects divided equally into three age groups (20–34, 35–55 and 60–75 years old). Perturbations consisted of six combinations of support-surface roll (laterally) and pitch (forward-backward) each with 7.5 deg amplitude (2 pure pitch, and 4 roll and pitch) delivered randomly. To reduce stimulus predictability further and to investigate scaling effects, perturbations were at either 30 or 60 deg s−1. In the legs, trunk and arms we observed age-related changes in balance corrections. The changes that appeared in the lower leg responses included smaller stretch reflexes in soleus and larger reflexes in tibialis anterior of the elderly compared with the young. For all perturbation directions, onsets of balance correcting responses in these ankle muscles were delayed by 20–30 ms and initially had smaller amplitudes (between 120–220 ms) in the elderly. This reduced early activity was compensated by increased lower leg activity after 240 ms. These EMG changes were paralleled by comparable differences in ankle torque responses, which were initially (after 160 ms) smaller in the elderly, but subsequently greater (after 280 ms). Findings in the middle-aged group were generally intermediate between the young and the elderly groups. Comparable results were obtained for the two different stimulus velocities. Stimulus-induced trunk roll, but not trunk pitch, changed dramatically with increasing age. Young subjects responded with early large roll movements of the trunk in the opposite direction to platform roll. A similarly directed but reduced amplitude of trunk roll was observed in the middle-aged. The elderly had very little initial roll modulation and also had smaller stretch reflexes in paraspinals. Balance-correcting responses (over 120–220 ms) in gluteus medius and paraspinals were equally well tuned to roll in the elderly, as in the young, but were reduced in amplitude. Onset latencies were delayed with age in gluteus medius muscles. Following the onset of trunk and hip balance corrections, trunk roll was in the same direction as support-surface motion for all age groups and resulted in overall trunk roll towards the fall side in the elderly, but not in the young. Protective arm movements also changed with age. Initial arm roll movements were largest in the young, smaller in the middle aged, and smallest in the elderly. Initial arm roll movements were in the same direction as initial trunk motion in the young and middle aged. Thus initial roll arm movements in the elderly were directed oppositely to those in the young. Initial pitch motion of the arms was similar across age groups. Subsequent arm movements were related to the amplitude of deltoid muscle responses which commenced at 100 ms in the young and 20–30 ms later in the elderly. These deltoid muscle responses preceded additional arm roll motion which left the arms directed ‘downhill’ (in the direction of the fall) in the elderly, but ‘uphill’ (to counterbalance motion of the pelvis) in the young. We conclude that increased trunk roll stiffness is a key biomechanical change with age. This interferes with early compensatory trunk movements and leads to trunk displacements in the direction of the impending fall. The reversal of protective arm movements in the elderly may reflect an adaptive strategy to cushion the fall. The uniform delay and amplitude reduction of balance-correcting responses across many segments (legs, hips and arms) suggests a neurally based alteration in processing times and response modulation with age. Interestingly, the elderly compensated for these ‘early abnormalities’ with enlarged later responses in the legs, but no similar adaptation was noted in the arms and trunk. These changes with age provide an insight into possible mechanisms underlying falls in the elderly. PMID:12122159

Biochemical markers of bone turnover in patients with spinal metastases after resistance training under radiotherapy--a randomized trial.

PubMed

Rief, Harald; Omlor, Georg; Akbar, Michael; Bruckner, Thomas; Rieken, Stefan; Förster, Robert; Schlampp, Ingmar; Welzel, Thomas; Bostel, Tilman; Roth, Heinz Jürgen; Debus, Jürgen

2016-03-17

To compare the effects of resistance training versus passive physical therapy on bone turnover markers (BTM) in the metastatic bone during radiation therapy (RT) in patients with spinal bone metastases. Secondly, to evaluate an association of BTM to local response, skeletal-related events (SRE), and number of metastases. In this randomized trial, 60 patients were allocated from September 2011 to March 2013 into one of the two arms: resistance training (Arm A) or passive physical therapy (Arm B) with thirty patients in each arm during RT. Biochemical markers such as pyridinoline (PYD), desoxy-pyridinoline (DPD), bone alkaline phosphatase (BAP), total amino-terminal propeptide of type I collagen (PINP), beta-isomer of carboxy-terminal telopeptide of type I collagen (CTX-I), and cross-linked N-telopeptide of type I collagen (NTX) were analyzed at baseline, and three months after RT. Mean change values of PYD and CTX-I were significantly lower at 3 months after RT (p = 0.035 and p = 0.043) in Arm A. Importantly, all markers decreased in both arms, except of PYD and CTX-I in arm B, although significance was not reached for some biomarkers. In arm A, the local response was significantly higher (p = 0.003) and PINP could be identified as a predictor for survivors (OR 0.968, 95%CI 0.938-0.999, p = 0.043). BAP (OR 0.974, 95%CI 0.950-0.998, p = 0.034) and PINP (OR 1.025, 95%CI 1.001-1.049, p = 0.044) were related with an avoidance of SRE. In this group of patients with spinal bone metastases, we were able to show that patients with guided resistance training of the paravertebral muscles can influence BTM. PYD and CTX-I decreased significantly in arm A. PINP can be considered as a complementary tool for prediction of local response, and PINP as well as BAP for avoidance of SRE. Clinical trial identifier NCT 01409720. August 2, 2011.

Do dominant and non-dominant arms respond similarly to maximal eccentric exercise of the elbow flexors?

PubMed

Newton, Michael J; Sacco, Paul; Chapman, Dale; Nosaka, Kazunori

2013-03-01

Two common models to investigate the effect of interventions on muscle damage include using two groups in which one group receives an intervention while the other acts as control, and using contralateral limbs of one group. The latter model is based on the assumption that changes in markers of muscle damage are similar between limbs, but this has not been examined systematically. This study compared changes in muscle damage markers between dominant and non-dominant arms following maximal eccentric exercise of the elbow flexors. Eighteen men performed 60 maximal eccentric elbow flexions of each arm separated by 4 weeks with the order of testing between arms randomised. Maximal voluntary isometric torque, range of motion, upper arm circumference, plasma creatine kinase (CK) activity and muscle soreness before and for 7 days following exercise were compared between arms using two-way repeated measures ANOVA. No significant differences between arms were evident for any of the markers, but significant (P<0.05) differences between first and second bouts were evident for changes in strength, circumference and CK with smaller changes following the second bout. A poor correlation was found for the magnitude of changes in the markers between dominant and non-dominant arms, suggesting that responses to eccentric exercise were not necessarily the same between arms. These results show that the order affected the responses of dominant and non-dominant arms to the eccentric exercise; however, the contralateral limb design appears to be usable if bout order is counterbalanced and randomised among participants. Copyright © 2012. Published by Elsevier Ltd.

Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

PubMed

Popov, I P; Jelić, S B; Krivokapić, Z V; Jezdić, S D; Pesko, P M; Micev, M T; Babić, D R

2008-01-01

To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. Histologically confirmed measurable advanced gastric cancer, age < 72 yr, ECOG performance status 0-2, no prior chemo- and radiotherapy, adequate organ functions. EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.

A randomized study to compare sequential chemoradiotherapy with concurrent chemoradiotherapy for unresectable locally advanced esophageal cancer.

PubMed

Gupta, Arunima; Roy, Somnath; Majumdar, Anup; Hazra, Avijit; Mallik, Chandrani

2014-01-01

Chemotherapy combined with radiotherapy can improve outcome in locally advanced esophageal cancer. This study aimed to compare efficacy and toxicity between concurrent chemoradiotherapy (CCRT) and sequential chemoradiotherapy (SCRT) in unresectable, locally advanced, esophageal squamous cell carcinoma (ESSC). Forty-one patients with unresectable, locally advanced ESCC were randomized into two arms. In the CCRT arm (Arm A), 17 patients received 50.4 Gy at 1.8 Gy per fraction over 5.6 weeks along with concurrent cisplatin (75 mg m(-2) intravenously on day 1 and 5-fluorouracil (1000 mg m(-2) continuous intravenous infusion on days 1-4 starting on the first day of irradiation and given after 28 days. In the SCRT arm (Arm B), 20 patients received two cycles of chemotherapy, using the same schedule, followed by radiotherapy fractionated in a similar manner. The endpoints were tumor response, acute and late toxicities, and disease-free survival. With a median follow up of 12.5 months, the complete response rate was 82.4% in Arm A and 35% in Arm B (P = 0.003). Statistically significant differences in frequencies of acute skin toxicity (P = 0.016), gastrointestinal toxicity (P = 0.005) and late radiation pneumonitis (P = 0.002) were found, with greater in the CCRT arm. A modest but non-significant difference was observed in median time to recurrence among complete responders in the two arms (Arm A 13 months and Arm B 15.5 months, P = 0.167) and there was also no significant difference between the Kaplan Meier survival plots (P = 0.641) of disease-free survival. Compared to sequential chemoradiotherapy, concurrent chemoradiotherapy can significantly improve local control rate but with greater risk of adverse reactions.

Phase II trial of temozolomide and sorafenib in advanced melanoma patients with or without brain metastases

PubMed Central

Amaravadi, Ravi K.; Schuchter, Lynn M.; McDermott, David F.; Kramer, Amy; Giles, Lydia; Gramlich, Kristi; Carberry, Mary; Troxel, Andrea B.; Letrero, Richard; Nathanson, Katherine L.; Atkins, Michael B.; O’Dwyer, Peter J.; Flaherty, Keith T.

2009-01-01

Purpose The combination of the oral alkylating agent temozolomide and the oral multi-kinase inhibitor sorafenib was evaluated in advanced melanoma patients. Patients and Methods Patients with metastatic melanoma (N=167) were treated on four arms. All patients received sorafenib at 400 mg orally twice daily without interruption. Patients without brain metastases or prior temozolomide were randomized between Arm A: extended dosing of temozolomide (EDT; 75 mg/m2 temozolomide daily for 6/8 weeks) and Arm B: standard dosing (SDT; 150 mg/m2 temozolomide daily for 5/28 days). Patients previously treated with temozolomide were enrolled on Arm C: EDT. Patients with brain metastases and no prior temozolomide were assigned to Arm D: SDT. The primary endpoint was 6-month progression-free survival (PFS) rate. Secondary endpoints included response rate, toxicity rates, and the rates of BRAF or NRAS mutations. Results The 6-month PFS rate for arms A, B, C, and D were 50%, 40%, 11%, and 23%. The median PFS for patients on arm A, B, C, and D was 5.9, 4.2, 2.2, and 3.5 months, respectively. No significant differences were observed between Arms A and B in 6-month PFS rate, median PFS, or response rates. Treatment was well tolerated in all arms. No significant differences in toxicity were observed between arms A and B except for more grade 3–4 lymphopenia in arm A. Conclusion Temozolomide plus sorafenib was well tolerated and demonstrated activity in melanoma patients without prior history of temozolomide. The activity of this combination regimen warrants further investigation. PMID:19996224

Physiologic Responses of Able-Bodied and Paraplegic Males to Maximal Arm Ergometry.

ERIC Educational Resources Information Center

Israel, Richard G.; And Others

A study compared physiologic responses of healthy paraplegic males to those of healthy, able-bodied males during maximal arm ergometry. Fifteen able-bodied, healthy adult males and 13 healthy adult male paraplegics followed an exercise program involving heart rate, increased exercise loads, and oxygen uptake. Results from an analysis of the data…

Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial.

PubMed

Richardson, Paul G; Soiffer, Robert J; Antin, Joseph H; Uno, Hajime; Jin, Zhezhen; Kurtzberg, Joanne; Martin, Paul L; Steinbach, Gideon; Murray, Karen F; Vogelsang, Georgia B; Chen, Allen R; Krishnan, Amrita; Kernan, Nancy A; Avigan, David E; Spitzer, Thomas R; Shulman, Howard M; Di Salvo, Donald N; Revta, Carolyn; Warren, Diane; Momtaz, Parisa; Bradwin, Gary; Wei, L J; Iacobelli, Massimo; McDonald, George B; Guinan, Eva C

2010-07-01

Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for > or =14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day +100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day +100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD.

CD22 and Siglec-G in B cell function and tolerance

PubMed Central

Poe, Jonathan C.; Tedder, Thomas F.

2012-01-01

The immune system has evolved into two main arms, the primitive innate arm that is the first line of defense but relatively short-lived and broad acting, and the advanced adaptive arm that generates immunologic “memory” allowing rapid, specific recall responses. T cell-independent type-2 (TI-2) antigens (Ags) invoke innate immune responses. However, due to its “at the ready” nature, how the innate arm of the immune system maintains tolerance to potentially abundant host TI-2 Ags remains elusive. Therefore, it is important to define the mechanisms that establish innate immune tolerance. This review highlights recent insights into B cell tolerance to theoretical self TI-2 Ags, and examines how the B cell-restricted Siglecs, CD22 and Siglec-G, might contribute to this process. PMID:22677186

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study

PubMed Central

Kanda, S.; Goto, K.; Shiraishi, H.; Kubo, E.; Tanaka, A.; Utsumi, H.; Sunami, K.; Kitazono, S.; Mizugaki, H.; Horinouchi, H.; Fujiwara, Y.; Nokihara, H.; Yamamoto, N.; Hozumi, H.; Tamura, T.

2016-01-01

Background The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle. Results As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively. Conclusions Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC. Clinical trials number Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071. PMID:27765756

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study.

PubMed

Kanda, S; Goto, K; Shiraishi, H; Kubo, E; Tanaka, A; Utsumi, H; Sunami, K; Kitazono, S; Mizugaki, H; Horinouchi, H; Fujiwara, Y; Nokihara, H; Yamamoto, N; Hozumi, H; Tamura, T

2016-12-01

The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle. As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively. Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC. Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

PubMed

Goadsby, P J; Grosberg, B M; Mauskop, A; Cady, R; Simmons, K A

2014-10-01

We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Immobilization of free-ranging maned wolf (Chrysocyon brachyurus) with tiletamine and zolazepam in central Brazil.

PubMed

Furtado, Mariana Malzoni; Kashivakura, Cynthia Kayo; Ferro, Claudia; de Almeida, Jácomo Anah Tereza; Silveira, Leandro; Astete, Samuel

2006-03-01

A tiletamine hydrochloride-zolazepam hydrochloride combination was used successfully to immobilize 27 free-ranging maned wolves (Chrysocyon brachyurus) at a mean dose of 2.77+/-0.56 (mean+/-SD) mg/kg. The induction time ranged from 3-15 min. Animals remained immobilized for periods of 48.56 +/-12.65 min. Compulsive licking, excessive salivation, muscle twitching, muscle tremors, tachypnea, and bradycardia were observed associated with the induction of the anesthesia in 13 of 27 maned wolves. Muscle twitching, pedal withdrawal reflex, muscle tremors, and ataxia were observed during recovery in three (11%) maned wolves. There were no significant differences in heart rates (P = 0.44), respiratory rates (P = 0.82), and rectal temperatures (P = 0.54) recorded at 5, 15, and 25 min after induction at these dosages. The tiletamine hydrochloride-zolazepam hydrochloride combination was shown to be an effective and safe immobilizing agent for free-ranging maned wolves.

L-acetylcarnitine enhances functional muscle re-innervation.

PubMed

Pettorossi, V E; Brunetti, O; Carobi, C; Della Torre, G; Grassi, S

1991-01-01

The efficacy of L-acetylcarnitine and L-carnitine treatment on motor re-innervation was analyzed by evaluating different muscular parameters describing functional muscle recovery after denervation and re-innervation. The results show that L-acetylcarnitine markedly enhances functional muscle re-innervation, which on the contrary is unaffected by L-carnitine. The medial gastrocnemius muscle was denervated by cutting the nerve at the muscle entry point. After 20 days the sectioned nerve was resutured into the medial gastrocnemius muscle, and the extent of re-innervation was monitored 45 days later. L-acetylcarnitine-treated animals show significantly higher twitch and tetanic tensions of re-innervated muscle. Furthermore the results, obtained by analysing the twitch time to peak and tetanic contraction-relaxation times, suggest that L-acetylcarnitine mostly affects the functional re-innervation of slow motor units. The possible mechanisms by which L-acetylcarnitine facilitates such motor and nerve recovery are discussed.

[Acupuncture therapy for regaining consciousness in terms of acupoint location, needle insertion and needle manipulation].

PubMed

Meng, Xianggang; Gu, Wenlong; Ma, Fen; Du, Yuzheng; Zhao, Qi

2015-03-01

Acupuncture therapy for regaining consciousness activates soreness, numbness, distention, heaviness, radiating and moving, electric shock and ant climbing sensations at the specific acupoints in the stroke patients. Radiating and moving sensations are the summary of needling sensations such as soreness, numbness and twitching presenting during lifting and thrusting manipulation. These sensations are the essential factors of the therapeutic effect of regaining consciousness. Radiating sensation refers to the conduction along meridians and radiation of soreness and numbness. Moving sensation refers to the local muscular twitching at acupoints and the involuntary movement of limbs, joints and the distal. Acupuncture at the specific acupoints achieves radiating and moving sensations for promoting the circulation in meridians, regulating qi and mind and balancing yin and yang in stroke patients. This therapy was introduced in the paper in view of acupoint location, needle insertion and manipulation.

Hindlimb immobilization - Length-tension and contractile properties of skeletal muscle

NASA Technical Reports Server (NTRS)

Witzmann, F. A.; Kim, D. H.; Fitts, R. H.

1982-01-01

Casts were placed around rat feet in plantar flexion position to immobilize the soleus muscle in a shortened position, while the other foot was fixed in dorsal flexion to set the extensor digitorum longus in a shortened position. The total muscular atrophy and contractile properties were measured at 1, 2, 4, 7, 14, 21, 28, 35, and 42 days after immobilization, with casts being replaced every two weeks. The slow twitch soleus and the fast-twitch vastus lateralis and longus muscles were excised after termination of the experiment. The muscles were then stretched and subjected to electric shock to elicit peak tetanic tension and peak tetanic tension development. Force velocity features of the three muscles were assayed in a series of afterloaded contractions and fiber lengths were measured from subsequently macerated muscle. All muscles atrophied during immobilization, reaching a new steady state by day 21. Decreases in fiber and sarcomere lengths were also observed.

Dissociation between neural and vascular responses to sympathetic stimulation : contribution of local adrenergic receptor function

NASA Technical Reports Server (NTRS)

Jacob, G.; Costa, F.; Shannon, J.; Robertson, D.; Biaggioni, I.

2000-01-01

Sympathetic activation produced by various stimuli, eg, mental stress or handgrip, evokes regional vascular responses that are often nonhomogeneous. This phenomenon is believed to be the consequence of the recruitment of differential central neural pathways or of a sympathetically mediated vasodilation. The purpose of this study was to determine whether a similar heterogeneous response occurs with cold pressor stimulation and to test the hypothesis that local differences in adrenergic receptor function could be in part responsible for this diversity. In 8 healthy subjects, local norepinephrine spillover and blood flow were measured in arms and legs at baseline and during sympathetic stimulation induced by baroreflex mechanisms (nitroprusside infusion) or cold pressor stimulation. At baseline, legs had higher vascular resistance (27+/-5 versus 17+/-2 U, P=0.05) despite lower norepinephrine spillover (0.28+/-0.04 versus 0.4+/-0.05 mg. min(-1). dL(-1), P=0.03). Norepinephrine spillover increased similarly in both arms and legs during nitroprusside infusion and cold pressor stimulation. On the other hand, during cold stimulation, vascular resistance increased in arms but not in legs (20+/-9% versus -7+/-4%, P=0.03). Increasing doses of isoproterenol and phenylephrine were infused intra-arterially in arms and legs to estimate beta-mediated vasodilation and alpha-induced vasoconstriction, respectively. beta-Mediated vasodilation was significantly lower in legs compared with arms. Thus, we report a dissociation between norepinephrine spillover and vascular responses to cold stress in lower limbs characterized by a paradoxical decrease in local resistance despite increases in sympathetic activity. The differences observed in adrenergic receptor responses cannot explain this phenomenon.

Response of slow and fast muscle to hypothyroidism: maximal shortening velocity and myosin isoforms

NASA Technical Reports Server (NTRS)

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

1992-01-01

This study examined both the shortening velocity and myosin isoform distribution of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased in response to the hypothyroid treatment. The effects were such that the hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms while repressing native intermediate myosin and type IIA MHC. In the plantaris, the relative content of native SM and type I MHC isoforms increased from 5 to 13% and from 4 to 10% of the total myosin pool, respectively. Maximal shortening velocity of the soleus and plantaris as measured by the slack test decreased by 32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal shortening velocity as estimated by force-velocity data decreased only in the soleus (-19%). No significant change was observed for the plantaris.

Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Steffen, J. M.; Deavers, D. R.

1983-01-01

Hypokinetic/hyupodynamic (H/H) whole body suspension of rats eliminates hindlimb load bearing functions while permitting continued use of the forelimbs. Responses of hindlimb muscles were assessed in terms of absolute and relative weights during 1 and 2 weeks of H/H suspension. Muscle mass loss was in the order soleus greater than gastrocnemius equal to plantaris greater than extensor digitorum longus (EDL). The soleus, a postural antigravity muscle composed mainly of slow twitch fibers, was most sensitive, losing 35 and 45 percent of its weight during the first and second weeks, respectively. The gastrocnemius and plantaris showed losses during the first week but no significant loss during the second wee. The EDL showed little or no weight loss. During post suspension recovery all muscles showed a weight gain. H/H suspended rats failed to grow; following removal from suspension they gained weight linearly, comparable to controls. Products of muscle metabolism including urea, ammonia, and 3-methylhistidine increased in the urine during H/H suspension and were significantly reduced approaching control levels during recovery. This suspension model offers considerable promise for comparison with H/H responses during weightlessness.

Distinct unfolded protein responses mitigate or mediate effects of nonlethal deprivation of C. elegans sleep in different tissues.

PubMed

Sanders, Jarred; Scholz, Monika; Merutka, Ilaria; Biron, David

2017-08-28

Disrupting sleep during development leads to lasting deficits in chordates and arthropods. To address lasting impacts of sleep deprivation in Caenorhabditis elegans, we established a nonlethal deprivation protocol. Deprivation triggered protective insulin-like signaling and two unfolded protein responses (UPRs): the mitochondrial (UPR mt ) and the endoplasmic reticulum (UPR ER ) responses. While the latter is known to be triggered by sleep deprivation in rodent and insect brains, the former was not strongly associated with sleep deprivation previously. We show that deprivation results in a feeding defect when the UPR mt is deficient and in UPR ER -dependent germ cell apoptosis. In addition, when the UPR ER is deficient, deprivation causes excess twitching in vulval muscles, mirroring a trend caused by loss of egg-laying command neurons. These data show that nonlethal deprivation of C. elegans sleep causes proteotoxic stress. Unless mitigated, distinct types of deprivation-induced proteotoxicity can lead to anatomically and genetically separable lasting defects. The relative importance of different UPRs post-deprivation likely reflects functional, developmental, and genetic differences between the respective tissues and circuits.

Tailored Treatment Strategy for Locally Advanced Rectal Carcinoma Based on the Tumor Response to Induction Chemotherapy: Preliminary Results of the French Phase II Multicenter GRECCAR4 Trial.

PubMed

Rouanet, Philippe; Rullier, Eric; Lelong, Bernard; Maingon, Philippe; Tuech, Jean-Jacques; Pezet, Denis; Castan, Florence; Nougaret, Stéphanie

2017-07-01

Preoperative radiochemotherapy and total mesorectal excision are the standard-of-care for locally advanced rectal carcinoma, but some patients could be over- or undertreated. This study aimed to assess the feasibility of radiochemotherapy tailored based on the tumor response to induction chemotherapy (FOLFIRINOX) to obtain a minimum R0 resection rate of 90% in the 4 arms of the study. This study is a multicenter randomized trial (NCT01333709). This study was conducted at 16 French cancer specialty centers. Two hundred six patients with locally advanced rectal carcinoma were enrolled between 2011 and 2014. Good responders (≥75% tumor volume reduction) were randomly assigned to immediate surgery (arm A) or standard radiochemotherapy (Cap 50: 50 Gy irradiation and 1600 mg/m oral capecitabine daily) plus surgery (arm B). Poor responders were randomly assigned to Cap 50 (arm C) or intensive radiochemotherapy (Cap 60, 60 Gy irradiation, arm D) before surgery. The primary end point was a R0 resection rate (circumferential resection margin >1 mm). The experimental strategies were to be considered effective if at least 28 successes (R0 resection) among 31 patients in each arm of stratum I and 34 successes among 40 patients in each arm of stratum II were reported (Simon 2-stage design). After induction treatment (good compliance), 194 patients were classified as good (n = 30, 15%) or poor (n = 164, 85%) responders who were included in arms A and B (16 and 14 patients) and arms C and D (113 and 51 patients). The trial was prematurely stopped because of low accrual in arms A and B and recruitment completion in arms C and D. Data from 133 randomly assigned patients were analyzed: 11, 19, 52, and 51 patients in arms A, B, C, and D. Good responders had smaller tumors than poor responders (23 cm vs 45 cm; p < 0.001). The surgical procedure was similar among groups. The R0 resection rates [90% CI] were 100% [70-100], 100% [85-100], 83% [72-91], and 88% [77-95]. Among the first 40 patients, 34 successes were reported in arms C and D (85% R0 resection rate). The circumferential resection margin ≤1 rates were 0%, 0%, 12%, and 5% in arms A, B, C, and D. The rate of transformation from positive to negative circumferential resection margin was 93%. There was low accrual in arms A and B. Tailoring preoperative radiochemotherapy based on the induction treatment response appears safe for poor responders and promising for good responders. Long-term clinical results are needed to confirm its efficacy. See Video Abstract at http://links.lww.com/DCR/A359.

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial.

PubMed

Rochlitz, Christoph; Bigler, Martin; von Moos, Roger; Bernhard, Jürg; Matter-Walstra, Klazien; Wicki, Andreas; Zaman, Khalil; Anchisi, Sandro; Küng, Marc; Na, Kyung-Jae; Bärtschi, Daniela; Borner, Markus; Rordorf, Tamara; Rauch, Daniel; Müller, Andreas; Ruhstaller, Thomas; Vetter, Marcus; Trojan, Andreas; Hasler-Strub, Ursula; Cathomas, Richard; Winterhalder, Ralph

2016-10-10

Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3-5 adverse events (AE) including: febrile neutropenia, infection, sensory/motor neuropathy, and mucositis. Secondary endpoints included objective response rate, disease control rate, PFS, overall survival (OS), quality of life (QoL), and pharmacoeconomics. The study was registered prospectively with ClinicalTrials.gov, number NCT01131195 on May 25, 2010. Between September 2010 and December 2012, 147 patients were included at 22 centers. The incidence of primary endpoint-defining AEs was similar in arm A (25 % [18/71]; 95 % CI 15-35 %) and arm B (24 % [16/68]; 95 % CI 13-34 %; P = 0.96). Objective response rates were 58 % (42/73; 95 % CI 0.46-0.69) and 50 % (37/74; 95 % CI 0.39-0.61) in arms A and B, respectively (P = 0.45). Median PFS was 10.3 months (95 % CI 8.7-11.3) in arm A and 8.5 months (95 % CI 6.5-11.9) in arm B (P = 0.90). Other secondary efficacy endpoints were not significantly different between study arms. The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent. This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3-5 AEs with metronomic bevacizumab, cyclophosphamide and capecitabine.

Muscle spindle response at the onset of isometric voluntary contractions in man. Time difference between fusimotor and skeletomotor effects

PubMed Central

Vallbo, Å. B.

1971-01-01

1. Impulses in single muscle afferents were recorded from the median nerves of waking human subjects with percutaneously inserted tungsten needle electrodes. During isometric voluntary contractions, unitary discharges were analysed from muscle spindle endings in the wrist and finger flexor muscles and the electromyographic activity from these muscles was recorded simultaneously. 2. When the subject activated the muscle portion in which a spindle was located, the afferent discharge increased in spite of the mechanical unloading effects of the skeletomotor contraction indicating a concomitant fusimotor activation. This was valid for slowly rising contractions as well as small fast rising twitches. 3. The time of onset of spindle acceleration was determined in relation to the time of onset of the electromyographic activity for thirty-one units studied altogether in more than seven hundred contractions. It was found that spindle acceleration regularly occurred after the onset of the electromyographic activity. 4. There was a considerable variation from one test to the other, for the individual units, with regard to the exact time of onset of spindle acceleration, although spindle acceleration occurred mostly within 0·5 sec after the onset of the electromyographic activity in sustained contractions and within 0·1 sec in small fast rising twitches. It was not possible to assess to what extent this variation was accounted for by variations in the mechanical unloading effects of the skeletomotor contraction or variations in the timing of the fusimotor outflow. 5. For many units, spindle acceleration did not occur until 10-50 msec after the onset of the skeletomotor contraction. This time is of the same order of magnitude as the time difference in latency from the spinal cord to the recording points in the two systems, as estimated from reasonable assumptions. 6. It was concluded that the fusimotor system does not participate in the initiation of voluntary contractions in man, but that the skeletomotor activity is initiated by descending impulses from supraspinal structures and their effects on the neuronal organization within the spinal cord. 7. The fact that fusimotor activation occurs also in very small and short lasting twitches, when spindle acceleration must have a negligible influence on the skeletomotor outflow, suggests that the fusimotor and the skeletomotor systems are rigidly co-activated in voluntary contractions. 8. The finding that spindle acceleration does not occur until 10-50 msec after the onset of the electromyographic activity suggests that there is an approximately simultaneous onset of the fusimotor and the skeletomotor outflows from the spinal cord. PMID:4256547

Interactions between the S-Domain Receptor Kinases and AtPUB-ARM E3 Ubiquitin Ligases Suggest a Conserved Signaling Pathway in Arabidopsis1[W][OA

PubMed Central

Samuel, Marcus A.; Mudgil, Yashwanti; Salt, Jennifer N.; Delmas, Frédéric; Ramachandran, Shaliny; Chilelli, Andrea; Goring, Daphne R.

2008-01-01

The Arabidopsis (Arabidopsis thaliana) genome encompasses multiple receptor kinase families with highly variable extracellular domains. Despite their large numbers, the various ligands and the downstream interacting partners for these kinases have been deciphered only for a few members. One such member, the S-receptor kinase, is known to mediate the self-incompatibility (SI) response in Brassica. S-receptor kinase has been shown to interact and phosphorylate a U-box/ARM-repeat-containing E3 ligase, ARC1, which, in turn, acts as a positive regulator of the SI response. In an effort to identify conserved signaling pathways in Arabidopsis, we performed yeast two-hybrid analyses of various S-domain receptor kinase family members with representative Arabidopsis plant U-box/ARM-repeat (AtPUB-ARM) E3 ligases. The kinase domains from S-domain receptor kinases were found to interact with ARM-repeat domains from AtPUB-ARM proteins. These kinase domains, along with M-locus protein kinase, a positive regulator of SI response, were also able to phosphorylate the ARM-repeat domains in in vitro phosphorylation assays. Subcellular localization patterns were investigated using transient expression assays in tobacco (Nicotiana tabacum) BY-2 cells and changes were detected in the presence of interacting kinases. Finally, potential links to the involvement of these interacting modules to the hormone abscisic acid (ABA) were investigated. Interestingly, AtPUB9 displayed redistribution to the plasma membrane of BY-2 cells when either treated with ABA or coexpressed with the active kinase domain of ARK1. As well, T-DNA insertion mutants for ARK1 and AtPUB9 lines were altered in their ABA sensitivity during germination and acted at or upstream of ABI3, indicating potential involvement of these proteins in ABA responses. PMID:18552232

Impact of shear rate modulation on vascular function in humans

PubMed Central

Tinken, Toni M.; Thijssen, Dick H.J.; Hopkins, Nicola; Black, Mark A.; Dawson, Ellen A.; Minson, Christopher T.; Newcomer, Sean C.; Laughlin, M. Harold; Cable, N. Timothy; Green, Daniel J.

2010-01-01

Shear stress is an important stimulus to arterial adaptation in response to exercise and training in humans. We recently observed significant reverse arterial flow and shear during exercise and different antegrade/retrograde patterns of shear and flow in response to different types of exercise. The purpose of this study was to simultaneously examine flow mediated dilation (FMD), a largely nitric oxide mediated vasodilator response, in both brachial arteries of healthy young men before and after 30-minute interventions consisting of bilateral forearm heating, recumbent leg cycling and bilateral handgrip exercise. During each intervention, a cuff inflated to 60mmHg was placed on one arm to unilaterally manipulate the shear rate stimulus. In the non-cuffed arm, antegrade flow and shear increased similarly in response to each intervention (ANOVA; P<0.001, no interaction between interventions; P=0.71). Baseline FMD (4.6, 6.9 and 6.7%) increased similarly in response to heating, handgrip and cycling (8.1, 10.4 and 8.9%, ANOVA; P<0.001, no interaction; 0.89). In contrast, cuffed arm antegrade shear rate was lower than in the non-cuffed arm for all conditions (P<0.05) and the increase in FMD was abolished in this arm (4.7, 6.7 and 6.1%) (2-way ANOVA: all conditions interacted P<0.05). These results suggest that differences in the magnitude of antegrade shear rate transduce differences in endothelial vasodilator function in humans, a finding which may have relevance for the impact of different exercise interventions on vascular adaptation in humans. PMID:19546374

Cerebellar damage diminishes long-latency responses to multijoint perturbations

PubMed Central

Trautman, Paxson; Rasquinha, Russell J.; Bhanpuri, Nasir H.; Scott, Stephen H.; Bastian, Amy J.

2013-01-01

Damage to the cerebellum can cause significant problems in the coordination of voluntary arm movements. One prominent idea is that incoordination stems from an inability to predictively account for the complex mechanical interactions between the arm's several joints. Motivated by growing evidence that corrective feedback control shares important capabilities and neural substrates with feedforward control, we asked whether cerebellar damage impacts feedback stabilization of the multijoint arm appropriate for the arm's intersegmental dynamics. Specifically, we tested whether cerebellar dysfunction impacts the ability of posterior deltoid to incorporate elbow motion in its long-latency response (R2 = 45–75 ms and R3 = 75–100 ms after perturbation) to an unexpected torque perturbation. Healthy and cerebellar-damaged subjects were exposed to a selected pattern of shoulder-elbow displacements to probe the response pattern from this shoulder extensor muscle. The healthy elderly subjects expressed a long-latency response linked to both shoulder and elbow motion, including an increase/decrease in shoulder extensor activity with elbow flexion/extension. Critically, cerebellar-damaged subjects displayed the normal pattern of activity in the R3 period indicating an intact ability to rapidly integrate multijoint motion appropriate to the arm's intersegmental dynamics. However, cerebellar-damaged subjects had a lower magnitude of activity that was specific to the long-latency period (both R2 and R3) and a slightly delayed onset of multijoint sensitivity. Taken together, our results suggest that the basic motor pattern of the long-latency response is housed outside the cerebellum and is scaled by processes within the cerebellum. PMID:23390311

Aging alters contractile properties and fiber morphology in pigeon skeletal muscle.

PubMed

Pistilli, Emidio E; Alway, Stephen E; Hollander, John M; Wimsatt, Jeffrey H

2014-12-01

In this study, we tested the hypothesis that skeletal muscle from pigeons would display age-related alterations in isometric force and contractile parameters as well as a shift of the single muscle fiber cross-sectional area (CSA) distribution toward smaller fiber sizes. Maximal force output, twitch contraction durations and the force-frequency relationship were determined in tensor propatagialis pars biceps muscle from young 3-year-old pigeons, middle-aged 18-year-old pigeons, and aged 30-year-old pigeons. The fiber CSA distribution was determined by planimetry from muscle sections stained with hematoxylin and eosin. Maximal force output of twitch and tetanic contractions was greatest in muscles from young pigeons, while the time to peak force of twitch contractions was longest in muscles from aged pigeons. There were no changes in the force-frequency relationship between the age groups. Interestingly, the fiber CSA distribution in aged muscles revealed a greater number of larger sized muscle fibers, which was verified visually in histological images. Middle-aged and aged muscles also displayed a greater amount of slow myosin containing muscle fibers. These data demonstrate that muscles from middle-aged and aged pigeons are susceptible to alterations in contractile properties that are consistent with aging, including lower force production and longer contraction durations. These functional changes were supported by the appearance of slow myosin containing muscle fibers in muscles from middle-aged and aged pigeons. Therefore, the pigeon may represent an appropriate animal model for the study of aging-related alterations in skeletal muscle function and structure.

The expression of NFATc1 in adult rat skeletal muscle fibres.

PubMed

Mutungi, Gabriel

2008-03-01

Although numerous studies have recently implicated the calcineurin-nuclear factor of activated T-cells (Cn-NFAT) signalling pathway in the regulation of activity-dependent fibre type switching in adult mammalian skeletal muscles, little is known about the endogenous expression of NFAT proteins in the various fibre types present in these muscles. In this study, the immunolocalization of NFATc1 (also known as NFATc or NFAT2) in the extensor digitorum longus (EDL; a mainly fast-twitch muscle) and the soleus (a predominantly slow-twitch muscle) muscles of adult ( approximately 90-day-old) Wistar rats was investigated. The results show that NFATc1 is expressed only in oxidative fibres (i.e. type I and type IIA fibres) that stain intensely for succinate dehydrogenase activity irrespective of whether they are from the fast- or slow-twitch muscle. Thus, 99 +/- 4% (n = 7 rats) of the muscle fibres in the soleus and 42 +/- 2% (n = 7 rats) of those in the EDL expressed NFATc1. In the soleus muscle fibres, NFATc1 was localized mainly in the fibre nuclei, whereas in the EDL fibres it was localized in both the cytoplasm and the nuclei. However, no difference in its localization was observed between type I and type IIA fibres in both muscles. Western blot experiments showed that the soleus expressed more NFATc1 proteins than the EDL. From these results, we suggest that NFATc1 controls the number and distribution of both type I and type IIA fibres, as well as the oxidative capacity of adult mammalian skeletal muscles.

An in vivo model for studying the dynamics of intracellular free calcium changes in slow- and fast-twitch muscle fibres.

PubMed

Bátkai, S; Rácz, I B; Ivanics, T; Tóth, A; Hamar, J; Slaaf, D W; Reneman, R S; Ligeti, L

1999-10-01

The understanding of the regulation of the free cytosolic [Ca2+] ([Ca2+]i) in skeletal muscle is hampered by the lack of techniques for quantifying free [Ca2+]i in muscle fibres in situ. We describe a model for studying the dynamics of free [Ca2+]i in the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus (SOL) muscles of the rat in vivo using caffeine superfusion to induce changes in free [Ca2+]i. We assumed that differences in sensitivity between the two muscle types for this substance reflect differences in intracellular Ca2+ handling in the fibres of which these muscles consist. The Indo-1 ratiometric method, using intravital microscopy with incident light, was adapted to measure free [Ca2+]i in vivo. Fluorescence images were collected by means of a digital camera. Caffeine superfusion at 37 degrees C for 2 min, at concentrations of 1, 2, 5, 10 or 20 mmol/l, induced a concentration-dependent increase in free [Ca2+]i and revealed differences in caffeine sensitivity between the muscle types, with the SOL being more sensitive. In a separate set of experiments the contracture threshold, as assessed by topical application of caffeine, was determined in both muscle types. EDL had a higher threshold for developing contracture than SOL. These finding are in agreement with previous in vitro studies. We may conclude that the dynamics of free [Ca2+]i can be assessed reliably in intact mammalian muscle in vivo.

Novel locomotor muscle design in extreme deep-diving whales.

PubMed

Velten, B P; Dillaman, R M; Kinsey, S T; McLellan, W A; Pabst, D A

2013-05-15

Most marine mammals are hypothesized to routinely dive within their aerobic dive limit (ADL). Mammals that regularly perform deep, long-duration dives have locomotor muscles with elevated myoglobin concentrations that are composed of predominantly large, slow-twitch (Type I) fibers with low mitochondrial volume densities (V(mt)). These features contribute to extending ADL by increasing oxygen stores and decreasing metabolic rate. Recent tagging studies, however, have challenged the view that two groups of extreme deep-diving cetaceans dive within their ADLs. Beaked whales (including Ziphius cavirostris and Mesoplodon densirostris) routinely perform the deepest and longest average dives of any air-breathing vertebrate, and short-finned pilot whales (Globicephala macrorhynchus) perform high-speed sprints at depth. We investigated the locomotor muscle morphology and estimated total body oxygen stores of several species within these two groups of cetaceans to determine whether they (1) shared muscle design features with other deep divers and (2) performed dives within their calculated ADLs. Muscle of both cetaceans displayed high myoglobin concentrations and large fibers, as predicted, but novel fiber profiles for diving mammals. Beaked whales possessed a sprinter's fiber-type profile, composed of ~80% fast-twitch (Type II) fibers with low V(mt). Approximately one-third of the muscle fibers of short-finned pilot whales were slow-twitch, oxidative, glycolytic fibers, a rare fiber type for any mammal. The muscle morphology of beaked whales likely decreases the energetic cost of diving, while that of short-finned pilot whales supports high activity events. Calculated ADLs indicate that, at low metabolic rates, both beaked and short-finned pilot whales carry sufficient onboard oxygen to aerobically support their dives.

Morphological classification and comparison of suboccipital muscle fiber characteristics

PubMed Central

Yamamoto, Masahito; Kitamura, Kei; Morita, Sumiharu; Nagakura, Ryotaro; Matsunaga, Satoru; Abe, Shinichi

2017-01-01

In an attempt to clarify the function of the suboccipital muscles, we performed morphological observation of the suboccipital muscles for variations in the muscle belly and compared the morphology of their muscle fibers in terms of cross-sectional area by immunostaining with anti-myosin heavy chain antibodies. The cadavers of 25 Japanese individuals were used: 22 for morphological examinations and three for histological examinations. Among samples of the rectus capitis posterior major muscle (RCPma) and rectus capitis posterior minor muscle (RCPmi), 86.4% had a typical muscle appearance with a single belly, and 13.6% had an anomalous morphology. None of the samples of the obliquus capitis superior (OCS) or obliquus capitis inferior (OCI) muscles had an anomalous appearance. Measurement of cross-sectional area revealed that fast-twitch muscle fibers in the RCPma and OCI had a significantly greater cross-sectional area than those of the RCPmi and OCS. The cross-sectional area of intermediate muscle fibers was also significantly greater in the OCS than in the RCPma, RCPmi, and OCI. The cross-sectional area of slow-twitch muscle fibers was significantly greater in the OCS than in the RCPma, RCPmi, and OCI, and the RCPmi showed a significantly greater cross-sectional area for slow-twitch muscle fibers than did the RCPma, and OCI. Our findings indicate that the RCPmi and OCS exert a greater force than the RCPma and OCI, and act as anti-gravity agonist muscles of the head. Prolonged head extension in individuals with anomalous suboccipital muscle groups could result in dysfunction due to undue stress. PMID:29354295

Morphological classification and comparison of suboccipital muscle fiber characteristics.

PubMed

Yamauchi, Masato; Yamamoto, Masahito; Kitamura, Kei; Morita, Sumiharu; Nagakura, Ryotaro; Matsunaga, Satoru; Abe, Shinichi

2017-12-01

In an attempt to clarify the function of the suboccipital muscles, we performed morphological observation of the suboccipital muscles for variations in the muscle belly and compared the morphology of their muscle fibers in terms of cross-sectional area by immunostaining with anti-myosin heavy chain antibodies. The cadavers of 25 Japanese individuals were used: 22 for morphological examinations and three for histological examinations. Among samples of the rectus capitis posterior major muscle (RCPma) and rectus capitis posterior minor muscle (RCPmi), 86.4% had a typical muscle appearance with a single belly, and 13.6% had an anomalous morphology. None of the samples of the obliquus capitis superior (OCS) or obliquus capitis inferior (OCI) muscles had an anomalous appearance. Measurement of cross-sectional area revealed that fast-twitch muscle fibers in the RCPma and OCI had a significantly greater cross-sectional area than those of the RCPmi and OCS. The cross-sectional area of intermediate muscle fibers was also significantly greater in the OCS than in the RCPma, RCPmi, and OCI. The cross-sectional area of slow-twitch muscle fibers was significantly greater in the OCS than in the RCPma, RCPmi, and OCI, and the RCPmi showed a significantly greater cross-sectional area for slow-twitch muscle fibers than did the RCPma, and OCI. Our findings indicate that the RCPmi and OCS exert a greater force than the RCPma and OCI, and act as anti-gravity agonist muscles of the head. Prolonged head extension in individuals with anomalous suboccipital muscle groups could result in dysfunction due to undue stress.

Thoracoscopic patch insulation to correct phrenic nerve stimulation secondary to cardiac resynchronization therapy.

PubMed

Mediratta, Neeraj; Barker, Diane; McKevith, James; Davies, Peter; Belchambers, Sandra; Rao, Archana

2012-07-01

Cardiac resynchronization therapy is an established therapy for heart failure, improving quality of life and prognosis. Despite advances in technique, available leads and delivery systems, trans-venous left ventricular (LV) lead positioning remains dependent on the patient's underlying venous anatomy. The left phrenic nerve courses over the surface of the pericardium laterally and may be stimulated by the LV pacing lead, causing uncomfortable diaphragmatic twitch. This paper describes a video-assisted thoracoscopic (VATS) procedure to correct phrenic nerve stimulation secondary to cardiac resynchronization therapy. Most current ways of avoiding phrenic stimulation involve either electronic reprogramming to distance the phrenic nerve from the stimulation circuit or repositioning the lead. We describe a case where the phrenic nerve was surgically insulated from the stimulating current by insinuating a patch of bovine pericardium between the epicardium and native pericardium of the heart thus completely resolving previously intolerable and incessant diaphragmatic twitch. The procedure was performed under general anaesthesia with single-lung ventilation and minimal use of neuromuscular blocking agents. Surgical patch insulation of the phrenic nerve was performed using minimally invasive VATS surgery, as a short-stay procedure, with no complications. No diaphragmatic twitch occurred post-surgery and the patient continued to gain symptomatic benefit from cardiac synchronization therapy (New York Heart Association Class III to II), enabling return to work. In cases where the trans-venous position of a LV lead is limited by troublesome phrenic nerve stimulation, thoracoscopic surgical patch insulation of the phrenic nerve could be considered to allow beneficial cardiac resynchronization therapy.

Neuromuscular changes and the rapid adaptation following a bout of damaging eccentric exercise.

PubMed

Goodall, S; Thomas, K; Barwood, M; Keane, K; Gonzalez, J T; St Clair Gibson, A; Howatson, G

2017-08-01

An initial bout of eccentric exercise is known to protect against muscle damage following a repeated bout of the same exercise; however, the neuromuscular adaptations owing to this phenomenon are unknown. To determine whether neuromuscular disturbances are modulated following a repeated bout of eccentric exercise. Following eccentric exercise performed with the elbow flexors, we measured maximal voluntary force, resting twitch force, muscle soreness, creatine kinase (CK) and voluntary activation (VA) using motor point and motor cortex stimulation at baseline, immediately post-exercise and at 1, 2, 3, 4 and 7 days post-exercise on two occasions, separated by 3 weeks. Significant muscle damage and fatigue were evident following the first exercise bout; maximal voluntary contraction (MVC) was reduced immediately by 35% and remained depressed at 7 days post-exercise. Soreness and CK release peaked at 3 and 4 days post-exercise respectively. Resting twitch force remained significantly reduced at 7 days (-48%), whilst VA measured with motor point and motor cortex stimulation was reduced until 2 and 3 days respectively. A repeated bout effect (RBE) was observed with attenuated soreness and CK release and a quicker recovery of MVC and resting twitch force. A similar decrement in VA was observed following both bouts; however, following the repeated bout there was a significantly smaller reduction in, and a faster recovery of, VA measured using motor cortical stimulation. Our data suggest that the RBE may be explained, partly, by a modification in motor corticospinal drive. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Eyebrow ptosis after blowout fracture indicates impairment of trigeminal proprioceptive evocation that induces reflex contraction of the frontalis muscle.

PubMed

Ban, Ryokuya; Matsuo, Kiyoshi; Ban, Midori; Yuzuriha, Shunsuke

2013-01-01

The mixed levator and frontalis muscles lack the interior muscle spindles normally required to induce involuntary contraction of their slow-twitch fibers. To involuntarily move the eyelid and eyebrow, voluntary contraction of the levator nonskeletal fast-twitch muscle fibers stretches the mechanoreceptors in Müller's muscle to evoke trigeminal proprioception, which then induces reflex contraction of the levator and frontalis skeletal slow-twitch muscle fibers. The trigeminal proprioceptive nerve has a long intraorbital course from the mechanoreceptors in Müller's muscle to the superior orbital fissure. Since external force to the globe may cause impairment of trigeminal proprioceptive evocation, we confirmed how unilateral blowout fracture due to a hydraulic mechanism affects ipsilateral eyebrow movement as compared with unilateral zygomatic fracture. In 16 unilateral blowout fracture patients, eyebrow heights were measured on noninjured and injured sides in primary and 60° upward gaze and statistically compared. Eyebrow heights were also measured in primary gaze in 24 unilateral zygomatic fracture patients and statistically compared. In the blowout fracture patients, eyebrow heights on the injured side were significantly smaller than on the noninjured side in both gaze. In the zygomatic fracture patients, eyebrow heights on the injured side were significantly larger than on the noninjured side in primary gaze. Since 60° upward gaze did not recover the eyebrow ptosis observed in primary gaze in blowout fracture patients, such ptosis indicated impairment of trigeminal proprioceptive evocation and the presence of a hydraulic mechanism that may require ophthalmic examination.

Eyebrow Ptosis After Blowout Fracture Indicates Impairment of Trigeminal Proprioceptive Evocation That Induces Reflex Contraction of the Frontalis Muscle

PubMed Central

Ban, Ryokuya; Matsuo, Kiyoshi; Ban, Midori; Yuzuriha, Shunsuke

2013-01-01

Objective: The mixed levator and frontalis muscles lack the interior muscle spindles normally required to induce involuntary contraction of their slow-twitch fibers. To involuntarily move the eyelid and eyebrow, voluntary contraction of the levator nonskeletal fast-twitch muscle fibers stretches the mechanoreceptors in Müller's muscle to evoke trigeminal proprioception, which then induces reflex contraction of the levator and frontalis skeletal slow-twitch muscle fibers. The trigeminal proprioceptive nerve has a long intraorbital course from the mechanoreceptors in Müller's muscle to the superior orbital fissure. Since external force to the globe may cause impairment of trigeminal proprioceptive evocation, we confirmed how unilateral blowout fracture due to a hydraulic mechanism affects ipsilateral eyebrow movement as compared with unilateral zygomatic fracture. Methods: In 16 unilateral blowout fracture patients, eyebrow heights were measured on noninjured and injured sides in primary and 60° upward gaze and statistically compared. Eyebrow heights were also measured in primary gaze in 24 unilateral zygomatic fracture patients and statistically compared. Results: In the blowout fracture patients, eyebrow heights on the injured side were significantly smaller than on the noninjured side in both gaze. In the zygomatic fracture patients, eyebrow heights on the injured side were significantly larger than on the noninjured side in primary gaze. Conclusion: Since 60° upward gaze did not recover the eyebrow ptosis observed in primary gaze in blowout fracture patients, such ptosis indicated impairment of trigeminal proprioceptive evocation and the presence of a hydraulic mechanism that may require ophthalmic examination. PMID:23814636

Species-specific loss of sexual dimorphism in vocal effectors accompanies vocal simplification in African clawed frogs (Xenopus)

PubMed Central

Leininger, Elizabeth C.; Kitayama, Ken; Kelley, Darcy B.

2015-01-01

ABSTRACT Phylogenetic studies can reveal patterns of evolutionary change, including the gain or loss of elaborate courtship traits in males. Male African clawed frogs generally produce complex and rapid courtship vocalizations, whereas female calls are simple and slow. In a few species, however, male vocalizations are also simple and slow, suggesting loss of male-typical traits. Here, we explore features of the male vocal organ that could contribute to loss in two species with simple, slow male calls. In Xenopus boumbaensis, laryngeal morphology is more robust in males than in females. Larynges are larger, have a more complex cartilaginous morphology and contain more muscle fibers. Laryngeal muscle fibers are exclusively fast-twitch in males but are both fast- and slow-twitch in females. The laryngeal electromyogram, a measure of neuromuscular synaptic strength, shows greater potentiation in males than in females. Male-specific physiological features are shared with X. laevis, as well as with a species of the sister clade, Silurana tropicalis, and thus are likely ancestral. In X. borealis, certain aspects of laryngeal morphology and physiology are sexually monomorphic rather than dimorphic. In both sexes, laryngeal muscle fibers are of mixed-twitch type, which limits the production of muscle contractions at rapid intervals. Muscle activity potentiation and discrete tension transients resemble female rather than male X. boumbaensis. The de-masculinization of these laryngeal features suggests an alteration in sensitivity to the gonadal hormones that are known to control the sexual differentiation of the larynx in other Xenopus and Silurana species. PMID:25788725