Muscle-specific expression of hypoxia-inducible factor in human skeletal muscle

DEFF Research Database (Denmark)

Mounier, Rémi; Pedersen, Bente Klarlund; Plomgaard, Peter

2010-01-01

fibres that possess unique patterns of protein and gene expression, producing different capillarization and energy metabolism systems. In this work, we analysed HIF-1alpha mRNA and protein expression related to the fibre-type composition in untrained human skeletal muscle by obtaining muscle biopsies...... from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1......alpha protein level. Interestingly, none of the HIF-1alpha target genes, like the most studied angiogenic factor involved in muscle angiogenesis, vascular endothelial growth factor (VEGF), exhibited a muscle fibre-specific-related mRNA expression at rest in normoxia. However, soleus presented...

Development of Human Muscle Protein Measurement with MRI

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Lin, Chen; Evans, Harlan; Leblanc, Adrian D.

1997-01-01

It is known that micro-gravity has a strong influence on the human musculoskeletal system. A number of studies have shown that significant changes in skeletal muscles occur in both space flight and bedrest simulation. In our 5 week bedrest study, the cross-sectional area of soleus-gastrocnemius decreased about 12% while the cross-sectional area of anterior calf muscles decreased about 4%. Using volume measurements, these losses increased after 17 weeks to approximately 30% and 21% respectively. Significant muscle atrophy was also found on the SL-J crew members after only 8 days in space. It is important that these effects are fully understood so that countermeasures can be developed. The same knowledge might also be useful in preventing muscle atrophy related to other medical problems. A major problem with anatomical measurements of muscle during bed rest and microgravity is the influence of fluid shifts and water balance on the measurement of muscle volume, especially when the exposure duration is short and the atrophy is relatively small. Fluid shifts were documented in Skylab by visual observations of blood vessel distention, rapid changes in limb volume, center of mass measurements and subjective descriptions such as puffy faces and head fullness. It has been reported that the muscle water content of biopsied soleus muscles decreased following 8 hours of head down tilt bed rest. Three aspects of fluid shifts that can affect volume measurements are: first, the shift of fluid that occurs whenever there is a change from upright to a recumbent position and vice versa; second, the potential for fluid accumulation in the lower limbs resulting from muscle damage caused by overextending atrophied muscle or swelling caused by deconditioned precapillary sphincter muscles during reambulation; third, the net change of hydration level during and after bed rest or spaceflight. Because of these transitory fluid shifts, muscle protein is expected to represent muscle capacity

The effects of short versus long inter-set rest intervals in resistance training on measures of muscle hypertrophy: A systematic review.

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Grgic, Jozo; Lazinica, Bruno; Mikulic, Pavle; Krieger, James W; Schoenfeld, Brad Jon

2017-09-01

Although the effects of short versus long inter-set rest intervals in resistance training on measures of muscle hypertrophy have been investigated in several studies, the findings are equivocal and the practical implications remain unclear. In an attempt to provide clarity on the topic, we performed a systematic literature search of PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, and Physiotherapy Evidence Database (PEDro) electronic databases. Six studies were found to have met the inclusion criteria: (a) an experimental trial published in an English-language peer-reviewed journal; (b) the study compared the use of short (≤60 s) to long (>60 s) inter-set rest intervals in a traditional dynamic resistance exercise using both concentric and eccentric muscle actions, with the only difference in resistance training among groups being the inter-set rest interval duration; (c) at least one method of measuring changes in muscle mass was used in the study; (d) the study lasted for a minimum of four weeks, employed a training frequency of ≥2 resistance training days per week, and (e) used human participants without known chronic disease or injury. Current evidence indicates that both short and long inter-set rest intervals may be useful when training for achieving gains in muscle hypertrophy. Novel findings involving trained participants using measures sensitive to detect changes in muscle hypertrophy suggest a possible advantage for the use of long rest intervals to elicit hypertrophic effects. However, due to the paucity of studies with similar designs, further research is needed to provide a clear differentiation between these two approaches.

Lateral abdominal muscle size at rest and during abdominal drawing-in manoeuvre in healthy adolescents.

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Linek, Pawel; Saulicz, Edward; Wolny, Tomasz; Myśliwiec, Andrzej; Kokosz, Mirosław

2015-02-01

Lateral abdominal wall muscles in children and adolescents have not been characterised to date. In the present report, we examined the reliability of the ultrasound measurement and thickness of the oblique external muscle (OE), oblique internal muscle (OI) and transverse abdominal muscle (TrA) at rest and during abdominal drawing-in manoeuvre (ADIM) on both sides of the body in healthy adolescents. We also determined possible differences between boys and girls and defined any factors-such as body mass, height and BMI-that may affect the thickness of the abdominal muscles. B-mode ultrasound was used to assess OE, OI and TrA on both sides of the body in the supine position. Ultrasound measurements at rest and during ADIM were reliable in this age group (ICC3,3 > 0.92). OI was always the thickest and TrA the thinnest muscle on both sides of the body. In this group, an identical pattern of the contribution of the individual muscles to the structure of the lateral abdominal wall (OI > OE > TrA) was observed. At rest and during ADIM, no statistically significant side-to-side differences were demonstrated in either gender. The body mass constitutes between 30% and <50% of the thickness differences in all muscles under examination at rest and during ADIM. The structure of lateral abdominal wall in adolescents is similar to that of adults. During ADIM, the abdominal muscles in adolescents react similarly to those in adults. This study provided extensive information regarding the structure of the lateral abdominal wall in healthy adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Skeletal muscle microvascular and interstitial PO2 from rest to contractions.

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Hirai, Daniel M; Craig, Jesse C; Colburn, Trenton D; Eshima, Hiroaki; Kano, Yutaka; Sexton, William L; Musch, Timothy I; Poole, David C

2018-03-01

Oxygen pressure gradients across the microvascular walls are essential for oxygen diffusion from blood to tissue cells. At any given flux, the magnitude of these transmural gradients is proportional to the local resistance. The greatest resistance to oxygen transport into skeletal muscle is considered to reside in the short distance between red blood cells and myocytes. Although crucial to oxygen transport, little is known about transmural pressure gradients within skeletal muscle during contractions. We evaluated oxygen pressures within both the skeletal muscle microvascular and interstitial spaces to determine transmural gradients during the rest-contraction transient in anaesthetized rats. The significant transmural gradient observed at rest was sustained during submaximal muscle contractions. Our findings support that the blood-myocyte interface provides substantial resistance to oxygen diffusion at rest and during contractions and suggest that modulations in microvascular haemodynamics and red blood cell distribution constitute primary mechanisms driving increased transmural oxygen flux with contractions. Oxygen pressure (PO2) gradients across the blood-myocyte interface are required for diffusive O 2 transport, thereby supporting oxidative metabolism. The greatest resistance to O 2 flux into skeletal muscle is considered to reside between the erythrocyte surface and adjacent sarcolemma, although this has not been measured during contractions. We tested the hypothesis that O 2 gradients between skeletal muscle microvascular (PO2 mv ) and interstitial (PO2 is ) spaces would be present at rest and maintained or increased during contractions. PO2 mv and PO2 is   were determined via phosphorescence quenching (Oxyphor probes G2 and G4, respectively) in the exposed rat spinotrapezius during the rest-contraction transient (1 Hz, 6 V; n = 8). PO2 mv was higher than PO2 is in all instances from rest (34.9 ± 6.0 versus 15.7 ± 6.4) to contractions (28.4 ± 5

Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation.

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Tanner, Ruth E; Brunker, Lucille B; Agergaard, Jakob; Barrows, Katherine M; Briggs, Robert A; Kwon, Oh Sung; Young, Laura M; Hopkins, Paul N; Volpi, Elena; Marcus, Robin L; LaStayo, Paul C; Drummond, Micah J

2015-09-15

Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P protein synthesis increased before bed rest in both age groups (P protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

LBNP/ergometer effects on female cardiovascular and muscle deconditioning in 15d head-down bed rest

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Wang, Lin-Jie

2012-07-01

Female has already been an important part of astronaut corps but gender characteristics in weightlessness and countermeasure effects still not clearly elucidated. In this study the LBNP/Ergometer effects on female cardiovascular deconditioning and muscle atrophy in 15d head-down bed rest were explored. 22 female university students were recruited as volunteers that participated in the 15d head-down bed rest. They were divided into control group (Con,n=8), LBNP exercise group (LBNP,n=7) and LBNP combined with ergometer exercise group (LBNP+Ergo, n=7). Grade negative pressures of -10,-20,-30,-40mmHg 20 or 55min were used in LBNP exercise. In ergometer exercises the subjects must maintain 60-80% VO2peak of pre-bed rest at pedal speed of about 70cycle/min for 15min and the entire exercise duration was 30min. LBNP were performed at 6th,8th,10th,12th,and 13th day and Ergometer were operated at 4th,5th,7th,9th,11th day during bed rest. Before and after bed rest, cardiovascular tilt test were performed to evaluate orthostatic intolerance, supine cycle ergometer were used to test the cardiopulmonary function, MRI tests were operated to examine the volume variations of leg muscle groups and isokinetic test were given to test the muscle strength and endurance of knee. 40% of female subjects did not pass the tilt table test after bed rest and exercises made no difference. Compared with pre-BR, VO2max and VO2max /body weight, VO2/HRmax, maximal power and duration significantly decreased in CON group and LBNP group. For the ERGO+LBNP group, there were no visible different in the parameters of cardiopulmonary function except that maximal power and duration decreased. Muscle maximal voluntary contraction and muscle (quadriceps, rectus femoris, gastrocnemius and soleus) volume decreasing in non-predominant leg was larger in Con group than in LBNP+Ergo group. It is suggested that LBNP combined with ergometer in some degrees can counteract the cardiovascular and muscle deconditioning

Effects of Flotation-REST on Muscle Tension Pain

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Anette Kjellgren

2001-01-01

Full Text Available The purpose of the present study was to investigate whether the floating form of the restricted environmental stimulation technique (REST may be applied within the field of pain relief. Flotation-REST consists of a procedure whereby an individual is immersed in a tank filled with water of an extremely high salt concentration. Thirty-seven patients (14 men and 23 women suffering from chronic pain consisting of aching muscles in the neck and back area participated in the study. They were randomly assigned to either a control group (17 participants or an experimental group (20 participants. The experimental group received nine opportunities to use the flotation-REST technique in the water tank over a three-week period. The results indicated that the most severe perceived pain intensity was significantly reduced, whereas low perceived pain intensity was not influenced by the floating technique. Further, the results indicated that circulating levels of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethyleneglycol were reduced significantly in the experimental group but not in the control group following treatment, whereas endorphin levels were not affected by flotation. Flotation-REST treatment also elevated the participants' optimism and reduced the degree of anxiety or depression; at nighttime, patients who underwent flotation fell asleep more easily. The present findings describe possible changes, for the better, in patients presenting with chronic pain complaints.

Effects of flotation-REST on muscle tension pain.

Science.gov (United States)

Kjellgren, A; Sundequist, U; Norlander, T; Archer, T

2001-01-01

The purpose of the present study was to investigate whether the floating form of the restricted environmental stimulation technique (REST) may be applied within the field of pain relief. Flotation-REST consists of a procedure whereby an individual is immersed in a tank filled with water of an extremely high salt concentration. Thirty-seven patients (14 men and 23 women) suffering from chronic pain consisting of aching muscles in the neck and back area participated in the study. They were randomly assigned to either a control group (17 participants) or an experimental group (20 participants). The experimental group received nine opportunities to use the flotation-REST technique in the water tank over a three-week period. The results indicated that the most severe perceived pain intensity was significantly reduced, whereas low perceived pain intensity was not influenced by the floating technique. Further, the results indicated that circulating levels of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethyleneglycol were reduced significantly in the experimental group but not in the control group following treatment, whereas endorphin levels were not affected by flotation. Flotation-REST treatment also elevated the participants' optimism and reduced the degree of anxiety or depression; at nighttime, patients who underwent flotation fell asleep more easily. The present findings describe possible changes, for the better, in patients presenting with chronic pain complaints.

Lactate kinetics in human tissues at rest and during exercise

DEFF Research Database (Denmark)

van Hall, Gerrit

2010-01-01

lactate metabolism at rest and during exercise and suggestions are put forward to explain the simultaneous lactate uptake and release; and (2) lactate metabolism in the heart, liver, kidneys, brain, adipose tissue and lungs will be discussed and its potential importance in these tissues.......Lactate production in skeletal muscle has now been studied for nearly two centuries and still its production and functional role at rest and during exercise is much debated. In the early days skeletal muscle was mainly seen as the site of lactate production during contraction and lactate production...... associated with a lack of muscle oxygenation and fatigue. Later it was recognized that skeletal muscle not only played an important role in lactate production but also in lactate clearance and this led to a renewed interest, not the least from the Copenhagen School in the 1930s, in the metabolic role...

The expression of HSP in human skeletal muscle. Effects of muscle fiber phenotype and training background

DEFF Research Database (Denmark)

Folkesson, Mattias; Mackey, Abigail L; Langberg, Henning

2013-01-01

AIM: Exercise-induced adaptations of skeletal muscle are related to training mode and can be muscle fibre type specific. This study aimed to investigate heat shock protein expression in type I and type II muscle fibres in resting skeletal muscle of subjects with different training backgrounds...... myosin heavy chain I and IIA, αB-crystallin, HSP27, HSP60 and HSP70. RESULTS: In ACT and RES, but not in END, a fibre type specific expression with higher staining intensity in type I than type II fibres was seen for αB-crystallin. The opposite (II>I) was found for HSP27 in subjects from ACT (6 of 12...... HSPs in human skeletal muscle is influenced by muscle fibre phenotype. The fibre type specific expression of HSP70 is influenced by resistance and endurance training whereas those of αB-crystallin and HSP27 are influenced only by endurance training suggesting the existence of a training...

Effect of exercise on insulin action in human skeletal muscle

DEFF Research Database (Denmark)

Richter, Erik; Mikines, K J; Galbo, Henrik

1989-01-01

The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... was performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction

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Ramos, Sofhia V.; Vandenboom, Rene; Roy, Brian D.; Peters, Sandra J.

2013-01-01

Evidence indicates that skeletal muscle lipid droplet-associated proteins (PLINs) regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN1 is thought to regulate lipolysis by directly interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to fully activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. Our purpose was to examine interactions between PLIN2, PLIN3, and PLIN5, with ATGL and its coactivator CGI-58 at rest and following contraction. Isolated rat solei were incubated for 30 min at rest or during 30 min of intermittent tetanic stimulation [150-ms volleys at 60 Hz with a train rate of 20 tetani/min (25°C)] to maximally stimulate intramuscular lipid breakdown. Results show that the interaction between ATGL and CGI-58 increased 128% following contraction (P = 0.041). Further, ATGL interacts with PLIN2, PLIN3, and PLIN5 at rest and following contraction. The PLIN2-ATGL interaction decreased significantly by 21% following stimulation (P = 0.013). Both PLIN3 and PLIN5 coprecipitated with CGI-58 at rest and following contraction, while there was no detectable interaction between PLIN2 and CGI-58 in either condition. Therefore, our findings indicate that in skeletal muscle, during contraction-induced muscle lipolysis, ATGL and CGI-58 strongly associate and that the PLIN proteins work together to regulate lipolysis, in part, by preventing ATGL and CGI-58 interactions at rest. PMID:23408028

Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction.

Science.gov (United States)

MacPherson, Rebecca E K; Ramos, Sofhia V; Vandenboom, Rene; Roy, Brian D; Peters, Sandra J

2013-04-15

Evidence indicates that skeletal muscle lipid droplet-associated proteins (PLINs) regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN1 is thought to regulate lipolysis by directly interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to fully activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. Our purpose was to examine interactions between PLIN2, PLIN3, and PLIN5, with ATGL and its coactivator CGI-58 at rest and following contraction. Isolated rat solei were incubated for 30 min at rest or during 30 min of intermittent tetanic stimulation [150-ms volleys at 60 Hz with a train rate of 20 tetani/min (25°C)] to maximally stimulate intramuscular lipid breakdown. Results show that the interaction between ATGL and CGI-58 increased 128% following contraction (P = 0.041). Further, ATGL interacts with PLIN2, PLIN3, and PLIN5 at rest and following contraction. The PLIN2-ATGL interaction decreased significantly by 21% following stimulation (P = 0.013). Both PLIN3 and PLIN5 coprecipitated with CGI-58 at rest and following contraction, while there was no detectable interaction between PLIN2 and CGI-58 in either condition. Therefore, our findings indicate that in skeletal muscle, during contraction-induced muscle lipolysis, ATGL and CGI-58 strongly associate and that the PLIN proteins work together to regulate lipolysis, in part, by preventing ATGL and CGI-58 interactions at rest.

Blood flow distribution in dog gastrocnemius muscle at rest and during stimulation

International Nuclear Information System (INIS)

Piiper, J.; Pendergast, D.R.; Marconi, C.; Meyer, M.; Heisler, N.; Cerretelli, P.

1985-01-01

The distribution of blood flow within the isolated perfused dog gastrocnemius muscle (weight 100-240 g) was studied by intra-arterial injection of radioactively labeled microspheres (diameter 15 micron) at rest and during supramaximal stimulation to rhythmic isotonic tetanic contractions of varied frequency against varied loads. After the experiment the muscle was cut into 180-250 pieces of approximately 0.75 g each, and the blood flow to each muscle piece was determined from its radioactivity. The inhomogeneity of blood flow was represented as the frequency distribution of the ratios of regional specific blood flow, i.e., blood flow per unit tissue weight of the piece, QR, to the overall specific blood flow of the muscle, Q. The QR/Q values for the individual pieces of a muscle were found to vary widely both at rest and during stimulation. With rising work load the frequency distribution had a tendency to broaden and flatten, indicating increasing perfusion inhomogeneity. On the average of the experiments, there was no significant difference in specific blood flow between the three anatomic components of the gastrocnemius (lateral and medial heads of gastrocnemius and flexor digitorum superficialis) nor between the superficial and deep portions within these anatomic components, only the distal third of the muscle was relatively less perfused compared with the proximal two-thirds. The considerable inhomogeneity of blood flow as revealed by microsphere embolization and by other methods is expected to exert important limiting effects on local O 2 supply, particularly during exercise

Effect of repeated forearm muscle cooling on the adaptation of skeletal muscle metabolism in humans

Science.gov (United States)

Wakabayashi, Hitoshi; Nishimura, Takayuki; Wijayanto, Titis; Watanuki, Shigeki; Tochihara, Yutaka

2017-07-01

This study aimed to investigate the effect of repeated cooling of forearm muscle on adaptation in skeletal muscle metabolism. It is hypothesized that repeated decreases of muscle temperature would increase the oxygen consumption in hypothermic skeletal muscle. Sixteen healthy males participated in this study. Their right forearm muscles were locally cooled to 25 °C by cooling pads attached to the skin. This local cooling was repeated eight times on separate days for eight participants (experimental group), whereas eight controls received no cold exposure. To evaluate adaptation in skeletal muscle metabolism, a local cooling test was conducted before and after the repeated cooling period. Change in oxy-hemoglobin content in the flexor digitorum at rest and during a 25-s isometric handgrip (10% maximal voluntary construction) was measured using near-infrared spectroscopy at every 2 °C reduction in forearm muscle temperature. The arterial blood flow was occluded for 15 s by upper arm cuff inflation at rest and during the isometric handgrip. The oxygen consumption in the flexor digitorum muscle was evaluated by a slope of the oxy-hemoglobin change during the arterial occlusion. In the experimental group, resting oxygen consumption in skeletal muscle did not show any difference between pre- and post-intervention, whereas muscle oxygen consumption during the isometric handgrip was significantly higher in post-intervention than in pre-test from thermoneutral baseline to 31 °C muscle temperature ( P cooling might facilitate oxidative metabolism in the skeletal muscle. In summary, skeletal muscle metabolism during submaximal isometric handgrip was facilitated after repeated local muscle cooling.

Influence of glutamate-evoked pain and sustained elevated muscle activity on blood oxygenation in the human masseter muscle.

Science.gov (United States)

Suzuki, Shunichi; Arima, Taro; Kitagawa, Yoshimasa; Svensson, Peter; Castrillon, Eduardo

2017-12-01

This study aimed to investigate the effect of glutamate-evoked masseter muscle pain on intramuscular oxygenation during rest and sustained elevated muscle activity (SEMA). Seventeen healthy individuals participated in two sessions in which they were injected with glutamate and saline in random order. Each session was divided into three, 10-min periods. During the first (period 1) and the last (period 3) 10-min periods, participants performed five intercalated 1-min bouts of masseter SEMA with 1-min periods of 'rest'. At onset of the second 10-min period, glutamate (0.5 ml, 1 M; Ajinomoto, Tokyo, Japan) or isotonic saline (0.5 ml; 0.9%) was injected into the masseter muscle and the participants kept the muscle relaxed in a resting position for 10 min (period 2). The hemodynamic characteristics of the masseter muscle were recorded simultaneously during the experiment by a laser blood-oxygenation monitor. The results demonstrated that glutamate injections caused significant levels of self-reported pain in the masseter muscle; however, this nociceptive input did not have robust effects on intramuscular oxygenation during rest or SEMA tasks. Interestingly, these findings suggest an uncoupling between acute nociceptive activity and hemodynamic parameters in both resting and low-level active jaw muscles. Further studies are needed to explore the pathophysiological significance of blood-flow changes for persistent jaw-muscle pain conditions. © 2017 Eur J Oral Sci.

Influence of erythrocyte oxygenation and intravascular ATP on resting and exercising skeletal muscle blood flow in humans with mitochondrial myopathy

DEFF Research Database (Denmark)

Jeppesen, Tina D; Vissing, John; González-Alonso, José

2012-01-01

Oxygen (O(2)) extraction is impaired in exercising skeletal muscle of humans with mutations of mitochondrial DNA (mtDNA), but the muscle hemodynamic response to exercise has never been directly investigated. This study sought to examine the extent to which human skeletal muscle perfusion can incr...

Resting mechanomyographic amplitude for the erector spinae and trapezius muscles following resistance exercise in a healthy population

International Nuclear Information System (INIS)

Wages, Nathan P; Beck, Travis W; Ye, Xin; Hofford, Craig W

2013-01-01

Musculoskeletal disorders are some of the most commonly occurring chronic conditions affecting the US population, with the most self-reported and diagnosed disorder being low back pain. Low back pain is often due to suboptimal back muscle function, at least in part, as a result of muscle inactivity and disuse. Resistance exercise has been shown to be successful in the treatment of low back pain. The purpose of the present investigation was to examine resting mechanomyographic (MMG) amplitude for the erector spinae and trapezius muscles prior to and following resistance exercise. Twenty healthy, college-aged men were measured for resting MMG amplitude levels prior to, and following a resistance training workout. The workout consisted of three sets of ten repetitions on the conventional deadlift, bent-over row, and lat pulldown exercises, with 1 min of rest between all sets and exercises. The results showed that there were approximate 10% and 15% decreases in normalized MMG amplitude after exercise for the erector spinae and trapezius muscles, respectively. These findings demonstrate a relaxation effect in the back muscles after exercise that could potentially be helpful in alleviating low back pain. (paper)

Effects of respiratory alkalosis on human skeletal muscle metabolism at the onset of submaximal exercise.

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LeBlanc, P J; Parolin, M L; Jones, N L; Heigenhauser, G J F

2002-10-01

The purpose of this study was to examine the effects of respiratory alkalosis on human skeletal muscle metabolism at rest and during submaximal exercise. Subjects exercised on two occasions for 15 min at 55 % of their maximal oxygen uptake while either hyperventilating (R-Alk) or breathing normally (Con). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to R-Alk. In the first minute of exercise, there was a delayed activation of pyruvate dehydrogenase (PDH) in R-Alk compared with Con, resulting in a reduced rate of pyruvate oxidation. Also, glycogenolysis was higher in R-Alk compared with Con, which was attributed to a higher availability of the monoprotonated form of inorganic phosphate (P(i)), resulting in an elevated rate of pyruvate production. The mismatch between pyruvate production and its oxidation resulted in net lactate accumulation. These effects were not seen after 15 min of exercise, with no further differences in muscle metabolism between conditions. The results from the present study suggest that respiratory alkalosis may play an important role in lactate accumulation during the transition from rest to exercise in acute hypoxic conditions, but that other factors mediate lactate accumulation during steady-state exercise.

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

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Ferrando, A. A.; Lane, H. W.; Stuart, C. A.; Davis-Street, J.; Wolfe, R. R.

1996-01-01

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P protein synthesis (PS; P protein also decreased by 46% (P protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

Exercise-induced metallothionein expression in human skeletal muscle fibres

DEFF Research Database (Denmark)

Penkowa, Milena; Keller, Pernille; Keller, Charlotte

2005-01-01

in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

Influence of supplementation with branched-chain amino acids in combination with resistance exercise on p70S6 kinase phosphorylation in resting and exercising human skeletal muscle.

Science.gov (United States)

Apró, W; Blomstrand, E

2010-11-01

Skeletal muscle growth is thought to be regulated by the mammalian target of rapamycin (mTOR) pathway, which can be activated by resistance exercise and branched-chain amino acids (BCAA). The major aim of the present study was to distinguish between the influence of resistance exercise and BCAA on key enzymes considered to be involved in the regulation of protein synthesis, including p70(S6) kinase (p70(S6k)). Nine healthy subjects (four men and five women) performed unilateral resistance exercise on two occasions separated by 1 month. Subjects were randomly supplied either a mixture of BCAA or flavoured water. Muscle biopsies were taken from both resting and exercising muscle before, after and 1 h after exercise. Phosphorylation of Akt was unaltered by either resistance exercise and/or BCAA supplementation whereas mTOR phosphorylation was enhanced (Pexercising and resting muscle following exercise in the absence (70-90%) and presence of BCAA supplementation (80-130%). Phosphorylation of p70(S6k) was unaffected by resistance exercise alone; however, BCAA intake increased (Pexercise. In resting muscle, a 5- and 16-fold increase in p70(S6k) was observed immediately after and 1 h after exercise, respectively, as compared to 11- and 30-fold increases in the exercising muscle. Phosphorylation of eukaryotic elongation factor 2 was attenuated 1 h after exercise (Pexercising muscle (30-50%) under both conditions. The present findings indicate that resistance exercise and BCAA exert both separate and combined effects on the p70(S6k) phosphorylation in an Akt-independent manner. © 2010 The Authors. Journal compilation © 2010 Scandinavian Physiological Society.

Leptin signaling in skeletal muscle after bed rest in healthy humans

DEFF Research Database (Denmark)

Guerra, Borja; Ponce-Gonzalez, Jesus Gustavo; Morales-Alamo, David

2014-01-01

. Leptin receptor isoforms (OB-Rs), suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) protein expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation were analyzed by Western blot. RESULTS: After bed rest basal insulin concentration.......4-fold after bed rest (P PTP1B in the deltoid. PTP1B was increased by 90% with bed rest in the vastus lateralis (P ... between the increase in vastus lateralis PTP1B and the increase in both basal insulin concentrations (r = 0.66, P

Subcellular localization of skeletal muscle lipid droplets and PLIN family proteins OXPAT and ADRP at rest and following contraction in rat soleus muscle.

Science.gov (United States)

MacPherson, Rebecca E K; Herbst, Eric A F; Reynolds, Erica J; Vandenboom, Rene; Roy, Brian D; Peters, Sandra J

2012-01-01

Skeletal muscle lipid droplet-associated proteins (PLINs) are thought to regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN2 [adipocyte differentiation-related protein (ADRP)] is found only on lipid droplets, while PLIN5 (OXPAT, expressed only in oxidative tissues) is found both on and off the lipid droplet and may be recruited to lipid droplet membranes when needed. Our purpose was to determine whether PLIN5 is recruited to lipid droplets with contraction and to investigate the myocellular location and colocalization of lipid droplets, PLIN2, and PLIN5. Rat solei were isolated, and following a 30-min equilibration period, they were assigned to one of two groups: 1) 30 min of resting incubation and 2) 30 min of stimulation (n = 10 each). Immunofluorescence microscopy was used to determine subcellular content, distribution, and colocalization of lipid droplets, PLIN2, and PLIN5. There was a main effect for lower lipid and PLIN2 content in stimulated compared with rested muscles (P muscles (P = 0.001, r(2) = 0.99) and linearly in stimulated muscles (slope = -0.0023 ± 0.0006, P muscles (P contraction in isolated skeletal muscle.

Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.

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Catoire, Milène; Mensink, Marco; Boekschoten, Mark V; Hangelbroek, Roland; Müller, Michael; Schrauwen, Patrick; Kersten, Sander

2012-01-01

Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max). Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.

Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.

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Milène Catoire

Full Text Available Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max. Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.

Bioenergetic profile of human coronary artery smooth muscle cells and effect of metabolic intervention.

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Mingming Yang

Full Text Available Bioenergetics of artery smooth muscle cells is critical in cardiovascular health and disease. An acute rise in metabolic demand causes vasodilation in systemic circulation while a chronic shift in bioenergetic profile may lead to vascular diseases. A decrease in intracellular ATP level may trigger physiological responses while dedifferentiation of contractile smooth muscle cells to a proliferative and migratory phenotype is often observed during pathological processes. Although it is now possible to dissect multiple building blocks of bioenergetic components quantitatively, detailed cellular bioenergetics of artery smooth muscle cells is still largely unknown. Thus, we profiled cellular bioenergetics of human coronary artery smooth muscle cells and effects of metabolic intervention. Mitochondria and glycolysis stress tests utilizing Seahorse technology revealed that mitochondrial oxidative phosphorylation accounted for 54.5% of ATP production at rest with the remaining 45.5% due to glycolysis. Stress tests also showed that oxidative phosphorylation and glycolysis can increase to a maximum of 3.5 fold and 1.25 fold, respectively, indicating that the former has a high reserve capacity. Analysis of bioenergetic profile indicated that aging cells have lower resting oxidative phosphorylation and reduced reserve capacity. Intracellular ATP level of a single cell was estimated to be over 1.1 mM. Application of metabolic modulators caused significant changes in mitochondria membrane potential, intracellular ATP level and ATP:ADP ratio. The detailed breakdown of cellular bioenergetics showed that proliferating human coronary artery smooth muscle cells rely more or less equally on oxidative phosphorylation and glycolysis at rest. These cells have high respiratory reserve capacity and low glycolysis reserve capacity. Metabolic intervention influences both intracellular ATP concentration and ATP:ADP ratio, where subtler changes may be detected by the latter.

Effects of experimental muscle pain on muscle activity and co-ordination during static and dynamic motor function.

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Graven-Nielsen, T; Svensson, P; Arendt-Nielsen, L

1997-04-01

The relation between muscle pain, muscle activity, and muscle co-ordination is still controversial. The present human study investigates the influence of experimental muscle pain on resting, static, and dynamic muscle activity. In the resting and static experiments, the electromyography (EMG) activity and the contraction force of m. tibialis anterior were assessed before and after injection of 0.5 ml hypertonic saline (5%) into the same muscle. In the dynamic experiment, injections of 0.5 ml hypertonic saline (5%) were performed into either m. tibialis anterior (TA) or m. gastrocnemius (GA) and the muscle activity and co-ordination were investigated during gait on a treadmill by EMG recordings from m. TA and m. GA. At rest no evidence of EMG hyperactivity was found during muscle pain. The maximal voluntary contraction (MVC) during muscle pain was significantly lower than the control condition (P Fibromyalgia and Myofascial Pain. Elsevier, Amsterdam, 1993, pp. 311-327.) which predicts increased activity of antagonistic muscle and decreased activity of agonistic muscle during experimental and clinical muscle pain.

Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: a PET study with nitric oxide and cyclooxygenase inhibition

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Heinonen, Ilkka; Saltin, Bengt; Kemppainen, Jukka

2011-01-01

The aim of the present study was to determine the effect of nitric oxide and prostanoids on microcirculation and oxygen uptake specifically in the active skeletal muscle by use of positron emission tomography (PET). Healthy males performed 3 five min bouts of light knee-extensor exercise. Skeletal...... muscle blood flow and oxygen uptake were measured at rest and during the exercise using PET with H(2)O(15) and (15)O(2) during: 1) control conditions; 2) nitric oxide synthase (NOS) inhibition by arterial infusion of L-NMMA and 3) combined NOS and cyclooxygenase (COX) inhibition by arterial infusion of L...

High-energy phosphate transfer in human muscle: diffusion of phosphocreatine.

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Gabr, Refaat E; El-Sharkawy, Abdel-Monem M; Schär, Michael; Weiss, Robert G; Bottomley, Paul A

2011-07-01

The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a spatial shuttle of high-energy phosphate between sites of energy production in the mitochondria and sites of energy utilization in the myofibrils via diffusion. Knowledge of the diffusion coefficient of PCr (D(PCr)) is thus critical for modeling and understanding energy transport in the myocyte, but D(PCr) has not been measured in humans. Using localized phosphorus magnetic resonance spectroscopy, we measured D(PCr) in the calf muscle of 11 adults as a function of direction and diffusion time. The results show that the diffusion of PCr is anisotropic, with significantly higher diffusion along the muscle fibers, and that the diffusion of PCr is restricted to a ∼28-μm pathlength assuming a cylindrical model, with an unbounded diffusion coefficient of ∼0.69 × 10(-3) mm(2)/s. This distance is comparable in size to the myofiber radius. On the basis of prior measures of CK reaction kinetics in human muscle, the expected diffusion distance of PCr during its half-life in the CK reaction is ∼66 μm. This distance is much greater than the average distances between mitochondria and myofibrils. Thus these first measurements of PCr diffusion in human muscle in vivo support the view that PCr diffusion is not a factor limiting high-energy phosphate transport between the mitochondria and the myofibrils in healthy resting myocytes.

Effects of long-duration bed rest on structural compartments of m. soleus in man

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Belozerova, I.; Shenkman, B.; Mazin, M.; Leblanc, A.; LeBlanc, A. D. (Principal Investigator)

2001-01-01

Magnetic resonance imaging (MRI), histomorphometry and electron microscopy of muscle demonstrate that long-term exposure to actual or simulated weightlessness (including head down bed rest) leads to decreased volume of antigravity muscles in mammals. In muscles interbundle space is occupied by the connective tissue. Rat studies show that hindlimb unloading induces muscle fiber atrophy along with increase in muscle non-fiber connective tissue compartment. Beside that, usually 20% of the muscle fiber volume is comprised by non-contractile (non-myofibrillar) compartment. The aim of the present study was to compare changes in muscle volume, and in muscle fiber size with alterations in myofibrillar apparatus, and in connective tissue compartment in human m. soleus under conditions of 120 day long head down bed rest (HDBR).

Interstitial and arterial-venous [K+] in human calf muscle during dynamic exercise

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Green, S; Langberg, Henning; Skovgaard, D

2000-01-01

+. Calf muscle pain was assessed using a visual analogue scale. On average, [K+]I was 4.4 mmol l(-1) at rest and increased during minutes 3-5 of incremental exercise by approximately 1-7 mmol l(-1) as a positive function of power output. K+ release also increased as a function of exercise intensity......Changes in the concentration of interstitial K+ surrounding skeletal muscle fibres ([K+]I) probably play some role in the regulation of cardiovascular adjustments to muscular activity, as well as in the aetiology of muscle pain and fatigue during high-intensity exercise. However, there is very...... little information on the response of [K+]I to exercise in human skeletal muscle. Five young healthy subjects performed plantar flexion exercise for four 5 min periods at increasing power outputs ( approximately 1-6 W) with 10 min intervening recovery periods, as well as for two 5 min periods...

Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

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Barbora de Courten

Full Text Available Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists.Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography, % body fat (bioimpedance, abdominal subcutaneous and visceral adiposity (magnetic resonance imaging, insulin sensitivity (euglycaemic hyperinsulinemic clamp, resting energy expenditure (REE, indirect calorimetry, free-living ambulatory physical activity (accelerometers and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04 and subcutaneous (r = 0.38, p = 0.02 but not visceral fat (r = 0.17, p = 0.33. Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008, REE (r = -0.58, p<0.001 and HDL-cholesterol levels (r = -0.34, p = 0.048. Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity.Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

31P magnetization transfer measurements of Pi→ATP flux in exercising human muscle.

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Sleigh, Alison; Savage, David B; Williams, Guy B; Porter, David; Carpenter, T Adrian; Brindle, Kevin M; Kemp, Graham J

2016-03-15

Fundamental criticisms have been made over the use of (31)P magnetic resonance spectroscopy (MRS) magnetization transfer estimates of inorganic phosphate (Pi)→ATP flux (VPi-ATP) in human resting skeletal muscle for assessing mitochondrial function. Although the discrepancy in the magnitude of VPi-ATP is now acknowledged, little is known about its metabolic determinants. Here we use a novel protocol to measure VPi-ATP in human exercising muscle for the first time. Steady-state VPi-ATP was measured at rest and over a range of exercise intensities and compared with suprabasal oxidative ATP synthesis rates estimated from the initial rates of postexercise phosphocreatine resynthesis (VATP). We define a surplus Pi→ATP flux as the difference between VPi-ATP and VATP. The coupled reactions catalyzed by the glycolytic enzymes GAPDH and phosphoglycerate kinase (PGK) have been shown to catalyze measurable exchange between ATP and Pi in some systems and have been suggested to be responsible for this surplus flux. Surplus VPi-ATP did not change between rest and exercise, even though the concentrations of Pi and ADP, which are substrates for GAPDH and PGK, respectively, increased as expected. However, involvement of these enzymes is suggested by correlations between absolute and surplus Pi→ATP flux, both at rest and during exercise, and the intensity of the phosphomonoester peak in the (31)P NMR spectrum. This peak includes contributions from sugar phosphates in the glycolytic pathway, and changes in its intensity may indicate changes in downstream glycolytic intermediates, including 3-phosphoglycerate, which has been shown to influence the exchange between ATP and Pi catalyzed by GAPDH and PGK. Copyright © 2016 the American Physiological Society.

Hyperadditive Ventilatory Response Arising from Interaction between the Carotid Chemoreflex and the Muscle Mechanoreflex in Healthy Humans.

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Silva, Talita M; Aranda, Liliane C; Paula-Ribeiro, Marcelle; Oliveira, Diogo M; Medeiros, Wladimir Musetti; Vianna, Lauro C; Nery, Luiz E; Silva, Bruno M

2018-03-22

Physical exercise potentiates the carotid chemoreflex control of ventilation (VE). Hyperadditive neural interactions may partially mediate the potentiation. However, some neural interactions remain incompletely explored. As the potentiation occurs even during low-intensity exercise, we tested the hypothesis that the carotid chemoreflex and the muscle mechanoreflex could interact in a hyperadditive fashion. Fourteen young healthy subjects inhaled, randomly, in separate visits, 12% O 2 to stimulate the carotid chemoreflex, and 21% O 2 as control. A rebreathing circuit maintained isocapnia. During gases administration, subjects either remained at rest (i.e., normoxic and hypoxic rest) or the muscle mechanoreflex was stimulated, via passive knee movement (i.e., normoxic and hypoxic movement). Surface muscle electrical activity did not increase during the passive movement, confirming the absence of active contractions. Hypoxic rest and normoxic movement similarly increased VE [change (mean {plus minus} SEM) = 1.24 {plus minus} 0.72 vs. 0.73 {plus minus} 0.43 L/min, respectively; P = 0.46], but hypoxic rest only increased tidal volume (Vt) and normoxic movement only increased breathing frequency (BF). Hypoxic movement induced greater VE and mean inspiratory flow (Vt/Ti) increase than the sum of hypoxic rest and normoxic movement isolated responses (VE change: hypoxic movement = 3.72 {plus minus} 0.81 vs. sum = 1.96 {plus minus} 0.83 L/min, P = 0.01; Vt/Ti change: hypoxic movement = 0.13 {plus minus} 0.03 vs. sum = 0.06 {plus minus} 0.03 L/s, P = 0.02). Moreover, hypoxic movement increased both Vt and BF. Collectively, the results indicate the carotid chemoreflex and the muscle mechanoreflex interacted mediating a hyperadditive ventilatory response in healthy humans.

Chronic Effects of Different Rest Intervals Between Sets on Dynamic and Isometric Muscle Strength and Muscle Activity in Trained Older Women.

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Jambassi Filho, José Claudio; Gurjão, André Luiz Demantova; Ceccato, Marilia; Prado, Alexandre Konig Garcia; Gallo, Luiza Herminia; Gobbi, Sebastião

2017-09-01

This study investigated the chronic effects of different rest intervals (RIs) between sets on dynamic and isometric muscle strength and muscle activity. We used a repeated-measures design (pretraining and posttraining) with independent groups (different RI). Twenty-one resistance-trained older women (66.4 ± 4.4 years) were randomly assigned to either a 1-minute RI group (G-1 min; n = 10) or 3-minute RI group (G-3 min; n = 11). Both groups completed 3 supervised sessions per week during 8 weeks. In each session, participants performed 3 sets of 15 repetitions of leg press exercise, with a load that elicited muscle failure in the third set. Fifteen maximum repetitions, maximal voluntary contraction, peak rate of force development, and integrated electromyography activity of the vastus lateralis and vastus medialis muscles were assessed pretraining and posttraining. There was a significant increase in load of 15 maximum repetitions posttraining for G-3 min only (3.6%; P 0.05). The findings suggest that different RIs between sets did not influence dynamic and isometric muscle strength and muscle activity in resistance-trained older women.

Combined speed endurance and endurance exercise amplify the exercise-induced PGC-1α and PDK4 mRNA response in trained human muscle

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Skovgaard, Casper; Brandt, Nina; Pilegaard, Henriette

2016-01-01

The aim of this study was to investigate the mRNA response related to mitochondrial biogenesis, metabolism, angiogenesis, and myogenesis in trained human skeletal muscle to speed endurance exercise (S), endurance exercise (E), and speed endurance followed by endurance exercise (S + E). Seventeen...... trained male subjects (maximum oxygen uptake (VO2-max): 57.2 ± 3.7 (mean ± SD) mL·min(-1)·kg(-1)) performed S (6 × 30 sec all-out), E (60 min ~60% VO2-max), and S + E on a cycle ergometer on separate occasions. Muscle biopsies were obtained at rest and 1, 2, and 3 h after the speed endurance exercise (S...... and S + E) and at rest, 0, 1, and 2 h after exercise in E In S and S + E, muscle peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1α) and pyruvate dehydrogenase kinase-4 (PDK4) mRNA were higher (P endurance exercise than at rest. Muscle PGC-1α and PDK4 m...

Impact of adrenaline and metabolic stress on exercise-induced intracellular signaling and PGC-1α mRNA response in human skeletal muscle

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Brandt, Nina; Gunnarsson, Thomas Gunnar Petursson; Hostrup, Morten

2016-01-01

This study tested the hypothesis that elevated plasma adrenaline or metabolic stress enhances exercise-induced PGC-1α mRNA and intracellular signaling in human muscle. Trained (VO2-max: 53.8 ± 1.8 mL min(-1) kg(-1)) male subjects completed four different exercise protocols (work load of the legs...... exercise than at rest in all protocols, and higher (P adrenaline nor muscle metabolic stress determines the magnitude of PGC-1α mRNA response in human muscle. Furthermore, higher exercise-induced changes in AMPK, p38, and CREB...

Single muscle fiber gene expression in human skeletal muscle: validation of internal control with exercise

International Nuclear Information System (INIS)

Jemiolo, Bozena; Trappe, Scott

2004-01-01

Reverse transcription and real-time PCR have become the method of choice for the detection of low-abundance mRNA transcripts obtained from small human muscle biopsy samples. GAPDH, β-actin, β-2M, and 18S rRNA are widely employed as endogenous control genes, with the assumption that their expression is unregulated and constant for given experimental conditions. The aim of this study was to determine if mRNA transcripts could be performed on isolated human single muscle fibers and to determine reliable housekeeping genes (HKGs) using quantitative gene expression protocols at rest and in response to an acute exercise bout. Muscle biopsies were obtained from the gastrocnemius of three adult males before, immediately after, and 4 h following 30 min of treadmill running at 70% of VO 2 max. A total of 40 single fibers (MHC I and IIa) were examined for GAPDH, β-actin, β-2M, and 18S rRNA using quantitative RT-PCR and SYBR Green detection. All analyzed single fiber segments showed ribosomal RNA (28S/18S). No degradation or additional bands below ribosomal were detected (rRNA ratio 1.5-1.8). Also, no high or low-molecular weight genomic DNA contamination was observed. For each housekeeping gene the duplicate average SD was ±0.13 with a CV of 0.58%. Stable expression of GAPDH was observed at all time points for each fiber type (MHC I and IIa). Inconsistent expression of β-actin, β-2M, and 18S rRNA was observed during the post-exercise time points for each fiber type. These data indicate that successful extraction of high quality RNA from human single muscle fibers along with quantification of mRNA of selected genes can be performed. Furthermore, exercise does influence the expression of certain HKGs with GAPDH being the most stable

Simultaneous 31P NMR spectroscopy and EMG in exercising and recovering human skeletal muscle: technical aspects

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Vestergaard-Poulsen, P; Thomsen, C; Sinkjaer, T

1994-01-01

The bioenergetics of human skeletal muscle can be studied by 31P NMR spectroscopy (31P-MRS) and by surface electromyography (SEMG). Simultaneous 31P-MRS and SEMG permit accurate and noninvasive studies of the correlation between metabolic and electrical changes in exercising and recovering human....... A nonmagnetic ergometer was used for ankle dorsiflexions that activated only the anterior tibial muscle as verified by post exercise imaging. The coil design and the adiabatic sech/tanh pulse improved sensitivity by 45% and 56% respectively, compared with standard techniques. Simultaneous electromyographic...... recordings did not deteriorate the NMR spectra. The VARPRO time domain fitting routine was very suitable for estimating 31P muscle spectra. With these methods it was possible to accurately estimate parameters describing metabolic and electrical changes during rest, exercise and the entire recovery period...

Woman skeletal muscle transcriptome with bed rest and countermeasures.

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National Aeronautics and Space Administration — Microgravity has a dramatic impact on human physiology illustrated in particular with skeletal muscle impairment. A thorough understanding of the mechanisms leading...

Collagen content in the vastus lateralis and the soleus muscle following a 90-day bed rest period with or without resistance exercises

DEFF Research Database (Denmark)

Nielsen, Rasmus Oestergaard; Schjerling, Peter; Tesch, Per

2015-01-01

training serves as a proxy for the conditions in space. Therefore, ground-based studies may improve the understanding of the consequences of long-term inactivity. PURPOSE: the purpose is to compare the change in collagen protein in the vastus lateralis (VL) and the soleus (SOL) muscle amongst persons......INTRODUCTION: spaceflight seems associated with deterioration of the function of the skeletal muscles. Since muscle collagen is critical for muscle function, an improved understanding of the content of the muscle collagen during long-term inactivity seems important. Bed-rest with in-bed resistance...... collagen/mg protein [95% CI: -25.6; 12.6], p=0.50). There was no difference in the effect of BR versus BRE over time (mean difference -2.78 μg collagen/mg protein [95% CI: -29.7; 24.1], p=0.82). CONCLUSION: muscle collagen content in the VL or SOL muscle does not seem to differ after a 90-day bed rest...

Pneumatic Artificial Muscles Based on Biomechanical Characteristics of Human Muscles

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N. Saga

2006-01-01

Full Text Available This article reports the pneumatic artificial muscles based on biomechanical characteristics of human muscles. A wearable device and a rehabilitation robot that assist a human muscle should have characteristics similar to those of human muscle. In addition, since the wearable device and the rehabilitation robot should be light, an actuator with a high power to weight ratio is needed. At present, the McKibben type is widely used as an artificial muscle, but in fact its physical model is highly nonlinear. Therefore, an artificial muscle actuator has been developed in which high-strength carbon fibres have been built into the silicone tube. However, its contraction rate is smaller than the actual biological muscles. On the other hand, if an artificial muscle that contracts axially is installed in a robot as compactly as the robot hand, big installing space is required. Therefore, an artificial muscle with a high contraction rate and a tendon-driven system as a compact actuator were developed, respectively. In this study, we report on the basic structure and basic characteristics of two types of actuators.

Repeated static contractions increase mitochondrial vulnerability toward oxidative stress in human skeletal muscle

DEFF Research Database (Denmark)

Sahlin, Kent; Nielsen, Jens Steen; Mogensen, Martin

2006-01-01

Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmic reticulum (SR) Ca(2......+) kinetics in human muscle. Ten male subjects performed five bouts of static knee extension with 10-min rest in between. Each bout of RSC (target torque 66% of maximal voluntary contraction torque) was maintained to fatigue. Muscle biopsies were taken preexercise and 0.3 and 24 h postexercise from vastus...... lateralis. Mitochondria were isolated and respiratory function measured after incubation with H(2)O(2) (HPX) or control medium (Con). Mitochondrial function was not affected by RSC during Con. However, RSC exacerbated mitochondrial dysfunction during HPX, resulting in decreased respiratory control index...

Effects of age and inactivity due to prolonged bed rest on atrophy of trunk muscles.

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Ikezoe, Tome; Mori, Natsuko; Nakamura, Masatoshi; Ichihashi, Noriaki

2012-01-01

This study investigated the effects of age and inactivity due to being chronically bedridden on atrophy of trunk muscles. The subjects comprised 33 young women (young group) and 41 elderly women who resided in nursing homes or chronic care institutions. The elderly subjects were divided into two groups: independent elderly group who were able to perform activities of daily living involving walking independently (n = 28) and dependent elderly group who were chronically bedridden (n = 13). The thickness of the following six trunk muscles was measured by B-mode ultrasound: the rectus abdominis, external oblique, internal oblique, transversus abdominis, thoracic erector spinae (longissimus) and lumbar multifidus muscles. All muscles except for the transversus abdominis and lumbar multifidus muscles were significantly thinner in the independent elderly group compared with those in the young group. The thicknesses of all muscles in the dependent elderly group was significantly smaller than that in the young group, whereas there were no differences between the dependent elderly and independent elderly groups in the muscle thicknesses of the rectus abdominis and internal oblique muscles. In conclusion, our results suggest that: (1) age-related atrophy compared with young women was less in the deep antigravity trunk muscles than the superficial muscles in the independent elderly women; (2) atrophy associated with chronic bed rest was more marked in the antigravity muscles, such as the back and transversus abdominis.

Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

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Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats Authors: Gary E. Hatch, John McKee, James Brown, Bill McDonnell, Elston Seal, Joleen Soukup, Ralph Slade, Kay Crissman and Robert Devlin, National Health and Environmental...

Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise

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Rodrigo Martins Pereira

2017-05-01

Full Text Available Abstract Glucose uptake is an important phenomenon for cell homeostasis and for organism health. Under resting conditions, skeletal muscle is dependent on insulin to promote glucose uptake.Insulin, after binding to its membrane receptor, triggers a cascade of intracellular reactions culminating in activation of the glucose transporter 4, GLUT4, among other outcomes.This transporter migrates to the plasma membrane and assists in glucose internalization.However, under special conditions such as physical exercise, alterations in the levels of intracellular molecules such as ATP and calcium actto regulate GLUT4 translocation and glucose uptake in skeletal muscle, regardless of insulinlevels.Regular physical exercise, due to stimulating pathways related to glucose uptake, is an important non-pharmacological intervention for improving glycemic control in obese and diabetic patients. In this mini-review the main mechanisms involved in glucose uptake in skeletal muscle in response to muscle contraction will be investigated.

Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes

DEFF Research Database (Denmark)

Zhao, Xiaolu; Leon, Ileana R; Bak, Steffen

2011-01-01

. In skeletal muscle, mitochondrial dysfunction is linked to insulin resistance in humans with obesity and type 2 diabetes. We performed a phosphoproteomic study of functional mitochondria isolated from human muscle biopsies with the aim to obtain a comprehensive overview of mitochondrial phosphoproteins...... in insulin resistance. We also assigned phosphorylation sites in mitochondrial proteins involved in amino acid degradation, importers and transporters, calcium homeostasis, and apoptosis. Bioinformatics analysis of kinase motifs revealed that many of these mitochondrial phosphoproteins are substrates....... Future comparative phosphoproteome analysis of mitochondria from healthy and diseased individuals will provide insights into the role of abnormal phosphorylation in pathologies, such as type 2 diabetes....

Recruitment of single human low-threshold motor units with increasing loads at different muscle lengths.

Science.gov (United States)

McNulty, P A; Cresswell, A G

2004-06-01

We investigated the recruitment behaviour of low threshold motor units in flexor digitorum superficialis by altering two biomechanical constraints: the load against which the muscle worked and the initial muscle length. The load was increased using isotonic (low load), loaded dynamic (intermediate load) and isometric (high load) contractions in two studies. The initial muscle position reflected resting muscle length in series A, and a longer length with digit III fully extended in series B. Intramuscular EMG was recorded from 48 single motor units in 10 experiments on five healthy subjects, 21 units in series A and 27 in series B, while subjects performed ramp up, hold and ramp down contractions. Increasing the load on the muscle decreased the force, displacement and firing rate of single motor units at recruitment at shorter muscle lengths (Precruitment pattern was observed between loaded dynamic and isotonic contractions, but not between isometric and loaded dynamic contractions. Thus, the recruitment properties of single motor units in human flexor digitorum superficialis are sensitive to changes in both imposed external loads and the initial length of the muscle.

Exercise countermeasures for bed-rest deconditioning

Science.gov (United States)

Greenleaf, John (Editor)

1993-01-01

The purpose for this 30-day bed rest study was to investigate the effects of short-term, high intensity isotonic and isokinetic exercise training on maintenance of working capacity (peak oxygen uptake), muscular strength and endurance, and on orthostatic tolerance, posture and gait. Other data were collected on muscle atrophy, bone mineralization and density, endocrine analyses concerning vasoactivity and fluid-electrolyte balance, muscle intermediary metabolism, and on performance and mood of the subjects. It was concluded that: The subjects maintained a relatively stable mood, high morale, and high esprit de corps throughout the study. Performance improved in nearly all tests in almost all the subjects. Isotonic training, as opposed to isokinetic exercise training, was associated more with decreasing levels of psychological tension, concentration, and motivation; and improvement in the quality of sleep. Working capacity (peak oxygen uptake) was maintained during bed rest with isotonic exercise training; it was not maintained with isokinetic or no exercise training. In general, there was no significant decrease in strength or endurance of arm or leg muscles during bed rest, in spite of some reduction in muscle size (atrophy) of some leg muscles. There was no effect of isotonic exercise training on orthostasis, since tilt-table tolerance was reduced similarly in all three groups following bed rest. Bed rest resulted in significant decreases of postural stability and self-selected step length, stride length, and walking velocity, which were not influenced by either exercise training regimen. Most pre-bed rest responses were restored by the fourth day of recovery.

The Artificial Gravity Bed Rest Pilot Project: Effects on Knee Extensor and Plantar Flexor Muscle Groups

Science.gov (United States)

Caiozzo, V. J.; Haddad, F.; Lee, S.; Baker, M.; Baldwin, K. M.

2007-01-01

The goal of this project was to examine the effects of artificial gravity (2.5 g) on skeletal muscle strength and key anabolic/catabolic markers known to regulate muscle mass. Two groups of subjects were selected for study: 1) a 21 day-bed rest (BR) control (C) group (N=7); and 2) an AG group (N=8), which was exposed to 21 days of bed-rest plus daily 1 hr exposures to AG (2.5 g). This particular experiment was part of an integrated AG Pilot Project sponsored by NASA/Johnson Space Center. The in vivo torque-velocity relationships of the knee extensors and plantar flexors of the ankle were determined pre and post treatment. Also, pre- and post treatment biopsy samples were obtained from both the vastus lateralis and soleus muscles and were used, in part, for a series of analyses on gene expression (mRNA abundance) of key factors implicated in the anabolic versus catabolic state of the muscle. Post/Pre toque-velocity determinations revealed greater decrements in knee extensor performance in the C versus AG group (P less than 0.04). The plantar flexor muscle group of the AG subjects actually demonstrated a net gain in torque-velocity relationship; whereas, in the C group the overall post/pre responses declined (AG vs C; P less than 0.001). Measurements of muscle fiber cross-sectional area (for both muscles) demonstrated a loss of approx. 20% in the C group while no losses were evident in the AG group. RT-PCR analyses of muscle biopsy specimens demonstrated that markers of growth and cytoskeletal integrity (IGF-1, IGF-1 BP4, mechano growth factor, total RNA, and pro-collagen 3a) were higher in the AG group, whereas catabolic markers (myostatin and atrogen) were elevated in the C group. Importantly, these patterns were seen in both muscles. Based on these observations we conclude that paradigms of AG have the potential to maintain the functional, biochemical, and structural homeostasis of skeletal muscle in the face of chronic unloading states. These findings also

Skeletal muscle PLIN3 and PLIN5 are serine phosphorylated at rest and following lipolysis during adrenergic or contractile stimulation

Science.gov (United States)

MacPherson, Rebecca E K; Vandenboom, Rene; Roy, Brian D; Peters, Sandra J

2013-01-01

In adipose tissue, access of adipose triglyceride and hormone-sensitive lipases (ATGL and HSL) to the lipid droplet depends on PLIN1 phosphorylation, however, PLIN1 is not expressed in skeletal muscle and the phosphorylation of the expressed PLINs has yet to be investigated. Further, direct interactions between skeletal muscle PLINs and HSL are unknown. We investigated the isolated and combined effects of epinephrine and contraction on PLIN-to-lipase interactions as well as phosphorylation. Isolated rat solei were assigned to one of four 30 min in vitro conditions (25°C): (1) rest; (2) intermittent tetanic stimulation (60 Hz for 150 msec; train rate 20/min); (3) 5 nmol/L epinephrine; (4) intermittent tetanic stimulation and 5 nmol/L epinephrine. Immunoprecipitation of serine phosphorylated proteins followed by Western blotting for PLIN2, PLIN3, PLIN5, revealed that only PLIN2 is not phosphorylated under any of the experimental conditions. This is the first study to show that in whole rat skeletal muscle PLIN3 and PLIN5 are serine phosphorylated. The degree of serine phosphorylation remained unchanged following adrenergic and/or contractile stimulation. Oil red O staining of muscle sections for lipid content shows a significant decrease following each condition, confirming lipolysis occurred (P < 0.05). PLIN2, 3, and 5 all interact with HSL and ATGL, but these interactions were unchanged following treatments. Our results show that in skeletal muscle, PLIN2 is not serine phosphorylated at rest or with lipolytic stimulation and that while PLIN3, PLIN5 are serine phosphorylated at rest, the degree of phosphorylation does not change with lipolytic stimulation. PMID:24303154

Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through microdialysis catheters in human skeletal muscle

DEFF Research Database (Denmark)

Mikkelsen, Ulla Ramer; Helmark, Ida Carøe; Kjaer, Michael

2008-01-01

of nonsteroidal anti-inflammatory drugs (NSAIDs). However, to study the local role of prostaglandins, the formation of prostaglandins within the tissue must be controlled. Microdialysis enables determination of local concentrations of water-soluble substances within the tissue. In the present study......, the microdialysis method was used to infuse NSAIDs locally into human skeletal muscles producing a local block of prostaglandin formation. In addition, the graded blockade at various distances from the infusion site within the muscle during rest, exercise and recovery was determined. Microdialysis was performed...... in thigh muscles (vastus lateralis muscle) in six healthy men. One of the microdialysis catheters was used to block prostaglandin synthesis by infusion of the NSAID indomethacin. Additional catheters were placed 1 and 4 cm away from the infusion and in the contralateral leg (working control). Following 2 h...

Muscle metabolism from near infrared spectroscopy during rhythmic handgrip in humans

DEFF Research Database (Denmark)

Boushel, Robert Christopher; Pott, F; Madsen, P

1998-01-01

The rate of metabolism in forearm flexor muscles (MO2) was derived from near-infrared spectroscopy (NIRS-O2) during ischaemia at rest rhythmic handgrip at 15% and 30% of maximal voluntary contraction (MVC), post-exercise muscle ischaemia (PEMI), and recovery in seven subjects. The MO2 was compared...

Satellite cells in human skeletal muscle plasticity

Directory of Open Access Journals (Sweden)

Tim eSnijders

2015-10-01

Full Text Available Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodelling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodelling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodelling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

Satellite cells in human skeletal muscle plasticity.

Science.gov (United States)

Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

2015-01-01

Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

Human skeletal muscle releases leptin in vivo

DEFF Research Database (Denmark)

Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

2012-01-01

Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...

Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to insulin sensitivity and respond to acute exercise in humans.

Science.gov (United States)

Newsom, Sean A; Brozinick, Joseph T; Kiseljak-Vassiliades, Katja; Strauss, Allison N; Bacon, Samantha D; Kerege, Anna A; Bui, Hai Hoang; Sanders, Phil; Siddall, Parker; Wei, Tao; Thomas, Melissa; Kuo, Ming Shang; Nemkov, Travis; D'Alessandro, Angelo; Hansen, Kirk C; Perreault, Leigh; Bergman, Bryan C

2016-06-01

Several recent reports indicate that the balance of skeletal muscle phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant of muscle contractile function and metabolism. The purpose of this study was to determine relationships between skeletal muscle PC, PE and insulin sensitivity, and whether PC and PE are dynamically regulated in response to acute exercise in humans. Insulin sensitivity was measured via intravenous glucose tolerance in sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n = 15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle biopsies were obtained at rest, immediately after 90 min of cycle ergometry at 50% maximal oxygen consumption (V̇o2 max), and 2-h postexercise (recovery). Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass spectrometry analysis. ATH had greater levels of muscle PC and PE compared with OB and T2D (P insulin sensitivity (both P insulin sensitivity among the entire cohort (r = -0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE ratio remained unchanged in all groups. In summary, total muscle PC and PE are positively related to insulin sensitivity while PC:PE ratio is inversely related to insulin sensitivity in humans. A single session of exercise significantly alters skeletal muscle PC and PE levels, but not PC:PE ratio. Copyright © 2016 the American Physiological Society.

Comparison of GLUT1, GLUT3, and GLUT4 mRNA and the subcellular distribution of their proteins in normal human muscle

Science.gov (United States)

Stuart, C. A.; Wen, G.; Gustafson, W. C.; Thompson, E. A.

2000-01-01

Basal, "insulin-independent" glucose uptake into skeletal muscle is provided by glucose transporters positioned at the plasma membrane. The relative amount of the three glucose transporters expressed in muscle has not been previously quantified. Using a combination of qualitative and quantitative ribonuclease protection assay (RPA) methods, we found in normal human muscle that GLUT1, GLUT3, and GLUT4 mRNA were expressed at 90 +/- 10, 46 +/- 4, and 156 +/- 12 copies/ng RNA, respectively. Muscle was fractionated by DNase digestion and differential sedimentation into membrane fractions enriched in plasma membranes (PM) or low-density microsomes (LDM). GLUT1 and GLUT4 proteins were distributed 57% to 67% in LDM, whereas GLUT3 protein was at least 88% in the PM-enriched fractions. These data suggest that basal glucose uptake into resting human muscle could be provided in part by each of these three isoforms.

Human skeletal muscle fibroblasts stimulate in vitro myogenesis and in vivo muscle regeneration.

Science.gov (United States)

Mackey, Abigail L; Magnan, Mélanie; Chazaud, Bénédicte; Kjaer, Michael

2017-08-01

Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. The extent of cross-talk between fibroblasts, as the source of matrix protein, and satellite cells in humans is unknown. We studied this in human muscle biopsies and cell-culture studies. We observed a strong stimulation of myogenesis by human fibroblasts in cell culture. In biopsies collected 30 days after a muscle injury protocol, fibroblast number increased to four times control levels, where fibroblasts were found to be preferentially located immediately surrounding regenerating muscle fibres. These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell-cell cross-talk during physiological and pathological muscle remodelling. Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration, there is emerging evidence in rodents for a regulatory influence on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle injury protocol in young healthy men (n = 7), the number of fibroblasts (TCF7L2+), satellite cells (Pax7+), differentiating myogenic cells (myogenin+) and regenerating fibres (neonatal/embryonic myosin+) was determined from biopsy cross-sections. Fibroblasts and myogenic precursor cells (MPCs) were also isolated from human skeletal muscle (n = 4) and co-cultured using different cell ratios, with the two cell populations either in direct contact with each other or separated by a permeable

Human skeletal muscle fibroblasts stimulate in vitro myogenesis and in vivo muscle regeneration

DEFF Research Database (Denmark)

Mackey, Abigail L; Magnan, Mélanie; Chazaud, Bénédicte

2017-01-01

immediately surrounding regenerating muscle fibres. These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell-cell cross......-talk during physiological and pathological muscle remodelling. ABSTRACT: Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration......, there is emerging evidence in rodents for a regulatory influence on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle...

Contraction-induced increases in Na+-K+-ATPase mRNA levels in human skeletal muscle are not amplified by activation of additional muscle mass

DEFF Research Database (Denmark)

Nordsborg, Nikolai; Thomassen, Martin; Lundby, Carsten

2005-01-01

The present study tested the hypothesis that exercise with a large compared with a small active muscle mass results in a higher contraction-induced increase in Na+-K+-ATPase mRNA expression due to greater hormonal responses. Furthermore, the relative abundance of Na+-K+-ATPase subunit a1, a2, a3, a......% of the a2 expression, and no reliable detection of a3 and a4 was possible. In conclusion, activation of additional muscle mass does not result in a higher exercise-induced increase in Na+-K+-ATPase subunit-specific mRNA.......4, ß1, ß2, and ß3 mRNA in human skeletal muscle was investigated. On two occasions, eight subjects performed one-legged knee extension exercise (L) or combined one-legged knee extension and bilateral arm cranking (AL) for 5.00, 4.25, 3.50, 2.75, and 2.00 min separated by 3 min of rest. Leg exercise...

Regenerating human muscle fibres express GLUT3 protein

DEFF Research Database (Denmark)

Gaster, M; Beck-Nielsen, H; Schrøder, H D

2002-01-01

The presence of the GLUT3 glucose transporter protein in human muscle cells is a matter of debate. The present study was designed to establish whether GLUT3 is expressed in mature human skeletal muscle fibres and, if so, whether its expression changes under different conditions, such as metabolic...... muscle fibres, nor did metabolic stress, training or de- and re-innervation induce GLUT3 expression, while a few GLUT3 expressing fibres were seen in some cases of polymyositis. In contrast, GLUT4 was expressed in all investigated muscle fibres. GLUT3 immunoreactivity was found in perineural...... and endoneural cells, indicating that GLUT3 is important for glucose transport into nerves through the perineurium. Taken together, these data suggest that GLUT3 expression is restricted to regenerating muscle fibres and nerves in adult human muscle. Although the significance of GLUT3 in adult human muscle...

Aerobic metabolism of human quadriceps muscle: in vivo data parallel measurements on isolated mitochondria

DEFF Research Database (Denmark)

Rasmussen, U.F.; Rasmussen, H.N.; Krustrup, Peter

2001-01-01

The aim of the present study was to examine whether parameters of isolated mitochondria could account for the in vivo maximum oxygen uptake ( O2 max) of human skeletal muscle. O2 max and work performance of the quadriceps muscle of six volunteers were measured in the knee extensor model (range 10......-18 mmol O2 · min 1 · kg 1 at work rates of 22-32 W/kg). Mitochondria were isolated from the same muscle at rest. Strong correlations were obtained between O2 max and a number of mitochondrial parameters (mitochondrial protein, cytochrome aa3, citrate synthase, and respiratory activities). The activities...... of citrate synthase, succinate dehydrogenase, and pyruvate dehydrogenase, measured in isolated mitochondria, corresponded to, respectively, 15, 3, and 1.1 times the rates calculated from O2 max. The respiratory chain activity also appeared sufficient. Fully coupled in vitro respiration, which is limited...

Changes in Oxidative Stress Markers and Biological Markers of Muscle Injury with Aging at Rest and in Response to an Exhaustive Exercise

Science.gov (United States)

Bouzid, Mohamed Amine; Hammouda, Omar; Matran, Regis; Robin, Sophie; Fabre, Claudine

2014-01-01

Purpose The aim of this study was to evaluate whether oxidative stress markers and biomarkers of muscle injury would be affected by aging at rest and in response to an incremental exhaustive exercise. Methods Fifteen young (20.3±2.8 years) and fifteen older adults (65.1±3.5 years) performed an incremental cycle ergometer test to exhaustion. Before and after exercise, oxidative stress [superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), ascorbic acid, α-Tocopherol, malondialdehyde (MDA)] and muscle injury [creatine kinase (CK), lactate deshydrogenase (LDH)] biomarkers were assessed. Results At rest, there was no difference in oxidative stress markers and LDH level between the groups, however CK was significantly higher in the young group than the elderly group (pantioxidant efficiency and an increase in oxidative stress damage. Furthermore, older adults would not more susceptible to exercise-induced muscle injury than young people. PMID:24618679

Biomarkers of Dose and Effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

Science.gov (United States)

Background: Human controlled exposure studies have generally focused on subjects exposed to ozone (O3) while exercising while exposures in rats have been done at rest. We exposed resting subjects to labeled O3 (18O3, 0.4 ppm, for 2 hr) and compared O3 dose and effects with our...

Exercise increases TBC1D1 phosphorylation in human skeletal muscle

Science.gov (United States)

Jessen, Niels; An, Ding; Lihn, Aina S.; Nygren, Jonas; Hirshman, Michael F.; Thorell, Anders

2011-01-01

Exercise and weight loss are cornerstones in the treatment and prevention of type 2 diabetes, and both interventions function to increase insulin sensitivity and glucose uptake into skeletal muscle. Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1. Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation. In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood. In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle. Ten obese (BMI 33.4 ± 2.4, M-value 4.3 ± 0.5) subjects were studied at baseline and after a 2-wk dietary intervention. Muscle biopsies were obtained from the subjects in the resting (basal) state and immediately following a 30-min exercise bout (70% V̇o2 max). Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser711 (AMPK), TBC1D1 Ser231 (AMPK), TBC1D1 Ser660 (AMPK), TBC1D1 Ser700 (AMPK), and TBC1D1 Thr590 (Akt). The diet intervention that consisted of a major shift in the macronutrient composition resulted in a 4.2 ± 0.4 kg weight loss (P < 0.001) and a significant increase in insulin sensitivity (M value 5.6 ± 0.6), but surprisingly, there was no effect on expression or phosphorylation of any of the muscle-signaling proteins. Exercise increased muscle AMPKα2 activity but did not increase Akt phosphorylation. Exercise increased phosphorylation on AS160 Ser711, TBC1D1 Ser231, and TBC1D1 Ser660 but had no effect on TBC1D1 Ser700. Exercise did not increase TBC1D1 Thr590 phosphorylation or TBC1D1/AS160 PAS

Supersonic shear imaging provides a reliable measurement of resting muscle shear elastic modulus

International Nuclear Information System (INIS)

Lacourpaille, Lilian; Hug, François; Bouillard, Killian; Nordez, Antoine; Hogrel, Jean-Yves

2012-01-01

The aim of the present study was to assess the reliability of shear elastic modulus measurements performed using supersonic shear imaging (SSI) in nine resting muscles (i.e. gastrocnemius medialis, tibialis anterior, vastus lateralis, rectus femoris, triceps brachii, biceps brachii, brachioradialis, adductor pollicis obliquus and abductor digiti minimi) of different architectures and typologies. Thirty healthy subjects were randomly assigned to the intra-session reliability (n = 20), inter-day reliability (n = 21) and the inter-observer reliability (n = 16) experiments. Muscle shear elastic modulus ranged from 2.99 (gastrocnemius medialis) to 4.50 kPa (adductor digiti minimi and tibialis anterior). On the whole, very good reliability was observed, with a coefficient of variation (CV) ranging from 4.6% to 8%, except for the inter-operator reliability of adductor pollicis obliquus (CV = 11.5%). The intraclass correlation coefficients were good (0.871 ± 0.045 for the intra-session reliability, 0.815 ± 0.065 for the inter-day reliability and 0.709 ± 0.141 for the inter-observer reliability). Both the reliability and the ease of use of SSI make it a potentially interesting technique that would be of benefit to fundamental, applied and clinical research projects that need an accurate assessment of muscle mechanical properties. (note)

Oxidation of urate in human skeletal muscle during exercise

DEFF Research Database (Denmark)

Hellsten, Ylva; Tullson, P. C.; Richter, Erik

1997-01-01

the level was more than twofold higher and remained elevated throughout recovery (p exercise, probably due to generation of free radicals. Furthermore, the findings support the suggested importance of urate......The purpose of the present study was to investigate whether high metabolic stress to skeletal muscle, induced by intensive exercise, would lead to an oxidation of urate to allantoin in the exercised muscle. Seven healthy male subjects performed short term (4.39 +/- 0.04 [+/-SE] min) exhaustive...... cycling exercise. Muscle samples were obtained from m. v. lateralis before and during the first few minutes after the exercise. Venous blood samples were obtained before and up to 45 min after the exercise. The concentration of urate in muscle decreased from a resting level of 0.26 +/- 0.023 to 0...

Regulation of PDH, GS and insulin signalling in skeletal muscle

DEFF Research Database (Denmark)

Biensø, Rasmus Sjørup

of inflammation on resting and exercise-induced PDH regulation in human skeletal muscle and 4) The effect of IL-6 on PDH regulation in mouse skeletal muscle. Study I demonstrated that bed rest–induced insulin resistance was associated with reduced insulinstimulated GS activity and Akt signaling as well...

Glucose transporter expression in human skeletal muscle fibers

DEFF Research Database (Denmark)

Gaster, M; Handberg, A; Beck-Nielsen, H

2000-01-01

, but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas...... after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle...... amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation...

Electromyographic evaluation of high-intensity elastic resistance exercises for lower extremity muscles during bed rest

DEFF Research Database (Denmark)

Vinstrup, Jonas; Skals, Sebastian; Calatayud, Joaquin

2017-01-01

PURPOSE: Prolonged hospital bed rest after severe injury or disease leads to rapid muscle atrophy and strength loss. Therefore, the main aim of this study was to evaluate the efficacy of lower extremity strengthening exercises using elastic resistance that can be performed while lying in a hospit......, the present study has the potential to provide a reference table of exercises to select from when individualizing and progressing strengthening exercises during the early rehabilitation of bedridden individuals....

Age-related differences in the response of leg muscle cross-sectional area and water diffusivity measures to a period of supine rest.

Science.gov (United States)

Lorbergs, Amanda L; Noseworthy, Michael D; MacIntyre, Norma J

2015-06-01

The object was to assess whether cross-sectional area (CSA) and water diffusion properties of leg muscles in young and older women change with increased time spent in supine rest. Healthy young (n = 9, aged 20-30 years) and older (n = 9, aged 65-75 years) women underwent MRI scanning of the right leg at baseline, 30 and 60 min of supine rest. Muscle CSA was derived from proton density images. Water diffusion properties [apparent diffusion coefficient (ADC) and fractional anisotropy (FA)] of the tibialis anterior and posterior, soleus, and medial and lateral heads of the gastrocnemius were derived from diffusion tensor imaging (DTI). Repeated measures ANOVAs and Bonferroni post hoc tests determined the effects of time and group on each muscle outcome. In both groups, muscle CSA and FA did not significantly change over time, whereas ADC significantly decreased. A greater decline at 30 min for young women was only observed for ADC in the medial gastrocnemius. Regardless of age, ADC values decreased with fluid shift associated with time spent supine, whereas CSA and FA were not affected. For leg muscle assessment in young and older women, DTI scanning protocols should consider the amount of time spent in a recumbent position.

The effect of physical and psychosocial loads on the trapezius muscle activity during computer keying tasks and rest periods

DEFF Research Database (Denmark)

Blangsted, Anne Katrine; Søgaard, Karen; Christensen, Hanne

2004-01-01

hand keying task-interspaced with short (30 s) and long (4 min) breaks-in sessions with and without a combination of cognitive and emotional stressors. Adding psychosocial loads to the same physical work did not increase the activity of the trapezius muscle on either the keying or the control side......The overall aim was to investigate the effect of psychosocial loads on trapezius muscle activity during computer keying work and during short and long breaks. In 12 female subjects, surface electromyography (EMG) was recorded bilaterally from the upper trapezius muscle during a standardized one...... resting level. During both short and long breaks, exposure to psychosocial loads also did not increase the activity of the trapezius muscle either on the side of the keying or the control hand. Of note is that during long breaks the muscle activity of the keying side as well as that of the control side...

Phosphocreatine recovery overshoot after high intensity exercise in human skeletal muscle is associated with extensive muscle acidification and a significant decrease in phosphorylation potential.

Science.gov (United States)

Zoladz, Jerzy A; Korzeniewski, Bernard; Kulinowski, Piotr; Zapart-Bukowska, Justyna; Majerczak, Joanna; Jasiński, Andrzej

2010-09-01

The phosphocreatine (PCr) recovery overshoot in skeletal muscle is a transient increase of PCr concentration above the resting level after termination of exercise. In the present study [PCr], [ATP], [P(i)] and pH were measured in calf muscle during rest, during plantar flexion exercise until exhaustion and recovery, using the (31)P NMR spectroscopy. A significantly greater acidification of muscle cells and significantly lower phosphorylation potential (DeltaG (ATP)) at the end of exercise was encountered in the group of subjects that evidenced the [PCr] overshoot as well as [ADP] and [P(i)] undershoots than in the group that did not. We postulate that the role of the PCr overshoot-related transiently elevated [ATP]/[ADP(free)] ratio is to activate different processes (including protein synthesis) that participate in repairing numerous damages of the muscle cells caused by intensive exercise-induced stressing factors, such as extensive muscle acidification, a significant decrease in DeltaG (ATP), an elevated level of reactive oxygen species or mechanical disturbances.

Coordinated collagen and muscle protein synthesis in human patella tendon and quadriceps muscle after exercise

DEFF Research Database (Denmark)

Miller, Benjamin F; Olesen, Jens L; Hansen, Mette

2005-01-01

We hypothesized that an acute bout of strenuous, non-damaging exercise would increase rates of protein synthesis of collagen in tendon and skeletal muscle but these would be less than those of muscle myofibrillar and sarcoplasmic proteins. Two groups (n = 8 and 6) of healthy young men were studied...... collagen (0.077% h(-1)), muscle collagen (0.054% h(-1)), myofibrillar protein (0.121% h(-1)), and sarcoplasmic protein (0.134% h(-1))). The rates decreased toward basal values by 72 h although rates of tendon collagen and myofibrillar protein synthesis remained elevated. There was no tissue damage...... of muscle visible on histological evaluation. Neither tissue microdialysate nor serum concentrations of IGF-I and IGF binding proteins (IGFBP-3 and IGFBP-4) or procollagen type I N-terminal propeptide changed from resting values. Thus, there is a rapid increase in collagen synthesis after strenuous exercise...

Muscle metaboreflex and autonomic regulation of heart rate in humans

DEFF Research Database (Denmark)

Fisher, James P; Adlan, Ahmed M; Shantsila, Alena

2013-01-01

) conditions, but attenuated with β-adrenergic blockade (0.2 ± 1 beats min(-1); P > 0.05 vs. rest). Thus muscle metaboreflex activation-mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg......We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi-lateral thigh cuff inflation) during leg cycling...... exercise, (2) isolated muscle metaboreflex activation (post-exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), β1-adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR...

Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise

DEFF Research Database (Denmark)

Pilegaard, Henriette; Osada, Takuya; Andersen, Lisbeth Tingsted

2005-01-01

before exercise and 2, 5, 8, and 24 hours after exercise. Muscle glycogen was restored to near resting levels within 5 hours in the HC trial, but remained depressed through 24 hours in the LC trial. During the 2- to 8-hour recovery period, leg glucose uptake was 5- to 15-fold higher with HC ingestion......In skeletal muscle of humans, transcription of several metabolic genes is transiently induced during recovery from exercise when no food is consumed. To determine the potential influence of substrate availability on the transcriptional regulation of metabolic genes during recovery from exercise, 9...... male subjects (aged 22-27) completed 75 minutes of cycling exercise at 75% V¿o2max on 2 occasions, consuming either a high-carbohydrate (HC) or low-carbohydrate (LC) diet during the subsequent 24 hours of recovery. Nuclei were isolated and tissue frozen from vastus lateralis muscle biopsies obtained...

Ammonia uptake in inactive muscles during exercise in humans

DEFF Research Database (Denmark)

Bangsbo, Jens; Kiens, Bente; Richter, Erik

1996-01-01

The present study examined NH3 (ammonia and ammonium) uptake in resting leg muscle. Six male subjects performed intermittent arm exercise at various intensities in two separate 32-min periods (part I and part II) and in one subsequent 20-min period in which one-legged exercise was also performed ...

Pronounced effects of accute endurance exercise on gene expression in resting and exercising human skeletal muscle

NARCIS (Netherlands)

Catoire, M.; Mensink, M.R.; Boekschoten, M.V.; Hangelbroek, R.W.J.; Muller, M.R.; Schrauwen, P.; Kersten, A.H.

2012-01-01

Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated

Src-family kinases negatively regulate NFAT signaling in resting human T cells.

Directory of Open Access Journals (Sweden)

Alan Baer

Full Text Available T cell signaling is required for activation of both natural and therapeutic T cells including chimeric antigen receptor (CAR T cells. Identification of novel factors and pathways regulating T cell signaling may aid in development of effective T cell therapies. In resting human T cells, the majority of Src-family of tyrosine kinases (SFKs are inactive due to phosphorylation of a conserved carboxy-terminal tyrosine residue. Recently, a pool of enzymatically active SFKs has been identified in resting T cells; however, the significance of these is incompletely understood. Here, we characterized the role of active SFKs in resting human T cells. Pharmacologic inhibition of active SFKs enhanced distal TCR signaling as measured by IL-2 release and CD25 surface expression following TCR-independent activation. Mechanistically, inhibition of the active pool of SFKs induced nuclear translocation of NFAT1, and enhanced NFAT1-dependent signaling in resting T cells. The negative regulation of NFAT1 signaling was in part mediated by the Src-kinase Lck as human T cells lacking Lck had increased levels of nuclear NFAT1 and demonstrated enhanced NFAT1-dependent gene expression. Inhibition of active SFKs in resting primary human T cells also increased nuclear NFAT1 and enhanced NFAT1-dependent signaling. Finally, the calcineurin inhibitor FK506 and Cyclosporin A reversed the effect of SFKs inhibition on NFAT1. Together, these data identified a novel role of SFKs in preventing aberrant NFAT1 activation in resting T cells, and suggest that maintaining this pool of active SFKs in therapeutic T cells may increase the efficacy of T cell therapies.

Soy-dairy protein blend and whey protein ingestion after resistance exercise increases amino acid transport and transporter expression in human skeletal muscle

Science.gov (United States)

Reidy, P. T.; Walker, D. K.; Dickinson, J. M.; Gundermann, D. M.; Drummond, M. J.; Timmerman, K. L.; Cope, M. B.; Mukherjea, R.; Jennings, K.; Volpi, E.

2014-01-01

Increasing amino acid availability (via infusion or ingestion) at rest or postexercise enhances amino acid transport into human skeletal muscle. It is unknown whether alterations in amino acid availability, from ingesting different dietary proteins, can enhance amino acid transport rates and amino acid transporter (AAT) mRNA expression. We hypothesized that the prolonged hyperaminoacidemia from ingesting a blend of proteins with different digestion rates postexercise would enhance amino acid transport into muscle and AAT expression compared with the ingestion of a rapidly digested protein. In a double-blind, randomized clinical trial, we studied 16 young adults at rest and after acute resistance exercise coupled with postexercise (1 h) ingestion of either a (soy-dairy) protein blend or whey protein. Phenylalanine net balance and transport rate into skeletal muscle were measured using stable isotopic methods in combination with femoral arteriovenous blood sampling and muscle biopsies obtained at rest and 3 and 5 h postexercise. Phenylalanine transport into muscle and mRNA expression of select AATs [system L amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, system A amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, cationic amino acid transporter 1/SLC7A1] increased to a similar extent in both groups (P protein blend resulted in a prolonged and positive net phenylalanine balance during postexercise recovery compared with whey protein (P protein synthesis increased similarly between groups. We conclude that, while both protein sources enhanced postexercise AAT expression, transport into muscle, and myofibrillar protein synthesis, postexercise ingestion of a protein blend results in a slightly prolonged net amino acid balance across the leg compared with whey protein. PMID:24699854

Esterase profile of human masseter muscle

DEFF Research Database (Denmark)

Kirkeby, S; Moe, D; Vilmann, H

1988-01-01

The esterase profile of fresh human masseter muscle was investigated by use of histochemistry and electrophoresis. The histochemical methods included reactions for alpha-naphthyl esterase, myofibrillar ATPase, reverse myofibrillar ATPase and succinic dehydrogenase. In frozen sections of the muscle...... the coloured reaction product for esterases was present both as a diffuse sarcoplasmic coloration and as distinct granules. The intensity of diffuse reaction was used to classify the muscle fibres as strongly, moderately and weakly reacting. The fibres with strong esterase activity belonged to Type I and ii......C. iM and Type II A fibres showed a moderate esterase reaction and Type II B fibres had a low activity. The electrophoretic gels stained for esterase activity showed that the human masseter muscle possesses a slow migrating double band with high enzyme activity and a cascade of faster migrating...

Comparison of in vivo postexercise phosphocreatine recovery and resting ATP synthesis flux for the assessment of skeletal muscle mitochondrial function

NARCIS (Netherlands)

Broek, van den N.M.A.; Ciapaite, J.; Nicolay, K.; Prompers, J.J.

2010-01-01

31P magnetic resonance spectroscopy (MRS) has been used to assess skeletal muscle mitochondrial function in vivo by measuring 1) phosphocreatine (PCr) recovery after exercise or 2) resting ATP synthesis flux with saturation transfer (ST). In this study, we compared both parameters in a rat model of

Trichinella spiralis in human muscle (image)

Science.gov (United States)

This is the parasite Trichinella spiralis in human muscle tissue. The parasite is transmitted by eating undercooked meats, especially pork. The cysts hatch in the intestines and produce large numbers of larvae that migrate into muscle tissue. The cysts ...

Protein translation, proteolysis and autophagy in human skeletal muscle atrophy after spinal cord injury.

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Lundell, L S; Savikj, M; Kostovski, E; Iversen, P O; Zierath, J R; Krook, A; Chibalin, A V; Widegren, U

2018-02-08

Spinal cord injury-induced loss of skeletal muscle mass does not progress linearly. In humans, peak muscle loss occurs during the first 6 weeks postinjury, and gradually continues thereafter. The aim of this study was to delineate the regulatory events underlying skeletal muscle atrophy during the first year following spinal cord injury. Key translational, autophagic and proteolytic proteins were analysed by immunoblotting of human vastus lateralis muscle obtained 1, 3 and 12 months following spinal cord injury. Age-matched able-bodied control subjects were also studied. Several downstream targets of Akt signalling decreased after spinal cord injury in skeletal muscle, without changes in resting Akt Ser 473 and Akt Thr 308 phosphorylation or total Akt protein. Abundance of mTOR protein and mTOR Ser 2448 phosphorylation, as well as FOXO1 Ser 256 phosphorylation and FOXO3 protein, decreased in response to spinal cord injury, coincident with attenuated protein abundance of E3 ubiquitin ligases, MuRF1 and MAFbx. S6 protein and Ser 235/236 phosphorylation, as well as 4E-BP1 Thr 37/46 phosphorylation, increased transiently after spinal cord injury, indicating higher levels of protein translation early after injury. Protein abundance of LC3-I and LC3-II decreased 3 months postinjury as compared with 1 month postinjury, but not compared to able-bodied control subjects, indicating lower levels of autophagy. Proteins regulating proteasomal degradation were stably increased in response to spinal cord injury. Together, these data provide indirect evidence suggesting that protein translation and autophagy transiently increase, while whole proteolysis remains stably higher in skeletal muscle within the first year after spinal cord injury. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Giometti, C.S. (Argonne National Lab., IL); Barany, M.; Danon, M.J.; Anderson, N.G.

1980-07-01

High-resolution two-dimensional electrophoresis was used to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.

Effect of exercise and recovery on muscle protein synthesis in human subjects

International Nuclear Information System (INIS)

Carraro, F.; Stuart, C.A.; Hartl, W.H.; Rosenblatt, J.; Wolfe, R.R.

1990-01-01

Previous studies using indirect means to assess the response of protein metabolism to exercise have led to conflicting conclusions. Therefore, in this study we have measured the rate of muscle protein synthesis in normal volunteers at rest, at the end of 4 h of aerobic exercise (40% maximal O2 consumption), and after 4 h of recovery by determining directly the rate of incorporation of 1,2-[13C]leucine into muscle. The rate of muscle protein breakdown was assessed by 3-methylhistidine (3-MH) excretion, and total urinary nitrogen excretion was also measured. There was an insignificant increase in 3-MH excretion in exercise of 37% and a significant increase (P less than 0.05) of 85% during 4 h of recovery from exercise (0.079 +/- 0.008 vs. 0.147 +/- 0.0338 mumol.kg-1.min-1 for rest and recovery from exercise, respectively). Nonetheless, there was no effect of exercise on total nitrogen excretion. Muscle fractional synthetic rate was not different in the exercise vs. the control group at the end of exercise (0.0417 +/- 0.004 vs. 0.0477 +/- 0.010%/h for exercise vs. control), but there was a significant increase in fractional synthetic rate in the exercise group during the recovery period (0.0821 +/- 0.006 vs. 0.0654 +/- 0.012%/h for exercise vs. control, P less than 0.05). Thus we conclude that although aerobic exercise may stimulate muscle protein breakdown, this does not result in a significant depletion of muscle mass because muscle protein synthesis is stimulated in recovery

Performance comparison of the MOXY and PortaMon near-infrared spectroscopy muscle oximeters at rest and during exercise

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McManus, Chris J.; Collison, Jay; Cooper, Chris E.

2018-01-01

The purpose of the study was to compare muscle oxygenation as measured by two portable, wireless near-infrared spectroscopy (NIRS) devices under resting and dynamic conditions. A recently developed low-cost NIRS device (MOXY) was compared against an established PortaMon system that makes use of the spatially resolved spectroscopy algorithm. The influence of increasing external pressure on tissue oxygen saturation index (TSI) indicated that both devices are stable between 2 and 20 mmHg. However, above this pressure, MOXY reports declining TSI values. Analysis of adipose tissue thickness (ATT) and TSI shows a significant, nonlinear difference between devices at rest. The devices report similar TSI (%) values at a low ATT (major subsequent change between the devices occurring between 7 and 10 mm at ATT values >10 mm the difference remains constant (-14.7±2.8%). The most likely explanation for this difference is the small source-detector separation (2.5 cm) in the MOXY resulting in lower tissue penetration into muscle in subjects with higher ATT. Interday test-retest reliability of resting TSI was evaluated on five separate occasions, with the PortaMon reporting a lower coefficient of variation (1.8% to 2.5% versus 5.7% to 6.2%). In studies on male subjects with low ATT, decreases in the TSI were strongly correlated during isometric exercise, arterial occlusion, and incremental arm crank exercise. However, the MOXY reports a greater dynamic range, particularly during ischemia induced by isometric contraction or occlusion (Δ74.3% versus Δ43.7% hyperemia MAX-occlusion MIN). This study shows that in this subject group both MOXY and PortaMon produce physiologically credible TSI measures during rest and exercise. However, the absolute values obtained during exercise are generally not comparable between devices unless corrected by physiological calibration following an arterial occlusion.

Contribution of proton leak to oxygen consumption in skeletal muscle during intense exercise is very low despite large contribution at rest.

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Bernard Korzeniewski

Full Text Available A computer model was used to simulate the dependence of protonmotive force (Δp, proton leak and phenomenological (involving proton leak ATP/O2 ratio on work intensity in skeletal muscle. Δp, NADH and proton leak decreased with work intensity. The contribution of proton leak to oxygen consumption ([Formula: see text] decreased from about 60% at rest to about 3 and 1% at moderate and heavy/severe exercise, respectively, while the ATP/O2 ratio increased from 2.1 to 5.5 and 5.7. A two-fold increase in proton leak activity or its decrease to zero decreased/increased the ATP/O2 ratio by only about 3 and 1% during moderate and heavy/severe exercise, respectively. The low contribution of proton leak to [Formula: see text] in intensively working skeletal muscle was mostly caused by a huge increase in ATP usage intensity during rest-to-work transition, while OXPHOS, and thus oxidative ATP supply and [Formula: see text] related to it, was mostly stimulated by high each-step activation (ESA of OXPHOS complexes. The contribution of proton leak to [Formula: see text] and ATP/O2 ratio in isolated mitochondria should not be directly extrapolated to working muscle, as mitochondria lack ESA, at least in the absence of Ca2+, and therefore [Formula: see text] cannot be elevated as much as in intact muscle.

Hypoxic responses in resting hyperthermic humans

OpenAIRE

Curtis, Andrew

2005-01-01

This thesis investigated the interaction between steady state hypoxia and passive hyperthermia on human ventilation and the influence of the PETCO2 on this interaction. On one of two days males twice breathed 12% oxygen for 20 min while either normothermic or hyperthermic with PETCO2 clamped -1 mm Hg above resting (iHVR). On the other day the same tests were performed except P&02 was uncontrolled (pHVR). Hyperthermia increased euoxic ventilation compared to normothermia (plO.OO1). During ...

Anabolic resistance assessed by oral stable isotope ingestion following bed rest in young and older adult volunteers: Relationships with changes in muscle mass.

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Biolo, Gianni; Pišot, Rado; Mazzucco, Sara; Di Girolamo, Filippo Giorgio; Situlin, Roberta; Lazzer, Stefano; Grassi, Bruno; Reggiani, Carlo; Passaro, Angelina; Rittweger, Joern; Gasparini, Mladen; Šimunič, Boštjan; Narici, Marco

2017-10-01

Aging and experimental bed rest are associated with muscle atrophy and resistance to post-prandial stimulation of protein synthesis or anabolic resistance (AR). We have used in young and older adult volunteers, during short-term bed rest, a quick and non-invasive method, based on a single oral bolus of the stable isotope L[ring- 2 H 5 ]phenylalanine (D 5 Phe), to determine post-prandial AR, defined as ratio between irreversible hydroxylation and incorporation into body protein of ingested phenylalanine. We compared in older (O, 59 ± 1 y) and young (Y, 23 ± 1 y) healthy male volunteers the effects of two-week bed rest on post-prandial protein kinetics, assessed during absorption of a standard ready-to-use oral nutritional supplement, through stable-labeled isotope amino acid D 5 Phe, diluted in water, given as single oral load. The metabolic fate of D 5 Phe is either utilization for protein synthesis or irreversible hydroxylation to L[ring- 2 H 4 ]tyrosine (D 4 Tyr). AR was defined as ratio between the areas under the curves of D 4 Tyr-to-D 5 Phe plasma concentrations over 6 h meal absorption. To determine the relationships between AR and muscle changes following bed rest, quadriceps muscle volume (QMV) was determined by magnetic resonance imaging (MRI). At baseline, in pooled Y and O subjects, values of AR were inversely correlated with QMV (R = -0.75; p < 0.03). Following 2-weeks of inactivity, there were significant bed rest effects on AR (p < 0.01) and QMV (p < 0.03), as well as significant bed rest × group interaction for AR (p < 0.03; +9.2% in Y; +21.9% in O) and QMV (p < 0.05; -5.7% in Y; -%7.3 in O). In pooled subjects, the percentage delta changes in AR and QMV, induced by bed rest, were inversely correlated (R = -0.57; p < 0.05). Bed rest-induced AR is much greater in the older than in younger adults. We have developed a new, simple, non-invasive method for the assessment of AR. The results indicate that this metabolic

Effects of nifedipine on anorectal smooth muscle in vitro.

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Cook, T A; Brading, A F; Mortensen, N J

1999-06-01

Glyceryl trinitrate reduces anal resting pressure and aids the healing of anal fissures. However, some patients develop tachyphylaxis and the fissure fails to heal, suggesting that other agents are needed. This study assesses the effects of nifedipine (a calcium channel antagonist) in modulating resting tone and agonist-induced contractions in human internal anal sphincter (IAS) and rectal circular muscle. Smooth muscle strips from the IAS and rectal circular muscle from ten patients undergoing surgical resection were mounted for isometric tension recording in a superfusion organ bath. The effects of noradrenaline and carbachol were assessed in the presence of various perfusates. LAS strips developed tone and spontaneous activity. Noradrenaline produced dose-dependent contractions. In calcium-free Krebs solution, tone and activity were abolished and no contractions were elicited in response to noradrenaline. Nifedipine also abolished tone and spontaneous activity, but contractions to noradrenaline were only slightly attenuated. In contrast, rectal smooth muscle strips developed spontaneous activity but no resting tone and contracted in response to carbachol. In calcium-free Krebs solution, the spontaneous activity and carbachol contractions were abolished. Addition of nifedipine to the perfusate abolished spontaneous activity and greatly reduced contractions. These data suggest that spontaneous activity and resting tone are dependent on extracellular calcium and flux across the cells. Agonist-induced contraction in the IAS is attributable mainly to the release of calcium from intracellular stores, whereas rectal circular smooth muscle depends principally on extracellular calcium entering the cell for contraction. The attenuation of contractions in both tissues and the abolition of resting tone in the IAS suggest that nifedipine may be useful in the management of patients with anorectal disorders.

Muscle inflammatory signaling in response to 9 days of physical inactivity in young men with low compared to normal birth weight

DEFF Research Database (Denmark)

Friedrichsen, Martin; Ribel-Madsen, Rasmus; Mortensen, Brynjulf

2012-01-01

OBJECTIVE: The molecular mechanisms linking physical inactivity and muscle insulin resistance in humans has been suggested to include increased muscle inflammation, possibly associated with impaired oxidative metabolism. We employed a human bed rest study including 20 young males with normal birth...

REST/NRSF Knockdown Alters Survival, Lineage Differentiation and Signaling in Human Embryonic Stem Cells.

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Kaushali Thakore-Shah

Full Text Available REST (RE1 silencing transcription factor, also known as NRSF (neuron-restrictive silencer factor, is a well-known transcriptional repressor of neural genes in non-neural tissues and stem cells. Dysregulation of REST activity is thought to play a role in diverse diseases including epilepsy, cancer, Down's syndrome and Huntington's disease. The role of REST/NRSF in control of human embryonic stem cell (hESC fate has never been examined. To evaluate the role of REST in hESCs we developed an inducible REST knockdown system and examined both growth and differentiation over short and long term culture. Interestingly, we have found that altering REST levels in multiple hESC lines does not result in loss of self-renewal but instead leads to increased survival. During differentiation, REST knockdown resulted in increased MAPK/ERK and WNT signaling and increased expression of mesendoderm differentiation markers. Therefore we have uncovered a new role for REST in regulation of growth and early differentiation decisions in human embryonic stem cells.

Physiology Of Prolonged Bed Rest

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Greenleaf, John E.

1991-01-01

Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

Upper-limb exoskeleton for human muscle fatigue

OpenAIRE

Ali, SK; Tokhi, MO

2017-01-01

Human muscle fatigue is identified as one of the causes to musculuskeletal disorder (MSD). The objective of this paper is to investigate the effect of an exoskeleton in dealing with muscle fatigue in a virtual environment. The focus of this work is, for the exoskeleton to provide support as needed by human joint. A (Proportional, Integration and Derivative) controller is used for both human and exoskeleton. Simmechanics and Simulink are used to evaluate the performance of the exoskeleton. Exp...

Molecular aging and rejuvenation of human muscle stem cells

DEFF Research Database (Denmark)

Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J

2009-01-01

. Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth...... factor beta (TGF-beta)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular......Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans...

Towards human exploration of space: the THESEUS review series on muscle and bone research priorities.

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Lang, Thomas; Van Loon, Jack J W A; Bloomfield, Susan; Vico, Laurence; Chopard, Angele; Rittweger, Joern; Kyparos, Antonios; Blottner, Dieter; Vuori, Ilkka; Gerzer, Rupert; Cavanagh, Peter R

2017-01-01

Without effective countermeasures, the musculoskeletal system is altered by the microgravity environment of long-duration spaceflight, resulting in atrophy of bone and muscle tissue, as well as in deficits in the function of cartilage, tendons, and vertebral disks. While inflight countermeasures implemented on the International Space Station have evidenced reduction of bone and muscle loss on low-Earth orbit missions of several months in length, important knowledge gaps must be addressed in order to develop effective strategies for managing human musculoskeletal health on exploration class missions well beyond Earth orbit. Analog environments, such as bed rest and/or isolation environments, may be employed in conjunction with large sample sizes to understand sex differences in countermeasure effectiveness, as well as interaction of exercise with pharmacologic, nutritional, immune system, sleep and psychological countermeasures. Studies of musculoskeletal biomechanics, involving both human subject and computer simulation studies, are essential to developing strategies to avoid bone fractures or other injuries to connective tissue during exercise and extravehicular activities. Animal models may be employed to understand effects of the space environment that cannot be modeled using human analog studies. These include studies of radiation effects on bone and muscle, unraveling the effects of genetics on bone and muscle loss, and characterizing the process of fracture healing in the mechanically unloaded and immuno-compromised spaceflight environment. In addition to setting the stage for evidence-based management of musculoskeletal health in long-duration space missions, the body of knowledge acquired in the process of addressing this array of scientific problems will lend insight into the understanding of terrestrial health conditions such as age-related osteoporosis and sarcopenia.

Impact of a single bout of high-intensity interval exercise and short-term interval training on interleukin-6, FNDC5, and METRNL mRNA expression in human skeletal muscle

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Malcolm Eaton

2018-04-01

Full Text Available Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed “myokines”. The purpose of this study was to examine the effects of high-intensity interval training (HIIT on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6 (IL-6, and recently identified myokines fibronectin type III domain-containing protein 5 (FNDC5 (irisin and meteorin-like protein (METRNL. Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males (20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise (HIIE; 5 × 4 min at ~80% pretraining peak power output with skeletal muscle biopsy samples (vastus lateralis obtained at rest, immediately following exercise, and at 3 h recovery. Results: Before training, a single bout of HIIE increased IL-6 (p < 0.05 and METRNL (p < 0.05 mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest (both p < 0.05. Resting METRNL and FNDC5 mRNA expression were higher following training (p < 0.05, and there was an overall increase in FNDC5 mRNA post-training (main effect of training, p < 0.05. Conclusion: In human skeletal muscle (1 an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT; (2 Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and (3 METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans. Keywords: Brown adipose tissue

Norepinephrine spillover from skeletal muscle during exercise in humans

DEFF Research Database (Denmark)

Savard, G K; Richter, Erik; Strange, S

1989-01-01

The purpose of this study was to determine the effect of increasing muscle mass involvement in dynamic exercise on both sympathetic nervous activation and local hemodynamic variables of individual active and inactive skeletal muscle groups. Six male subjects performed 15-min bouts of one...... legs, with a steeper rise occurring approximately 70% VO2max. These increases were not associated with any significant changes in leg blood flow or leg vascular conductance at the exercise intensities examined. These results suggest that, as the total active muscle mass increases, the rise...... in both legs. Arterial and venous plasma concentrations of norepinephrine (NE) and epinephrine were analyzed, and the calculated NE spillover was used as an index of sympathetic nervous activity to the limb. NE spillover increased gradually both in the resting, and to a larger extent in the exercising...

Effects of thyroid hormone on Na+-K+ transport in resting and stimulated rat skeletal muscle

International Nuclear Information System (INIS)

Everts, M.E.; Clausen, T.

1988-01-01

The effects of hypothyroidism and 3,5,3'-triiodothyronine (T 3 ) treatment on passive Na + -K + fluxes and Na + -K + pump concentration were investigated in isolated rat muscle. Within 12 h after a single dose of T 3 (20 μg/100 g body wt), K + efflux had increased by 21% in soleus and by 20% in extensor digitorum longus muscle. In the presence of ouabain, even larger effects were observed. These changes were associated with a 12% rise in amiloride-suppressible Na + influx but no significant increase in [ 3 H]ouabain binding site concentration. After 3 days of T 3 treatment, the stimulating effect on K + efflux and Na + influx in soleus reached a plateau ∼80 and 40% above control levels, respectively, whereas the maximum increase in [ 3 H]ouabain binding site concentration (103%) was only fully developed after 8 days. Hypothyroidism decreased 86 Rb efflux by 30%. The efflux of K + and the influx of Na + per contraction (both ∼7 nmol/g wet wt) as well as the net loss of K + induced by electrical stimulation were unaffected by T 3 treatment. The rise in resting K + efflux after 12-24 h of T 3 treatment could be partly blocked by dantrolene or trifluoroperazine, indicating that an increase in the cytoplasmic Ca 2+ concentration may contribute to the early rise in K + efflux. It is concluded that the early rise in the resting passive leaks of Na + and K + induced by T 3 is a major driving force for Na + -K + pump synthesis

Phosphorylation potential in the dominant leg is lower, and [ADPfree] is higher in calf muscles at rest in endurance athletes than in sprinters and in untrained subjects.

Science.gov (United States)

Zoladz, J A; Kulinowski, P; Zapart-Bukowska, J; Grandys, M; Majerczak, J; Korzeniewski, B; Jasiński, A

2007-12-01

It has been reported that various types of mammalian muscle fibers differ regarding the content of several metabolites at rest. However, to our knowledge no data have been reported in the literature, concerning the muscle energetic status at rest in high class athletes when considering the dominant and non-dominant leg separately. We have hypothesised that due to higher mechanical loads on the dominant leg in athletes, the metabolic profile in the dominant leg at rest in the calf muscles, characterized by [PCr], [ADP(free)], [AMP(free)] and DeltaG(ATP), will significantly differ among endurance athletes, sprinters and untrained individuals. In this study we determined the DeltaG(ATP) and adenine phosphates concentrations in the dominant and non-dominant legs in untrained subjects (n = 6), sprinters (n = 10) and endurance athletes (n = 7) at rest. The (mean +/- SD) age of the subjects was 23.4 +/- 4.3 years. Muscle metabolites were measured in the calf muscles at rest, by means of (31)P-MRS, using a 4.7 T superconducting magnet (Bruker). When taking into account mean values in the left and right leg, phosphocreatine concentration ([PCr]) and DeltaG(ATP) were significantly lower (p<0.05, Wilcoxon-Mann-Whitney test), and [ADP(free)] was significantly higher (p = 0.04) in endurance athletes than in untrained subjects. When considering the differences between the left and right leg, [PCr] in the dominant leg was significantly lower in endurance athletes than in sprinters (p = 0.01) and untrained subjects (p = 0.02) (25.91 +/- 2.87 mM; 30.02 +/- 3.12 mM and 30.71 +/- 2.88 mM, respectively). The [ADP(free)] was significantly higher (p = 0.02) in endurance athletes than in sprinters and untrained subjects (p = 0.02) (42.19 +/- 13.44 microM; 27.86 +/- 10.19 microM; 25.35 +/- 10.97 microM, respectively). The DeltaG(ATP) in the dominant leg was significantly lower (p = 0.02) in endurance athletes than in sprinters and untrained subjects (p = 0.01) (-60.53 +/- 2.03 kJ.M(-1

Muscle cooling delays activation of the muscle metaboreflex in humans.

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Ray, C A; Hume, K M; Gracey, K H; Mahoney, E T

1997-11-01

Elevation of muscle temperature has been shown to increase muscle sympathetic nerve activity (MSNA) during isometric exercise in humans. The purpose of the present study was to evaluate the effect of muscle cooling on MSNA responses during exercise. Eight subjects performed ischemic isometric handgrip at 30% of maximal voluntary contraction to fatigue followed by 2 min of postexercise muscle ischemia (PEMI), with and without local cooling of the forearm. Local cooling of the forearm decreased forearm muscle temperature from 31.8 +/- 0.4 to 23.1 +/- 0.8 degrees C (P = 0.001). Time to fatigue was not different during the control and cold trials (156 +/- 11 and 154 +/- 5 s, respectively). Arterial pressures and heart rate were not significantly affected by muscle cooling during exercise, although heart rate tended to be higher during the second minute of exercise (P = 0.053) during muscle cooling. Exercise-induced increases in MSNA were delayed during handgrip with local cooling compared with control. However, MSNA responses at fatigue and PEMI were not different between the two conditions. These findings suggest that muscle cooling delayed the activation of the muscle metaboreflex during ischemic isometric exercise but did not prevent its full expression during fatiguing contraction. These results support the concept that muscle temperature can play a role in the regulation of MSNA during exercise.

Determination of human muscle protein fractional synthesis rate

DEFF Research Database (Denmark)

Bornø, Andreas; Hulston, Carl J; van Hall, Gerrit

2014-01-01

In the present study, different MS methods for the determination of human muscle protein fractional synthesis rate (FSR) using [ring-(13)C6 ]phenylalanine as a tracer were evaluated. Because the turnover rate of human skeletal muscle is slow, only minute quantities of the stable isotopically...

The Human Skeletal Muscle Proteome Project

DEFF Research Database (Denmark)

Gonzalez-Freire, Marta; Semba, Richard D.; Ubaida-Mohien, Ceereena

2017-01-01

Skeletal muscle is a large organ that accounts for up to half the total mass of the human body. A progressive decline in muscle mass and strength occurs with ageing and in some individuals configures the syndrome of ‘sarcopenia’, a condition that impairs mobility, challenges autonomy, and is a ri...

REST controls self-renewal and tumorigenic competence of human glioblastoma cells.

Directory of Open Access Journals (Sweden)

Luciano Conti

Full Text Available The Repressor Element 1 Silencing Transcription factor (REST/NRSF is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets.

Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation

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Tanner, Ruth E; Brunker, Lucille B; Agergaard, Jakob

2015-01-01

during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related...... to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P protein synthesis increased before bed rest in both age groups...... (P protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P

Physiological and methodological aspects of rate of force development assessment in human skeletal muscle.

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Rodríguez-Rosell, David; Pareja-Blanco, Fernando; Aagaard, Per; González-Badillo, Juan José

2017-12-20

Rate of force development (RFD) refers to the ability of the neuromuscular system to increase contractile force from a low or resting level when muscle activation is performed as quickly as possible, and it is considered an important muscle strength parameter, especially for athletes in sports requiring high-speed actions. The assessment of RFD has been used for strength diagnosis, to monitor the effects of training interventions in both healthy populations and patients, discriminate high-level athletes from those of lower levels, evaluate the impairment in mechanical muscle function after acute bouts of eccentric muscle actions and estimate the degree of fatigue and recovery after acute exhausting exercise. Notably, the evaluation of RFD in human skeletal muscle is a complex task as influenced by numerous distinct methodological factors including mode of contraction, type of instruction, method used to quantify RFD, devices used for force/torque recording and ambient temperature. Another important aspect is our limited understanding of the mechanisms underpinning rapid muscle force production. Therefore, this review is primarily focused on (i) describing the main mechanical characteristics of RFD; (ii) analysing various physiological factors that influence RFD; and (iii) presenting and discussing central biomechanical and methodological factors affecting the measurement of RFD. The intention of this review is to provide more methodological and analytical coherency on the RFD concept, which may aid to clarify the thinking of coaches and sports scientists in this area. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

THE CAPILLARY PATTERN IN HUMAN MASSETER MUSCLE DURING AGEING

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Erika Cvetko

2013-10-01

Full Text Available The effect of ageing on the capillary network in skeletal muscles has produced conflicting results in both, human and animals studies. Some of the inconsistencies are due to non-comparable and biased methods that were applied on thin transversal sections, especially in muscles with complicated morphological structures, such as in human masseter muscle. We present a new immunohistochemical method for staining capillaries and muscle fibres in 100 µm thick sections as well as novel approach to 3D visualization of capillaries and muscle fibres. Applying confocal microscopy and virtual 3D stereological grids, or tracing capillaries in virtual reality, length of capillaries within a muscle volume or length of capillaries adjacent to muscle fibre per fibre length, fibre surface or fibre volume were evaluated in masseter muscle of young and old subjects by an unbiased approach. Our findings show that anatomic capillarity is well maintained in masseter muscle in old subjects; however, vascular remodelling occurs with age, which could be a response to changed muscle function and age-related muscle fibre type transformations.

Differential effects of human activity on Hawaiian spinner dolphins in their resting bays

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Heather L. Heenehan

2017-04-01

Full Text Available Hawaiian spinner dolphins display predictable daily behavior, using shallow bays to rest during the daytime, bays that are also frequented by humans. All previous research on the potential response of Hawaiian spinner dolphins to human activity has been conducted visually, at the surface. In this study we take a different approach by using passive acoustic monitoring to analyze dolphin behavior and assess whether human activity affects the behavior of the animals. We used days (n=99 and hours (n=641 when dolphins were confirmed present in visual surveys between January 9, 2011 and August 15, 2012 and metrics generated from concomitant 30-second sound recordings (n=9615. Previous research found that the dolphins were predictably silent during rest and that acoustic activity matched general activity of the dolphins with higher acoustic activity before and after rest, and silence during rest. The daily pattern of dolphin whistle activity in Bay 2 and 4 (Kealakekua and Kauhako matched what would be expected from this earlier work. However, in Bay 1 and 3 (Makako and Honaunau there was no drop in dolphin whistle activity during rest. After assessing the relationship between time of day and dolphin acoustic activity, data on human presence were used to determine how variability in the dolphins’ acoustic activity might be explained by human activity (i.e. the number of vessels, kayaks and swimmer snorkelers present. Bay 2, the bay with the most human activity, showed no relationship between dolphin whistle activity and human presence (either vessels, kayaks, or swimmer/snorkelers. Although the relationships were weak, Bay 1 displayed a positive relationship between dolphin whistle activity and the number of vessels and swimmer/snorkelers present in the bay. Bay 4 also showed a positive relationship between dolphin whistle activity and the number of swimmer snorkelers. We also documented less sound being added to the soundscape with each additional

Physiological and methodological aspects of rate of force development assessment in human skeletal muscle

DEFF Research Database (Denmark)

Rodríguez-Rosell, David; Pareja-Blanco, Fernando; Aagaard, Per

2018-01-01

Rate of force development (RFD) refers to the ability of the neuromuscular system to increase contractile force from a low or resting level when muscle activation is performed as quickly as possible, and it is considered an important muscle strength parameter, especially for athletes in sports re......, which may aid to clarify the thinking of coaches and sports scientists in this area....

Relationships between resting conductances, excitability, and t-system ionic homeostasis in skeletal muscle.

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Fraser, James A; Huang, Christopher L-H; Pedersen, Thomas H

2011-07-01

Activation of skeletal muscle fibers requires rapid sarcolemmal action potential (AP) conduction to ensure uniform excitation along the fiber length, as well as successful tubular excitation to initiate excitation-contraction coupling. In our companion paper in this issue, Pedersen et al. (2011. J. Gen. Physiol. doi:10.1085/jgp.201010510) quantify, for subthreshold stimuli, the influence upon both surface conduction velocity and tubular (t)-system excitation of the large changes in resting membrane conductance (G(M)) that occur during repetitive AP firing. The present work extends the analysis by developing a multi-compartment modification of the charge-difference model of Fraser and Huang to provide a quantitative description of the conduction velocity of actively propagated APs; the influence of voltage-gated ion channels within the t-system; the influence of t-system APs on ionic homeostasis within the t-system; the influence of t-system ion concentration changes on membrane potentials; and the influence of Phase I and Phase II G(M) changes on these relationships. Passive conduction properties of the novel model agreed with established linear circuit analysis and previous experimental results, while key simulations of AP firing were tested against focused experimental microelectrode measurements of membrane potential. This study thereby first quantified the effects of the t-system luminal resistance and voltage-gated Na(+) channel density on surface AP propagation and the resultant electrical response of the t-system. Second, it demonstrated the influence of G(M) changes during repetitive AP firing upon surface and t-system excitability. Third, it showed that significant K(+) accumulation occurs within the t-system during repetitive AP firing and produces a baseline depolarization of the surface membrane potential. Finally, it indicated that G(M) changes during repetitive AP firing significantly influence both t-system K(+) accumulation and its influence on the

Exercise and training effects on ceramide metabolism in human skeletal muscle

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Helge, Jørn Wulff; Dobrzyn, Agnieszka; Saltin, Bengt

2004-01-01

in skeletal muscle in untrained and trained subjects before and after prolonged exercise. Healthy male subjects were recruited into an untrained (n = 8, VO2,max 3.8 +/- 0.2 1 min1) and a trained (n = 8, Vo2,max 5.1 +/- 0.1 1 min2) group. Before and after a 3-h exercise bout (58 +/- 1% VO2,max) a muscle biopsy...... was measured using N-[14CH3]-sphingomyelin as a substrate. Prior to exercise, the muscle total ceramide fatty acid content in both groups was similar (201 +/- 18 and 197 +/- 9 nmol g(-1) in the untrained and trained group, respectively) and after exercise a 25% increase in the content was observed in each...... group. At rest, the muscle total sphingomyelin fatty acid content was higher in untrained than in trained subjects (456 +/- 10, 407 +/- 7 nmol g(-1), respectively; P trained subjects. The muscle neutral, Mg...

Induction of GLUT-1 protein in adult human skeletal muscle fibers

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Gaster, M; Franch, J; Staehr, P

2000-01-01

Prompted by our recent observations that GLUT-1 is expressed in fetal muscles, but not in adult muscle fibers, we decided to investigate whether GLUT-1 expression could be reactivated. We studied different stimuli concerning their ability to induce GLUT-1 expression in mature human skeletal muscle...... fibers. Metabolic stress (obesity, non-insulin-dependent diabetes mellitus), contractile activity (training), and conditions of de- and reinnervation (amyotrophic lateral sclerosis) could not induce GLUT-1 expression in human muscle fibers. However, regenerating muscle fibers in polymyositis expressed...... GLUT-1. In contrast to GLUT-1, GLUT-4 was expressed in all investigated muscle fibers. Although the significance of GLUT-1 in adult human muscle fibers appears limited, GLUT-1 may be of importance for the glucose supplies in immature and regenerating muscle....

Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis.

NARCIS (Netherlands)

Serlie, M.J.; Haan, J.H.A. de; Tack, C.J.J.; Verberne, H.J.; Ackermans, M.T.; Heerschap, A.; Sauerwein, H.P.

2005-01-01

The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis

NARCIS (Netherlands)

Serlie, Mireille J. M.; de Haan, Jacco H.; Tack, Cees J.; Verberne, Hein J.; Ackermans, Mariette T.; Heerschap, Arend; Sauerwein, Hans P.

2005-01-01

The introduction of C-13 magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

Rest-Stress Limb Perfusion Imaging in Humans with Contrast Ultrasound Using Intermediate-Power Imaging and Microbubbles Resistant to Inertial Cavitation.

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Davidson, Brian P; Hodovan, James; Belcik, J Todd; Moccetti, Federico; Xie, Aris; Ammi, Azzdine Y; Lindner, Jonathan R

2017-05-01

Contrast-enhanced ultrasound (CEU) limb perfusion imaging is a promising approach for evaluating peripheral artery disease (PAD). However, low signal enhancement in skeletal muscle has necessitated high-power intermittent imaging algorithms, which are not clinically feasible. We hypothesized that CEU using a combination of intermediate power and a contrast agent resistant to inertial cavitation would allow real-time limb stress perfusion imaging. In normal volunteers, CEU of the calf skeletal muscle was performed on separate days with Sonazoid, Optison, or Definity. Progressive reduction in the ultrasound pulsing interval was used to assess the balance between signal enhancement and agent destruction at escalating mechanical indices (MI, 0.1-0.4). Real-time perfusion imaging at MI 0.1-0.4 using postdestructive replenishment kinetics was performed at rest and during 25 W plantar flexion contractile exercise. For Optison, limb perfusion imaging was unreliable at rest due to very low signal enhancement generated at all MIs and was possible during exercise-induced hyperemia only at MI 0.1 due to agent destruction at higher MIs. For Definity, signal intensity progressively increased with MI but was offset by microbubble destruction, which resulted in modest signal enhancement during CEU perfusion imaging and distortion of replenishment curves at MI ≥ 0.2. For Sonazoid, there strong signal enhancement at MI ≥ 0.2, with little destruction detected only at MI 0.4. Accordingly, high signal intensity and nondistorted perfusion imaging was possible at MI 0.2-0.3 and detected an 8.0- ± 5.7-fold flow reserve. Rest-stress limb perfusion imaging in humans with real-time CEU, which requires only seconds to perform, is possible using microbubbles with viscoelastic properties that produce strong nonlinear signal generation without destruction at intermediate acoustic pressures. Copyright © 2016 American Society of Echocardiography. All rights reserved.

Effect of acute inspiratory muscle exercise on blood flow of resting and exercising limbs and glucose levels in type 2 diabetes.

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Corrêa, Ana Paula dos Santos; Antunes, Cristiano Fetter; Figueira, Franciele Ramos; de Castro, Marina Axmann; Ribeiro, Jorge Pinto; Schaan, Beatriz D'Agord

2015-01-01

To evaluate the effects of inspiratory loading on blood flow of resting and exercising limbs in patients with diabetic autonomic neuropathy. Ten diabetic patients without cardiovascular autonomic neuropathy (DM), 10 patients with cardiovascular autonomic neuropathy (DM-CAN) and 10 healthy controls (C) were randomly assigned to inspiratory muscle load of 60% or 2% of maximal inspiratory pressure (PImax) for approximately 5 min, while resting calf blood flow (CBF) and exercising forearm blood flow (FBF) were measured. Reactive hyperemia was also evaluated. From the 20 diabetic patients initially allocated, 6 wore a continuous glucose monitoring system to evaluate the glucose levels during these two sessions (2%, placebo or 60%, inspiratory muscle metaboreflex). Mean age was 58 ± 8 years, and mean HbA1c, 7.8% (62 mmol/mol) (DM and DM-CAN). A PImax of 60% caused reduction of CBF in DM-CAN and DM (Pexercise was blunted during 60% of PImax in DM-CAN and DM, and augmented in C (Pexercise that recruits the diaphragm can abruptly reduce glucose levels.

Liver and Muscle Contribute Differently to the Plasma Acylcarnitine Pool During Fasting and Exercise in Humans

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Xu, G.; Hansen, J S; Zhao, Jian-xin

2016-01-01

BACKGROUND: Plasma acylcarnitine levels are elevated by physiological conditions such as fasting and exercise but also in states of insulin resistance and obesity. AIM: To elucidate the contribution of liver and skeletal muscle to plasma acylcarnitines in the fasting state and during exercise...... in humans. METHODS: In 2 independent studies, young healthy males were fasted overnight and performed an acute bout of exercise to investigate either acylcarnitines in skeletal muscle biopsies and arterial-to-venous plasma differences over the exercising and resting leg (n = 9) or the flux over the hepato......-splanchnic bed (n = 10). RESULTS: In the fasting state, a pronounced release of C2- and C3-carnitines from the hepato-splanchnic bed and an uptake of free carnitine by the legs were detected. Exercise further increased the release of C3-carnitine from the hepato-splanchnic bed and the uptake of free carnitine...

Morphometric and Statistical Analysis of the Palmaris Longus Muscle in Human and Non-Human Primates

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Aversi-Ferreira, Roqueline A. G. M. F.; Bretas, Rafael Vieira; Maior, Rafael Souto; Davaasuren, Munkhzul; Paraguassú-Chaves, Carlos Alberto; Nishijo, Hisao; Aversi-Ferreira, Tales Alexandre

2014-01-01

The palmaris longus is considered a phylogenetic degenerate metacarpophalangeal joint flexor muscle in humans, a small vestigial forearm muscle; it is the most variable muscle in humans, showing variation in position, duplication, slips and could be reverted. It is frequently studied in papers about human anatomical variations in cadavers and in vivo, its variation has importance in medical clinic, surgery, radiological analysis, in studies about high-performance athletes, in genetics and anthropologic studies. Most studies about palmaris longus in humans are associated to frequency or case studies, but comparative anatomy in primates and comparative morphometry were not found in scientific literature. Comparative anatomy associated to morphometry of palmaris longus could explain the degeneration observed in this muscle in two of three of the great apes. Hypothetically, the comparison of the relative length of tendons and belly could indicate the pathway of the degeneration of this muscle, that is, the degeneration could be associated to increased tendon length and decreased belly from more primitive primates to those most derivate, that is, great apes to modern humans. In conclusion, in primates, the tendon of the palmaris longus increase from Lemuriformes to modern humans, that is, from arboreal to terrestrial primates and the muscle became weaker and tending to be missing. PMID:24860810

Morphometric and Statistical Analysis of the Palmaris Longus Muscle in Human and Non-Human Primates

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Roqueline A. G. M. F. Aversi-Ferreira

2014-01-01

Full Text Available The palmaris longus is considered a phylogenetic degenerate metacarpophalangeal joint flexor muscle in humans, a small vestigial forearm muscle; it is the most variable muscle in humans, showing variation in position, duplication, slips and could be reverted. It is frequently studied in papers about human anatomical variations in cadavers and in vivo, its variation has importance in medical clinic, surgery, radiological analysis, in studies about high-performance athletes, in genetics and anthropologic studies. Most studies about palmaris longus in humans are associated to frequency or case studies, but comparative anatomy in primates and comparative morphometry were not found in scientific literature. Comparative anatomy associated to morphometry of palmaris longus could explain the degeneration observed in this muscle in two of three of the great apes. Hypothetically, the comparison of the relative length of tendons and belly could indicate the pathway of the degeneration of this muscle, that is, the degeneration could be associated to increased tendon length and decreased belly from more primitive primates to those most derivate, that is, great apes to modern humans. In conclusion, in primates, the tendon of the palmaris longus increase from Lemuriformes to modern humans, that is, from arboreal to terrestrial primates and the muscle became weaker and tending to be missing.

A 3-Dimensional Atlas of Human Tongue Muscles

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SANDERS, IRA; MU, LIANCAI

2013-01-01

The human tongue is one of the most important yet least understood structures of the body. One reason for the relative lack of research on the human tongue is its complex anatomy. This is a real barrier to investigators as there are few anatomical resources in the literature that show this complex anatomy clearly. As a result, the diagnosis and treatment of tongue disorders lags behind that for other structures of the head and neck. This report intended to fill this gap by displaying the tongue’s anatomy in multiple ways. The primary material used in this study was serial axial images of the male and female human tongue from the Visible Human (VH) Project of the National Library of Medicine. In addition, thick serial coronal sections of three human tongues were rendered translucent. The VH axial images were computer reconstructed into serial coronal sections and each tongue muscle was outlined. These outlines were used to construct a 3-dimensional computer model of the tongue that allows each muscle to be seen in its in vivo anatomical position. The thick coronal sections supplement the 3-D model by showing details of the complex interweaving of tongue muscles throughout the tongue. The graphics are perhaps the clearest guide to date to aid clinical or basic science investigators in identifying each tongue muscle in any part of the human tongue. PMID:23650264

Branched-chain amino acid supplementation during bed rest: effect on recovery

Science.gov (United States)

Stein, T. P.; Donaldson, M. R.; Leskiw, M. J.; Schluter, M. D.; Baggett, D. W.; Boden, G.

2003-01-01

Bed rest is associated with a loss of protein from the weight-bearing muscle. The objectives of this study are to determine whether increasing dietary branched-chain amino acids (BCAAs) during bed rest improves the anabolic response after bed rest. The study consisted of a 1-day ambulatory period, 14 days of bed rest, and a 4-day recovery period. During bed rest, dietary intake was supplemented with either 30 mmol/day each of glycine, serine, and alanine (group 1) or with 30 mmol/day each of the three BCAAs (group 2). Whole body protein synthesis was determined with U-(15)N-labeled amino acids, muscle, and selected plasma protein synthesis with l-[(2)H(5)]phenylalanine. Total glucose production and gluconeogenesis from alanine were determined with l-[U-(13)C(3)]alanine and [6,6-(2)H(2)]glucose. During bed rest, nitrogen (N) retention was greater with BCAA feeding (56 +/- 6 vs. 26 +/- 12 mg N. kg(-1). day(-1), P < 0.05). There was no effect of BCAA supplementation on either whole body, muscle, or plasma protein synthesis or the rate of 3-MeH excretion. Muscle tissue free amino acid concentrations were increased during bed rest with BCAA (0.214 +/- 0.066 vs. 0.088 +/- 0.12 nmol/mg protein, P < 0.05). Total glucose production and gluconeogenesis from alanine were unchanged with bed rest but were significantly reduced (P < 0.05) with the BCAA group in the recovery phase. In conclusion, the improved N retention during bed rest is due, at least in part, to accretion of amino acids in the tissue free amino acid pools. The amount accreted is not enough to impact protein kinetics in the recovery phase but does improve N retention by providing additional essential amino acids in the early recovery phase.

Branched-chain amino acid supplementation during bed rest: effect on recovery

Science.gov (United States)

Stein, T. P.; Donaldson, M. R.; Leskiw, M. J.; Schluter, M. D.; Baggett, D. W.; Boden, G.

2003-01-01

Bed rest is associated with a loss of protein from the weight-bearing muscle. The objectives of this study are to determine whether increasing dietary branched-chain amino acids (BCAAs) during bed rest improves the anabolic response after bed rest. The study consisted of a 1-day ambulatory period, 14 days of bed rest, and a 4-day recovery period. During bed rest, dietary intake was supplemented with either 30 mmol/day each of glycine, serine, and alanine (group 1) or with 30 mmol/day each of the three BCAAs (group 2). Whole body protein synthesis was determined with U-(15)N-labeled amino acids, muscle, and selected plasma protein synthesis with l-[(2)H(5)]phenylalanine. Total glucose production and gluconeogenesis from alanine were determined with l-[U-(13)C(3)]alanine and [6,6-(2)H(2)]glucose. During bed rest, nitrogen (N) retention was greater with BCAA feeding (56 +/- 6 vs. 26 +/- 12 mg N. kg(-1). day(-1), P BCAA supplementation on either whole body, muscle, or plasma protein synthesis or the rate of 3-MeH excretion. Muscle tissue free amino acid concentrations were increased during bed rest with BCAA (0.214 +/- 0.066 vs. 0.088 +/- 0.12 nmol/mg protein, P BCAA group in the recovery phase. In conclusion, the improved N retention during bed rest is due, at least in part, to accretion of amino acids in the tissue free amino acid pools. The amount accreted is not enough to impact protein kinetics in the recovery phase but does improve N retention by providing additional essential amino acids in the early recovery phase.

Pneumatic Muscles Actuated Lower-Limb Orthosis Model Verification with Actual Human Muscle Activation Patterns

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Dzahir M.A.M

2017-01-01

Full Text Available A review study was conducted on existing lower-limb orthosis systems for rehabilitation which implemented pneumatic muscle type of actuators with the aim to clarify the current and on-going research in this field. The implementation of pneumatic artificial muscle will play an important role for the development of the advanced robotic system. In this research a derivation model for the antagonistic mono- and bi-articular muscles using pneumatic artificial muscles of a lower limb orthosis will be verified with actual human’s muscle activities models. A healthy and young male 29 years old subject with height 174cm and weight 68kg was used as a test subject. Two mono-articular muscles Vastus Medialis (VM and Vastus Lateralis (VL were selected to verify the mono-articular muscle models and muscle synergy between anterior muscles. Two biarticular muscles Rectus Femoris (RF and Bicep Femoris (BF were selected to verify the bi-articular muscle models and muscle co-contraction between anterior-posterior muscles. The test was carried out on a treadmill with a speed of 4.0 km/h, which approximately around 1.25 m/s for completing one cycle of walking motion. The data was collected for about one minute on a treadmill and 20 complete cycles of walking motion were successfully recorded. For the evaluations, the mathematical model obtained from the derivation and the actual human muscle activation patterns obtained using the surface electromyography (sEMG system were compared and analysed. The results shown that, high correlation values ranging from 0.83 up to 0.93 were obtained in between the derivation model and the actual human muscle’s model for both mono- and biarticular muscles. As a conclusion, based on the verification with the sEMG muscle activities data and its correlation values, the proposed derivation models of the antagonistic mono- and bi-articular muscles were suitable to simulate and controls the pneumatic muscles actuated lower limb

Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy.

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Sun, S; Henriksen, K; Karsdal, M A; Armbrecht, G; Belavý, D L; Felsenberg, D; Rittweger, J; Wang, Y; Zheng, Q; Nedergaard, A F

2014-10-01

In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass. Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competitive ELISA assay for measurement in serum. Rat tissue extractions in the presence or absence of a series of proteases of interest were used to identify its enzymatic origin. A rat model of dexamethasone (DEX) induced muscle atrophy and a human 56-day bed rest study with and without vibration therapy were used to assess biological and clinical relevance. A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up at a 16.4 (±4.6) % increase at day 47. We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy. Copyright © 2014 Elsevier Inc. All rights reserved.

Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle

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Daniel eBoulton

2016-05-01

Full Text Available During voluntary contractions, muscle sympathetic nerve activity (MSNA to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-minute isometric dorsiflexion contractions (left leg separated by 2-minute rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5-10 % of maximum. MSNA was recorded continuously (microneurography from the left peroneal nerve and quantified from cardiac-synchronised, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34 % (P 0.05. MSNA analysed at 15-s intervals revealed that this effect of voluntary contraction appeared 15-30 s after contraction onset (P < 0.01, remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction.

GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance

DEFF Research Database (Denmark)

Biensø, Rasmus Sjørup; Jørgensen, Stine Ringholm; Kiilerich, Kristian

2012-01-01

To elucidate the molecular mechanisms behind physical inactivity-induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both...... than before bed rest. This bed rest-induced insulin resistance occurred together with reduced muscle GLUT4, hexokinase II, protein kinase B/Akt1, and Akt2 protein level, and a tendency for reduced 3-hydroxyacyl-CoA dehydrogenase activity. The ability of insulin to phosphorylate Akt and activate....... The present findings demonstrate that physical inactivity-induced insulin resistance in muscle is associated with lower content/activity of key proteins in glucose transport/phosphorylation and storage....

Regulation of pH in human skeletal muscle: adaptations to physical activity

DEFF Research Database (Denmark)

Juel, C

2008-01-01

-transport) and describes the contribution of each transport system in pH regulation at rest and during muscle activity. It is reported that the mechanisms involved in pH regulation can undergo adaptational changes in association with physical activity and that these changes are of functional importance....... resonance technique to exercise experiments including blood sampling and muscle biopsies. The present review characterizes the cellular buffering system as well as the most important membrane transport systems involved (Na(+)/H(+) exchange, Na-bicarbonate co-transport and lactate/H(+) co...

Physical inactivity and muscle oxidative capacity in humans.

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Gram, Martin; Dahl, Rannvá; Dela, Flemming

2014-01-01

Physical inactivity is associated with a high prevalence of type 2 diabetes and is an independent predictor of mortality. It is possible that the detrimental effects of physical inactivity are mediated through a lack of adequate muscle oxidative capacity. This short review will cover the present literature on the effects of different models of inactivity on muscle oxidative capacity in humans. Effects of physical inactivity include decreased mitochondrial content, decreased activity of oxidative enzymes, changes in markers of oxidative stress and a decreased expression of genes and contents of proteins related to oxidative phosphorylation. With such a substantial down-regulation, it is likely that a range of adenosine triphosphate (ATP)-dependent pathways such as calcium signalling, respiratory capacity and apoptosis are affected by physical inactivity. However, this has not been investigated in humans, and further studies are required to substantiate this hypothesis, which could expand our knowledge of the potential link between lifestyle-related diseases and muscle oxidative capacity. Furthermore, even though a large body of literature reports the effect of physical training on muscle oxidative capacity, the adaptations that occur with physical inactivity may not always be opposite to that of physical training. Thus, it is concluded that studies on the effect of physical inactivity per se on muscle oxidative capacity in functional human skeletal muscle are warranted.

Effects of Bed Rest on Conduction Velocity of the Triceps Surae Stretch Reflex and Postural Control

Science.gov (United States)

Reschke, M. F.; Wood, S. J.; Cerisano, J. M.; Kofman, I. S.; Fisher, E. A.; Esteves, J. T.; Taylor, L. C.; DeDios, Y. E.; Harm, D. L.

2011-01-01

Despite rigorous exercise and nutritional management during space missions, astronauts returning from microgravity exhibit neuromuscular deficits and a significant loss in muscle mass in the postural muscles of the lower leg. Similar changes in the postural muscles occur in subjects participating in long-duration bed rest studies. These adaptive muscle changes manifest as a reduction in reflex conduction velocity during head-down bed rest. Because the stretch reflex encompasses both the peripheral (muscle spindle and nerve axon) and central (spinal synapse) components involved in adaptation to calf muscle unloading, it may be used to provide feedback on the general condition of neuromuscular function, and might be used to evaluate the effectiveness of countermeasures aimed at preserving muscle mass and function during periods of unloading. Stretch reflexes were measured on 18 control subjects who spent 60 to 90 days in continuous 6 deg head-down bed rest. Using a motorized system capable of rotating the foot around the ankle joint (dorsiflexion) through an angle of 10 degrees at a peak velocity of about 250 deg/sec, a stretch reflex was recorded from the subject's left triceps surae muscle group. Using surface electromyography, about 300 reflex responses were obtained and ensemble-averaged on 3 separate days before bed rest, 3 to 4 times in bed, and 3 times after bed rest. The averaged responses for each test day were examined for reflex latency and conduction velocity (CV) across gender. Computerized posturography was also conducted on these same subjects before and after bed rest as part of the standard measures. Peak-to-peak sway was measured during Sensory Organization Tests (SOTs) to evaluate changes in the ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Although no gender differences were found, a significant increase in reflex latency and a significant decrease in CV were observed during the bed

Muscle Coordination and Locomotion in Humans.

Science.gov (United States)

Sylos-Labini, Francesca; Zago, Myrka; Guertin, Pierre A; Lacquaniti, Francesco; Ivanenko, Yury P

2017-01-01

Locomotion is a semi-automatic daily task. Several studies show that muscle activity is fairly stereotyped during normal walking. Nevertheless, each human leg contains over 50 muscles and locomotion requires flexibility in order to adapt to different conditions as, for instance, different speeds, gaits, turning, obstacle avoidance, altered gravity levels, etc. Therefore, locomotor control has to deal with a certain level of flexibility and non-linearity. In this review, we describe and discuss different findings dealing with both simplicity and variability of the muscular control, as well as with its maturation during development. Despite complexity and redundancy, muscle activity patterns and spatiotemporal maps of spinal motoneuron output during human locomotion show both stereotypical features as well as functional re-organization. Flexibility and different solutions to adjust motor patterns should be considered when considering new rehabilitation strategies to treat disorders involving deficits in gait. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Lifelong training preserves some redox-regulated adaptive responses after an acute exercise stimulus in aged human skeletal muscle.

Science.gov (United States)

Cobley, J N; Sakellariou, G K; Owens, D J; Murray, S; Waldron, S; Gregson, W; Fraser, W D; Burniston, J G; Iwanejko, L A; McArdle, A; Morton, J P; Jackson, M J; Close, G L

2014-05-01

acute exercise bout. Collectively, these data support many but not all of the findings from previous animal studies and suggest parallel aging effects in humans and mice at rest and after exercise that are not modulated by training status in human skeletal muscle. Copyright © 2014 Elsevier Inc. All rights reserved.

Unique expression of cytoskeletal proteins in human soft palate muscles.

Science.gov (United States)

Shah, Farhan; Berggren, Diana; Holmlund, Thorbjörn; Levring Jäghagen, Eva; Stål, Per

2016-03-01

The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles. © 2015 Anatomical Society.

Decellularized Human Skeletal Muscle as Biologic Scaffold for Reconstructive Surgery

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Andrea Porzionato

2015-07-01

Full Text Available Engineered skeletal muscle tissues have been proposed as potential solutions for volumetric muscle losses, and biologic scaffolds have been obtained by decellularization of animal skeletal muscles. The aim of the present work was to analyse the characteristics of a biologic scaffold obtained by decellularization of human skeletal muscles (also through comparison with rats and rabbits and to evaluate its integration capability in a rabbit model with an abdominal wall defect. Rat, rabbit and human muscle samples were alternatively decellularized with two protocols: n.1, involving sodium deoxycholate and DNase I; n.2, trypsin-EDTA and Triton X-NH4OH. Protocol 2 proved more effective, removing all cellular material and maintaining the three-dimensional networks of collagen and elastic fibers. Ultrastructural analyses with transmission and scanning electron microscopy confirmed the preservation of collagen, elastic fibres, glycosaminoglycans and proteoglycans. Implantation of human scaffolds in rabbits gave good results in terms of integration, although recellularization by muscle cells was not completely achieved. In conclusion, human skeletal muscles may be effectively decellularized to obtain scaffolds preserving the architecture of the extracellular matrix and showing mechanical properties suitable for implantation/integration. Further analyses will be necessary to verify the suitability of these scaffolds for in vitro recolonization by autologous cells before in vivo implantation.

Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

DEFF Research Database (Denmark)

Lundby, Carsten; Hellsten, Ylva; Jensen, Mie B. F.

2008-01-01

The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study...... the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects...... was studied in subjects (n = 8) who received long-term Epo administration, and muscle biopsies were obtained before and after. Epo treatment did not alter mean fiber area (0.84 +/- 0.2 vs. 0.72 +/- 0.3 mm(2)), capillaries per fiber (4.3 +/- 0.5 vs. 4.4 +/- 1.3), or number of proliferating endothelial cells...

Functional Echomyography of the human denervated muscle: first results

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Riccardo Zanato

2011-03-01

Full Text Available In this study we followed with ultrasound three patients with permanent denervation to evaluate changes in morphology, thickness, contraction and vascularisation of muscles undergoing the home-based electrical stimulation program of the Rise2-Italy project. During a period of 1 year for the first subject, 6 months for the second subject and 3 months for the third subject we studied with ultrasound the denervated muscle comparing it (if possible to the contralateral normal muscle. We evaluated: 1. Changes in morphology and sonographic structure of the pathologic muscle; 2. Muscular thickness in response to the electrical stimulation therapy; 3. Short-term modifications in muscle perfusion and arterial flow patterns after stimulation; 4. Contraction-relaxation kinetic induced by volitional activity or electrical stimulation. Morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete muscular atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third than in the proximal and distal third of the denervated muscle, reaching in the last measurements of the first subject approximately the same thickness as the contralateral normal muscle. In all the measurements done within this study, arterial flow of the denervated muscle showed at rest a low-resistance pattern with Doppler Ultra Sound (US, and a pulsed pattern after electrical stimulation. The stimulation- induced pattern is similar to the trifasic high-resistance pattern of the normal muscle. Contraction- relaxation kinetic, measured by recording the muscular movements during electrical stimulation, showed an abnormal behaviour of the denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle (880 msec in the denervated muscle vs 240 msec in the contralateral normal one

Detection of melatonin receptor mRNA in human muscle

International Nuclear Information System (INIS)

Li Lei

2004-01-01

To verify the expression of melatonin receptor mRNA in human, muscle, muscle beside vertebrae was collected to obtain total RNA and the mRNA of melatonin receptor was detected by RT-PCR method. The electrophoretic results of RT-PCR products by mt 1 and MT 2 primer were all positive and the sequence is corresponding with human melatonin receptor cDNA. It suggests that melatonin may act on the muscle beside vertebrae directly and regulate its growth and development. (authors)

Regulation of the skeletal muscle blood flow in humans

DEFF Research Database (Denmark)

Mortensen, Stefan; Saltin, Bengt

2014-01-01

In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... concentration does not increase during exercise. In the skeletal muscle interstitium, there is a marked increase in the concentration of ATP and adenosine and this increase is tightly coupled to the increase in blood flow. The sources of interstitial ATP and adenosine are thought to be skeletal muscle cells...... hyperaemia whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation...

Adaptation of signal transduction and muscle proteome in trained horses

NARCIS (Netherlands)

Ginneken, Mireille Maria Elisabeth van

2006-01-01

In the present thesis the localization and activation of signaling proteins, known from human studies, in equine muscle were investigated under conditions of rest, after an acute bout of exercise and before and after a period of (intensified) training. Proteins of interest (protein kinase C (PKC),

Female hormones: do they influence muscle and tendon protein metabolism?

DEFF Research Database (Denmark)

Hansen, Mette

2018-01-01

(or lack of female hormones) on skeletal muscle protein turnover at rest and in response to exercise. This review is primarily based on data from human trials. Many elderly post-menopausal women experience physical disabilities and loss of independence related to sarcopenia, which reduces life quality...

Prior acetaminophen consumption impacts the early adaptive cellular response of human skeletal muscle to resistance exercise.

Science.gov (United States)

D'Lugos, Andrew C; Patel, Shivam H; Ormsby, Jordan C; Curtis, Donald P; Fry, Christopher S; Carroll, Chad C; Dickinson, Jared M

2018-04-01

Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation. Previous data demonstrate that cyclooxygenase (COX)-inhibiting drugs alter the cellular mechanisms regulating the adaptive response of skeletal muscle. The purpose of this study was to determine whether prior consumption of the COX inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in human skeletal muscle after RE. In a double-blinded, randomized, crossover design, healthy young men ( n = 8, 25 ± 1 yr) performed two trials of unilateral knee extension RE (8 sets, 10 reps, 65% max strength). Subjects ingested either APAP (1,000 mg/6 h) or placebo (PLA) for 24 h before RE (final dose consumed immediately after RE). Muscle biopsies (vastus lateralis) were collected at rest and 1 h and 3 h after exercise. Mammalian target of rapamycin (mTOR) complex 1 signaling was assessed through immunoblot and immunohistochemistry, and mRNA expression of myogenic genes was examined via RT-qPCR. At 1 h p-rpS6 Ser240/244 was increased in both groups but to a greater extent in PLA. At 3 h p-S6K1 Thr389 was elevated only in PLA. Furthermore, localization of mTOR to the lysosome (LAMP2) in myosin heavy chain (MHC) II fibers increased 3 h after exercise only in PLA. mTOR-LAMP2 colocalization in MHC I fibers was greater in PLA vs. APAP 1 h after exercise. Myostatin mRNA expression was reduced 1 h after exercise only in PLA. MYF6 mRNA expression was increased 1 h and 3 h after exercise only in APAP. APAP consumption appears to alter the early adaptive cellular response of skeletal muscle to RE. These findings further highlight the mechanisms through which COX-inhibiting drugs impact the adaptive response of skeletal muscle to exercise. NEW & NOTEWORTHY The extent to which the cellular reaction to acetaminophen impacts the mechanisms regulating the adaptive response of human skeletal muscle to resistance exercise is not well understood. Consumption of acetaminophen before

Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

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Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

2016-07-01

Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies

Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy

DEFF Research Database (Denmark)

Sun, S; Henriksen, K; Karsdal, M A

2014-01-01

used to assess biological and clinical relevance. RESULTS: A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy...... model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up...... at a 16.4 (±4.6) % increase at day 47. CONCLUSIONS: We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy....

Alpha adrenergic receptor blockade increases capillarisation and fractional O2 extraction and lowers blood flow in contracting human skeletal muscle

DEFF Research Database (Denmark)

Mortensen, Stefan P; Egginton, Stuart; Madsen, Mads

2017-01-01

AIM: To investigate the effect of elevated basal shear stress on angiogenesis in humans, and the role of enhanced skeletal muscle capillarisation on blood flow and O2 extraction. METHODS: Limb haemodynamics and O2 extraction was measured at rest and during one-leg knee-extensor exercise (12 and 24W......) in 10 healthy untrained young men before and after 4 weeks treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day(-1) ). Corresponding biopsies were taken from the m. vastus lateralis. RESULTS: Resting leg blood flow was increased by 57% 6 hours following Terazosin treatment (P... basal capillary-to-fibre ratio was 1.69±0.08 and increased to 1.90±0.08 after treatment (Pblood flow and venous lactate levels lower (6-7%; P

Cryopreservation of human skeletal muscle impairs mitochondrial function

DEFF Research Database (Denmark)

Larsen, Steen; Wright-Paradis, C; Gnaiger, E

2012-01-01

functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...

Microdialysis and the measurement of muscle interstitial K+ during rest and exercise in humans

DEFF Research Database (Denmark)

Green, Stefan Mathias; Bülow, J; Saltin, B

1999-01-01

The purpose of this study was to examine whether microdialysis and the internal reference thallium-201 ((201)Tl) could accurately measure muscle interstitial K+ (Ki+) before, during, and after exercise. The relative loss of (201)Tl and simultaneous relative recovery of K+ were measured in vitro...

Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy

DEFF Research Database (Denmark)

Suetta, Charlotte Arneboe; Frandsen, Ulrik; Jensen, Line

2012-01-01

Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle...... atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2......-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1α and PGC-1β (1-4 days) and a ∼10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast...

Muscle injections with lidocaine improve resting fatigue and pain in patients with chronic fatigue syndrome

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Staud R

2017-06-01

Full Text Available Roland Staud,1 Taylor Kizer,1 Michael E Robinson2 1Department of Medicine, College of Medicine, 2Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA Objective: Patients with chronic fatigue syndrome (CFS complain of long-lasting fatigue and pain which are not relieved by rest and worsened by physical exertion. Previous research has implicated metaboreceptors of muscles to play an important role for chronic fatigue and pain. Therefore, we hypothesized that blocking impulse input from deep tissues with intramuscular lidocaine injections would improve not only the pain but also fatigue of CFS patients. Methods: In a double-blind, placebo-controlled study, 58 CFS patients received 20 mL of 1% lidocaine (200 mg or normal saline once into both trapezius and gluteal muscles. Study outcomes included clinical fatigue and pain, depression, and anxiety. In addition, mechanical and heat hyperalgesia were assessed and serum levels of lidocaine were obtained after the injections. Results: Fatigue ratings of CFS patients decreased significantly more after lidocaine compared to saline injections (p = 0.03. In contrast, muscle injections reduced pain, depression, and anxiety (p < 0.001, but these changes were not statistically different between lidocaine and saline (p > 0.05. Lidocaine injections increased mechanical pain thresholds of CFS patients (p = 0.04 but did not affect their heat hyperalgesia. Importantly, mood changes or lidocaine serum levels did not significantly predict fatigue reductions. Conclusion: These results demonstrate that lidocaine injections reduce clinical fatigue of CFS patients significantly more than placebo, suggesting an important role of peripheral tissues for chronic fatigue. Future investigations will be necessary to evaluate the clinical benefits of such interventions. Keywords: muscle injections, lidocaine, metaboreceptor, chronic fatigue 

Selective activation of neuromuscular compartments within the human trapezius muscle

DEFF Research Database (Denmark)

Holtermann, A; Roeleveld, K; Mork, P J

2009-01-01

of the human trapezius muscle can be independently activated by voluntary command, indicating neuromuscular compartmentalization of the trapezius muscle. The independent activation of the upper and lower subdivisions of the trapezius is in accordance with the selective innervation by the fine cranial and main...... branch of the accessory nerve to the upper and lower subdivisions. These findings provide new insight into motor control characteristics, learning possibilities, and function of the clinically relevant human trapezius muscle....

Differences in intramuscular vascular connections of human and dog latissimus dorsi muscles.

Science.gov (United States)

Yang, D; Morris, S F

1999-02-01

Distal ischemia and necrosis of the dog latissimus dorsi muscle flap used in experimental cardiomyoplasty have been reported. However, little information on the intramuscular vascular anatomy of the dog latissimus dorsi is available. It is unclear whether there are any anatomic factors relating to the muscle flap ischemia and necrosis, and whether the dog latissimus dorsi is a suitable experimental model. To study the intramuscular vascular territories in the dog latissimus dorsi muscle, and to compare the intramuscular vasculature of the dog with that of the human, 5 fresh dog cadavers and 7 fresh human cadavers were injected with a mixture of lead oxide, gelatin, and water (200 mL/kg) through the carotid artery. Both the dog and the human latissimus dorsi muscles and neurovascular pedicles were dissected and radiographed. The intramuscular vascular anatomy of the latissimus dorsi muscles was compared. Radiographs demonstrate clearly that the pattern of latissimus dorsi intramuscular anastomoses between branches of the thoracodorsal artery and the perforators of posterior intercostal arteries in the proximal half of the muscle are different between the dog and the human. In the dog muscle, vascular connections between the thoracodorsal artery and the posterior intercostal arteries are formed by reduced-caliber choke arteries, whereas four to six true anastomoses without a change in caliber between them are found in the human muscle. The portion of the latissimus dorsi muscle supplied by the dominant thoracodorsal vascular territory was 25.9% +/- 0.3% in the dog and 23.9% +/- 0.5% in the human. For further comparison, an extended vascular territory in the latissimus dorsi muscle was demonstrated, including both the thoracodorsal territory and the posterior intercostal territories. The area of the extended vascular territory was 52% +/- 0.5% of the total muscle. The dog latissimus dorsi model may not be a perfect predictor of the behavior of the human latissimus

The effect of dynamic knee-extension exercise on patellar tendon and quadriceps femoris muscle glucose uptake in humans studied by positron emission tomography

DEFF Research Database (Denmark)

Kalliokoski, Kari K; Langberg, Henning; Ryberg, Ann Kathrine

2005-01-01

Both tendon and peritendinous tissue show evidence of metabolic activity, but the effect of acute exercise on substrate turnover is unknown. We therefore examined the influence of acute exercise on glucose uptake in the patellar and quadriceps tendons during dynamic exercise in humans. Glucose...... that tendon glucose uptake is increased during exercise. However, the increase in tendon glucose uptake is less pronounced than in muscle and the increases are uncorrelated. Thus tendon glucose uptake is likely to be regulated by mechanisms independently of those regulating skeletal muscle glucose uptake....... uptake was measured in five healthy men in the patellar and quadriceps tendons and the quadriceps femoris muscle at rest and during dynamic knee-extension exercise (25 W) using positron emission tomography and [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG). Glucose uptake index was calculated by dividing...

Xanthine oxidase in human skeletal muscle following eccentric exercise

DEFF Research Database (Denmark)

Hellsten, Ylva; Frandsen, Ulrik; Orthenblad, N.

1997-01-01

the increase in xanthine oxidase in the muscle there were no detectable changes in the levels of muscle malondialdehyde or in plasma antioxidant capacity up to 4 days post-exercise. 5. It is concluded that eccentric exercise leads to an increased level of xanthine oxidase in human muscle and that the increase...

Effect of sprint cycle training on activities of antioxidant enzymes in human skeletal muscle

DEFF Research Database (Denmark)

Hellsten, Ylva; Apple, F. S.; Sjödin, B.

1996-01-01

(P anaerobic capacity in the trained muscle. The present study demonstrates that intermittent sprint cycle training that induces an enhanced capacity for anaerobic energy generation also improves......The effect of intermittent sprint cycle training on the level of muscle antioxidant enzyme protection was investigated. Resting muscle biopsies, obtained before and after 6 wk of training and 3, 24, and 72 h after the final session of an additional 1 wk of more frequent training, were analyzed...... for activities of the antioxidant enzymes glutathione peroxidase (GPX), glutathione reductase (GR), and superoxide dismutase (SOD). Activities of several muscle metabolic enzymes were determined to assess the effectiveness of the training. After the first 6-wk training period, no change in GPX, GR, or SOD...

Nutrition and muscle loss in humans during spaceflight

Science.gov (United States)

Stein, T. P.

1999-01-01

The protein loss in humans during spaceflight is partly due to a normal adaptive response to a decreased work load on the muscles involved in weight bearing. The process is mediated by changes in prostaglandin release, secondary to the decrease in tension on the affected muscles. On missions, where there is a high level of physical demands on the astronauts, there tends to be an energy deficit, which adds to the muscle protein loss and depletes the body fat reserves. While the adaptive response is a normal part of homeostasis, the additional protein loss from an energy deficit can, in the long run, have a negative effect on health and capability of humans to live and work in space and afterward return to Earth.

Protein kinase C {alpha} activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle

DEFF Research Database (Denmark)

Thomassen, Martin; Rose, Adam John; Jensen, Thomas Elbenhardt

2011-01-01

Exercise induced phosphorylation of FXYD1 is a potential important regulator of Na(+), K(+) pump activity. It was investigated if skeletal muscle contractions induce phosphorylation of FXYD1 and if Protein Kinase C a (PKCa) activity is a prerequisite for this possible mechanism. In part 1, human...... muscle biopsies were obtained at rest, after 30 s of high intensity exercise (166±31% of VO(2max)) and after a subsequent 20 min of moderate intensity exercise (79±8% of VO(2max)). In general, FXYD1 phosphorylation was increased compared to rest both after 30 s (P...

Contraction induced secretion of VEGF from skeletal muscle cells is mediated by adenosine

DEFF Research Database (Denmark)

Høier, Birgitte; Olsen, Karina; Nyberg, Michael Permin

2010-01-01

and that the contraction induced secretion of VEGF is partially mediated via adenosine acting on A(2B) adenosine receptors. Moreover, the contraction induced secretion of VEGF protein from muscle is dependent on both PKA and MAPK activation, but only the MAPK pathway appears to be adenosine dependent.......The role of adenosine and contraction for secretion of VEGF in skeletal muscle was investigated in human subjects and rat primary skeletal muscle cells. Microdialysis probes were inserted into the thigh muscle of seven male subjects and dialysate was collected at rest, during infusion of adenosine...... and contraction caused secretion of VEGF (pcontraction induced secretion of VEGF protein was abolished by the A(2B) antagonist enprofyllin and markedly reduced by inhibition of PKA or MAPK. The results demonstrate that adenosine causes secretion of VEGF from human skeletal muscle cells...

T2 mapping of muscle activity using ultrafast imaging

International Nuclear Information System (INIS)

Tawara, Noriyuki; Nitta, Osamu; Kuruma, Hironobu; Niitsu, Mamoru; Itoh, Akiyoshi

2011-01-01

Measuring exercise-induced muscle activity is essential in sports medicine. Previous studies proposed measuring transverse relaxation time (T 2 ) using muscle functional magnetic resonance imaging (mfMRI) to map muscle activity. However, mfMRI uses a spin-echo (SE) sequence that requires several minutes for acquisition. We evaluated the feasibility of T 2 mapping of muscle activity using ultrafast imaging, called fast-acquired mfMRI (fast-mfMRI), to reduce image acquisition time. The current method uses 2 pulse sequences, spin-echo echo-planar imaging (SE-EPI) and true fast imaging with steady precession (TrueFISP). SE-EPI images are used to calculate T 2 , and TrueFISP images are used to obtain morphological information. The functional image is produced by subtracting the image of muscle activity obtained using T 2 at rest from that produced after exercise. Final fast-mfMRI images are produced by fusing the functional images with the morphologic images. Ten subjects repeated ankle plantar flexion 200 times. In the fused images, the areas of activated muscle in the fast-mfMRI and SE-EPI images were identical. The geometric location of the fast-mfMRI did not differ between the morphologic and functional images. Morphological and functional information from fast-mfMRI can be applied to the human trunk, which requires limited scan duration. The difference obtained by subtracting T 2 at rest from T 2 after exercise can be used as a functional image of muscle activity. (author)

Intrinsic Resting-State Functional Connectivity in the Human Spinal Cord at 3.0 T.

Science.gov (United States)

San Emeterio Nateras, Oscar; Yu, Fang; Muir, Eric R; Bazan, Carlos; Franklin, Crystal G; Li, Wei; Li, Jinqi; Lancaster, Jack L; Duong, Timothy Q

2016-04-01

To apply resting-state functional magnetic resonance (MR) imaging to map functional connectivity of the human spinal cord. Studies were performed in nine self-declared healthy volunteers with informed consent and institutional review board approval. Resting-state functional MR imaging was performed to map functional connectivity of the human cervical spinal cord from C1 to C4 at 1 × 1 × 3-mm resolution with a 3.0-T clinical MR imaging unit. Independent component analysis (ICA) was performed to derive resting-state functional MR imaging z-score maps rendered on two-dimensional and three-dimensional images. Seed-based analysis was performed for cross validation with ICA networks by using Pearson correlation. Reproducibility analysis of resting-state functional MR imaging maps from four repeated trials in a single participant yielded a mean z score of 6 ± 1 (P 3, P 3.0-T clinical MR imaging unit and standard MR imaging protocols and hardware reveals prominent functional connectivity patterns within the spinal cord gray matter, consistent with known functional and anatomic layouts of the spinal cord.

Human skeletal muscle contains no detectable guanidinoacetic acid

DEFF Research Database (Denmark)

Ostojic, Sergej M; Ostojic, Jelena

2018-01-01

We analyzed data from previously completed trials to determine the effects of supplemental guanidinoacetic acid (GAA) on markers of muscle bioenergetics in healthy men using 1.5 T magnetic resonance spectroscopy. No detectable GAA (<0.1 μmol/L) was found in the vastus medialis muscle at baseline ...... nor at follow-up. This implies deficient GAA availability in the human skeletal muscle, suggesting absent or negligible potential for creatine synthesis from GAA inside this tissue, even after GAA loading....

Skeletal muscle gene expression in response to resistance exercise: sex specific regulation

Directory of Open Access Journals (Sweden)

Burant Charles F

2010-11-01

Full Text Available Abstract Background The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, such as resistance exercise (RE, might provide insight to the contributors of sexual dimorphism of muscle phenotypes. We used microarrays to profile the transcriptome of the biceps brachii of young men and women who underwent an acute unilateral RE session following 12 weeks of progressive training. Bilateral muscle biopsies were obtained either at an early (4 h post-exercise or late recovery (24 h post-exercise time point. Muscle transcription profiles were compared in the resting state between men (n = 6 and women (n = 8, and in response to acute RE in trained exercised vs. untrained non-exercised control muscle for each sex and time point separately (4 h post-exercise, n = 3 males, n = 4 females; 24 h post-exercise, n = 3 males, n = 4 females. A logistic regression-based method (LRpath, following Bayesian moderated t-statistic (IMBT, was used to test gene functional groups and biological pathways enriched with differentially expressed genes. Results This investigation identified extensive sex differences present in the muscle transcriptome at baseline and following acute RE. In the resting state, female muscle had a greater transcript abundance of genes involved in fatty acid oxidation and gene transcription/translation processes. After strenuous RE at the same relative intensity, the time course of the transcriptional modulation was sex-dependent. Males experienced prolonged changes while females exhibited a rapid restoration. Most of the biological processes involved in the RE-induced transcriptional regulation were observed in both males and females, but sex specificity was suggested for several signaling pathways including activation of notch signaling and TGF-beta signaling in females

Human activity and rest in situ.

Science.gov (United States)

Roenneberg, Till; Keller, Lena K; Fischer, Dorothee; Matera, Joana L; Vetter, Céline; Winnebeck, Eva C

2015-01-01

Our lives are structured by the daily alternation of activity and rest, of wake and sleep. Despite significant advances in circadian and sleep research, we still lack answers to many of the most fundamental questions about this conspicuous behavioral pattern. We strongly believe that investigating this pattern in entrained conditions, real-life and daily contexts-in situ-will help the field to elucidate some of these central questions. Here, we present two common approaches for in situ investigation of human activity and rest: the Munich ChronoType Questionnaire (MCTQ) and actimetry. In the first half of this chapter, we provide detailed instructions on how to use and interpret the MCTQ. In addition, we give an overview of the main insights gained with this instrument over the past 10 years, including some new findings on the interaction of light and age on sleep timing. In the second half of this chapter, we introduce the reader to the method of actimetry and share our experience in basic analysis techniques, including visualization, smoothing, and cosine model fitting of in situ recorded data. Additionally, we describe our new approach to automatically detect sleep from activity recordings. Our vision is that the broad use of such easy techniques in real-life settings combined with automated analyses will lead to the creation of large databases. The resulting power of big numbers will promote our understanding of such fundamental biological phenomena as sleep. © 2015 Elsevier Inc. All rights reserved.

Muscle Adaptations Following Short-Duration Bed Rest with Integrated Resistance, Interval, and Aerobic Exercise

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Hackney, Kyle J.; Scott, Jessica M.; Buxton, Roxanne; Redd-Goetchius, Elizabeth; Crowell, J. Brent; Everett, Meghan E.; Wickwire, Jason; Ryder, Jeffrey W.; Bloomberg, Jacob J.; Ploutz-Snyder, Lori L.

2011-01-01

Unloading of the musculoskeletal system during space flight results in deconditioning that may impair mission-related task performance in astronauts. Exercise countermeasures have been frequently tested during bed rest (BR) and limb suspension; however, high-intensity, short-duration exercise prescriptions have not been fully explored. PURPOSE: To determine if a high intensity resistance, interval, and aerobic exercise program could protect against muscle atrophy and dysfunction when performed during short duration BR. METHODS: Nine subjects (1 female, 8 male) performed a combination of supine exercises during 2 weeks of horizontal BR. Resistance exercise (3 d / wk) consisted of squat, leg press, hamstring curl, and heel raise exercises (3 sets, 12 repetitions). Aerobic (6 d / wk) sessions alternated continuous (75% VO2 peak) and interval exercise (30 s, 2 min, and 4 min) and were completed on a supine cycle ergometer and vertical treadmill, respectively. Muscle volumes of the upper leg were calculated pre, mid, and post-BR using magnetic resonance imaging. Maximal isometric force (MIF), rate of force development (RFD), and peak power of the lower body extensors were measured twice before BR (averaged to represent pre) and once post BR. ANOVA with repeated measures and a priori planned contrasts were used to test for differences. RESULTS: There were no changes to quadriceps, hamstring, and adductor muscle volumes at mid and post BR time points compared to pre BR (Table 1). Peak power increased significantly from 1614 +/- 372 W to 1739 +/- 359 W post BR (+7.7%, p = 0.035). Neither MIF (pre: 1676 +/- 320 N vs. post: 1711 +/- 250 N, +2.1%, p = 0.333) nor RFD (pre: 7534 +/- 1265 N/ms vs. post: 6951 +/- 1241 N/ms, -7.7%, p = 0.136) were significantly impaired post BR.

Effect of prior immobilization on muscular glucose clearance in resting and running rats

International Nuclear Information System (INIS)

Vissing, J.; Ohkuwa, Tetsuo; Ploug, T.; Galbo, H.

1988-01-01

In vitro studies have shown that prior disuse impairs the glucose clearance of red skeletal muscle because of a developed insensitivity to insulin. We studied whether an impaired glucose clearance is present in vivo in 42-h immobilized muscles of resting rats and, furthermore, whether the exercise-induced increase in glucose clearance of red muscles is affected by prior immobilization. The 2-[ 3 H]deoxy-D-glucose (2DG) bolus injection method was used to determine glucose clearance of individual muscles. At rest, glucose clearance was markedly impaired in rats with previously immobilized red muscles compared with nonimmobilized control rats. During running, glucose clearance did not differ between muscles in previously immobilized and control rats. Insulin levels were always similar in the two groups and decreased during exercise. Intracellular nonphosphorylated 2DG was present in tissues with high glucose clearances. In conclusion, 42 h of immobilization markedly impairs glucose clearance of resting red muscle fibers in vivo. Apparently, physical inactivity in particular affects steps involved in insulin-mediated action that are not part of contraction-induced glucose uptake and metabolism. Presence of intracellular 2DG shows that separate determination of phosphorylated 2DG is necessary for accurate estimates of glucose metabolism and that accumulation of phosphorylated 2DG does not accurately reflect glucose transport

Multi-frequency bioimpedance in human muscle assessment

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Bartels, Else Marie; Sørensen, Emma Rudbæk; Harrison, Adrian Paul

2015-01-01

Bioimpedance analysis (BIA) is a well-known and tested method for body mass and muscular health assessment. Multi-frequency BIA (mfBIA) equipment now makes it possible to assess a particular muscle as a whole, as well as looking at a muscle at the fiber level. The aim of this study was to test...... healthy human control subjects and three selected cases were examined to demonstrate the extent to which this method may be used clinically, and in relation to training in sport. The electrode setup is shown to affect the mfBIA parameters recorded. Our recommendation is the use of noble metal electrodes......, contracted state, and cell transport/metabolic activity, which relate to muscle performance. Our findings indicate that mfBIA provides a noninvasive, easily measurable and very precise momentary assessment of skeletal muscles....

The twitch interpolation technique for study of fatigue of human quadriceps muscle

DEFF Research Database (Denmark)

Bülow, P M; Nørregaard, J; Mehlsen, J

1995-01-01

The aim of the study was to examine if the twitch interpolation technique could be used to objectively measure fatigue in the quadriceps muscle in subjects performing submaximally. The 'true' maximum isometric quadriceps torque was determined in 21 healthy subject using the twitch interpolation...... technique. Then an endurance test was performed in which the subjects made repeated isometric contractions at 50% of the 'true' maximum torque for 4 s, separated by 6 s rest periods. During the test, the force response to single electrical stimulation (twitch amplitude) was measured at 50% and 25......). In conclusion, the twitch technique can be used for objectively measuring fatigue of the quadriceps muscle....

Morphological analysis of the hindlimb in apes and humans. I. Muscle architecture.

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Payne, R C; Crompton, R H; Isler, K; Savage, R; Vereecke, E E; Günther, M M; Thorpe, S K S; D'Août, K

2006-06-01

We present quantitative data on the hindlimb musculature of Pan paniscus, Gorilla gorilla gorilla, Gorilla gorilla graueri, Pongo pygmaeus abelii and Hylobates lar and discuss the findings in relation to the locomotor habits of each. Muscle mass and fascicle length data were obtained for all major hindlimb muscles. Physiological cross-sectional area (PCSA) was estimated. Data were normalized assuming geometric similarity to allow for comparison of animals of different size/species. Muscle mass scaled closely to (body mass)(1.0) and fascicle length scaled closely to (body mass)(0.3) in most species. However, human hindlimb muscles were heavy and had short fascicles per unit body mass when compared with non-human apes. Gibbon hindlimb anatomy shared some features with human hindlimbs that were not observed in the non-human great apes: limb circumferences tapered from proximal-to-distal, fascicle lengths were short per unit body mass and tendons were relatively long. Non-human great ape hindlimb muscles were, by contrast, characterized by long fascicles arranged in parallel, with little/no tendon of insertion. Such an arrangement of muscle architecture would be useful for locomotion in a three dimensionally complex arboreal environment.

Calprotectin is released from human skeletal muscle tissue during exercise

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Mortensen, Ole Hartvig; Andersen, Kasper; Fischer, Christian

2008-01-01

Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained...... in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at approximately 60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known...... as an acute phase reactant. Plasma calprotectin increased 5-fold following acute cycle ergometer exercise in humans, but not following IL-6 infusion. To identify the source of calprotectin, healthy males (n = 7) performed two-legged dynamic knee extensor exercise for 3 h with a work load of approximately 50...

Effects of β-hydroxy-β-methylbutyrate on skeletal muscle mitochondrial content and dynamics, and lipids after 10 days of bed rest in older adults.

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Standley, Robert A; Distefano, Giovanna; Pereira, Suzette L; Tian, Min; Kelly, Owen J; Coen, Paul M; Deutz, Nicolaas E P; Wolfe, Robert R; Goodpaster, Bret H

2017-11-01

Loss of muscle mass during periods of disuse likely has negative health consequences for older adults. We have previously shown that β-hydroxy-β-methylbutyrate (HMB) supplementation during 10 days of strict bed rest (BR) attenuates the loss of lean mass in older adults. To elucidate potential molecular mechanisms of HMB effects on muscle during BR and resistance training rehabilitation (RT), we examined mediators of skeletal muscle mitochondrial dynamics, autophagy and atrophy, and intramyocellular lipids. Nineteen older adults (60-76 yr) completed 10 days BR followed by 8-wk RT rehabilitation. Subjects were randomized to either HMB (3 g/day HMB; n = 11) or control (CON; n = 8) groups. Skeletal muscle cross-sectional area (CSA) was determined by histology from percutaneous vastus lateralis biopsies. We measured protein markers of mitochondrial content [oxidative phosphorylation (OXPHOS)], fusion and fission (MFN2, OPA1, FIS1, and DRP1), autophagy (Beclin1, LC3B, and BNIP3), and atrophy [poly-ubiquinated proteins (poly-ub)] by Western blot. Fatty acid composition of several lipid classes in skeletal muscle was measured by infusion-MS analysis. Poly-ub proteins and OXPHOS complex I increased in both groups following BR ( P HMB group ( P = 0.055). RT rehabilitation increased OXPHOS complex II protein ( P HMB group. In addition, higher levels of DRP1 and MFN2 were maintained in the HMB group after RT ( P HMB influences mitochondrial dynamics and lipid metabolism during disuse atrophy and rehabilitation. NEW & NOTEWORTHY Mitochondrial content and dynamics remained unchanged over 10 days of BR in older adults. HMB stimulated intramuscular lipid storage as triacylglycerol following 10 days of bed rest (BR) and maintained higher mitochondrial OXPHOS content and dynamics during the 8-wk resistance exercise rehabilitation program. Copyright © 2017 the American Physiological Society.

Enhanced Local Skeletal Muscle Oxidative Capacity and Microvascular Blood Flow Following 7-Day Ischemic Preconditioning in Healthy Humans

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Owen Jeffries

2018-05-01

Full Text Available Ischemic preconditioning (IPC, which involves intermittent periods of ischemia followed by reperfusion, is an effective clinical intervention that reduces the risk of myocardial injury and confers ischemic tolerance to skeletal muscle. Repeated bouts of IPC have been shown to stimulate long-term changes vascular function, however, it is unclear what metabolic adaptations may occur locally in the muscle. Therefore, we investigated 7 days of bilateral lower limb IPC (4 × 5 min above limb occlusion pressure (220 mmHg; n = 10, or sham (20 mmHg; n = 10, on local muscle oxidative capacity and microvascular blood flow. Oxidative capacity was measured using near-infrared spectroscopy (NIRS during repeated short duration arterial occlusions (300 mmHg. Microvascular blood flow was assessed during the recovery from submaximal isometric plantar flexion exercises at 40 and 60% of maximal voluntary contraction (MVC. Following the intervention period, beyond the late phase of protection (72 h, muscle oxidative recovery kinetics were speeded by 13% (rate constant pre 2.89 ± 0.47 min-1 vs. post 3.32 ± 0.69 min-1; P < 0.05 and resting muscle oxygen consumption (mO2 was reduced by 16.4% (pre 0.39 ± 0.16%.s-1 vs. post 0.33 ± 0.14%.s-1; P < 0.05. During exercise, changes in deoxygenated hemoglobin (HHb from rest to steady state were reduced at 40 and 60% MVC (16 and 12%, respectively, P < 0.05 despite similar measures of total hemoglobin (tHb. At the cessation of exercise, the time constant for recovery in oxygenated hemoglobin (O2Hb was accelerated at 40 and 60% MVC (by 33 and 43%, respectively suggesting enhanced reoxygenation in the muscle. No changes were reported for systemic measures of resting heart rate or blood pressure. In conclusion, repeated bouts of IPC over 7 consecutive days increased skeletal muscle oxidative capacity and microvascular muscle blood flow. These findings are consistent with enhanced mitochondrial and vascular function following

Hypoxia Aggravates Inactivity-Related Muscle Wasting

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Tadej Debevec

2018-05-01

Full Text Available Poor musculoskeletal state is commonly observed in numerous clinical populations such as chronic obstructive pulmonary disease (COPD and heart failure patients. It, however, remains unresolved whether systemic hypoxemia, typically associated with such clinical conditions, directly contributes to muscle deterioration. We aimed to experimentally elucidate the effects of systemic environmental hypoxia upon inactivity-related muscle wasting. For this purpose, fourteen healthy, male participants underwent three 21-day long interventions in a randomized, cross-over designed manner: (i bed rest in normoxia (NBR; PiO2 = 133.1 ± 0.3 mmHg, (ii bed rest in normobaric hypoxia (HBR; PiO2 = 90.0 ± 0.4 mmHg and ambulatory confinement in normobaric hypoxia (HAmb; PiO2 = 90.0 ± 0.4 mmHg. Peripheral quantitative computed tomography and vastus lateralis muscle biopsies were performed before and after the interventions to obtain thigh and calf muscle cross-sectional areas and muscle fiber phenotype changes, respectively. A significant reduction of thigh muscle size following NBR (-6.9%, SE 0.8%; P < 0.001 was further aggravated following HBR (-9.7%, SE 1.2%; P = 0.027. Bed rest-induced muscle wasting in the calf was, by contrast, not exacerbated by hypoxic conditions (P = 0.47. Reductions in both thigh (-2.7%, SE 1.1%, P = 0.017 and calf (-3.3%, SE 0.7%, P < 0.001 muscle size were noted following HAmb. A significant and comparable increase in type 2× fiber percentage of the vastus lateralis muscle was noted following both bed rest interventions (NBR = +3.1%, SE 2.6%, HBR = +3.9%, SE 2.7%, P < 0.05. Collectively, these data indicate that hypoxia can exacerbate inactivity-related muscle wasting in healthy active participants and moreover suggest that the combination of both, hypoxemia and lack of activity, as seen in COPD patients, might be particularly harmful for muscle tissue.

Duchenne Muscular Dystrophy Gene Expression in Normal and Diseased Human Muscle

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Oronzi Scott, M.; Sylvester, J. E.; Heiman-Patterson, T.; Shi, Y.-J.; Fieles, W.; Stedman, H.; Burghes, A.; Ray, P.; Worton, R.; Fischbeck, K. H.

1988-03-01

A probe for the 5' end of the Duchenne muscular dystrophy (DMD) gene was used to study expression of the gene in normal human muscle, myogenic cell cultures, and muscle from patients with DMD. Expression was found in RNA from normal fetal muscle, adult cardiac and skeletal muscle, and cultured muscle after myoblast fusion. In DMD muscle, expression of this portion of the gene was also revealed by in situ RNA hybridization, particularly in regenerating muscle fibers.

Near infrared spectroscopy of human muscles

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Gasbarrone, R.; Currà, A.; Cardillo, A.; Bonifazi, G.; Serranti, S.

2018-02-01

Optical spectroscopy is a powerful tool in research and industrial applications. Its properties of being rapid, non-invasive and not destructive make it a promising technique for qualitative as well as quantitative analysis in medicine. Recent advances in materials and fabrication techniques provided portable, performant, sensing spectrometers readily operated by user-friendly cabled or wireless systems. We used such a system to test whether infrared spectroscopy techniques, currently utilized in many areas as primary/secondary raw materials sector, cultural heritage, agricultural/food industry, environmental remote and proximal sensing, pharmaceutical industry, etc., could be applied in living humans to categorize muscles. We acquired muscles infrared spectra in the Vis-SWIR regions (350-2500 nm), utilizing an ASD FieldSpec 4 Standard-Res Spectroradiometer with a spectral sampling capability of 1.4 nm at 350-1000 nm and 1.1 nm at 1001-2500 nm. After a preliminary spectra pre-processing (i.e. signal scattering reduction), Principal Component Analysis (PCA) was applied to identify similar spectral features presence and to realize their further grouping. Partial Least-Squares Discriminant Analysis (PLS-DA) was utilized to implement discrimination/prediction models. We studied 22 healthy subjects (age 25-89 years, 11 females), by acquiring Vis-SWIR spectra from the upper limb muscles (i.e. biceps, a forearm flexor, and triceps, a forearm extensor). Spectroscopy was performed in fixed limb postures (elbow angle approximately 90‡). We found that optical spectroscopy can be applied to study human tissues in vivo. Vis-SWIR spectra acquired from the arm detect muscles, distinguish flexors from extensors.

Three-dimensional geometrical changes of the human tibialis anterior muscle and its central aponeurosis measured with three-dimensional ultrasound during isometric contractions

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Brent J. Raiteri

2016-07-01

Full Text Available Background. Muscles not only shorten during contraction to perform mechanical work, but they also bulge radially because of the isovolumetric constraint on muscle fibres. Muscle bulging may have important implications for muscle performance, however quantifying three-dimensional (3D muscle shape changes in human muscle is problematic because of difficulties with sustaining contractions for the duration of an in vivo scan. Although two-dimensional ultrasound imaging is useful for measuring local muscle deformations, assumptions must be made about global muscle shape changes, which could lead to errors in fully understanding the mechanical behaviour of muscle and its surrounding connective tissues, such as aponeurosis. Therefore, the aims of this investigation were (a to determine the intra-session reliability of a novel 3D ultrasound (3DUS imaging method for measuring in vivo human muscle and aponeurosis deformations and (b to examine how contraction intensity influences in vivo human muscle and aponeurosis strains during isometric contractions. Methods. Participants (n = 12 were seated in a reclined position with their left knee extended and ankle at 90° and performed isometric dorsiflexion contractions up to 50% of maximal voluntary contraction. 3DUS scans of the tibialis anterior (TA muscle belly were performed during the contractions and at rest to assess muscle volume, muscle length, muscle cross-sectional area, muscle thickness and width, fascicle length and pennation angle, and central aponeurosis width and length. The 3DUS scan involved synchronous B-mode ultrasound imaging and 3D motion capture of the position and orientation of the ultrasound transducer, while successive cross-sectional slices were captured by sweeping the transducer along the muscle. Results. 3DUS was shown to be highly reliable across measures of muscle volume, muscle length, fascicle length and central aponeurosis length (ICC ≥ 0.98, CV < 1%. The TA remained

Bilateral responses of upper limb muscles to transcranial magnetic stimulation in human subjects.

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Bawa, P; Hamm, J D; Dhillon, P; Gross, P A

2004-10-01

Anatomical and behavioural work on primates has shown bilateral innervation of axial and proximal limb muscles, and contralateral control of distal limb muscles. The following study examined if a clear boundary exists between the distal and proximal upper limb muscles that are controlled contralaterally or bilaterally. The right motor cortical area representing the upper limb was stimulated, while surface EMG was recorded bilaterally from various upper limb muscles during rest and phasic voluntary contractions. Peak-to-peak amplitude of motor evoked potential (MEP) was measured for each muscle on both sides. The ratio R = (ipsilateral MEP: contralateral MEP) was calculated for seven pairs of muscles. For each of the seven pairs, R was less than 1.0, implying that for each muscle and subject, the contralateral control is stronger. The boundary where R changed from almost zero to a clearly measurable magnitude depended on the subject. Ipsilateral MEPs from trapezius and pectoralis could be recorded with a small background contraction from almost all subjects; on the other hand, in deltoid and biceps brachii, ipsilateral MEPs were observed only with bimanual phasic contractions. The forearm and hand muscles, in general, did not show any ipsilateral MEPs. Major differences between subjects lay in the presence or the absence of ipsilateral MEPs in biceps brachii and deltoid, without defining a sharp boundary between proximal and distal muscles.

Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6

DEFF Research Database (Denmark)

Steensberg, A; Van Hall, Gerrit; Osada, T

2000-01-01

1. Plasma interleukin (IL)-6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL-The question addressed in the present study was whether the IL-6 production by contracting skeletal muscle is of such a magnitude that it can account for the IL...... and every hour during the exercise. Leg blood flow was measured in parallel by the ultrasound Doppler technique. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA). 3. Arterial plasma concentrations for IL-6 increased 19-fold compared to rest. The a-fv difference for IL-6 over the exercising leg...... followed the same pattern as did the net IL-6 release. Over the resting leg, there was no significant a-fv difference or net IL-6 release. The work was produced by 2.5 kg of active muscle, which means that during the last 2 h of exercise, the median IL-6 production was 6.8 ng min-1 (kg active muscle)-1...

Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise

DEFF Research Database (Denmark)

Rosendal, Lars; Søgaard, Karen; Kjaer, Michael

2005-01-01

Interleukin (IL)-6, which is released from muscle tissue during intense exercise, possesses important metabolic and probably anti-inflammatory properties. To evaluate the IL-6 response to low-intensity exercise, we conducted two studies: 1) a control study with insertion of microdialysis catheters...... in muscle and determination of interstitial muscle IL-6 response over 2 h of rest and 2) an exercise study to investigate the IL-6 response to 20 min of repetitive low-force exercise. In both studies, a microdialysis catheter (cutoff: 3,000 kDa) was inserted into the upper trapezius muscle of six male...... subjects, and the catheters were perfused with Ringer-acetate at 5 microl/min. Venous plasma samples were taken in the exercise study. The insertion of microdialysis catheters into muscle resulted in an increase in IL-6 from 8 +/- 0 to 359 +/- 171 and 484 +/- 202 pg/ml after 65 and 110 min, respectively (P...

Localization of nitric oxide synthase in human skeletal muscle

DEFF Research Database (Denmark)

Frandsen, Ulrik; Lopez-Figueroa, M.; Hellsten, Ylva

1996-01-01

The present study investigated the cellular localization of the neuronal type I and endothelial type III nitric oxide synthase in human skeletal muscle. Type I NO synthase immunoreactivity was found in the sarcolemma and the cytoplasm of all muscle fibres. Stronger immunoreactivity was expressed...

Human skeletal muscle drug transporters determine local exposure and toxicity of statins.

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Knauer, Michael J; Urquhart, Bradley L; Meyer zu Schwabedissen, Henriette E; Schwarz, Ute I; Lemke, Christopher J; Leake, Brenda F; Kim, Richard B; Tirona, Rommel G

2010-02-05

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are important drugs used in the treatment and prevention of cardiovascular disease. Although statins are well tolerated, many patients develop myopathy manifesting as muscle aches and pain. Rhabdomyolysis is a rare but severe toxicity of statins. Interindividual differences in the activities of hepatic membrane drug transporters and metabolic enzymes are known to influence statin plasma pharmacokinetics and risk for myopathy. Interestingly, little is known regarding the molecular determinants of statin distribution into skeletal muscle and its relevance to toxicity. We sought to identify statin transporters in human skeletal muscle and determine their impact on statin toxicity in vitro. We demonstrate that the uptake transporter OATP2B1 (human organic anion transporting polypeptide 2B1) and the efflux transporters, multidrug resistance-associated protein (MRP)1, MRP4, and MRP5 are expressed on the sarcolemmal membrane of human skeletal muscle fibers and that atorvastatin and rosuvastatin are substrates of these transporters when assessed using a heterologous expression system. In an in vitro model of differentiated, primary human skeletal muscle myoblast cells, we demonstrate basal membrane expression and drug efflux activity of MRP1, which contributes to reducing intracellular statin accumulation. Furthermore, we show that expression of human OATP2B1 in human skeletal muscle myoblast cells by adenoviral vectors increases intracellular accumulation and toxicity of statins and such effects were abrogated when cells overexpressed MRP1. These results identify key membrane transporters as modulators of skeletal muscle statin exposure and toxicity.

Effects of thyroid hormone on Na sup + -K sup + transport in resting and stimulated rat skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Everts, M.E.; Clausen, T. (Aarhus Univ. (Denmark))

1988-11-01

The effects of hypothyroidism and 3,5,3{prime}-triiodothyronine (T{sub 3}) treatment on passive Na{sup +}-K{sup +} fluxes and Na{sup +}-K{sup +} pump concentration were investigated in isolated rat muscle. Within 12 h after a single dose of T{sub 3} (20 {mu}g/100 g body wt), K{sup +} efflux had increased by 21% in soleus and by 20% in extensor digitorum longus muscle. In the presence of ouabain, even larger effects were observed. These changes were associated with a 12% rise in amiloride-suppressible Na{sup +} influx but no significant increase in ({sup 3}H)ouabain binding site concentration. After 3 days of T{sub 3} treatment, the stimulating effect on K{sup +} efflux and Na{sup +} influx in soleus reached a plateau {approximately}80 and 40% above control levels, respectively, whereas the maximum increase in ({sup 3}H)ouabain binding site concentration (103%) was only fully developed after 8 days. Hypothyroidism decreased {sup 86}Rb efflux by 30%. The efflux of K{sup +} and the influx of Na{sup +} per contraction (both {approximately}7 nmol/g wet wt) as well as the net loss of K{sup +} induced by electrical stimulation were unaffected by T{sub 3} treatment. The rise in resting K{sup +} efflux after 12-24 h of T{sub 3} treatment could be partly blocked by dantrolene or trifluoroperazine, indicating that an increase in the cytoplasmic Ca{sup 2+} concentration may contribute to the early rise in K{sup +} efflux. It is concluded that the early rise in the resting passive leaks of Na{sup +} and K{sup +} induced by T{sub 3} is a major driving force for Na{sup +}-K{sup +} pump synthesis.

Effects of graded exercise-induced dehydration and rehydration on circulatory markers of oxidative stress across the resting and exercising human leg.

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Laitano, Orlando; Kalsi, Kameljit Kaur; Pearson, James; Lotlikar, Makra; Reischak-Oliveira, Alvaro; González-Alonso, José

2012-05-01

Exercise in the heat enhances oxidative stress markers in the human circulation, but the contribution of active skeletal muscle and the influence of hydration status remain unknown. To address this question, we measured leg exchange of glutathione (GSH), glutathione disulfide (GSSG), superoxide dismutase activity (SOD) and isoprostanes in seven males at rest and during submaximal one-legged knee extensor exercise in the following four conditions: (1) control euhydration (0% reduction in body mass), (2) mild-dehydration (2%), (3) moderate-dehydration (3.5%), (4) rehydration (0%). In all resting and control exercise conditions, a net GSH uptake was observed across the leg. In contrast, a significant leg release of GSH into the circulation (-354 ± 221 μmol/min, P exercise with moderate-dehydration, which was still present following full rehydration (-206 ± 122 μmol/min, P exercise, mild and moderate-dehydration decreased both femoral venous erythrocyte SOD activity (195 ± 6 vs. 180 ± 5 U/L, P release GSH into the circulation under moderate dehydration and subsequent rehydration, possibly to enhance the antioxidant defense.

Metabolic control of muscle blood flow during exercise in humans

DEFF Research Database (Denmark)

Boushel, Robert Christopher

2003-01-01

that combined blockade of NOS and PGI2, and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans. Combined vasodilator blockade studies offer the potential to uncover important interactions and compensatory vasodilator responses. The signaling pathways that link metabolic events evoked...... to exert control of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarization factor (EDHF) are possible mediators of muscle vasodilation during exercise. In humans, adenosine has been shown to contribute to functional hyperemia as blood flow...... by muscle contraction to vasodilatory signals in the local vascular bed remains an important area of study....

Observational Study on the Occurrence of Muscle Spindles in Human Digastric and Mylohyoideus Muscles

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Daniele Saverino

2014-01-01

Full Text Available Although the occurrence of muscle spindles (MS is quite high in most skeletal muscles of humans, few MS, or even absence, have been reported in digastric and mylohyoideus muscles. Even if this condition is generally accepted and quoted in many papers and books, observational studies are scarce and based on histological sections of a low number of specimens. The aim of the present study is to confirm previous data, assessing MS number in a sample of digastric and mylohyoideus muscles. We investigated 11 digastric and 6 mylohyoideus muscles from 13 donors. Muscle samples were embedded in paraffin wax, cross-sectioned in a rostrocaudal direction, and stained using haematoxylin-eosin. A mean of 5.1 ± 1.1 (range 3–7 MS was found in digastric muscles and mean of 0.5 ± 0.8 (range 0–2 in mylohyoideus muscles. A significant difference (P<0.001 was found with the control sample, confirming the correctness of the histological procedure. Our results support general belief that the absolute number of spindles is sparse in digastric and mylohyoideus muscles. External forces, such as food resistance during chewing or gravity, do not counteract jaw-opening muscles. It is conceivable that this condition gives them a limited proprioceptive importance and a reduced need for having specific receptors as MS.

Regulation of increased blood flow (hyperemia) to muscles during exercise: a hierarchy of competing physiological needs.

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Joyner, Michael J; Casey, Darren P

2015-04-01

This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans. The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed. In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them. We highlight the very high muscle blood flow responses to exercise discovered in the 1980s. We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows. Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans. At this time, no one dominant dilator mechanism accounts for exercise hyperemia. Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans. Copyright © 2015 the American Physiological Society.

Artificial muscle: the human chimera is the future.

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Tozzi, P

2011-12-14

Severe heart failure and cerebral stroke are broadly associated with the impairment of muscular function that conventional treatments struggle to restore. New technologies enable the construction of "smart" materials that could be of great help in treating diseases where the main problem is muscle weakness. These materials "behave" similarly to biological systems, because the material directly converts energy, for example electrical energy into movement. The extension and contraction occur silently like in natural muscles. The real challenge is to transfer this amazing technology into devices that restore or replace the mechanical function of failing muscle. Cardiac assist devices based on artificial muscle technology could envelope a weak heart and temporarily improve its systolic function, or, if placed on top of the atrium, restore the atrial kick in chronic atrial fibrillation. Artificial sphincters could be used to treat urinary incontinence after prostatectomy or faecal incontinence associated with stomas. Artificial muscles can restore the ability of patients with facial paralysis due to stroke or nerve injury to blink. Smart materials could be used to construct an artificial oesophagus including peristaltic movement and lower oesophageal sphincter function to replace the diseased oesophagus thereby avoiding the need for laparotomy to mobilise stomach or intestine. In conclusion, in the near future, smart devices will integrate with the human body to fill functional gaps due to organ failure, and so create a human chimera.

The effect of sustained low-intensity contractions on supraspinal fatigue in human elbow flexor muscles

DEFF Research Database (Denmark)

Søgaard, Karen; Gandevia, Simon C; Todd, Gabrielle

2006-01-01

Subjects quickly fatigue when they perform maximal voluntary contractions (MVCs). Much of the loss of force is from processes within muscle (peripheral fatigue) but some occurs because voluntary activation of the muscle declines (central fatigue). The role of central fatigue during submaximal...... contractions is not clear. This study investigated whether central fatigue developed during prolonged low-force voluntary contractions. Subjects (n=9) held isometric elbow flexions of 15% MVC for 43 min. Voluntary activation was measured during brief MVCs every 3 min. During each MVC, transcranial magnetic...... several minutes while MVC torque only returned to approximately 85% baseline. The resting twitch showed no recovery. Thus, as well as fatigue in the muscle, the prolonged low-force contraction produced progressive central fatigue, and some of this impairment of the subjects' ability to drive the muscle...

K+ as a vasodilator in resting human muscle: implications for exercise hyperaemia

DEFF Research Database (Denmark)

Juel, C; Olsen, S; Rentsch, R L

2007-01-01

AIM: Potassium (K(+)) released from contracting skeletal muscle is considered a vasodilatory agent. This concept is mainly based on experiments infusing non-physiological doses of K(+). The aim of the present study was to investigate the role of K(+) in blood flow regulation. METHODS: We measured...... leg blood flow (LBF) and arterio-venous (A-V) O(2) difference in 13 subjects while infusing K(+) into the femoral artery at a rate of 0.2, 0.4, 0.6 and 0.8 mmol min(-1). RESULTS: The lowest dose increased the calculated femoral artery plasma K(+) concentration by approx.1 mmol L(-1). Graded K......(+) infusions increased LBF from 0.39 +/- 0.06 to 0.56 +/- 0.13, 0.58 +/- 0.17, 0.61 +/- 0.11 and 0.71 +/- 0.17 L min(-1), respectively, whereas the leg A-V O(2) difference decreased from 74 +/- 9 to 60 +/- 12, 52 +/- 11, 53 +/- 9 and 45 +/- 7 mL L(-1), respectively (P

Mitochondrial dysfunction in human skeletal muscle biopsies of lipid storage disorder.

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Debashree, Bandopadhyay; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Natarajan, Archana; Christopher, Rita; Nalini, Atchayaram; Bindu, Parayil Sankaran; Gayathri, Narayanappa; Srinivas Bharath, Muchukunte Mukunda

2018-02-09

Mitochondria regulate the balance between lipid metabolism and storage in the skeletal muscle. Altered lipid transport, metabolism and storage influence the bioenergetics, redox status and insulin signalling, contributing to cardiac and neurological diseases. Lipid storage disorders (LSDs) are neurological disorders which entail intramuscular lipid accumulation and impaired mitochondrial bioenergetics in the skeletal muscle causing progressive myopathy with muscle weakness. However, the mitochondrial changes including molecular events associated with impaired lipid storage have not been completely understood in the human skeletal muscle. We carried out morphological and biochemical analysis of mitochondrial function in muscle biopsies of human subjects with LSDs (n = 7), compared to controls (n = 10). Routine histology, enzyme histochemistry and ultrastructural analysis indicated altered muscle cell morphology and mitochondrial structure. Protein profiling of the muscle mitochondria from LSD samples (n = 5) (vs. control, n = 5) by high-throughput mass spectrometric analysis revealed that impaired metabolic processes could contribute to mitochondrial dysfunction and ensuing myopathy in LSDs. We propose that impaired fatty acid and respiratory metabolism along with increased membrane permeability, elevated lipolysis and altered cristae entail mitochondrial dysfunction in LSDs. Some of these mechanisms were unique to LSD apart from others that were common to dystrophic and inflammatory muscle pathologies. Many differentially regulated mitochondrial proteins in LSD are linked with other human diseases, indicating that mitochondrial protection via targeted drugs could be a treatment modality in LSD and related metabolic diseases. © 2018 International Society for Neurochemistry.

Brain entropy and human intelligence: A resting-state fMRI study

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Calderone, Daniel; Morales, Leah J.

2018-01-01

Human intelligence comprises comprehension of and reasoning about an infinitely variable external environment. A brain capable of large variability in neural configurations, or states, will more easily understand and predict variable external events. Entropy measures the variety of configurations possible within a system, and recently the concept of brain entropy has been defined as the number of neural states a given brain can access. This study investigates the relationship between human intelligence and brain entropy, to determine whether neural variability as reflected in neuroimaging signals carries information about intellectual ability. We hypothesize that intelligence will be positively associated with entropy in a sample of 892 healthy adults, using resting-state fMRI. Intelligence is measured with the Shipley Vocabulary and WASI Matrix Reasoning tests. Brain entropy was positively associated with intelligence. This relation was most strongly observed in the prefrontal cortex, inferior temporal lobes, and cerebellum. This relationship between high brain entropy and high intelligence indicates an essential role for entropy in brain functioning. It demonstrates that access to variable neural states predicts complex behavioral performance, and specifically shows that entropy derived from neuroimaging signals at rest carries information about intellectual capacity. Future work in this area may elucidate the links between brain entropy in both resting and active states and various forms of intelligence. This insight has the potential to provide predictive information about adaptive behavior and to delineate the subdivisions and nature of intelligence based on entropic patterns. PMID:29432427

Brain entropy and human intelligence: A resting-state fMRI study.

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Saxe, Glenn N; Calderone, Daniel; Morales, Leah J

2018-01-01

Human intelligence comprises comprehension of and reasoning about an infinitely variable external environment. A brain capable of large variability in neural configurations, or states, will more easily understand and predict variable external events. Entropy measures the variety of configurations possible within a system, and recently the concept of brain entropy has been defined as the number of neural states a given brain can access. This study investigates the relationship between human intelligence and brain entropy, to determine whether neural variability as reflected in neuroimaging signals carries information about intellectual ability. We hypothesize that intelligence will be positively associated with entropy in a sample of 892 healthy adults, using resting-state fMRI. Intelligence is measured with the Shipley Vocabulary and WASI Matrix Reasoning tests. Brain entropy was positively associated with intelligence. This relation was most strongly observed in the prefrontal cortex, inferior temporal lobes, and cerebellum. This relationship between high brain entropy and high intelligence indicates an essential role for entropy in brain functioning. It demonstrates that access to variable neural states predicts complex behavioral performance, and specifically shows that entropy derived from neuroimaging signals at rest carries information about intellectual capacity. Future work in this area may elucidate the links between brain entropy in both resting and active states and various forms of intelligence. This insight has the potential to provide predictive information about adaptive behavior and to delineate the subdivisions and nature of intelligence based on entropic patterns.

Muscle protein degradation and amino acid metabolism during prolonged knee-extensor exercise in humans

DEFF Research Database (Denmark)

Van Hall, Gerrit; Saltin, B; Wagenmakers, A J

1999-01-01

to a substantial increase in net muscle protein degradation, and that a lowering of the starting muscle glycogen content leads to a further increase. The carbon atoms of the branched-chain amino acids (BCAA), glutamate, aspartate and asparagine, liberated by protein degradation, and the BCAA and glutamate......The aim of this study was to investigate whether prolonged one-leg knee-extensor exercise enhances net protein degradation in muscle with a normal or low glycogen content. Net amino acid production, as a measure of net protein degradation, was estimated from leg exchange and from changes...... in the concentrations of amino acids that are not metabolized in skeletal muscle. Experiments were performed at rest and during one-leg knee-extensor exercise in six subjects having one leg with a normal glycogen content and the other with a low glycogen content. Exercise was performed for 90 min at a workload of 60...

The acute response of pericytes to muscle-damaging eccentric contraction and protein supplementation in human skeletal muscle.

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De Lisio, Michael; Farup, Jean; Sukiennik, Richard A; Clevenger, Nicole; Nallabelli, Julian; Nelson, Brett; Ryan, Kelly; Rahbek, Stine K; de Paoli, Frank; Vissing, Kristian; Boppart, Marni D

2015-10-15

Skeletal muscle pericytes increase in quantity following eccentric exercise (ECC) and contribute to myofiber repair and adaptation in mice. The purpose of the present investigation was to examine pericyte quantity in response to muscle-damaging ECC and protein supplementation in human skeletal muscle. Male subjects were divided into protein supplement (WHY; n = 12) or isocaloric placebo (CHO; n = 12) groups and completed ECC using an isokinetic dynamometer. Supplements were consumed 3 times/day throughout the experimental time course. Biopsies were collected prior to (PRE) and 3, 24, 48, and 168 h following ECC. Reflective of the damaging protocol, integrin subunits, including α7, β1A, and β1D, increased (3.8-fold, 3.6-fold and 3.9-fold, respectively, P muscle-damaging ECC increases α7β1 integrin content in human muscle, yet pericyte quantity is largely unaltered. Future studies should focus on the capacity for ECC to influence pericyte function, specifically paracrine factor release as a mechanism toward pericyte contribution to repair and adaptation postexercise. Copyright © 2015 the American Physiological Society.

Exercise increases circulating GDF15 in humans

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Maximilian Kleinert

2018-03-01

Full Text Available Objective: The growth differentiation factor 15 (GDF15 is a stress-sensitive circulating factor that regulates systemic energy balance. Since exercise is a transient physiological stress that has pleiotropic effects on whole-body energy metabolism, we herein explored the effect of exercise on a circulating GDF15 levels and b GDF15 release from skeletal muscle in humans. Methods: Seven healthy males either rested or exercised at 67% of their VO2max for 1 h and blood was sampled from the femoral artery and femoral vein before, during, and after exercise. Plasma GDF15 concentrations were determined in these samples. Results: Plasma GDF15 levels increased 34% with exercise (p < 0.001 and further increased to 64% above resting values at 120 min (p < 0.001 after the cessation of exercise. There was no difference between the arterial and venous GDF15 concentration before, during, and after exercise. During a resting control trial, GDF15 levels measured in the same subjects were unaltered. Conclusions: Vigorous submaximal exercise increases circulating GDF15 levels in humans, but skeletal muscle tissue does not appear to be the source. Keywords: Skeletal muscle, Growth differentiation factor 15, Recovery, Physical activity

Effect of prior immobilization on muscular glucose clearance in resting and running rats

DEFF Research Database (Denmark)

Vissing, J; Ohkuwa, T; Ploug, Thorkil

1988-01-01

with nonimmobilized control rats (red gastrocnemius 0.46 +/- 0.02 vs. 0.99 +/- 0.08 and soleus 1.10 +/- 0.30 vs. 3.97 +/- 0.54 ml.min-1.100 g-1, P less than 0.005). During running (18 m/min), glucose clearance did not differ between muscles in previously immobilized and control rats. Insulin levels were always......In vitro studies have shown that prior disuse impairs the glucose clearance of red skeletal muscle because of a developed insensitivity to insulin. We studied whether an impaired glucose clearance is present in vivo in 42-h immobilized muscles of resting rats and, furthermore, whether the exercise......-induced increase in glucose clearance of red muscles is affected by prior immobilization. The 2-[3H]deoxy-D-glucose (2DG) bolus injection method was used to determine glucose clearance of individual muscles. At rest, glucose clearance was markedly impaired in rats with previously immobilized red muscles compared...

Intermuscular force transmission between human plantarflexor muscles in vivo

DEFF Research Database (Denmark)

Bojsen-Møller, Jens; Schwartz, Sidse; Kalliokoski, Kari K

2010-01-01

of the present study was to investigate if intermuscular force transmission occurs within and between human plantarflexor muscles in vivo. Seven subjects performed four types of either active contractile tasks or passive joint manipulations: passive knee extension, voluntary isometric plantarflexion, voluntary...... surae muscles was seen during passive hallux extension. Large interindividual differences with respect to deep plantarflexor activation during voluntary contractions were observed. The present results suggest that force may be transmitted between the triceps surae muscles in vivo, while only limited...

Terrestrial applications of bone and muscle research in microgravity

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Booth, F. W.

1994-08-01

Major applications to people on Earth are possible from NASA-sponsored research on bone and muscle which is conducted either in microgravity or on Earth using models mimicking microgravity. In microgravity bone and muscle mass are lost. Humans experience a similar loss under certain conditions on Earth. Bone and muscle loss exist on Earth as humans age from adulthood to senescence, during limb immobilization for healing of orthopedic injuries, during wheelchair confinement because of certain diseases, and during chronic bed rest prescribed for curing of diseases. NASA-sponsored research is dedicated to learning both what cause bone and muscle loss as well as finding out how to prevent this loss. The health ramifications of these discoveries will have major impact. Objective 1.6 of Healthy People 2000, a report from the U.S. Department of Health and Human Services, states that the performance of physical activities that improve muscular strength, muscular endurance, and flexibility is particularly important to maintaining functional independence and social integration in older adults /1/. This objective further states that these types of physical activities are important because they may protect against disability, an event which costs the U.S. economy hugh sums of money. Thus NASA research related to bone and muscle loss has potential major impact on the quality of life in the U.S. Relative to its potential health benefits, NASA and Congressional support of bone and muscle research is funded is a very low level.

Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

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Fritzen, Andreas M.; Madsen, Agnete B.; Kleinert, Maximilian; Treebak, Jonas T.; Lundsgaard, Anne‐Marie; Jensen, Thomas E.; Richter, Erik A.; Wojtaszewski, Jørgen; Kiens, Bente

2016-01-01

Key points Regulation of autophagy in human muscle in many aspects differs from the majority of previous reports based on studies in cell systems and rodent muscle.An acute bout of exercise and insulin stimulation reduce human muscle autophagosome content.An acute bout of exercise regulates autophagy by a local contraction‐induced mechanism.Exercise training increases the capacity for formation of autophagosomes in human muscle.AMPK activation during exercise seems insufficient to regulate autophagosome content in muscle, while mTORC1 signalling via ULK1 probably mediates the autophagy‐inhibiting effect of insulin. Abstract Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one‐legged exercise, one‐legged exercise training and subsequent insulin stimulation in exercised and non‐exercised human muscle. Acute one‐legged exercise decreased (Pexercise in human muscle. The decrease in LC3‐II/LC3‐I ratio did not correlate with activation of 5′AMP activated protein kinase (AMPK) trimer complexes in human muscle. Consistently, pharmacological AMPK activation with 5‐aminoimidazole‐4‐carboxamide riboside (AICAR) in mouse muscle did not affect the LC3‐II/LC3‐I ratio. Four hours after exercise, insulin further reduced (Pexercised and non‐exercised leg in humans. This coincided with increased Ser‐757 phosphorylation of Unc51 like kinase 1 (ULK1), which is suggested as a mammalian target of rapamycin complex 1 (mTORC1) target. Accordingly, inhibition of mTOR signalling in mouse muscle prevented the ability of insulin to reduce the LC3‐II/LC3‐I ratio. In response to 3 weeks of one‐legged exercise training, the LC3‐II/LC3‐I ratio decreased (Pexercise and insulin stimulation reduce muscle autophagosome content, while exercise

Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

DEFF Research Database (Denmark)

Fritzen, Andreas Mæchel; Madsen, Agnete Louise Bjerregaard; Kleinert, Maximilian

2016-01-01

Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one-legged exer......Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one-legged exercise, one......-legged exercise training as well as in response to subsequent insulin stimulation in exercised and non-exercised human muscle. Acute one-legged exercise decreased (phuman muscle....... The decrease in LC3-II/LC3-I ratio did not correlate with activation of AMPK trimer complexes in human muscle. Consistently, pharmacological AMPK activation with AICAR in mouse muscle did not affect the LC3-II/LC3-I ratio. Four hours after exercise, insulin further reduced (p

Human muscle proteins: analysis by two-dimensional electrophoresis

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Giometti, C.S.; Danon, M.J.; Anderson, N.G.

1983-09-01

Proteins from single frozen sections of human muscle were separated by two-dimensional gel electrophoresis and detected by fluorography or Coomassie Blue staining. The major proteins were identical in different normal muscles obtained from either sex at different ages, and in Duchenne and myotonic dystrophy samples. Congenital myopathy denervation atrophy, polymyositis, and Becker's muscular dystrophy samples, however, showed abnormal myosin light chain compositions, some with a decrease of fast-fiber myosin light chains and others with a decrease of slow-fiber light chains. These protein alterations did not correlate with any specific disease, and may be cause by generalized muscle-fiber damage.

Human skeletal muscle perilipin 2 and 3 expression varies with insulin sensitivity

DEFF Research Database (Denmark)

Vigelsø Hansen, Andreas; Prats Gavalda, Clara; Ploug, Thorkil

2013-01-01

Background: Impaired insulin sensitivity may partly arise from a dysregulated lipid metabolism in human skeletal muscle. This study investigates the expression levels of perilipin 2, 3, and 5, and four key lipases in human skeletal muscle from the subjects that exhibit a range from normal to very...

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering

Directory of Open Access Journals (Sweden)

Sara Martina Maffioletti

2018-04-01

Full Text Available Summary: Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. : Maffioletti et al. generate human 3D artificial skeletal muscles from healthy donors and patient-specific pluripotent stem cells. These human artificial muscles accurately model severe genetic muscle diseases. They can be engineered to include other cell types present in skeletal muscle, such as vascular cells and motor neurons. Keywords: skeletal muscle, pluripotent stem cells, iPS cells, myogenic differentiation, tissue engineering, disease modeling, muscular dystrophy, organoids

The Metabolic Cost of a High Intensity Exercise Program During Bed Rest

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Hackney, Kyle; Everett, Meghan; Guined, Jamie; Cunningham, Daid

2012-01-01

Background: Given that disuse-related skeletal muscle atrophy may be exacerbated by an imbalance between energy intake and output, the amount of energy required to complete exercise countermeasures is an important consideration in the well being of subject health during bed rest and spaceflight. Objective: To evaluate the energy cost of a high intensity exercise program performed during short duration bed rest. Methods: 9 subjects (8 male and 1 female; 34.5 +/- 8.2 years) underwent 14 days of bed rest and exercise countermeasures. Exercise energy expenditure and excess post exercise oxygen consumption (EPOC) were collected once in each of 5 different exercise protocols (30 second, 2 minute and 4 minute intervals, continuous aerobic and a variety of resistance exercises) during bed rest. Body mass, basal metabolic rate (BMR), upper and lower leg muscle, subcutaneous, and intramuscular adipose tissue (IMAT) volumes were assessed before and at the end of bed rest. Results: There were no significant differences in body mass (pre: 75.1 +/- 10.5 kg; post: 75.2 +/- 10.1 kg), BMR (pre: 1649 +/- 216 kcal; post: 1657 +/- 177 kcal), muscle subcutaneous, or IMAT volumes (Table 2) after 14 days of bed rest and exercise. Body mass was maintained with an average daily intake of 2710 +/- 262 kcal (36.2 +/- 2.1 kcal/kg/day), while average daily energy expenditure was 2579 +/-311 kcal (34.5 +/- 3.6 kcal/kg/day). Exercise energy expenditure was significantly greater as a result of continuous aerobic exercise than all other exercise protocols.

The Physiology of Bed Rest. Chapter 39

Science.gov (United States)

Fortney, Suzanne M.; Schneider, Victor S.; Greenleaf, John E.

1996-01-01

Prolonged rest in bed has been utilized by physicians and other health-care workers to immobilize and confine patients for rehabilitation and restoration of health since time immemorial. The sitting or horizontal position is sought by the body to relieve the strain of the upright or vertical postures, for example during syncopal situations, bone fractures, muscle injuries, fatigue, and probably also to reduce energy expenditure. Most health-care personnel are aware that adaptive responses occurring during bed rest proceed concomitantly with the healing process; signs and symptoms associated with the former should be differentiated from those of the latter. Not all illnesses and infirmities benefit from prolonged bed rest. Considerations in prescribing bed rest for patients-including duration, body position, mode and duration of exercise, light-dark cycles, temperature, and humidity-have not been investigated adequately. More recently, adaptive physiological responses have been measured in normal, healthy subjects in the horizontal or slightly head-down postures during prolonged bed rest as analogs for the adaptive responses of astronauts exposed to the microgravity environment of outer and bed-rest research.

Morphology of muscle attachment sites in the modern human hand does not reflect muscle architecture.

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Williams-Hatala, E M; Hatala, K G; Hiles, S; Rabey, K N

2016-06-23

Muscle attachment sites (entheses) on dry bones are regularly used by paleontologists to infer soft tissue anatomy and to reconstruct behaviors of extinct organisms. This method is commonly applied to fossil hominin hand bones to assess their abilities to participate in Paleolithic stone tool behaviors. Little is known, however, about how or even whether muscle anatomy and activity regimes influence the morphologies of their entheses, especially in the hand. Using the opponens muscles from a sample of modern humans, we tested the hypothesis that aspects of hand muscle architecture that are known to be influenced by behavior correlate with the size and shape of their associated entheses. Results show no consistent relationships between these behaviorally-influenced aspects of muscle architecture and entheseal morphology. Consequently, it is likely premature to infer patterns of behavior, such as stone tool making in fossil hominins, from these same entheses.

The motor cortex drives the muscles during walking in human subjects

DEFF Research Database (Denmark)

Petersen, Tue Hvass; Willerslev-Olsen, Maria; Conway, B A

2012-01-01

Indirect evidence that the motor cortex and the corticospinal tract contribute to the control of walking in human subjects has been provided in previous studies. In the present study we used coherence analysis of the coupling between EEG and EMG from active leg muscles during human walking...... area and EMG from the anterior tibial muscle was found in the frequency band 24–40 Hz prior to heel strike during the swing phase of walking. This signifies that rhythmic cortical activity in the 24–40 Hz frequency band is transmitted via the corticospinal tract to the active muscles during walking...

Snack food as a modulator of human resting-state functional connectivity.

Science.gov (United States)

Mendez-Torrijos, Andrea; Kreitz, Silke; Ivan, Claudiu; Konerth, Laura; Rösch, Julie; Pischetsrieder, Monika; Moll, Gunther; Kratz, Oliver; Dörfler, Arnd; Horndasch, Stefanie; Hess, Andreas

2018-04-04

To elucidate the mechanisms of how snack foods may induce non-homeostatic food intake, we used resting state functional magnetic resonance imaging (fMRI), as resting state networks can individually adapt to experience after short time exposures. In addition, we used graph theoretical analysis together with machine learning techniques (support vector machine) to identifying biomarkers that can categorize between high-caloric (potato chips) vs. low-caloric (zucchini) food stimulation. Seventeen healthy human subjects with body mass index (BMI) 19 to 27 underwent 2 different fMRI sessions where an initial resting state scan was acquired, followed by visual presentation of different images of potato chips and zucchini. There was then a 5-minute pause to ingest food (day 1=potato chips, day 3=zucchini), followed by a second resting state scan. fMRI data were further analyzed using graph theory analysis and support vector machine techniques. Potato chips vs. zucchini stimulation led to significant connectivity changes. The support vector machine was able to accurately categorize the 2 types of food stimuli with 100% accuracy. Visual, auditory, and somatosensory structures, as well as thalamus, insula, and basal ganglia were found to be important for food classification. After potato chips consumption, the BMI was associated with the path length and degree in nucleus accumbens, middle temporal gyrus, and thalamus. The results suggest that high vs. low caloric food stimulation in healthy individuals can induce significant changes in resting state networks. These changes can be detected using graph theory measures in conjunction with support vector machine. Additionally, we found that the BMI affects the response of the nucleus accumbens when high caloric food is consumed.

Adrenaline and glycogenolysis in skeletal muscle during exercise

DEFF Research Database (Denmark)

Kjaer, M; Howlett, K; Langfort, J

2000-01-01

The role of adrenaline in regulating muscle glycogenolysis and hormone-sensitive lipase (HSL) activity during exercise was examined in six adrenaline-deficient bilaterally adrenalectomised, adrenocortico-hormonal-substituted humans (Adr) and in six healthy control individuals (Con). Subjects cycled...... for 45 min at approximately 70% maximal pulmonary O2 uptake (VO2,max) followed by 15 min at approximately 86% VO2,max either without (-Adr and Con) or with (+Adr) adrenaline infusion that elevated plasma adrenaline levels (45 min, 4.49+/-0.69 nmol l(-1); 60 min, 12.41+/-1.80 nmol l(-1)). Muscle samples...... were obtained at 0, 45 and 60 min of exercise. In -Adr and Con, muscle glycogen was similar at rest (-Adr, 409+/-19 mmol (kg dry wt)(-1); Con, 453+/-24 mmol (kg dry wt)(-1)) and following exercise (-Adr, 237+/-52 mmol (kg dry wt)(-1); Con, 227+/-50 mmol (kg dry wt)(-1)). Muscle lactate, glucose-6...

Pro- and anti-angiogenic factors in human skeletal muscle in response to acute exercise and training

DEFF Research Database (Denmark)

Høier, Birgitte; Nordsborg, Nikolai; Andersen, Søren

2012-01-01

This study examined the effect of acute exercise and 4 weeks of aerobic training on skeletal muscle gene and protein expression of pro- and anti-angiogenic factors in 14 young male subjects. Training consisted of 60 min of cycling (~ 60% of VO2 max), 3 times/week. Biopsies were obtained from m. v....... lateralis before and after training. Muscle interstitial fluid was collected during cycling at week 0 and 4. Training increased (P ... to acute exercise increased similarly (>6-fold; P training. Resting protein levels of soluble VEGF receptor-1 in interstitial fluid, and of VEGF, Thrombospondin-1 (TSP-1) and Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in muscle, were unaffected by training, whereas e...

Vibration sensitivity of human muscle spindles and Golgi tendon organs.

Science.gov (United States)

Fallon, James B; Macefield, Vaughan G

2007-07-01

The responses of the various muscle receptors to vibration are more complicated than a naïve categorization into stretch (muscle spindle primary ending), length (muscle spindle secondary endings), and tension (Golgi tendon organs) receptors. To emphasize the similarity of responses to small length changes, we recorded from 58 individual muscle afferents subserving receptors in the ankle or toe dorsiflexors of awake human subjects (32 primary endings, 20 secondary endings, and six Golgi tendon organs). Transverse sinusoidal vibration was applied to the distal tendon of the receptor-bearing muscle, while subjects either remained completely relaxed or maintained a weak isometric contraction of the appropriate muscle. In relaxed muscle, few units responded in a 1:1 manner to vibration, and there was no evidence of a preferred frequency of activation. In active muscle the response profiles of all three receptor types overlapped, with no significant difference in threshold between receptor types. These results emphasize that when intramuscular tension increases during a voluntary contraction, Golgi tendon organs and muscle spindle secondary endings, not just muscle spindle primary endings, can effectively encode small imposed length changes.

Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle

DEFF Research Database (Denmark)

Gaster, M; Poulsen, P; Handberg, A

2000-01-01

GLUT-4 expression in individual fibers of human skeletal muscles in younger and older adults was studied. Furthermore, the dependency of insulin-stimulated glucose uptake on fiber type distribution was investigated. Fiber type distribution was determined in cryosections of muscle biopsies from 8...... of slow fibers in the young (r = -0.45, P > 0.25) or in the elderly (r = 0. 11, P > 0.75) subjects. In conclusion, in human skeletal muscle, GLUT-4 expression is fiber type dependent and decreases with age, particularly in fast muscle fibers....

Three-dimensional architecture of the whole human soleus muscle in vivo

Science.gov (United States)

Finni, Taija; D’Souza, Arkiev; Eguchi, Junya; Clarke, Elizabeth C.; Herbert, Robert D.

2018-01-01

Background Most data on the architecture of the human soleus muscle have been obtained from cadaveric dissection or two-dimensional ultrasound imaging. We present the first comprehensive, quantitative study on the three-dimensional anatomy of the human soleus muscle in vivo using diffusion tensor imaging (DTI) techniques. Methods We report three-dimensional fascicle lengths, pennation angles, fascicle curvatures, physiological cross-sectional areas and volumes in four compartments of the soleus at ankle joint angles of 69 ± 12° (plantarflexion, short muscle length; average ± SD across subjects) and 108 ± 7° (dorsiflexion, long muscle length) of six healthy young adults. Microdissection and three-dimensional digitisation on two cadaveric muscles corroborated the compartmentalised structure of the soleus, and confirmed the validity of DTI-based muscle fascicle reconstructions. Results The posterior compartments of the soleus comprised 80 ± 5% of the total muscle volume (356 ± 58 cm3). At the short muscle length, the average fascicle length, pennation angle and curvature was 37 ± 8 mm, 31 ± 3° and 17 ± 4 /m, respectively. We did not find differences in fascicle lengths between compartments. However, pennation angles were on average 12° larger (p < 0.01) in the posterior compartments than in the anterior compartments. For every centimetre that the muscle-tendon unit lengthened, fascicle lengths increased by 3.7 ± 0.8 mm, pennation angles decreased by −3.2 ± 0.9° and curvatures decreased by −2.7 ± 0.8 /m. Fascicles in the posterior compartments rotated almost twice as much as in the anterior compartments during passive lengthening. Discussion The homogeneity in fascicle lengths and inhomogeneity in pennation angles of the soleus may indicate a functionally different role for the anterior and posterior compartments. The data and techniques presented here demonstrate how DTI can be used to obtain detailed, quantitative measurements of the

Mechanical stimulation improves tissue-engineered human skeletal muscle

Science.gov (United States)

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

2002-01-01

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

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study.

Science.gov (United States)

Gabard-Durnam, Laurel Joy; Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

2016-04-27

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long

Myoeletric indices of fatigue adopting different rest intervals during leg press sets.

Science.gov (United States)

Miranda, Humberto; Maia, Marianna; de Oliveira, Carlos G; Farias, Déborah; da Silva, Jurandir B; Lima, Vicente P; Willardson, Jeffrey M; Paz, Gabriel A

2018-01-01

The purpose of this study was to examine the acute effect of different rest intervals between multiple sets of the 45° angled leg press exercise (LP45) on surface electromyographic (SEMG) spectral and amplitude indices of fatigue. Fifteen recreationally trained females performed three protocols in a randomized crossover design; each consisting of four sets of 10 repetitions with 1 (P1), 3 (P3), or 5 (P5) minute rest intervals between sets. Each set was performed with 70% of the LP45 ten-repetition maximum load. The SEMG data for biceps femoris (BF), vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF) muscles was then evaluated. The SEMG amplitude change in the time coefficient (CRMS) and spectral fatigue index (Cf5) indicated higher levels of fatigue for all muscles evaluated during the P3 protocol versus the P1 and P5 protocols (p ≤ 0.05), respectively. The RF and VL muscles showed greater fatigue levels by the second and third sets; whereas, greater fatigue was shown in the VM and BF muscles by the fourth set (p ≤ 0.05). A three-minute rest interval between sets might represent a neuromuscular window between a fatigue stated and fully recovered state in the context of neural activation. Moreover, a three minute rest interval between sets might allow for consistent recruitment of high threshold motor units over multiple sets, and thus promote a more effective stimulus for strength gains. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of lipopolysaccharide on inflammation and insulin action in human muscle.

Science.gov (United States)

Liang, Hanyu; Hussey, Sophie E; Sanchez-Avila, Alicia; Tantiwong, Puntip; Musi, Nicolas

2013-01-01

Accumulating evidence from animal studies suggest that chronic elevation of circulating intestinal-generated lipopolysaccharide (LPS) (i.e., metabolic endotoxemia) could play a role in the pathogenesis of insulin resistance. However, the effect of LPS in human muscle is unclear. Moreover, it is unknown whether blockade/down regulation of toll-like receptor (TLR)4 can prevent the effect of LPS on insulin action and glucose metabolism in human muscle cells. In the present study we compared plasma LPS concentration in insulin resistant [obese non-diabetic and obese type 2 diabetic (T2DM)] subjects versus lean individuals. In addition, we employed a primary human skeletal muscle cell culture system to investigate the effect of LPS on glucose metabolism and whether these effects are mediated via TLR4. Obese non-diabetic and T2DM subjects had significantly elevated plasma LPS and LPS binding protein (LBP) concentrations. Plasma LPS (r = -0.46, P = 0.005) and LBP (r = -0.49, P = 0.005) concentrations negatively correlated with muscle insulin sensitivity (M). In human myotubes, LPS increased JNK phosphorylation and MCP-1 and IL-6 gene expression. This inflammatory response led to reduced insulin-stimulated IRS-1, Akt and AS160 phosphorylation and impaired glucose transport. Both pharmacologic blockade of TLR4 with TAK-242, and TLR4 gene silencing, suppressed the inflammatory response and insulin resistance caused by LPS in human muscle cells. Taken together, these findings suggest that elevations in plasma LPS concentration found in obese and T2DM subjects could play a role in the pathogenesis of insulin resistance and that antagonists of TLR4 may improve insulin action in these individuals.

Some factors determining the PCr recovery overshoot in skeletal muscle.

Science.gov (United States)

Korzeniewski, Bernard; Zoladz, Jerzy A

2005-07-01

It has been proposed recently that the phosphocreatine (PCr) overshoot (increase above the resting level) during muscle recovery after exercise is caused by a slow decay during this recovery of the direct activation of oxidative phosphorylation taking place during muscle work. In the present article the factors determining the appearance and size of the PCr overshoot are studied using the computer model of oxidative phosphorylation in intact skeletal muscle developed previously. It is demonstrated that the appearance and duration of this overshoot is positively correlated with the value of the characteristic decay time of the direct activation of oxidative phosphorylation. It is also shown that the size of PCr overshoot is increased by low resting PCr/Cr ratio (what is confirmed by our unpublished experimental data), by high intensity of the direct activation of oxidative phosphorylation, by high muscle work intensity and by low rate of the return of cytosolic pH to the resting value during muscle recovery.

Bed Rest and Immobilization: Risk Factors for Bone Loss

Science.gov (United States)

... Risk Factors for Bone Loss Bed Rest and Immobilization: Risk Factors for Bone Loss Like muscle, bone ... complications of pregnancy; and those who are experiencing immobilization of some part of the body because of ...

GH receptor blocker administration and muscle-tendon collagen synthesis in humans

DEFF Research Database (Denmark)

Nielsen, Rie Harboe; Doessing, Simon; Goto, Kazushige

2011-01-01

The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans.......The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans....

Human Leg Model Predicts Muscle Forces, States, and Energetics during Walking.

Science.gov (United States)

Markowitz, Jared; Herr, Hugh

2016-05-01

Humans employ a high degree of redundancy in joint actuation, with different combinations of muscle and tendon action providing the same net joint torque. Both the resolution of these redundancies and the energetics of such systems depend on the dynamic properties of muscles and tendons, particularly their force-length relations. Current walking models that use stock parameters when simulating muscle-tendon dynamics tend to significantly overestimate metabolic consumption, perhaps because they do not adequately consider the role of elasticity. As an alternative, we posit that the muscle-tendon morphology of the human leg has evolved to maximize the metabolic efficiency of walking at self-selected speed. We use a data-driven approach to evaluate this hypothesis, utilizing kinematic, kinetic, electromyographic (EMG), and metabolic data taken from five participants walking at self-selected speed. The kinematic and kinetic data are used to estimate muscle-tendon lengths, muscle moment arms, and joint moments while the EMG data are used to estimate muscle activations. For each subject we perform an optimization using prescribed skeletal kinematics, varying the parameters that govern the force-length curve of each tendon as well as the strength and optimal fiber length of each muscle while seeking to simultaneously minimize metabolic cost and maximize agreement with the estimated joint moments. We find that the metabolic cost of transport (MCOT) values of our participants may be correctly matched (on average 0.36±0.02 predicted, 0.35±0.02 measured) with acceptable joint torque fidelity through application of a single constraint to the muscle metabolic budget. The associated optimal muscle-tendon parameter sets allow us to estimate the forces and states of individual muscles, resolving redundancies in joint actuation and lending insight into the potential roles and control objectives of the muscles of the leg throughout the gait cycle.

Human Leg Model Predicts Muscle Forces, States, and Energetics during Walking.

Directory of Open Access Journals (Sweden)

Jared Markowitz

2016-05-01

Full Text Available Humans employ a high degree of redundancy in joint actuation, with different combinations of muscle and tendon action providing the same net joint torque. Both the resolution of these redundancies and the energetics of such systems depend on the dynamic properties of muscles and tendons, particularly their force-length relations. Current walking models that use stock parameters when simulating muscle-tendon dynamics tend to significantly overestimate metabolic consumption, perhaps because they do not adequately consider the role of elasticity. As an alternative, we posit that the muscle-tendon morphology of the human leg has evolved to maximize the metabolic efficiency of walking at self-selected speed. We use a data-driven approach to evaluate this hypothesis, utilizing kinematic, kinetic, electromyographic (EMG, and metabolic data taken from five participants walking at self-selected speed. The kinematic and kinetic data are used to estimate muscle-tendon lengths, muscle moment arms, and joint moments while the EMG data are used to estimate muscle activations. For each subject we perform an optimization using prescribed skeletal kinematics, varying the parameters that govern the force-length curve of each tendon as well as the strength and optimal fiber length of each muscle while seeking to simultaneously minimize metabolic cost and maximize agreement with the estimated joint moments. We find that the metabolic cost of transport (MCOT values of our participants may be correctly matched (on average 0.36±0.02 predicted, 0.35±0.02 measured with acceptable joint torque fidelity through application of a single constraint to the muscle metabolic budget. The associated optimal muscle-tendon parameter sets allow us to estimate the forces and states of individual muscles, resolving redundancies in joint actuation and lending insight into the potential roles and control objectives of the muscles of the leg throughout the gait cycle.

Resting State Functional Connectivity in Early Blind Humans

Directory of Open Access Journals (Sweden)

Harold eBurton

2014-04-01

Full Text Available Task-based neuroimaging studies in early blind humans (EB have demonstrated heightened visual cortex responses to non-visual paradigms. Several prior functional connectivity studies in EB have shown altered connections consistent with these task-based results. But these studies generally did not consider behavioral adaptations to lifelong blindness typically observed in EB. Enhanced cognitive abilities shown in EB include greater serial recall and attention to memory. Here, we address the question of the extent to which brain intrinsic activity in EB reflects such adaptations. We performed a resting-state functional magnetic resonance imaging study contrasting 14 EB with 14 age/gender matched normally sighted controls (NS. A principal finding was markedly greater functional connectivity in EB between visual cortex and regions typically associated with memory and cognitive control of attention. In contrast, correlations between visual cortex and non-deprived sensory cortices were significantly lower in EB. Thus, the available data, including that obtained in prior task-based and resting state fMRI studies, as well as the present results, indicate that visual cortex in EB becomes more heavily incorporated into functional systems instantiating episodic recall and attention to non-visual events. Moreover, EB appear to show a reduction in interactions between visual and non-deprived sensory cortices, possibly reflecting suppression of inter-sensory distracting activity.

Muscle gene expression patterns in human rotator cuff pathology.

Science.gov (United States)

Choo, Alexander; McCarthy, Meagan; Pichika, Rajeswari; Sato, Eugene J; Lieber, Richard L; Schenk, Simon; Lane, John G; Ward, Samuel R

2014-09-17

Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology. Biopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis. Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear. Gene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of myogenesis. These data highlight the

Expression of REST4 in human gliomas in vivo and influence of pioglitazone on REST in vitro

Energy Technology Data Exchange (ETDEWEB)

Ren, Huan [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Gao, Zhangfeng [Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410008 (China); Wu, Nayiyuan; Zeng, Liu; Tang, Xinyue; Chen, Xiaoping; Liu, Zhaoqian; Zhang, Wei; Wang, Liansheng [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Li, Zhi, E-mail: lizhi489@163.com [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China)

2015-08-07

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) has an irreplaceable role during the differentiation of neurons. REST has multiple splice variants which link to various types of cancer. Previous work had highlighted the role of REST in glioma, where the expression of REST is enhanced. But whether alternative splicing of REST is expressed in glioma has not been described. Here, we show that a specific isoform REST4 is expressed in glioma specimens, and will influence the mRNA level of REST in vivo. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have a role of antineoplastic in various tumor cells, which including glioma cells. Moreover, study indicated that PPARγ agonist pioglitazone can promote alternative splicing of REST pre-mRNA. In this study, we selected pioglitazone as a tool drug to explore whether the role of pioglitazone in anti-glioma is mediated by regulating REST expression or promoting alternative splicing of REST in glioma cells. Results show that pioglitazone can inhibit proliferation and induce apoptosis of glioma cell in vitro, which may be mediated by down-regulating REST mRNA level but not by inducing alternative splicing of REST pre-mRNA. Our study firstly reports the expression of REST4 in glioma tissue samples. And we recommend that pioglitazone, which can reduce the expression level of REST, represents a promising drug for therapy of glioma. - Highlights: • A specific isoform REST4 is expressed in glioma specimens in vivo. • REST4 will influence the mRNA level of REST in vivo. • Pioglitazone can inhibit proliferation and induce apoptosis of glioma cells. • The role of pioglitazone in anti-glioma may be mediated by down-regulating REST.

Expression of REST4 in human gliomas in vivo and influence of pioglitazone on REST in vitro

International Nuclear Information System (INIS)

Ren, Huan; Gao, Zhangfeng; Wu, Nayiyuan; Zeng, Liu; Tang, Xinyue; Chen, Xiaoping; Liu, Zhaoqian; Zhang, Wei; Wang, Liansheng; Li, Zhi

2015-01-01

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) has an irreplaceable role during the differentiation of neurons. REST has multiple splice variants which link to various types of cancer. Previous work had highlighted the role of REST in glioma, where the expression of REST is enhanced. But whether alternative splicing of REST is expressed in glioma has not been described. Here, we show that a specific isoform REST4 is expressed in glioma specimens, and will influence the mRNA level of REST in vivo. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have a role of antineoplastic in various tumor cells, which including glioma cells. Moreover, study indicated that PPARγ agonist pioglitazone can promote alternative splicing of REST pre-mRNA. In this study, we selected pioglitazone as a tool drug to explore whether the role of pioglitazone in anti-glioma is mediated by regulating REST expression or promoting alternative splicing of REST in glioma cells. Results show that pioglitazone can inhibit proliferation and induce apoptosis of glioma cell in vitro, which may be mediated by down-regulating REST mRNA level but not by inducing alternative splicing of REST pre-mRNA. Our study firstly reports the expression of REST4 in glioma tissue samples. And we recommend that pioglitazone, which can reduce the expression level of REST, represents a promising drug for therapy of glioma. - Highlights: • A specific isoform REST4 is expressed in glioma specimens in vivo. • REST4 will influence the mRNA level of REST in vivo. • Pioglitazone can inhibit proliferation and induce apoptosis of glioma cells. • The role of pioglitazone in anti-glioma may be mediated by down-regulating REST

Resting release of acetylcholine at the motor endplate

International Nuclear Information System (INIS)

Molenaar, P.C.; Polak, R.L.

1986-01-01

This paper reviews recent work on resting release of ACh in frog, rat and mouse skeletal muscle. Because of the effect of Ca 2+ on resting release it was of interest to know whether non-quantal release of ACh is increased under conditions of increased Ca 2+ influx, viz. during depolarization of the nerve terminals. It is shown that depolarization of the motor nerve terminals by K + ions led to an increase of both min.e.p.c. frequency and chemically detectable ACh release

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering.

Science.gov (United States)

Maffioletti, Sara Martina; Sarcar, Shilpita; Henderson, Alexander B H; Mannhardt, Ingra; Pinton, Luca; Moyle, Louise Anne; Steele-Stallard, Heather; Cappellari, Ornella; Wells, Kim E; Ferrari, Giulia; Mitchell, Jamie S; Tyzack, Giulia E; Kotiadis, Vassilios N; Khedr, Moustafa; Ragazzi, Martina; Wang, Weixin; Duchen, Michael R; Patani, Rickie; Zammit, Peter S; Wells, Dominic J; Eschenhagen, Thomas; Tedesco, Francesco Saverio

2018-04-17

Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Usefulness of ultrasonographic examination of diagnosis of muscle hernia

International Nuclear Information System (INIS)

Choi, Jin Soo; Lee, Sung Moon

2003-01-01

To evaluate the usefulness of ultrasonography in diagnosis of muscle hernia. Ultrasonographic findings of seven patients with muscle hernia were retrospectively reviewed. The subjects consisted of 6 males and 1 female, age ranged from 17 to 66 years (mean=45 years). Ultrasonographic examination was performed using a high-frequency (7-15 MHz) linear probe during rest and stress states of the affected muscle, and both tranverse and longitudinal views were obtained. Six muscle herniations were located in the lower extremity in six cases while only one muscle herniation, in the upper extremity. Four cases showed a focal defect of the fascia with a localized bulging out of the muscle substance through the defect. Herniated muscle in stress state was larger and harder than in rest state. In 3 cases, defect of the fascia was not noted on ultrasonography. However, the affected muscle showed an abnormal contraction with a focal bulging out appearance during stress state. Ultrasonographically, the herniated muscle substance was less echogenic than the normal muscle without any evidence of muscle tear or associated mass in all cases. Ultrasonography is a simple and useful dynamic study of muscle hernia in diagnosis and differentiation of muscle hernia.

Secreted Protein Acidic and Rich in Cysteine (SPARC) in Human Skeletal Muscle

Science.gov (United States)

Jørgensen, Louise H.; Petersson, Stine J.; Sellathurai, Jeeva; Andersen, Ditte C.; Thayssen, Susanne; Sant, Dorte J.; Jensen, Charlotte H.; Schrøder, Henrik D.

2009-01-01

Secreted protein acidic and rich in cysteine (SPARC)/osteonectin is expressed in different tissues during remodeling and repair, suggesting a function in regeneration. Several gene expression studies indicated that SPARC was expressed in response to muscle damage. Studies on myoblasts further indicated a function of SPARC in skeletal muscle. We therefore found it of interest to study SPARC expression in human skeletal muscle during development and in biopsies from Duchenne and Becker muscular dystrophy and congenital muscular dystrophy, congenital myopathy, inclusion body myositis, and polymyositis patients to analyze SPARC expression in a selected range of inherited and idiopathic muscle wasting diseases. SPARC-positive cells were observed both in fetal and neonatal muscle, and in addition, fetal myofibers were observed to express SPARC at the age of 15–16 weeks. SPARC protein was detected in the majority of analyzed muscle biopsies (23 of 24), mainly in mononuclear cells of which few were pax7 positive. Myotubes and regenerating myofibers also expressed SPARC. The expression-degree seemed to reflect the severity of the lesion. In accordance with these in vivo findings, primary human-derived satellite cells were found to express SPARC both during proliferation and differentiation in vitro. In conclusion, this study shows SPARC expression both during muscle development and in regenerating muscle. The expression is detected both in satellite cells/myoblasts and in myotubes and muscle fibers, indicating a role for SPARC in the skeletal muscle compartment. (J Histochem Cytochem 57:29–39, 2009) PMID:18796407

Science and Ecological Economics: Integrating of the Study of Humans and the Rest of Nature

Science.gov (United States)

Costanza, Robert

2009-01-01

Ecological economics is a transdisciplinary field that seeks to integrate the study of humans and the rest of nature as the basis for the creation of a sustainable and desirable future. It seeks to dissolve the barriers between the traditional disciplines and achieve a true "consilience" of all the sciences and humanities. This consilient,…

Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle

OpenAIRE

Cobley, James N; Sakellariou, George K; Murray, Scott; Waldron, Sarah; Gregson, Warren; Burniston, Jatin G; Morton, James P; Iwanejko, Lesley A; Close, Graeme L

2013-01-01

Background The aim of the present study was to determine the influence of age and habitual activity level, at rest and following a single bout of high-intensity exercise, on the levels of three proteins poly(ADP-ribose) polymerase-1 (PARP-1), cleaved-PARP-1 and poly(ADP-ribose) glycohydrolase (PARG), involved in the DNA repair and cell death responses to stress and genotoxic insults. Muscle biopsies were obtained from the vastus lateralis of young trained (22 ± 3 years, n = 6), young untraine...

Influence of exercise contraction mode and protein supplementation on human skeletal muscle satellite cell content and muscle fiber growth

DEFF Research Database (Denmark)

Farup, Jean; Rahbek, Stine Klejs; Riis, Simon

2014-01-01

-specific association between emergence of satellite cells (SCs), muscle growth, and remodeling in response to 12 wk unilateral resistance training performed as eccentric (Ecc) or concentric (Conc) resistance training ± whey protein (Whey, 19.5 g protein + 19.5 g glucose) or placebo (Placebo, 39 g glucose......Skeletal muscle satellite cells (SCs) are involved in remodeling and hypertrophy processes of skeletal muscle. However, little knowledge exists on extrinsic factors that influence the content of SCs in skeletal muscle. In a comparative human study, we investigated the muscle fiber type......) supplementation. Muscle biopsies (vastus lateralis) were analyzed for fiber type-specific SCs, myonuclei, and fiber cross-sectional area (CSA). Following training, SCs increased with Conc in both type I and type II fibers (P

Cardiac atrophy after bed rest and spaceflight

Science.gov (United States)

Perhonen, M. A.; Franco, F.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.; Zerwekh, J. E.; Peshock, R. M.; Weatherall, P. T.; Levine, B. D.

2001-01-01

Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity

Architecture and functional ecology of the human gastrocnemius muscle-tendon unit.

Science.gov (United States)

Butler, Erin E; Dominy, Nathaniel J

2016-04-01

The gastrocnemius muscle-tendon unit (MTU) is central to human locomotion. Structural variation in the human gastrocnemius MTU is predicted to affect the efficiency of locomotion, a concept most often explored in the context of performance activities. For example, stiffness of the Achilles tendon varies among individuals with different histories of competitive running. Such a finding highlights the functional variation of individuals and raises the possibility of similar variation between populations, perhaps in response to specific ecological or environmental demands. Researchers often assume minimal variation in human populations, or that industrialized populations represent the human species as well as any other. Yet rainforest hunter-gatherers, which often express the human pygmy phenotype, contradict such assumptions. Indeed, the human pygmy phenotype is a potential model system for exploring the range of ecomorphological variation in the architecture of human hindlimb muscles, a concept we review here. © 2015 Anatomical Society.

Temperature-dependent changes in the viscoelasticity of intact resting mammalian (rat) fast- and slow-twitch muscle fibres.

Science.gov (United States)

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

Detection of human muscle glycogen by natural abundance 13C NMR

International Nuclear Information System (INIS)

Avison, M.J.; Rothman, D.L.; Nadel, E.; Shulman, R.G.

1988-01-01

Natural abundance 13 C nuclear magnetic resonance spectroscopy was used to detect signals from glycogen in the human gastrocnemius muscle. The reproducibility of the measurement was demonstrated, and the ability to detect dynamic changes was confirmed by measuring a decrease in muscle glycogen levels after exercise and its subsequent repletion. Single frequency gated 1 H decoupling was used to obtain decoupled natural abundance 13 C NMR spectra of the C-1 position of muscle glycogen

Ultrastructure of striated muscle fibers in the middle third of the human esophagus

OpenAIRE

Faussone-Pellegrini, M.S; Cortesini, C.

1986-01-01

Striated muscle fibers and .their spatial relationship to smooth muscle cells have been studied in the middle third of human esophagus. Biopsies were obtained from 3 patients during surgery. In both the circular and longitudinal layers, the muscle coat of this transition zone was composed of fascicles of uniform dimensioi~ (100-200 pm of diameter); some of these bundles were made up of striated muscle fibers, others were pure bundles of smooth muscle cells and ...

Energy conservation attenuates the loss of skeletal muscle excitability during intense contractions

DEFF Research Database (Denmark)

Macdonald, W A; Ørtenblad, N; Nielsen, Ole Bækgaard

2007-01-01

High-frequency stimulation of skeletal muscle has long been associated with ionic perturbations, resulting in the loss of membrane excitability, which may prevent action potential propagation and result in skeletal muscle fatigue. Associated with intense skeletal muscle contractions are large...... with control muscles, the resting metabolites ATP, phosphocreatine, creatine, and lactate, as well as the resting muscle excitability as measured by M-waves, were unaffected by treatment with BTS plus dantrolene. Following 20 or 30 s of continuous 60-Hz stimulation, BTS-plus-dantrolene-treated muscles showed...... changes in muscle metabolites. However, the role of metabolites in the loss of muscle excitability is not clear. The metabolic state of isolated rat extensor digitorum longus muscles at 30 degrees C was manipulated by decreasing energy expenditure and thereby allowed investigation of the effects of energy...

Muscle oxygen kinetics at onset of intense dynamic exercise in humans

DEFF Research Database (Denmark)

Bangsbo, J; Krustrup, P; González-Alonso, J

2000-01-01

The present study examined the onset and the rate of rise of muscle oxidation during intense exercise in humans and whether oxygen availability limits muscle oxygen uptake in the initial phase of intense exercise. Six subjects performed 3 min of intense one-legged knee-extensor exercise [65.3 +/-...

Leucine incorporation into mixed skeletal muscle protein in humans

International Nuclear Information System (INIS)

Nair, K.S.; Halliday, D.; Griggs, R.C.

1988-01-01

Fractional mixed skeletal muscle protein synthesis (FMPS) was estimated in 10 postabsorptive healthy men by determining the increment in the abundance of [ 13 C]-leucine in quadriceps muscle protein during an intravenous infusion of L-[1- 13 C]leucine. Whole-body muscle protein synthesis (MPS) was calculated based on the estimation of muscle mass from creatinine excretion and compared with whole-body protein synthesis (WBPS) calculated from the nonoxidative portion of leucine flux. A significant correlation was found between MPS. The contribution of MPS to WBPS was 27 ± 1%, which is comparable to the reports in other species. Morphometric analyses of adjacent muscle samples in eight subjects demonstrated that the biopsy specimens consisted of 86.5 ± 2% muscular as opposed to other tissues. Because fiber type composition varies between biopsies, the authors examined the relationship between proportions of each fiber type and FMPS. Variation in the composition of biopsies and in fiber-type proportion did not affect the estimation of muscle protein synthesis rate. They conclude that stable isotope techniques using serial needle biopsies permit the direct measurement of FMPS in humans and that this estimation is correlated with an indirect estimation of WBPS

A predictive model of muscle excitations based on muscle modularity for a large repertoire of human locomotion conditions

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Jose eGonzalez-Vargas

2015-09-01

Full Text Available Humans can efficiently walk across a large variety of terrains and locomotion conditions with little or no mental effort. It has been hypothesized that the nervous system simplifies neuromuscular control by using muscle synergies, thus organizing multi-muscle activity into a small number of coordinative co-activation modules. In the present study we investigated how muscle modularity is structured across a large repertoire of locomotion conditions including five different speeds and five different ground elevations. For this we have used the non-negative matrix factorization technique in order to explain EMG experimental data with a low-dimensional set of four motor components. In this context each motor components is composed of a non-negative factor and the associated muscle weightings. Furthermore, we have investigated if the proposed descriptive analysis of muscle modularity could be translated into a predictive model that could: 1 Estimate how motor components modulate across locomotion speeds and ground elevations. This implies not only estimating the non-negative factors temporal characteristics, but also the associated muscle weighting variations. 2 Estimate how the resulting muscle excitations modulate across novel locomotion conditions and subjects.The results showed three major distinctive features of muscle modularity: 1 the number of motor components was preserved across all locomotion conditions, 2 the non-negative factors were consistent in shape and timing across all locomotion conditions, and 3 the muscle weightings were modulated as distinctive functions of locomotion speed and ground elevation. Results also showed that the developed predictive model was able to reproduce well the muscle modularity of un-modeled data, i.e. novel subjects and conditions. Muscle weightings were reconstructed with a cross-correlation factor greater than 70% and a root mean square error less than 0.10. Furthermore, the generated muscle excitations

Free-energy carriers in human cultured muscle cells

NARCIS (Netherlands)

Bolhuis, P. A.; de Zwart, H. J.; Ponne, N. J.; de Jong, J. M.

1985-01-01

Creatine phosphate (CrP), adenosine triphosphate (ATP), creatine kinase (CK), adenylate kinase (AK), protein, and DNA were quantified in human muscle cell cultures undergoing transition from dividing myoblasts to multinucleate myotubes. CrP is negligible in cultures grown in commonly applied media

Evaluation of Bioelectrical Activity of Pelvic Floor Muscles and Synergistic Muscles Depending on Orientation of Pelvis in Menopausal Women with Symptoms of Stress Urinary Incontinence: A Preliminary Observational Study

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Tomasz Halski

2014-01-01

Full Text Available Objectives. Evaluation of resting and functional bioelectrical activity of the pelvic floor muscles (PFM and the synergistic muscles, depending on the orientation of the pelvis, in anterior (P1 and posterior (P2 pelvic tilt. Design. Preliminary, prospective observational study. Setting. Department and Clinic of Urology, University Hospital in Wroclaw, Poland. Participants. Thirty-two menopausal and postmenopausal women with stress urinary incontinence were recruited. Based on inclusion and exclusion criteria, sixteen women aged 55 to 70 years were enrolled in the study. Primary Outcome Measures. Evaluation of resting and functional bioelectrical activity of the pelvic floor muscles by electromyography (sEMG and vaginal probe. Secondary Outcome Measures. Evaluation of activity of the synergistic muscles by sEMG and surface electrodes. Results. No significant differences between orientations P1 and P2 were found in functional and resting sEMG activity of the PFM. During resting and functional PFM activity, higher electrical activity in P2 than in P1 has been recorded in some of the synergistic muscles. Conclusions. This preliminary study does not provide initial evidence that pelvic tilt influences PFM activation. Although different activity of synergistic muscles occurs in various orientations of the pelvic tilt, it does not have to affect the sEMG activity of the PFM.

An animal model for human masseter muscle: histochemical characterization of mouse, rat, rabbit, cat, dog, pig, and cow masseter muscle

DEFF Research Database (Denmark)

Tuxen, A; Kirkeby, S

1990-01-01

The masseter muscle of several animal species was investigated by use of a histochemical method for the demonstration of acid-stable and alkali-stable myosin adenosine triphosphatase (ATPase). The following subdivisions of fiber types were used: Type I fibers show weak ATPase activity at pH 9...... II and I fibers, with type II predominating. Cow masseter muscle consisted mainly of type I fibers, although some cow masseter muscles contained a very small number of type II fibers. Pig masseter muscle had both type I, II, and IM fibers. One of the characteristics of human masseter muscle is type...... IM fibers, which are rarely seen in muscles other than the masticatory muscles. Therefore, pig masseter muscle might be a suitable animal model for experimental studies, such as an investigation of the distribution and diameter of fiber types in the masticatory muscles before and after orthognathic...

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

Science.gov (United States)

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

2016-04-01

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

Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

DEFF Research Database (Denmark)

Langberg, H; Bjørn, C; Boushel, Robert Christopher

2002-01-01

been established. Microdialysis (molecular mass cut-off 5 kDa) was performed simultaneously in calf muscle and peritendinous Achilles tissue at rest and during 10 min periods of incremental (0.75 W, 2 W, 3.5 W and 4.75 W) dynamic plantar flexion exercise in 10 healthy individuals (mean age 27 years...... increased both in muscle (from 0.48 +/- 0.07 micromol l(-1) to 1.59 +/- 0.35 micromol l(-1); P increases the interstitial concentrations......Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon-related connective tissue has not yet...

Examination of transcript amounts and activity of protein kinase CK2 in muscle lysates of different types of human muscle pathologies.

Science.gov (United States)

Heuss, Dieter; Klascinski, Janine; Schubert, Steffen W; Moriabadi, Tehmur; Lochmüller, Hanns; Hashemolhosseini, Said

2008-09-01

Motoneurons release the heparansulfate proteoglycan agrin and thereby activate the muscle-specific receptor tyrosine kinase (MuSK), which is the main organizer of subsynaptic specializations at the neuromuscular junction. Recently, we showed that (1) the protein kinase CK2 interacts with the intracellular region of MuSK; (2) the CK2 protein is enriched and co-localized with MuSK at postsynaptic specializations; (3) CK2-mediated phosphorylation of serine residues within a specific MuSK epitope, named the kinase insert, regulates acetylcholine receptor (AChR) clustering; (4) muscle-specific CK2beta knockout mice develop a myasthenic phenotype due to impaired muscle endplate structure and function (see Genes Dev 20(13):1800-1816, 2006). Here, we investigated for the first time if CK2 is modulated in biopsies from human patients. To this end, we measured transcript amounts of the subunits CK2alpha and CK2beta and determined holoenzyme CK2 activity in 34 muscle biopsies of human patients with different muscle pathologies.

Short-latency crossed responses in the human biceps femoris muscle

DEFF Research Database (Denmark)

Stevenson, Andrew J T; Kamavuako, Ernest N; Geertsen, Svend Sparre

2015-01-01

Interlimb reflexes contribute to the central neural coordination between different limbs in both humans and animals. Although commissural interneurons have only been directly identified in animals, spinally mediated interlimb reflexes have been discovered in a number of human lower limb muscles......, indicating their existence in humans. The aim of the present study was to investigate whether short-latency crossed-spinal reflexes are present in the contralateral biceps femoris (cBF) muscle following ipsilateral knee (iKnee) joint rotations during a sitting task, where participants maintained a slight pre...... pathways (likely involving commissural interneurons) from ipsilateral afferents to common motoneurons in the contralateral leg can likely explain the perturbation direction-dependent reversal in the sign of the short-latency cBF reflex. This article is protected by copyright. All rights reserved....

Steroids induce acetylcholine receptors on cultured human muscle: Implications for myasthenia gravis

International Nuclear Information System (INIS)

Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M.

1990-01-01

Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications

Steroids induce acetylcholine receptors on cultured human muscle: Implications for myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M. (Stanford Univ. School of Medicine, CA (USA))

1990-10-01

Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.

Mitochondrial function in human skeletal muscle following high-altitude exposure

DEFF Research Database (Denmark)

Jacobs, Robert A; Boushel, Robert; Wright-Paradis, Cynthia

2013-01-01

Studies regarding mitochondrial modifications in human skeletal muscle following acclimatization to high altitude are conflicting, and these inconsistencies may be due to the prevalence of representing mitochondrial function through static and isolated measurements of specific mitochondrial...... characteristics. The aim of this study, therefore, was to investigate mitochondrial function in response to high-altitude acclimatization through measurements of respiratory control in the vastus lateralis muscle. Skeletal muscle biopsies were obtained from 10 lowland natives prior to and again after a total of 9......-11 days of exposure to 4559 m. High-resolution respirometry was performed on the muscle samples to compare respiratory chain function and respiratory capacities. Respirometric analysis revealed that mitochondrial function was largely unaffected, because high-altitude exposure did not affect the capacity...

Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

Directory of Open Access Journals (Sweden)

Katarzyna Bozek

2014-05-01

Full Text Available Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

Reliability of Ultrasonographic Measurement of Cervical Multifidus Muscle Dimensions during Isometric Contraction of Neck Muscles

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Somayeh Amiri Arimi

2012-07-01

Full Text Available Background and Aim: Cervical multifidus is considered as one of the most important neck stabilizers. Weakness and muscular atrophy of this muscle were seen in patients with chronic neck pain. Ultrasonographic imaging is a non-invasive and feasible technique that commonly used to record such changes and measure muscle dimensions. Therefore, the aim of this study was to evaluate the reliability of ultrasonographic measurement of cervical multifidus muscle’s dimensions during isometric contraction of neck muscles. Materials and Method: Ten subjects (5 patients with chronic neck pain and 5 healthy subjects were recruited in this study. Cervical multifidus muscle’s dimensions were measured at the level of forth cervical vertebrae. Ultrasonographic measurement of cervical multifidus muscle at rest, 50% and 100% of maximal voluntary contraction (MVC were performed by one examiner within 1 week interval. The dimensions of cervical multifidus muscle including cross-sectional area (CSA, anterior posterior dimension (APD, and lateral dimension (LD were measured. Intraclass correlation coefficients (ICC, standard error of measurement (SEM and minimal detectable change (MDC were computed for data analysis.Results: The between days reliability of maximum strength of neck muscles and multifidus muscle dimensions at rest, 50% and 100% of MVC of neck muscles were good to excellent (ICC=0.75-0.99.Conclusion: The results of this study showed that ultrasonographic measuring of cervical multifidus muscle’s dimensions during isometric contraction of neck muscles at the level of C4 in females with chronic neck pain and healthy subjects is a reliable and repeatable method.

Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6

DEFF Research Database (Denmark)

Keller, Pernille; Penkowa, Milena; Keller, Charlotte

2005-01-01

Contracting muscle fibers produce and release IL-6, and plasma levels of this cytokine are markedly elevated in response to physical exercise. We recently showed autocrine regulation of IL-6 in human skeletal muscle in vivo and hypothesized that this may involve up-regulation of the IL-6 receptor....... Infusion of rhIL-6 to humans had no effect on the mRNA level of the IL-6 receptor, whereas there was an increase at the protein level. IL-6 receptor mRNA increased similarly in muscle of both IL-6 KO mice and wild-type mice in response to exercise. In conclusion, exercise increases IL-6 receptor production....... Therefore, we investigated IL-6 receptor regulation in response to exercise and IL-6 infusion in humans. Furthermore, using IL-6-deficient mice, we investigated the role of IL-6 in the IL-6 receptor response to exercise. Human skeletal muscle biopsies were obtained in relation to: 3 h of bicycle exercise...

Plasticity of human skeletal muscle: gene expression to in vivo function.

Science.gov (United States)

Harridge, Stephen D R

2007-09-01

Human skeletal muscle is a highly heterogeneous tissue, able to adapt to the different challenges that may be placed upon it. When overloaded, a muscle adapts by increasing its size and strength through satellite-cell-mediated mechanisms, whereby protein synthesis is increased and new nuclei are added to maintain the myonuclear domain. This process is regulated by an array of mechanical, hormonal and nutritional signals. Growth factors, such as insulin-like growth factor I (IGF-I) and testosterone, are potent anabolic agents, whilst myostatin acts as a negative regulator of muscle mass. Insulin-like growth factor I is unique in being able to stimulate both the proliferation and the differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterized by maximal velocity of shortening (V(max)), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHCs: MHC-I, -IIa and -IIx, in order of increasing V(max) and maximal power output. Training studies suggest that there is a subtle interplay between the MHC-IIa and -IIx isoforms, with the latter being downregulated by activity and upregulated by inactivity. However, switching between the two main isoforms appears to require significant challenges to a muscle. Upregulation of fast gene programs is caused by prolonged disuse, whilst upregulation of slow gene programs appears to require significant and prolonged activity. The potential mechanisms by which alterations in muscle composition are mediated are discussed. The implications in terms of contractile function of altering muscle phenotype are discussed from the single fibre to the whole muscle level.

Secreted Protein Acidic and Rich in Cysteine (SPARC) in Human Skeletal Muscle

DEFF Research Database (Denmark)

Jørgensen, Louise H; Petersson, Stine J; Sellathurai, Jeeva

2009-01-01

indicated a function of SPARC in skeletal muscle. We therefore found it of interest to study SPARC expression in human skeletal muscle during development and in biopsies from Duchenne and Becker muscular dystrophy and congenital muscular dystrophy, congenital myopathy, inclusion body myositis...

Intramyocellular lipids of muscle type in athletes of different sport disciplines

Directory of Open Access Journals (Sweden)

Nakagawa Y

2017-07-01

Full Text Available Yoshinao Nakagawa,1 Masaaki Hattori2 1Human Performance Lab, Otaru University, Otaru, Hokkaido, 2Department of Community Development, Tokai University, Sapporo, Japan Abstract: The present study used magnetic resonance spectroscopy (1H-MRS to examine quantitative differences in intramyocellular lipid (IMCL contents in various muscle types at rest for individual athletes from different sport disciplines. Five groups consisting of sprinters, alpine skiers, cross-country skiers, endurance runners and untrained healthy male subjects volunteered for this study. Data were acquired using 1H-MRS from the tibialis anterior (TA, medial gastrocnemius (MG and soleus (SOL muscles. No significant difference was found in the cross-sectional area (CSA of the TA, MG and SOL muscles, whereas the CSA of subcutaneous fat was significantly lower (p<0.01 for each athlete group compared with untrained subjects. In both TA and MG, IMCL concentrations in endurance runners were significantly higher than those of alpine skiers (p<0.01, sprinters (p<0.01 and untrained subjects (p<0.05. The IMCL concentrations in TA and MG of cross-country skiers were significantly higher than those of alpine skiers (p<0.05 and sprinters (TA, p<0.01; MG, p<0.05. There was no significant difference in the IMCL concentrations of TA and MG between alpine skiers or sprinters and untrained subjects. The IMCL concentration in SOL was significantly greater in endurance runners and showed no difference in cross-country skiers compared with that in alpine skiers and sprinters. There was no significant difference in the IMCL concentration of SOL between athletes and untrained subjects. These results suggest that differences in IMCL contents stored in various muscle types for athletes at rest are associated with the muscle cellular adaptation for differences in the type of exercise training and/or muscle fiber composition. Keywords: IMCL, alpine ski, skeletal muscle, sports

Endurance training enhances skeletal muscle interleukin-15 in human male subjects

DEFF Research Database (Denmark)

Rinnov, Anders; Yfanti, Christina; Nielsen, Søren

2014-01-01

Regular endurance exercise promotes metabolic and oxidative changes in skeletal muscle. Overexpression of interleukin-15 (IL-15) in mice exerts similar metabolic changes in muscle as seen with endurance exercise. Muscular IL-15 production has been shown to increase in mice after weeks of regular...... endurance running. With the present study we aimed to determine if muscular IL-15 production would increase in human male subjects following 12 weeks of endurance training. In two different studies we obtained plasma and muscle biopsies from young healthy subjects performing: (1) 12 weeks of ergometer...... weeks of regular endurance training induced a 40% increase in basal skeletal muscle IL-15 protein content (p...

Erythropoietin treatment enhances muscle mitochondrial capacity in humans

DEFF Research Database (Denmark)

Plenge, Ulla; Belhage, Bo; Guadalupe-Grau, Amelia

2012-01-01

in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis...

Motor unit activity after eccentric exercise and muscle damage in humans.

Science.gov (United States)

Semmler, J G

2014-04-01

It is well known that unaccustomed eccentric exercise leads to muscle damage and soreness, which can produce long-lasting effects on muscle function. How this muscle damage influences muscle activation is poorly understood. The purpose of this brief review is to highlight the effect of eccentric exercise on the activation of muscle by the nervous system, by examining the change in motor unit activity obtained from surface electromyography (EMG) and intramuscular recordings. Previous research shows that eccentric exercise produces unusual changes in the EMG–force relation that influences motor performance during isometric, shortening and lengthening muscle contractions and during fatiguing tasks. When examining the effect of eccentric exercise at the single motor unit level, there are substantial changes in recruitment thresholds, discharge rates, motor unit conduction velocities and synchronization, which can last for up to 1 week after eccentric exercise. Examining the time course of these changes suggests that the increased submaximal EMG after eccentric exercise most likely occurs through a decrease in motor unit conduction velocity and an increase in motor unit activity related to antagonist muscle coactivation and low-frequency fatigue. Furthermore, there is a commonly held view that eccentric exercise produces preferential damage to high-threshold motor units, but the evidence for this in humans is limited. Further research is needed to establish whether there is preferential damage to high-threshold motor units after eccentric exercise in humans, preferably by linking changes in motor unit activity with estimates of motor unit size using selective intramuscular recording techniques.

History-dependence of muscle slack length following contraction and stretch in the human vastus lateralis.

Science.gov (United States)

Stubbs, Peter W; Walsh, Lee D; D'Souza, Arkiev; Héroux, Martin E; Bolsterlee, Bart; Gandevia, Simon C; Herbert, Robert D

2018-06-01

In reduced muscle preparations, the slack length and passive stiffness of muscle fibres have been shown to be influenced by previous muscle contraction or stretch. In human muscles, such behaviours have been inferred from measures of muscle force, joint stiffness and reflex magnitudes and latencies. Using ultrasound imaging, we directly observed that isometric contraction of the vastus lateralis muscle at short lengths reduces the slack lengths of the muscle-tendon unit and muscle fascicles. The effect is apparent 60 s after the contraction. These observations imply that muscle contraction at short lengths causes the formation of bonds which reduce the effective length of structures that generate passive tension in muscles. In reduced muscle preparations, stretch and muscle contraction change the properties of relaxed muscle fibres. In humans, effects of stretch and contraction on properties of relaxed muscles have been inferred from measurements of time taken to develop force, joint stiffness and reflex latencies. The current study used ultrasound imaging to directly observe the effects of stretch and contraction on muscle-tendon slack length and fascicle slack length of the human vastus lateralis muscle in vivo. The muscle was conditioned by (a) strong isometric contractions at long muscle-tendon lengths, (b) strong isometric contractions at short muscle-tendon lengths, (c) weak isometric contractions at long muscle-tendon lengths and (d) slow stretches. One minute after conditioning, ultrasound images were acquired from the relaxed muscle as it was slowly lengthened through its physiological range. The ultrasound image sequences were used to identify muscle-tendon slack angles and fascicle slack lengths. Contraction at short muscle-tendon lengths caused a mean 13.5 degree (95% CI 11.8-15.0 degree) shift in the muscle-tendon slack angle towards shorter muscle-tendon lengths, and a mean 5 mm (95% CI 2-8 mm) reduction in fascicle slack length, compared to the

IMP metabolism in human skeletal muscle after exhaustive exercise

DEFF Research Database (Denmark)

Tullson, P. C.; Bangsbo, Jens; Hellsten, Ylva

1995-01-01

This study addressed whether AMP deaminase (AMPD)myosin binding occurs with deamination during intense exercise in humans and the extent of purine loss from muscle during the initial minutes of recovery. Male subjects performed cycle exercise (265 +/- 2 W for 4.39 +/- 0.04 min) to stimulate muscle...... inosine 5'-monophosphate (IMP) formation. After exercise, blood flow to one leg was occluded. Muscle biopsies (vastus lateralis) were taken before and 3.6 +/- 0.2 min after exercise from the occluded leg and 0.7 +/- 0.0, 1.1 +/- 0.0, and 2.9 +/- 0.1 min postexercise in the nonoccluded leg. Exercise...... activated AMPD; at exhaustion IMP was 3.5 +/- 0.4 mmol/kg dry muscle. Before exercise, 16.0 +/- 1.6% of AMPD cosedimented with the myosin fraction; the extent of AMPD:myosin binding was unchanged by exercise. Inosine content increased about threefold during exercise and twofold more during recovery; by 2...

Relationship between Human Aging Muscle and Oxidative System Pathway

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Enrico Doria

2012-01-01

Full Text Available Ageing is a complex process that in muscle is usually associated with a decrease in mass, strength, and velocity of contraction. One of the most striking effects of ageing on muscle is known as sarcopenia. This inevitable biological process is characterized by a general decline in the physiological and biochemical functions of the major systems. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS generated by the addition of a single electron to the oxygen molecule. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fibre composition, muscle type, and function.

Group Ia afferents likely contribute to short-latency interlimb reflexes in the human biceps femoris muscle

DEFF Research Database (Denmark)

Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre

2017-01-01

amplitudes (4 vs. 8°) at the same 150°/s velocity (p’s > 0.08). Conclusion: Because fast conducting group Ia muscle spindle afferents are sensitive to changes in muscle stretch velocity, while group II spindle afferents are sensitive to changes in amplitude (Grey et al., JPhysiol., 2001; Matthews, Trends...... Neurosci., 1991), group Ia velocity sensitive muscle spindle afferents likely contribute to the short-latency crossed spinal reflexes in the cBF muscle following iKnee joint rotations. This supports the findings for the short-latency crossed responses in the human soleus muscle (Stubbs & Mrachacz...... neurons in humans, with primary contributions from group Ia muscle spindle afferents....

Tendon vibration attenuates superficial venous vessel response of the resting limb during static arm exercise

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Ooue Anna

2012-11-01

Full Text Available Abstract Background The superficial vein of the resting limb constricts sympathetically during exercise. Central command is the one of the neural mechanisms that controls the cardiovascular response to exercise. However, it is not clear whether central command contributes to venous vessel response during exercise. Tendon vibration during static elbow flexion causes primary muscle spindle afferents, such that a lower central command is required to achieve a given force without altering muscle force. The purpose of this study was therefore to investigate whether a reduction in central command during static exercise with tendon vibration influences the superficial venous vessel response in the resting limb. Methods Eleven subjects performed static elbow flexion at 35% of maximal voluntary contraction with (EX + VIB and without (EX vibration of the biceps brachii tendon. The heart rate, mean arterial pressure, and rating of perceived exertion (RPE in overall and exercising muscle were measured. The cross-sectional area (CSAvein and blood velocity of the basilic vein in the resting upper arm were assessed by ultrasound, and blood flow (BFvein was calculated using both variables. Results Muscle tension during exercise was similar between EX and EX + VIB. However, RPEs at EX + VIB were lower than those at EX (P P vein in the resting limb at EX decreased during exercise from baseline (P vein at EX + VIB did not change during exercise. CSAvein during exercise at EX was smaller than that at EX + VIB (P vein did not change during the protocol under either condition. The decreases in circulatory response and RPEs during EX + VIB, despite identical muscle tension, showed that activation of central command was less during EX + VIB than during EX. Abolishment of the decrease in CSAvein during exercise at EX + VIB may thus have been caused by a lower level of central command at EX + VIB rather than EX. Conclusion Diminished central command induced by tendon

Long-Duration Space Flight and Bed Rest Effects on Testosterone and Other Steroids

Science.gov (United States)

Heer, Martina; Wang, Zuwei; Huntoon, Carolyn L.; Zwart, Sara R.

2012-01-01

Context: Limited data suggest that testosterone is decreased during space flight, which could contribute to bone and muscle loss. Objective: The main objective was to assess testosterone and hormone status in long- and short-duration space flight and bed rest environments and to determine relationships with other physiological systems, including bone and muscle. Design: Blood and urine samples were collected before, during, and after long-duration space flight. Samples were also collected before and after 12- to 14-d missions and from participants in 30- to 90-d bed rest studies. Setting: Space flight studies were conducted on the International Space Station and before and after Space Shuttle missions. Bed rest studies were conducted in a clinical research center setting. Data from Skylab missions are also presented. Participants: All of the participants were male, and they included 15 long-duration and nine short-duration mission crew members and 30 bed rest subjects. Main Outcome Measures: Serum total, free, and bioavailable testosterone were measured along with serum and urinary cortisol, serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and SHBG. Results: Total, free, and bioavailable testosterone was not changed during long-duration space flight but were decreased (P space flight. There were no changes in other hormones measured. Testosterone concentrations dropped before and soon after bed rest, but bed rest itself had no effect on testosterone. Conclusions: There was no evidence for decrements in testosterone during long-duration space flight or bed rest. PMID:22049169

The effects of methylmercury on the mitochondrial energetics of rat skeletal muscle

International Nuclear Information System (INIS)

Kuwabara, Takeo; Yuasa, Tatsuhiko; Nagashima, Masaru; Igarashi, Hironaka; Yonemochi, Yousuke; Atsumi, Tetsushi; Miyatake, Tadashi

1989-01-01

In this report it is shown that methylmercury chloride (MMC) affected the mitochondrial energetics of rat skeletal muscles in case of chronic intoxication. High energy phosphate compounds were measured by 31 P-NMR spectroscopy in the living rat hindleg skeletal muscle. Decreased value of phosphocreatine (PCr)/inorganic phosphate (Pi) ratio was observed in the resting muscle of the MMC intoxicated group, and suspend recovery of the ATP, PCr and intracellular pH after muscle contraction was found in the MMC intoxicated muscle. There was no difference in the ATP levels of the resting muscle between the control and MMC group. These results suggested that the synthesis of ATP was disturbed by the inhibition of mitochondrial respiration below TCA cycle. (author)

Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type

DEFF Research Database (Denmark)

Rose, Adam John; Bisiani, Bruno; Vistisen, Bodil

2009-01-01

that the increase in skeletal muscle eEF2 Thr(56) phosphorylation was restricted to type I myofibers. Taken together, these data suggest that the depression of skeletal muscle protein synthesis with endurance-type exercise may be regulated at both initiation (i.e. 4EBP1) and elongation (i.e. eEF2) steps, with eEF2......Protein synthesis in skeletal muscle is known to decrease during exercise and it has been suggested that this may depend on the magnitude of the relative metabolic stress within the contracting muscle. To examine the mechanisms behind this, the effect of exercise intensity on skeletal muscle......) increased during exercise but was not influenced by exercise intensity, and was lower than rest 30min after exercise. On the other hand, 4EBP1 phosphorylation at Thr(37/46) decreased during exercise and this decrease was greater at higher exercise intensities, and was similar to rest 30min after exercise...

Direct observation of glycogen synthesis in human muscle with 13C NMR

International Nuclear Information System (INIS)

Jue, T.; Rothman, D.L.; Shulman, G.I.; Tavitian, B.A.; DeFronzo, R.A.; Shulman, R.G.

1989-01-01

On the basis of previous indirect measurements, skeletal muscle has been implicated as the major site of glucose uptake and it has been suggested that muscle glycogen formation is the dominant pathway. However, direct measurements of the rates of glycogen synthesis have not been possible by previous techniques. The authors have developed 13 C NMR methods to measure directly the rate of human muscle glycogen formation from infused, isotopically labeled [1- 13 C]glucose. They show that under conditions of imposed hyperglycemia and hyperinsulinemia, a majority of the infused glucose was converted to muscle glycogen in a normal man. This directly shows that muscle is the major site of glucose disposal under these conditions, and provides quantitation of the glucose flux to muscle glycogen

Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system.

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Guo, Xiufang; Gonzalez, Mercedes; Stancescu, Maria; Vandenburgh, Herman H; Hickman, James J

2011-12-01

Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction (NMJ) system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were completely differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair. Copyright © 2011 Elsevier Ltd. All rights reserved.

Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury.

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Mackey, Abigail L; Kjaer, Michael

2017-03-01

Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibers as they undergo necrosis, followed closely by satellite cell-mediated myogenesis, have been mapped in detail. Much less is known about the adaptation throughout this process of both the connective tissue structures surrounding the myofibers and the fibroblasts, the cells responsible for synthesizing this connective tissue. However, the few studies investigating muscle connective tissue remodeling demonstrate a strong response that appears to be sustained for a long time after the major myofiber responses have subsided. While the use of electrical stimulation to induce eccentric contractions vs. voluntary eccentric contractions appears to lead to a greater extent of myofiber necrosis and regenerative response, this difference is not apparent when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning against this, however, is the association between muscle matrix protein remodeling and protection against reinjury, which suggests that a (so far undefined) period of vulnerability to reinjury may exist during the remodeling phases. The role of individual muscle matrix components and their spatial interaction during adaptation to eccentric contractions is an unexplored field in human skeletal muscle and may provide insight into the optimal timing of rest vs. return to activity after muscle injury. Copyright © 2017 the American Physiological Society.

Concentric resistance training increases muscle strength without affecting microcirculation

International Nuclear Information System (INIS)

Weber, Marc-Andre; Hildebrandt, Wulf; Schroeder, Leif; Kinscherf, Ralf; Krix, Martin; Bachert, Peter; Delorme, Stefan; Essig, Marco; Kauczor, Hans-Ulrich; Krakowski-Roosen, Holger

2010-01-01

Purpose: While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscle microcirculation in vivo. Materials and methods: Thirty-nine middle-aged subjects (15 female, 24 male; mean age, 54 ± 9 years) were trained twice a week on an isokinetic system (altogether 16 sessions lasting 50 min, intensity 75% of maximum isokinetic and isometric force of knee flexors and extensors). To evaluate success of training, cross-sectional area (CSA) of the quadriceps femoris muscle and its isokinetic and isometric force were quantified. Muscular capillarization was measured in biopsies of the vastus lateralis muscle. In vivo, muscular energy and lipid metabolites were quantified by magnetic resonance spectroscopy and parameters of muscular microcirculation, such as local blood volume, blood flow and velocity, by contrast-enhanced ultrasound analyzing replenishment kinetics. Results: The significant (P 2 after training) and in absolute muscle strength (isometric, 146 ± 44 vs. 174 ± 50 Nm; isokinetic, 151 ± 53 vs. 174 ± 62 Nm) demonstrated successful training. Neither capillary density ex vivo (351 ± 75 vs. 326 ± 62) nor ultrasonographic parameters of resting muscle perfusion were significantly different (blood flow, 1.2 ± 1.2 vs. 1.1 ± 1.1 ml/min/100 g; blood flow velocity, 0.49 ± 0.44 vs. 0.52 ± 0.74 mm s -1 ). Also, the intensities of high-energy phosphates phosphocreatine and β-adenosintriphosphate were not different after training within the skeletal muscle at rest (β-ATP/phosphocreatine, 0.29 ± 0.06 vs. 0.28 ± 0.04). Conclusion: The significant increase in muscle size and strength in response to concentric isokinetic and isometric resistance training occurs without an increase in the in vivo microcirculation of the skeletal muscles at

Concentric resistance training increases muscle strength without affecting microcirculation

Energy Technology Data Exchange (ETDEWEB)

Weber, Marc-Andre [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg (Germany)], E-mail: MarcAndre.Weber@med.uni-heidelberg.de; Hildebrandt, Wulf [Immunochemistry, German Cancer Research Center (dkfz), Heidelberg (Germany); Schroeder, Leif [Medical Physics in Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Kinscherf, Ralf [Department of Anatomy and Developmental Biology, University of Heidelberg, Heidelberg (Germany); Krix, Martin [Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Bachert, Peter [Medical Physics in Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Delorme, Stefan; Essig, Marco [Radiology, German Cancer Research Center (dkfz), Heidelberg (Germany); Kauczor, Hans-Ulrich [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg (Germany); Krakowski-Roosen, Holger [National Center for Tumor Diseases (NCT), Heidelberg (Germany)

2010-03-15

Purpose: While the evidence is conclusive regarding the positive effects of endurance training, there is still some controversy regarding the effects of resistance training on muscular capillarity. Thus, the purpose was to assess whether resistance strength training influences resting skeletal muscle microcirculation in vivo. Materials and methods: Thirty-nine middle-aged subjects (15 female, 24 male; mean age, 54 {+-} 9 years) were trained twice a week on an isokinetic system (altogether 16 sessions lasting 50 min, intensity 75% of maximum isokinetic and isometric force of knee flexors and extensors). To evaluate success of training, cross-sectional area (CSA) of the quadriceps femoris muscle and its isokinetic and isometric force were quantified. Muscular capillarization was measured in biopsies of the vastus lateralis muscle. In vivo, muscular energy and lipid metabolites were quantified by magnetic resonance spectroscopy and parameters of muscular microcirculation, such as local blood volume, blood flow and velocity, by contrast-enhanced ultrasound analyzing replenishment kinetics. Results: The significant (P < 0.001) increase in CSA (60 {+-} 16 before vs. 64 {+-} 15 cm{sup 2} after training) and in absolute muscle strength (isometric, 146 {+-} 44 vs. 174 {+-} 50 Nm; isokinetic, 151 {+-} 53 vs. 174 {+-} 62 Nm) demonstrated successful training. Neither capillary density ex vivo (351 {+-} 75 vs. 326 {+-} 62) nor ultrasonographic parameters of resting muscle perfusion were significantly different (blood flow, 1.2 {+-} 1.2 vs. 1.1 {+-} 1.1 ml/min/100 g; blood flow velocity, 0.49 {+-} 0.44 vs. 0.52 {+-} 0.74 mm s{sup -1}). Also, the intensities of high-energy phosphates phosphocreatine and {beta}-adenosintriphosphate were not different after training within the skeletal muscle at rest ({beta}-ATP/phosphocreatine, 0.29 {+-} 0.06 vs. 0.28 {+-} 0.04). Conclusion: The significant increase in muscle size and strength in response to concentric isokinetic and isometric

The pH heterogeneity in human calf muscle during neuromuscular electrical stimulation.

Science.gov (United States)

Stutzig, Norman; Rzanny, Reinhard; Moll, Kevin; Gussew, Alexander; Reichenbach, Jürgen R; Siebert, Tobias

2017-06-01

The aim of the study was to examine pH heterogeneity during fatigue induced by neuromuscular electrical stimulation (NMES) using phosphorus magnetic resonance spectroscopy ( 31 P-MRS). It is hypothesized that three pH components would occur in the 31 P-MRS during fatigue, representing three fiber types. The medial gastrocnemius of eight subjects was stimulated within a 3-Tesla whole body MRI scanner. The maximal force during stimulation (F stim ) was examined by a pressure sensor. Phosphocreatine (PCr), adenosintriphosphate, inorganic phosphate (Pi), and the corresponding pH were estimated by a nonvolume-selective 31 P-MRS using a small loop coil at rest and during fatigue. During fatigue, F stim and PCr decreased to 27% and 33% of their initial levels, respectively. In all cases, the Pi peak increased when NMES was started and split into three different peaks. Based on the single Pi peaks during fatigue, an alkaline (6.76 ± 0.08), a medium (6.40 ± 0.06), and an acidic (6.09 ± 0.05) pH component were observed compared to the pH (7.02 ± 0.02) at rest. It is suggested that NMES is able to induce pH heterogeneity in the medial gastrocnemius, and that the single Pi peaks represent the different muscle fiber types of the skeletal muscle. Magn Reson Med 77:2097-2106, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Activity of masticatory muscles in subjects with different orofacial pain conditions.

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Bodéré, Céline; Téa, Say Hack; Giroux-Metges, Marie Agnes; Woda, Alain

2005-07-01

The existence of a pathophysiological link between tonic muscle activity and chronic muscle pain is still being debated. The purpose of this retrospective, controlled study was to evaluate the electromyographic (EMG) activity of masticatory muscles in subjects with different orofacial pain conditions. The temporal and masseter EMG activity at rest and the masseteric reflex were recorded in two groups of patients with either myofascial pain (n=33) or neuropathic pain (n=20), one group of non-pain patients with disc derangement disorders (n=27) and one control group of healthy, asymptomatic subjects (n=32). The EMG activities of both muscles at rest were significantly higher in the pain patient groups compared to the asymptomatic control group. There was no significant difference between the disc derangement disorder group and the control group. The masseteric reflex amplitude was reduced in all patient groups when compared with the control group. In pain patient groups, the increased EMG activity at rest and the reduction of the masseteric reflex amplitude were equally distributed in the pain and non-pain sides. In addition, subjects presenting with bilateral pain showed higher EMG activity at rest than those with unilateral pain. These results suggested that the modulation of muscle activity was not the direct consequence of a peripheral nociceptive mechanism and seemed to indicate that a central mechanism was at work. The contrast between the increased EMG activity at rest and the reduction of the masseteric reflex amplitude may reflect modulations of motoneurones that differed in tonic versus phasic conditions in chronic pain patients.

Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

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Mohamad Hafizi Abu Bakar

2015-05-01

Full Text Available Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.

Activity of upper limb muscles during human walking.

Science.gov (United States)

Kuhtz-Buschbeck, Johann P; Jing, Bo

2012-04-01

The EMG activity of upper limb muscles during human gait has rarely been studied previously. It was examined in 20 normal volunteers in four conditions: walking on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while volitionally holding the arms still (Held), (3) with the arms immobilized (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e. opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak rhythmical lengthening and shortening contractions of arm and shoulder muscles. Phasic muscle activity was needed to keep the unrestricted arms still during walking (Held), indicating a passive component of arm swing. An active component, possibly programmed centrally, existed as well, because some EMG signals persisted when the arms were immobilized during walking (Bound). Anti-Normal gait involved stronger EMG activity than Normal walking and was uneconomical. The present results indicate that normal arm swing has both passive and active components. Copyright © 2011 Elsevier Ltd. All rights reserved.

Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

Science.gov (United States)

Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

1999-01-01

Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity.

Science.gov (United States)

van Moorsel, Dirk; Hansen, Jan; Havekes, Bas; Scheer, Frank A J L; Jörgensen, Johanna A; Hoeks, Joris; Schrauwen-Hinderling, Vera B; Duez, Helene; Lefebvre, Philippe; Schaper, Nicolaas C; Hesselink, Matthijs K C; Staels, Bart; Schrauwen, Patrick

2016-08-01

A disturbed day-night rhythm is associated with metabolic perturbations that can lead to obesity and type 2 diabetes mellitus (T2DM). In skeletal muscle, a reduced oxidative capacity is also associated with the development of T2DM. However, whether oxidative capacity in skeletal muscle displays a day-night rhythm in humans has so far not been investigated. Lean, healthy subjects were enrolled in a standardized living protocol with regular meals, physical activity and sleep to reflect our everyday lifestyle. Mitochondrial oxidative capacity was examined in skeletal muscle biopsies taken at five time points within a 24-hour period. Core-body temperature was lower during the early night, confirming a normal day-night rhythm. Skeletal muscle oxidative capacity demonstrated a robust day-night rhythm, with a significant time effect in ADP-stimulated respiration (state 3 MO, state 3 MOG and state 3 MOGS, p < 0.05). Respiration was lowest at 1 PM and highest at 11 PM (state 3 MOGS: 80.6 ± 4.0 vs. 95.8 ± 4.7 pmol/mg/s). Interestingly, the fluctuation in mitochondrial function was also observed in whole-body energy expenditure, with peak energy expenditure at 11 PM and lowest energy expenditure at 4 AM (p < 0.001). In addition, we demonstrate rhythmicity in mRNA expression of molecular clock genes in human skeletal muscle. Our results suggest that the biological clock drives robust rhythms in human skeletal muscle oxidative metabolism. It is tempting to speculate that disruption of these rhythms contribute to the deterioration of metabolic health associated with circadian misalignment.

Acute moderate elevation of TNF-{alpha} does not affect systemic and skeletal muscle protein turnover in healthy humans

DEFF Research Database (Denmark)

Petersen, Anne Marie; Plomgaard, Peter; Fischer, Christian P

2009-01-01

-alpha infusion (rhTNF-alpha). We hypothesize that TNF-alpha increases human muscle protein breakdown and/or inhibit synthesis. Subjects and Methods: Using a randomized controlled, crossover design post-absorptive healthy young males (n=8) were studied 2 hours under basal conditions followed by 4 hours infusion...... with the phenylalanine 3-compartment model showed similar muscle synthesis, breakdown and net muscle degradation after 2 hours basal and after 4 hours Control or rhTNF-alpha infusion. Conclusion: This study is the first to show in humans that TNF-alpha does not affect systemic and skeletal muscle protein turnover, when......Context: Skeletal muscle wasting has been associated with elevations in circulating inflammatory cytokines, in particular TNF-alpha. Objective: In this study, we investigated whether TNF-alpha affects human systemic and skeletal muscle protein turnover, via a 4 hours recombinant human TNF...

Genetic variability in the human cannabinoid receptor 1 is associated with resting state EEG theta power in humans.

Science.gov (United States)

Heitland, I; Kenemans, J L; Böcker, K B E; Baas, J M P

2014-11-01

It has long been postulated that exogenous cannabinoids have a profound effect on human cognitive functioning. These cannabinoid effects are thought to depend, at least in parts, on alterations of phase-locking of local field potential neuronal firing. The latter can be measured as activity in the theta frequency band (4-7Hz) by electroencephalogram. Theta oscillations are supposed to serve as a mechanism in neural representations of behaviorally relevant information. However, it remains unknown whether variability in endogenous cannabinoid activity is involved in theta rhythms and therefore, may serve as an individual differences index of human cognitive functioning. To clarify this issue, we recorded resting state EEG activity in 164 healthy human subjects and extracted EEG power across frequency bands (δ, θ, α, and β). To assess variability in the endocannabinoid system, two genetic polymorphisms (rs1049353, rs2180619) within the cannabinoid receptor 1 (CB1) were determined in all participants. As expected, we observed significant effects of rs1049353 on EEG power in the theta band at frontal, central and parietal electrode regions. Crucially, these effects were specific for the theta band, with no effects on activity in the other frequency bands. Rs2180619 showed no significant associations with theta power after Bonferroni correction. Taken together, we provide novel evidence in humans showing that genetic variability in the cannabinoid receptor 1 is associated with resting state EEG power in the theta frequency band. This extends prior findings of exogenous cannabinoid effects on theta power to the endogenous cannabinoid system. Copyright © 2014 Elsevier B.V. All rights reserved.

A human brain atlas derived via n-cut parcellation of resting-state and task-based fMRI data.

Science.gov (United States)

James, George Andrew; Hazaroglu, Onder; Bush, Keith A

2016-02-01

The growth of functional MRI has led to development of human brain atlases derived by parcellating resting-state connectivity patterns into functionally independent regions of interest (ROIs). All functional atlases to date have been derived from resting-state fMRI data. But given that functional connectivity between regions varies with task, we hypothesized that an atlas incorporating both resting-state and task-based fMRI data would produce an atlas with finer characterization of task-relevant regions than an atlas derived from resting-state alone. To test this hypothesis, we derived parcellation atlases from twenty-nine healthy adult participants enrolled in the Cognitive Connectome project, an initiative to improve functional MRI's translation into clinical decision-making by mapping normative variance in brain-behavior relationships. Participants underwent resting-state and task-based fMRI spanning nine cognitive domains: motor, visuospatial, attention, language, memory, affective processing, decision-making, working memory, and executive function. Spatially constrained n-cut parcellation derived brain atlases using (1) all participants' functional data (Task) or (2) a single resting-state scan (Rest). An atlas was also derived from random parcellation for comparison purposes (Random). Two methods were compared: (1) a parcellation applied to the group's mean edge weights (mean), and (2) a two-stage approach with parcellation of individual edge weights followed by parcellation of mean binarized edges (two-stage). The resulting Task and Rest atlases had significantly greater similarity with each other (mean Jaccard indices JI=0.72-0.85) than with the Random atlases (JI=0.59-0.63; all pRest atlas similarity was greatest for the two-stage method (JI=0.85), which has been shown as more robust than the mean method; these atlases also better reproduced voxelwise seed maps of the left dorsolateral prefrontal cortex during rest and performing the n-back working memory

Pelvic floor muscle thickness measured by perineal ultrasonography

DEFF Research Database (Denmark)

Bernstein, Inge Thomsen; Juul, N; Grønvall, S

1991-01-01

Pelvic floor muscle thickness was assessed in nine healthy female physiotherapists by perineal sonography. All measurements were performed as triple-measurements. The aims were to assess the reliability of the measurements and to establish a reference material. The muscle thickness at rest...

A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF-06252616), increases muscle volume in cynomolgus monkeys.

Science.gov (United States)

St Andre, Michael; Johnson, Mark; Bansal, Prashant N; Wellen, Jeremy; Robertson, Andrew; Opsahl, Alan; Burch, Peter M; Bialek, Peter; Morris, Carl; Owens, Jane

2017-11-09

The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for therapies that benefit all patients regardless of the underlying mutation. Myostatin is a member of the transforming growth factor-β (TGF-β) family of ligands and is a negative regulator of skeletal muscle mass. Loss of myostatin has been shown to increase muscle mass and improve muscle function in both normal and dystrophic mice. Therefore, myostatin blockade via a specific antibody could ameliorate the muscle weakness in DMD patients by increasing skeletal muscle mass and function, thereby reducing patients' functional decline. A murine anti-myostatin antibody, mRK35, and its humanized analog, domagrozumab, were developed and their ability to inhibit several TGB-β ligands was measured using a cell-based Smad-activity reporter system. Normal and mdx mice were treated with mRK35 to examine the antibody's effect on body weight, lean mass, muscle weights, grip strength, ex vivo force production, and fiber size. The humanized analog (domagrozumab) was tested in non-human primates (NHPs) for changes in skeletal muscle mass and volume as well as target engagement via modulation of circulating myostatin. Both the murine and human antibodies are specific and potent inhibitors of myostatin and GDF11. mRK35 is able to increase body weight, lean mass, and muscle weights in normal mice. In mdx mice, mRK35 significantly increased body weight, muscle weights, grip strength, and ex vivo force production in the extensor digitorum longus (EDL) muscle. Further, tibialis anterior (TA) fiber size was significantly increased. NHPs treated with domagrozumab demonstrated a dose-dependent increase in lean mass and muscle volume and exhibited increased circulating levels of myostatin demonstrating target engagement. We demonstrated that the potent anti-myostatin antibody mRK35 and

Muscle glycogenolysis during exercise

DEFF Research Database (Denmark)

Richter, Erik; Ruderman, N B; Gavras, H

1982-01-01

glycogenolysis during exercise: contractions principally stimulate glycogenolysis early in exercise, and a direct effect of epinephrine on muscle is needed for continued glycogenolysis. In addition, epinephrine increased oxygen consumption and glucose uptake in both resting and electrically stimulated...

Optimizing the measurement of mitochondrial protein synthesis in human skeletal muscle.

Science.gov (United States)

Burd, Nicholas A; Tardif, Nicolas; Rooyackers, Olav; van Loon, Luc J C

2015-01-01

The measurement of mitochondrial protein synthesis after food ingestion, contractile activity, and/or disease is often used to provide insight into skeletal muscle adaptations that occur in the longer term. Studies have shown that protein ingestion stimulates mitochondrial protein synthesis in human skeletal muscle. Minor differences in the stimulation of mitochondrial protein synthesis occur after a single bout of resistance or endurance exercise. There appear to be no measurable differences in mitochondrial protein synthesis between critically ill patients and aged-matched controls. However, the mitochondrial protein synthetic response is reduced at a more advanced age. In this paper, we discuss the challenges involved in the measurement of human skeletal muscle mitochondrial protein synthesis rates based on stable isotope amino acid tracer methods. Practical guidelines are discussed to improve the reliability of the measurement of mitochondrial protein synthesis rates. The value of the measurement of mitochondrial protein synthesis after a single meal or exercise bout on the prediction of the longer term skeletal muscle mass and performance outcomes in both the healthy and disease populations requires more work, but we emphasize that the measurements need to be reliable to be of any value to the field.

Substantial elevation of interleukin-6 concentration in peritendinous tissue, in contrast to muscle, following prolonged exercise in humans

DEFF Research Database (Denmark)

Langberg, Henning; Olesen, Jens; Gemmer, Carsten

2002-01-01

Plasma interleukin-6 (IL-6) concentration has been shown to increase with exercise and various cell types and tissues have been suggested to be responsible for this increase. At present no studies have measured the interstitial concentration of IL-6 in skeletal muscle and connective tissue......, 48 h, 72 h and 96 h post-exercise in both the medial gastrocnemius muscle (not measured at rest due to risk of disabling the subsequent exercise, and 24 h and 72 h post-exercise) and the peritendinous tissue around the Achilles tendon using microdialysis catheters with a high molecular mass cut...

Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb.

Science.gov (United States)

Heinonen, Ilkka; Wendelin-Saarenhovi, Maria; Kaskinoro, Kimmo; Knuuti, Juhani; Scheinin, Mika; Kalliokoski, Kari K

2013-07-15

The role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepinephrine (NE) and phentolamine. At rest, the α-adrenoceptor agonist NE reduced BF by ~40%, similarly in muscles (from 3.2 ± 1.9 to 1.4 ± 0.3 ml·min(-1)·100 g(-1) in quadriceps femoris muscle), bone (from 1.1 ± 0.4 to 0.5 ± 0.2 ml·min(-1)·100 g(-1)) and adipose tissue (AT) (from 1.2 ± 0.7 to 0.7 ± 0.3 ml·min(-1)·100 g(-1)). During exercise, NE reduced exercising muscle BF by ~16%. BF in AT was reduced similarly as rest. The α-adrenoceptor antagonist phentolamine increased BF similarly in the different muscles and other tissues of the limb at rest. During exercise, BF in inactive muscle was increased 3.4-fold by phentolamine compared with exercise without drug, but BF in exercising muscles was not influenced. Bone and AT (P = 0.055) BF were also increased by phentolamine in the exercise condition. NE increased and phentolamine decreased oxygen extraction in the limb during exercise. We conclude that inhibition of α-adrenergic tone markedly disturbs the distribution of BF and oxygen extraction in the exercising human limb by increasing BF especially around inactive muscle fibers. Moreover, although marked functional sympatholysis also occurs during exercise, the arterial NE infusion that mimics the exaggerated sympathetic nerve activity commonly seen in patients with cardiovascular disease was still capable of directly limiting BF in the exercising leg muscles.

Bionic Humans Using EAP as Artificial Muscles Reality and Challenges

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Yoseph Bar-Cohen

2008-11-01

Full Text Available For many years, the idea of a human with bionic muscles immediately conjures up science fiction images of a TV series superhuman character that was implanted with bionic muscles and portrayed with strength and speed far superior to any normal human. As fantastic as this idea may seem, recent developments in electroactive polymers (EAP may one day make such bionics possible. Polymers that exhibit large displacement in response to stimulation that is other than electrical signal were known for many years. Initially, EAP received relatively little attention due to their limited actuation capability. However, in the recent years, the view of the EAP materials has changed due to the introduction of effective new materials that significantly surpassed the capability of the widely used piezoelectric polymer, PVDF. As this technology continues to evolve, novel mechanisms that are biologically inspired are expected to emerge. EAP materials can potentially provide actuation with lifelike response and more flexible configurations. While further improvements in performance and robustness are still needed, there already have been several reported successes. In recognition of the need for cooperation in this multidisciplinary field, the author initiated and organized a series of international forums that are leading to a growing number of research and development projects and to great advances in the field. In 1999, he challenged the worldwide science and engineering community of EAP experts to develop a robotic arm that is actuated by artificial muscles to win a wrestling match against a human opponent. In this paper, the field of EAP as artificial muscles will be reviewed covering the state of the art, the challenges and the vision for the progress in future years.

Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate

DEFF Research Database (Denmark)

Green, C J; Bunprajun, T; Pedersen, B K

2013-01-01

in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance......  The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture...... and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism...

Bioenergetics of the calf muscle in Friedreich ataxia patients measured by 31P-MRS before and after treatment with recombinant human erythropoietin.

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Wolfgang Nachbauer

Full Text Available Friedreich ataxia (FRDA is caused by a GAA repeat expansion in the FXN gene leading to reduced expression of the mitochondrial protein frataxin. Recombinant human erythropoietin (rhuEPO is suggested to increase frataxin levels, alter mitochondrial function and improve clinical scores in FRDA patients. Aim of the present pilot study was to investigate mitochondrial metabolism of skeletal muscle tissue in FRDA patients and examine effects of rhuEPO administration by phosphorus 31 magnetic resonance spectroscopy (31P MRS. Seven genetically confirmed FRDA patients underwent 31P MRS of the calf muscles using a rest-exercise-recovery protocol before and after receiving 3000 IU of rhuEPO for eight weeks. FRDA patients showed more rapid phosphocreatine (PCr depletion and increased accumulation of inorganic phosphate (Pi during incremental exercise as compared to controls. After maximal exhaustive exercise prolonged regeneration of PCR and slowed decline in Pi can be seen in FRDA. PCr regeneration as hallmark of mitochondrial ATP production revealed correlation to activity of complex II/III of the respiratory chain and to demographic values. PCr and Pi kinetics were not influenced by rhuEPO administration. Our results confirm mitochondrial dysfunction and exercise intolerance due to impaired oxidative phosphorylation in skeletal muscle tissue of FRDA patients. MRS did not show improved mitochondrial bioenergetics after eight weeks of rhuEPO exposition in skeletal muscle tissue of FRDA patients.EU Clinical Trials Register2008-000040-13.

Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.

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Teruyo Oishi

Full Text Available Heterotopic ossification (HO is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+ and PDGFRα(+ cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+ cells and PDGFRα(+ cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+ cells formed bone-like tissue and showed successful engraftment, while CD56(+ cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+ cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+ cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+ cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+ cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+ cells. Our results suggest that PDGFRα(+ cells may be the major source of HO and that the newly identified mi

Effect of ionizing radiation on human skeletal muscle precursor cells

International Nuclear Information System (INIS)

Jurdana, Mihaela; Cemazar, Maja; Pegan, Katarina; Mars, Tomaz

2013-01-01

Long term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures. Human skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin – 6 (IL-6) release and stress response detected by the heat shock protein (HSP) level, while long term effects were followed by proliferation capacity and cell death. Compared with non-irradiated control and cells treated with inhibitor of cell proliferation Ara C, myoblast proliferation decreased 72 h post-irradiation, this effect was more pronounced with increasing doses. Post-irradiation myoblast survival determined by measurement of released LDH enzyme activity revealed increased activity after exposure to irradiation. The acute response of myoblasts to lower doses of irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher doses of irradiation triggered a stress response in myoblasts, determined by increased levels of stress markers (HSPs 27 and 70). Our results show that myoblasts are sensitive to irradiation in terms of their proliferation capacity and capacity to secret IL-6. Since myoblast proliferation and differentiation are a key stage in muscle regeneration, this effect of irradiation needs to be taken in account, particularly in certain clinical conditions

Evaluation of human muscle in vivo by potassium radiometric measuring

International Nuclear Information System (INIS)

Sousa, Wanderson de P.

2000-01-01

Potassium is an essential element to the human metabolism and is present in all living cells, mainly in the striated muscular fibers. K-40 is one of the natural potassium isotopes with mass percentage of 0,0118% . This isotope emits beta particle and gamma rays with 1460 keV. The energy of K-40 photon and its uniform distribution within the human body allows its in vivo measurement. The objective of this study is to optimize this technique and evaluate the possibility of its medical application in order to quantify muscle increase during recovering procedures. Subjects of both sexes measured until this moment were divided into two groups. Subjects of Group 1 do not exercise routinely and subjects of Group 2 does. In Group 1 the average potassium mass, muscle mass and potassium concentration were (101±16)g of K, (20±3)kg of muscle and (1,3±0,3)g of K/kg of body mass, respectively, while in Group 2 average values were (125±38)g of K, (25±8)kg of muscle and (1,7±0,2)g of K/kg of body mass. The comparison between average values shows a clear difference, which allows to correlate a higher K mass with routine body activity. The technique has shown enough sensitivity for this application. (author)

Nitric oxide and prostaglandins influence local skeletal muscle blood flow during exercise in humans: coupling between local substrate uptake and blood flow

DEFF Research Database (Denmark)

Kalliokoski, Kari K; Langberg, Henning; Ryberg, Ann Kathrine

2006-01-01

-legged dynamic knee-extension exercise. Local blockade was produced by infusing nitro-L-arginine methyl ester and indomethacin directly in the muscle via a microdialysis catheter. Blood flow and glucose uptake were measured in the region of blockade and in two additional regions of vastus lateralis muscle 1......Synergic action of nitric oxide (NO) and prostaglandins (PG) in the regulation of muscle blood flow during exercise has been demonstrated. In the present study, we investigated whether these vasodilators also regulate local blood flow, flow heterogeneity, and glucose uptake within the exercising...... skeletal muscle. Skeletal muscle blood flow was measured in seven healthy young men using near-infrared spectroscopy and indocyanine green and muscle glucose uptake using positron emission tomography and 2-fluoro-2-deoxy-D-[(18)F]glucose without and with local blockade of NO and PG at rest and during one...

Triangular human capital flows between sending, entrepot and the rest of the world regions

Directory of Open Access Journals (Sweden)

DeVoretz, Don J.

2002-01-01

Full Text Available EnglishA model of triangular movement of highly skilled immigrants between a sendingcountry (China/India to an entrepot country (Canada and then possibly to the rest of the world isdeveloped. The question of who stays or leaves after arrival in the entrpot country is considered. Theacquisition of subsidized human capital and the ascension to citizenship by immigrants are argued tobe key conditioners that reduce the probability of staying in the entropot country. Finally, the modelpredicts if the best or the mediocre highly skilled stay or leave the entrepot country for the sendingregion or the rest of the world.FrenchUn modèle de mouvement triangulaire d'immigrants très spécialisés entre un pays émetteur (Chine/Inde et un pays entrepôt (Canada et éventuellement le reste du monde s'est développé. La question de savoir qui reste dans le pays entrepôt et qui le quitte est considérée. L'acquisition de capital humain subventionné et la naturalisation d'immigrants sont traitées comme des éléments de conditionnement clés qui réduisent la probabilité de rester dans le pays entrepôt. Enfin, le modèle prédit si, parmi les travailleurs spécialisés, ce sont les meilleurs ou les médiocres qui restent dans le pays entrepôt ou qui le quittent pour la région émettrice ou le reste du monde.

Human-robot interaction: kinematics and muscle activity inside a powered compliant knee exoskeleton.

Science.gov (United States)

Knaepen, Kristel; Beyl, Pieter; Duerinck, Saartje; Hagman, Friso; Lefeber, Dirk; Meeusen, Romain

2014-11-01

Until today it is not entirely clear how humans interact with automated gait rehabilitation devices and how we can, based on that interaction, maximize the effectiveness of these exoskeletons. The goal of this study was to gain knowledge on the human-robot interaction, in terms of kinematics and muscle activity, between a healthy human motor system and a powered knee exoskeleton (i.e., KNEXO). Therefore, temporal and spatial gait parameters, human joint kinematics, exoskeleton kinetics and muscle activity during four different walking trials in 10 healthy male subjects were studied. Healthy subjects can walk with KNEXO in patient-in-charge mode with some slight constraints in kinematics and muscle activity primarily due to inertia of the device. Yet, during robot-in-charge walking the muscular constraints are reversed by adding positive power to the leg swing, compensating in part this inertia. Next to that, KNEXO accurately records and replays the right knee kinematics meaning that subject-specific trajectories can be implemented as a target trajectory during assisted walking. No significant differences in the human response to the interaction with KNEXO in low and high compliant assistance could be pointed out. This is in contradiction with our hypothesis that muscle activity would decrease with increasing assistance. It seems that the differences between the parameter settings of low and high compliant control might not be sufficient to observe clear effects in healthy subjects. Moreover, we should take into account that KNEXO is a unilateral, 1 degree-of-freedom device.

Nuclear fusion-independent smooth muscle differentiation of human adipose-derived stem cells induced by a smooth muscle environment.

Science.gov (United States)

Zhang, Rong; Jack, Gregory S; Rao, Nagesh; Zuk, Patricia; Ignarro, Louis J; Wu, Benjamin; Rodríguez, Larissa V

2012-03-01

Human adipose-derived stem cells hASC have been isolated and were shown to have multilineage differentiation capacity. Although both plasticity and cell fusion have been suggested as mechanisms for cell differentiation in vivo, the effect of the local in vivo environment on the differentiation of adipose-derived stem cells has not been evaluated. We previously reported the in vitro capacity of smooth muscle differentiation of these cells. In this study, we evaluate the effect of an in vivo smooth muscle environment in the differentiation of hASC. We studied this by two experimental designs: (a) in vivo evaluation of smooth muscle differentiation of hASC injected into a smooth muscle environment and (b) in vitro evaluation of smooth muscle differentiation capacity of hASC exposed to bladder smooth muscle cells. Our results indicate a time-dependent differentiation of hASC into mature smooth muscle cells when these cells are injected into the smooth musculature of the urinary bladder. Similar findings were seen when the cells were cocultured in vitro with primary bladder smooth muscle cells. Chromosomal analysis demonstrated that microenvironment cues rather than nuclear fusion are responsible for this differentiation. We conclude that cell plasticity is present in hASCs, and their differentiation is accomplished in the absence of nuclear fusion. Copyright © 2011 AlphaMed Press.

Ultrasonography as a tool to study afferent feedback from the muscle-tendon complex during human walking

DEFF Research Database (Denmark)

Cronin, Neil J.; Klint, Richard af; Grey, Michael James

2011-01-01

In humans, one of the most common tasks in everyday life is walking, and sensory afferent feedback from peripheral receptors, particularly the muscle spindles and Golgi tendon organs (GTO), makes an important contribution to the motor control of this task. One factor that can complicate the ability...... with an examination of muscle activation to give a broader insight to neuromuscular interaction during walking. Despite the advances in understanding that these techniques have brought, there is clearly still a need for more direct methods to study both neural and mechanical parameters during human walking in order...... of these receptors to act as length, velocity and force transducers is the complex pattern of interaction between muscle and tendinous tissues, as tendon length is often considerably greater than muscle fibre length in the human lower limb. In essence, changes in muscle-tendon mechanics can influence the firing...

Quantitative analysis of energy metabolism in human muscle using SLOOP 31P-MR-spectroscopy

International Nuclear Information System (INIS)

Beer, M.; Koestler, H.; Buchner, S.; Sandstede, J.; Hahn, D.

2002-01-01

Objective: Energy metabolism is vital for regular muscle function. In humans, in vivo analysis using 31 P-MR-spectroscopy (MRS) is mostly restricted to semiquantitative parameters due to technical demands. We applied spatial localization with optimal pointspread function (SLOOP) for quantification in human skeletal and cardiac muscle. Subjects/Methods: 10 healthy volunteers and 4 patients with myotonic dystrophy type 1 were examined using a 1.5 T system (Magnetom VISION) and chemical shift imaging (CSI) for data collection. Concentrations of PCr, ATP and P i as well as PCr/ATP ratios were calculated by SLOOP. Results: Concentrations of PCr, ATP and P i were 29.9±3.4, 7.1±0.9 and 5.7±1.2 [mmol/kg] in normal skeletal muscle, corresponding to previously published studies. Two of the patients with a duration of disease longer than 10 years and a pronounced muscle weakness showed a significant decrease of PCr and ATP in skeletal muscle below 10 and 5 mmol/kg. One of these patients had an additional reduction of PCr in cardiac muscle. (orig.) [de

Development of the epaxial muscles in the human embryo

NARCIS (Netherlands)

Mekonen, Hayelom K.; Hikspoors, Jill P. J. M.; Mommen, Greet; Eleonore KÖhler, S.; Lamers, Wouter H.

2016-01-01

Although the intrinsic muscles of the back are defined by their embryological origin and innervation pattern, no detailed study on their development is available. Human embryos (5-10 weeks development) were studied, using Amira3D® reconstruction and Cinema4D® remodeling software for visualization.

The capillary pattern in human masseter muscle during ageing

Czech Academy of Sciences Publication Activity Database

Cvetko, E.; Janáček, Jiří; Kubínová, Lucie; Eržen, I.

2013-01-01

Roč. 32, č. 3 (2013), s. 135-144 ISSN 1580-3139 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : 3D analysis * capillaries * confocal microscopy * human * masseter * muscle Subject RIV: EA - Cell Biology Impact factor: 0.697, year: 2013

Muscle spindle autogenetic inhibition in the extraocular muscles of lamb.

Science.gov (United States)

Pettorossi, V E; Filippi, G M

1981-09-01

The role of extraocular muscle (EOM) proprioceptors on eye motility has been investigated in lambs on "encéphale isolé", by evaluating the tension of EOMs at various lengths and velocities of stretch before and after proprioceptive blocks. The EOM tension, in the absence of proprioceptive input, was higher than in normal conditions. Such an effect occurred at lengthening values greater than 3 mm of stretch from resting muscle length, corresponding to 18 degrees of eye deviation and was dependent on the velocity of the stretch, being more effective at high velocity. The muscle receptors responsible for this effect was determined by comparing the sensitivity to vibratory stimulation of spindles and tendon organs to the amount of inhibition provoked by the same stimulation on an EOM electromyographic activity. The tension inhibition appeared to be correlated to muscle spindle activation. Thus, the presence of muscle spindles can determine a reduction of the tension within the stretched muscles. This result suggests that the EOM length and velocity signals operate moment to moment reduction on the stiffness of the muscle which antagonizes eye displacement, thus facilitating the ocular movements.

Blood flow in the peritendinous space of the human Achilles tendon during exercise

DEFF Research Database (Denmark)

Langberg, Henning; Bülow, J; Kjaer, M

1998-01-01

This study evaluated blood flow in the peritendinous space of the human Achilles tendon during rest and 40-min dynamical contraction of m. triceps surae. In 10 healthy volunteers 133Xe was injected in to the peritendinous space just ventrally to the Achilles tendon 2 and 5 cm proximal to the calc......This study evaluated blood flow in the peritendinous space of the human Achilles tendon during rest and 40-min dynamical contraction of m. triceps surae. In 10 healthy volunteers 133Xe was injected in to the peritendinous space just ventrally to the Achilles tendon 2 and 5 cm proximal....... Lymph drainage from the area was found to be negligible both during rest and exercise. We conclude that dynamical calf muscle contractions result in increased peritendinous blood flow at the Achilles tendon in humans....

Photobiomodulation in human muscle tissue: an advantage in sports performance?

Science.gov (United States)

Ferraresi, Cleber; Huang, Ying-Ying; Hamblin, Michael R

2016-12-01

Photobiomodulation (PBM) describes the use of red or near-infrared (NIR) light to stimulate, heal, and regenerate damaged tissue. Both preconditioning (light delivered to muscles before exercise) and PBM applied after exercise can increase sports performance in athletes. This review covers the effects of PBM on human muscle tissue in clinical trials in volunteers related to sports performance and in athletes. The parameters used were categorized into those with positive effects or no effects on muscle performance and recovery. Randomized controlled trials and case-control studies in both healthy trained and untrained participants, and elite athletes were retrieved from MEDLINE up to 2016. Performance metrics included fatigue, number of repetitions, torque, hypertrophy; measures of muscle damage and recovery such as creatine kinase and delayed onset muscle soreness. Searches retrieved 533 studies, of which 46 were included in the review (n = 1045 participants). Studies used single laser probes, cluster of laser diodes, LED clusters, mixed clusters (lasers and LEDs), and flexible LED arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase muscle mass gained after training, and decrease inflammation and oxidative stress in muscle biopsies. We raise the question of whether PBM should be permitted in athletic competition by international regulatory authorities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of hypothyroidism on the skeletal muscle blood flow response to contractions.

Science.gov (United States)

Bausch, L; McAllister, R M

2003-04-01

Hypothyroidism is associated with impaired blood flow to skeletal muscle under whole body exercise conditions. It is unclear whether poor cardiac and/or vascular function account for blunted muscle blood flow. Our experiment isolated a small group of hindlimb muscles and simulated exercise via tetanic contractions. We hypothesized that muscle blood flow would be attenuated in hypothyroid rats (HYPO) compared with euthyroid rats (EUT). Rats were made hypothyroid by mixing propylthiouracil in their drinking water (2.35 x 10-3 mol/l). Treatment efficacy was evidenced by lower serum T3 concentrations and resting heart rates in HYPO (both Pmuscles at a rate of 30 tetani/min were induced via sciatic nerve stimulation. Regional blood flows were determined by the radiolabelled microsphere method at three time points: rest, 2 min of contractions and 10 min of contractions. Muscle blood flow generally increased from rest ( approximately 5-10 ml/min per 100 g) through contractions for both groups. Further, blood flow during contractions did not differ between groups for any muscle (eg. red section of gastrocnemius muscle; EUT, 59.9 +/- 14.1; HYPO, 61.1 +/- 15.0; NS between groups). These findings indicate that hypothyroidism does not significantly impair skeletal muscle blood flow when only a small muscle mass is contracting. Our findings suggest that impaired blood flow under whole body exercise is accounted for by inadequate cardiac function rather than abnormal vascular function.

Exercise-induced muscle modifications

International Nuclear Information System (INIS)

Kerviler, E. de; Willig, A.L.; Jehenson, P.; Duboc, D.; Syrota, A.

1990-01-01

This paper compares changes in muscle proton T2 after exercise in normal subjects and in patients with muscular glycogenoses. Four patients suffering from muscular glycogenosis and eight normal volunteers were studied. Muscle T2s were measured in forearm muscles at rest and after exercise, with a 0.5-T imager. The exercise was performed with handgrips and was evaluated by P-31 spectroscopy (end-exercise decrease in pH and phosphocreatine) performed with a 2-T magnet. In normal subjects, a relative T2 increase, ranging from 14% to 44%, was observed in the exercised muscles. In the patients, who cannot produce lactate during exercise, weak pH variation occurred, and only a slight T2 increase (7% - 9%) was observed

Series elasticity of the human triceps surae muscle : Measurement by controlled-release vs. resonance methods.

NARCIS (Netherlands)

Hof, AL; Boom, H; Robinson, C; Rutten, W; Neuman, M; Wijkstra, H

1997-01-01

With a newly developed Controlled-Release Ergometer the complete characteristic of the series elastic component can be measured in human muscles. Previous estimates were based on the resonance method: muscle elasticity was assessed from the resonance frequency of the muscle elasticity connected to a

Characterisation of L-Type Amino Acid Transporter 1 (LAT1 Expression in Human Skeletal Muscle by Immunofluorescent Microscopy

Directory of Open Access Journals (Sweden)

Nathan Hodson

2017-12-01

Full Text Available The branch chain amino acid leucine is a potent stimulator of protein synthesis in skeletal muscle. Leucine rapidly enters the cell via the L-Type Amino Acid Transporter 1 (LAT1; however, little is known regarding the localisation and distribution of this transporter in human skeletal muscle. Therefore, we applied immunofluorescence staining approaches to visualise LAT1 in wild type (WT and LAT1 muscle-specific knockout (mKO mice, in addition to basal human skeletal muscle samples. LAT1 positive staining was visually greater in WT muscles compared to mKO muscle. In human skeletal muscle, positive LAT1 staining was noted close to the sarcolemmal membrane (dystrophin positive staining, with a greater staining intensity for LAT1 observed in the sarcoplasmic regions of type II fibres (those not stained positively for myosin heavy-chain 1, Type II—25.07 ± 5.93, Type I—13.71 ± 1.98, p < 0.01, suggesting a greater abundance of this protein in these fibres. Finally, we observed association with LAT1 and endothelial nitric oxide synthase (eNOS, suggesting LAT1 association close to the microvasculature. This is the first study to visualise the distribution and localisation of LAT1 in human skeletal muscle. As such, this approach provides a validated experimental platform to study the role and regulation of LAT1 in human skeletal muscle in response to various physiological and pathophysiological models.

Postmortem muscle protein degradation in humans as a tool for PMI delimitation.

Science.gov (United States)

Pittner, Stefan; Ehrenfellner, Bianca; Monticelli, Fabio C; Zissler, Angela; Sänger, Alexandra M; Stoiber, Walter; Steinbacher, Peter

2016-11-01

Forensic estimation of time since death relies on diverse approaches, including measurement and comparison of environmental and body core temperature and analysis of insect colonization on a dead body. However, most of the applied methods have practical limitations or provide insufficient results under certain circumstances. Thus, new methods that can easily be implemented into forensic routine work are required to deliver more and discrete information about the postmortem interval (PMI). Following a previous work on skeletal muscle degradation in the porcine model, we analyzed human postmortem skeletal muscle samples of 40 forensic cases by Western blotting and casein zymography. Our results demonstrate predictable protein degradation processes in human muscle that are distinctly associated with temperature and the PMI. We provide information on promising degradation markers for certain periods of time postmortem, which can be useful tools for time since death delimitation. In addition, we discuss external influencing factors such as age, body mass index, sex, and cause of death that need to be considered in future routine application of the method in humans.

Lack of skeletal muscle IL-6 influences hepatic glucose metabolism in mice during prolonged exercise

DEFF Research Database (Denmark)

Bertholdt, Lærke; Gudiksen, Anders; Schwartz, Camilla Lindgren

2017-01-01

The liver is essential in maintaining and regulating glucose homeostasis during prolonged exercise. IL-6 has been shown to be secreted from skeletal muscle during exercise and has been suggested to signal to the liver. Therefore, the aim of this study was to investigate the role of skeletal muscle...... IL-6 on hepatic glucose regulation and substrate choice during prolonged exercise. Skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice (age, 12-14 wk) and littermate lox/lox (Control) mice were either rested (Rest) or completed a single bout of exercise for 10, 60, or 120 min, and the liver....... Furthermore, IL-6 MKO mice had higher hepatic pyruvate dehydrogenase (PDH)Ser232 and PDHSer300 phosphorylation than control mice at rest. In conclusion, hepatic gluconeogenic capacity in mice is increased during prolonged exercise independent of muscle IL-6. Furthermore, Skeletal muscle IL-6 influences...

Morphological changes after pelvic floor muscle training measured by 3-dimensional ultrasonography: a randomized controlled trial.

Science.gov (United States)

Braekken, Ingeborg Hoff; Hoff Braekken, Ingeborg; Majida, Memona; Engh, Marie Ellström; Bø, Kari

2010-02-01

To investigate morphological and functional changes after pelvic floor muscle training in women with pelvic organ prolapse. This randomized controlled trial was conducted at a university hospital and a physical therapy clinic. One hundred nine women with pelvic organ prolapse stages I, II, and III were randomly allocated by a computer-generated random number system to pelvic floor muscle training (n=59) or control (n=50). Both groups received lifestyle advice and learned to contract the pelvic floor muscles before and during increases in intraabdominal pressure. In addition the pelvic floor muscle training group did individual strength training with a physical therapist and daily home exercise for 6 months. Primary outcome measures were pelvic floor muscle (pubovisceral muscle) thickness, levator hiatus area, pubovisceral muscle length at rest and Valsalva, and resting position of bladder and rectum, measured by three-dimensional ultrasonography. Seventy-nine percent of women in the pelvic floor muscle training group adhered to at least 80% of the training protocol. Compared with women in the control group, women in the pelvic floor muscle training group increased muscle thickness (difference between groups: 1.9 mm, 95% confidence interval [CI] 1.1-2.7, Ppelvic floor muscle stiffness. Supervised pelvic floor muscle training can increase muscle volume, close the levator hiatus, shorten muscle length, and elevate the resting position of the bladder and rectum. www.clinicaltrials.gov, NCT00271297. I.

Task vs. rest-different network configurations between the coactivation and the resting-state brain networks.

Science.gov (United States)

Di, Xin; Gohel, Suril; Kim, Eun H; Biswal, Bharat B

2013-01-01

There is a growing interest in studies of human brain networks using resting-state functional magnetic resonance imaging (fMRI). However, it is unclear whether and how brain networks measured during the resting-state exhibit comparable properties to brain networks during task performance. In the present study, we investigated meta-analytic coactivation patterns among brain regions based upon published neuroimaging studies, and compared the coactivation network configurations with those in the resting-state network. The strength of resting-state functional connectivity between two regions were strongly correlated with the coactivation strength. However, the coactivation network showed greater global efficiency, smaller mean clustering coefficient, and lower modularity compared with the resting-state network, which suggest a more efficient global information transmission and between system integrations during task performing. Hub shifts were also observed within the thalamus and the left inferior temporal cortex. The thalamus and the left inferior temporal cortex exhibited higher and lower degrees, respectively in the coactivation network compared with the resting-state network. These results shed light regarding the reconfiguration of the brain networks between task and resting-state conditions, and highlight the role of the thalamus in change of network configurations in task vs. rest.

Assessment of bioelectrical activity of synergistic muscles during pelvic floor muscles activation in postmenopausal women with and without stress urinary incontinence: a preliminary observational study.

Science.gov (United States)

Ptaszkowski, Kuba; Paprocka-Borowicz, Małgorzata; Słupska, Lucyna; Bartnicki, Janusz; Dymarek, Robert; Rosińczuk, Joanna; Heimrath, Jerzy; Dembowski, Janusz; Zdrojowy, Romuald

2015-01-01

Muscles such as adductor magnus (AM), gluteus maximus (GM), rectus abdominis (RA), and abdominal external and internal oblique muscles are considered to play an important role in the treatment of stress urinary incontinence (SUI), and the relationship between contraction of these muscles and pelvic floor muscles (PFM) has been established in previous studies. Synergistic muscle activation intensifies a woman's ability to contract the PFM. In some cases, even for continent women, it is not possible to fully contract their PFM without involving the synergistic muscles. The primary aim of this study was to assess the surface electromyographic activity of synergistic muscles to PFM (SPFM) during resting and functional PFM activation in postmenopausal women with and without SUI. This study was a preliminary, prospective, cross-sectional observational study and included volunteers and patients who visited the Department and Clinic of Urology, University Hospital in Wroclaw, Poland. Forty-two patients participated in the study and were screened for eligibility criteria. Thirty participants satisfied the criteria and were categorized into two groups: women with SUI (n=16) and continent women (n=14). The bioelectrical activity of PFM and SPFM (AM, RA, GM) was recorded with a surface electromyographic instrument in a standing position during resting and functional PFM activity. Bioelectrical activity of RA was significantly higher in the incontinent group than in the continent group. These results concern the RA activity during resting and functional PFM activity. The results for other muscles showed no significant difference in bioelectrical activity between groups. In women with SUI, during the isolated activation of PFM, an increased synergistic activity of RA muscle was observed; however, this activity was not observed in asymptomatic women. This may indicate the important accessory contribution of these muscles in the mechanism of continence.

Hand rest and wrist support are effective in preventing fatigue during prolonged typing.

Science.gov (United States)

Callegari, Bianca; de Resende, Marília Maniglia; da Silva Filho, Manoel

Case series (longitudinal). Only few reports concerning the efficacy of commonly used strategies for preventing upper limb occupational disorders associated with prolonged typing exist. We aimed to investigate whether the duration of typing and the use of 2 strategies (hand rest and wrist support) changes muscle physiological response and therefore the electromyography records. We enrolled 25 volunteers, who were unfamiliar with the task and did not have musculoskeletal disorders. The subjects underwent 3 prolonged typing protocols to investigate the efficacy of the 2 adopted strategies in reducing the trapezius, biceps brachii, and extensor digitorum communis fatigue. Typing for 1 hour induced muscular fatigue (60%-67% of the subjects). The extensor digitorum communis muscle exhibited the highest percentage of fatigue (72%-84%) after 1 and 4 hours of typing (1 hour, P = .04; 4 hours, P = .02). Fatigue levels in this muscle were significantly reduced (24%) with the use of pause typing (4 hours, P = .045), whereas biceps brachii muscle fatigue was reduced (32%) only with the use of wrist supports (P = .02, after 4 hours). Trapezius muscle fatigue was unaffected by the tested occupational strategies (1 hour, P = .62; 4 hours, P = .85). Despite presenting an overall tendency for fatigue detected during the application of the protocols, the assessed muscles exhibited different behavior patterns, depending on both the preventive strategy applied and the muscle mechanical role during the task. Hand rest and wrist support can successfully reduce muscle fatigue in specific upper limb muscles during prolonged typing, leading to a muscle-selective reduction in the occurrence of fatigue and thus provide direct evidence that they may prevent work-related musculoskeletal disorders. N/A. Copyright © 2016 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans

DEFF Research Database (Denmark)

Boushel, Robert Christopher; Gnaiger, Erich; Calbet, Jose A L

2011-01-01

Across a wide range of species and body mass a close matching exists between maximal conductive oxygen delivery and mitochondrial respiratory rate. In this study we investigated in humans how closely in-vivo maximal oxygen consumption (VO(2) max) is matched to state 3 muscle mitochondrial respira...

The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle.

Science.gov (United States)

Cooke, Roger

2011-03-01

Resting skeletal muscle is a major contributor to adaptive thermogenesis, i.e., the thermogenesis that changes in response to exposure to cold or to overfeeding. The identification of the "furnace" that is responsible for increased heat generation in resting muscle has been the subject of a number of investigations. A new state of myosin, the super relaxed state (SRX), with a very slow ATP turnover rate has recently been observed in skeletal muscle (Stewart et al. in Proc Natl Acad Sci USA 107:430-435, 2010). Inhibition of the myosin ATPase activity in the SRX was suggested to be caused by binding of the myosin head to the core of the thick filament in a structural motif identified earlier by electron microscopy. To be compatible with the basal metabolic rate observed in vivo for resting muscle, most myosin heads would have to be in the SRX. Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle. Transfer of only 20% of myosin heads from the SRX into the normal relaxed state would cause muscle thermogenesis to double. Phosphorylation of the myosin regulatory light chain was shown to transfer myosin heads from the SRX into the relaxed state, which would increase thermogenesis. In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding. Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels.

Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration

DEFF Research Database (Denmark)

Saclier, Marielle; Yacoub-Youssef, Houda; Mackey, Abigail

2013-01-01

, we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory...... anti-inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates......Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here...

Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms

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Bamman, M. M.; Clarke, M. S.; Talmadge, R. J.; Feeback, D. L.

1999-01-01

Talmadge and Roy (J. Appl. Physiol. 1993, 75, 2337-2340) previously established a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) protocol for separating all four rat skeletal muscle myosin heavy chain (MHC) isoforms (MHC I, IIa, IIx, IIb); however, when applied to human muscle, the type II MHC isoforms (Ila, IIx) are not clearly distinguished. In this brief paper we describe a modification of the SDS-PAGE protocol which yields distinct and consistent separation of all three adult human MHC isoforms (MHC I, IIa, IIx) in a minigel system. MHC specificity of each band was confirmed by Western blot using three monoclonal IgG antibodies (mAbs) immunoreactive against MHCI (mAb MHCs, Novacastra Laboratories), MHCI+IIa (mAb BF-35), and MHCIIa+IIx (mAb SC-71). Results provide a valuable SDS-PAGE minigel technique for separating MHC isoforms in human muscle without the difficult task of casting gradient gels.

Effects of Long Term Supplementation of Anabolic Androgen Steroids on Human Skeletal Muscle

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Yu, Ji-Guo; Bonnerud, Patrik; Eriksson, Anders; Stål, Per S.; Tegner, Yelverton; Malm, Christer

2014-01-01

The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained

Evaluation of normal masseter muscles on ultrasonography

International Nuclear Information System (INIS)

Hwang, Hyoung Zoo; Kim, Gyu Tae; Choi, Yong Suk; Hwang, Eui Hwan

2008-01-01

To assess the internal echo intensity and morphological variability of masseter muscles on ultrasonography and to establish diagnostic criterion of estimation. Participants consisted of 50 young adults (male 25, female 25) without pathologic conditions and with full natural dentitions. Sonographic examinations were done with real time ultrasound equipment as Logiq 500 (GE Medical Systems, Seoul, Korea) at 3 parts according to lines paralleling with ala-tragus line as reference line. The thickness and area of masseter muscles according to reference line in cross-sectional images were measured at rest and at maximum contraction. The visibility and width of the internal echogenic intensity of the masseter muscles were also assessed and the muscle appearance was classified into 4 types. Data were statistically analyzed by paired t-test and x2-test. 1. When comparing the thickness and area of masseter muscles concerning with gender, there was few significant difference between right and left sides, however, there were significant differences between males and females except for the greatest thickness of left side. 2. The changes of the greatest thickness and the area between rest and maximum contraction showed that the part of the least thickness manifested more increase at maximum contraction. 3. Each part the manifestations of the internal echogenic intensity of the masseter muscles were different depending on the locations. But there was no statistically significance. Changes of muscles thickness with contraction and internal echogenic intensity with locations showed great disparity within the masseter muscles, which will be diagnostic criteria for pathophysiologic and anatomic changes of masseter muscles.

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OpenAIRE

Santos, Marcelo R. dos; Sayegh, Ana L.C.; Armani, Rafael; Costa-Hong, Valéria; Souza, Francis R. de; Toschi-Dias, Edgar; Bortolotto, Luiz A.; Yonamine, Mauricio; Negrão, Carlos E.; Alves, Maria-Janieire N.N.

2018-01-01

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, ...

Subunit Stoichiometry of Human Muscle Chloride Channels

OpenAIRE

Fahlke, Christoph; Knittle, Timothy; Gurnett, Christina A.; Campbell, Kevin P.; George, Alfred L.

1997-01-01

Voltage-gated Cl? channels belonging to the ClC family appear to function as homomultimers, but the number of subunits needed to form a functional channel is controversial. To determine subunit stoichiometry, we constructed dimeric human skeletal muscle Cl? channels in which one subunit was tagged by a mutation (D136G) that causes profound changes in voltage-dependent gating. Sucrose-density gradient centrifugation experiments indicate that both monomeric and dimeric hClC-1 channels in their ...

Effects of muscle fatigue on the usability of a myoelectric human-computer interface.

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Barszap, Alexander G; Skavhaug, Ida-Maria; Joshi, Sanjay S

2016-10-01

Electromyography-based human-computer interface development is an active field of research. However, knowledge on the effects of muscle fatigue for specific devices is limited. We have developed a novel myoelectric human-computer interface in which subjects continuously navigate a cursor to targets by manipulating a single surface electromyography (sEMG) signal. Two-dimensional control is achieved through simultaneous adjustments of power in two frequency bands through a series of dynamic low-level muscle contractions. Here, we investigate the potential effects of muscle fatigue during the use of our interface. In the first session, eight subjects completed 300 cursor-to-target trials without breaks; four using a wrist muscle and four using a head muscle. The wrist subjects returned for a second session in which a static fatiguing exercise took place at regular intervals in-between cursor-to-target trials. In the first session we observed no declines in performance as a function of use, even after the long period of use. In the second session, we observed clear changes in cursor trajectories, paired with a target-specific decrease in hit rates. Copyright © 2016 Elsevier B.V. All rights reserved.

Gender Differences in Isokinetic Strength after 60 and 90 d Bed Rest

Science.gov (United States)

English, K. L.; Ploutz-Snyder, R. J.; Cromwell, R. L.; Ploutz-Snyder, L. L.

2010-01-01

Recent reports suggest that changes in muscle strength following disuse may differ between males and females. PURPOSE: To examine potential gender differences in strength changes following 60 and 90 d of experimental bed rest. METHODS: Isokinetic extensor and flexor strength of the knee (60deg and 180deg/s, concentric only), ankle (30deg/s, concentric and eccentric), and trunk (60deg/s, concentric only) were measured following 60 d (males: n=4, 34.5+/-9.6 y; females: n=4, 35.5+/-8.2 y) and 90 d (males: n=10, 31.4+/-4.8 y; females: n=5, 37.6+/-9.9 y) of 6-degree head-down-tilt bed rest (BR; N=23). Subjects were fed a controlled diet (55%/15%/ 30%, CHO/PRO/FAT) that maintained body weight within 3% of the weight recorded on Day 3 of bed rest. After a familiarization session, testing was conducted 6 d before BR and 2 d after BR completion. Peak torque and total work were calculated for the tests performed. To allow us to combine data from both 60- and 90-d subjects, we used a mixed-model statistical analysis in which time and gender were fixed effects and bed rest duration was a random effect. Log-transformations of strength measures were utilized when necessary in order to meet statistical assumptions. RESULTS: Main effects were seen for both time and gender (p<0.05), showing decreased strength in response to bed rest for both males and females, and males stronger than females for most strength measures. Only one interaction effect was observed: females exhibited a greater loss of trunk extensor peak torque at 60 d versus pre-BR, relative to males (p=0.004). CONCLUSION: Sixty and 90 d of BR induced significant losses in isokinetic muscle strength of the locomotor and postural muscles of the knee, ankle, and trunk. Although males were stronger than females for most of the strength measures that we examined, only changes in trunk extensor peak torque were greater for females than males at day 60 of bed rest

Unloaded shortening velocity of voluntarily and electrically activated human dorsiflexor muscles in vivo.

Directory of Open Access Journals (Sweden)

Kazushige Sasaki

Full Text Available We have previously shown that unloaded shortening velocity (V(0 of human plantar flexors can be determined in vivo, by applying the "slack test" to submaximal voluntary contractions (J Physiol 567:1047-1056, 2005. In the present study, to investigate the effect of motor unit recruitment pattern on V(0 of human muscle, we modified the slack test and applied this method to both voluntary and electrically elicited contractions of dorsiflexors. A series of quick releases (i.e., rapid ankle joint rotation driven by an electrical dynamometer was applied to voluntarily activated dorsiflexor muscles at three different contraction intensities (15, 50, and 85% of maximal voluntary contraction; MVC. The quick-release trials were also performed on electrically activated dorsiflexor muscles, in which three stimulus conditions were used: submaximal (equal to 15%MVC 50-Hz stimulation, supramaximal 50-Hz stimulation, and supramaximal 20-Hz stimulation. Modification of the slack test in vivo resulted in good reproducibility of V(0, with an intraclass correlation coefficient of 0.87 (95% confidence interval: 0.68-0.95. Regression analysis showed that V(0 of voluntarily activated dorsiflexor muscles significantly increased with increasing contraction intensity (R(2 = 0.52, P<0.001. By contrast, V(0 of electrically activated dorsiflexor muscles remained unchanged (R(2<0.001, P = 0.98 among three different stimulus conditions showing a large variation of tetanic torque. These results suggest that the recruitment pattern of motor units, which is quite different between voluntary and electrically elicited contractions, plays an important role in determining shortening velocity of human skeletal muscle in vivo.

Blood flow in exercising muscles by xenon clearance and by microsphere trapping

International Nuclear Information System (INIS)

Cerretelli, P.; Marconi, C.; Pendergast, D.; Meyer, M.; Heisler, N.; Piiper, J.

1984-01-01

The accuracy of muscle blood flow measurement by the 133 Xe clearance method (Qxe) was assessed against direct venous outflow (Qv) and microsphere trapping flow (Qμ) determinations in isolated perfused dog gastrocnemius both at rest and during graded stimulation [O 2 consumption (Vo 2 ) up to 12 ml x 100 g -1 x min -1 ] and in the gastrocnemius, vastus lateralis, and triceps of intact dogs at rest and while running on a treadmill at varied speeds up to maximum Vo 2 . In 29 measurements performed in 11 isolated muscles, Qμ was in good agreement with Qv at rest and at all stimulation levels (Qμ/Qv = 1.0 r = 0.98). 133 Xe clearance yielded much lower blood flows than the venous outflow and the microsphere trapping methods. In 43 measurements in 11 muscles, the mean Qxe/Qv ratio was 0.57 +/- 0.03 (SE), independent of blood flow. Similarly, in 65 measurements in 2 intact dogs, the mean Qxe/Qμ ratio in all tested muscles was 0.49 +/- 0.02 (SE), independent of blood flow. These results show that the 133 Xe clearance method considerably underestimates blood flow in dog muscles

Functional Echomyography: thickness, ecogenicity, contraction and perfusion of the LMN denervated human muscle before and during h-bFES

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Riccardo Zanato

2010-03-01

Full Text Available Permanent denervated muscles were evaluated by ultrasound to monitor changes in morphology, thickness, contraction-relaxation kinetics and perfusion due to the electrical stimulation program of the Rise2-Italy project. In a case of monolateral lesion, morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete denervation-induced muscle atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third of the denervated muscle, reaching the same value as the contralateral innervated muscle. Contraction-relaxation kinetics, measured by recording the muscle movements during electrical stimulation, showed an abnormal behavior of the chronically denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle. The long-term denervated muscles analyzed with Echo Doppler showed at rest a low resistance arterial flow that became pulsed during and after electrical stimulation. As expected, the ultra sound measured electrical stimulation-induced hyperemia lasted longer than the stimulation period. The higher than normal energy of the delivered electrical stimuli of the Vienna home-based Functional Electrical Stimulation strategy (h-b FES demonstrate that the explored muscles were still almost completely denervated during the one-year of training. In conclusion, this pilot study confirms the usefulness of Functional Echomyography in the follow-up and the positive effects of h-b FES of denervated muscles.

Effects of bed-rest on urea and creatinine: correlation with changes in fat-free mass.

Science.gov (United States)

Bilancio, Giancarlo; Lombardi, Cinzia; Pisot, Rado; De Santo, Natale G; Cavallo, Pierpaolo; Cirillo, Massimo

2014-01-01

Bed-rest experiments are designed for investigation on catabolic effects of hypokinetic conditions and/or for microgravity simulation in on-ground aerospace research. Bed-rest effects include a reduction in fat-free mass and muscle mass. Urea and creatinine are catabolites of endogenous protein and of muscular energetic metabolism which are excreted mainly by the kidney. The study investigated on urea, creatinine, and kidney function during bed-rest. Twenty healthy young men underwent a 7-day adaptation period (day-6 to day-0) and a 35-day bed-rest experiment (day1 to day35) during normocaloric diet. Urine were collected from day-3 to day0 (baseline) and from day1 to day35. Blood samples and anthropometrical data were collected at day0 (baseline) and bed-rest days 7, 14, 21, 28, and 35. Bed-rest reduced plasma volume, weight, fat-free mass, and muscle mass (Pcreatinine, and no change in urinary creatinine. The overall integral of changes from day0 to day35 was on average +101.7 mg/dL for plasma urea (95%CI = +43.4/+159.9), +82.2 g/24 h for urinary urea (95%CI = +55.8/+108.7), -2.5 mg/dL for plasma creatinine (95%CI = -3.1/-1.9). Bed-rest reduced plasma cistatyn C also, which was used as mass-independent marker of glomerular filtration rate (-13.1%, P<0.05). Correlations with final reduction in fat-free mass and muscle mass were significant for the overall integral of changes in urinary urea from day0 to day35 (R = 0.706, P<0.001) and for early changes in urinary urea and plasma urea from day0 to day7 (R = 0.566, P = 0.009 and R = 0.715, P<0.001, respectively). Study results shows that urea is a marker of catabolic conditions secondary to hypokinetic conditions.

Effects of branched-chain amino acids supplementation on both plasma amino acids concentration and muscle energetics changes resulting from muscle damage: A randomized placebo controlled trial.

Science.gov (United States)

Fouré, Alexandre; Nosaka, Kazunori; Gastaldi, Marguerite; Mattei, Jean-Pierre; Boudinet, Hélène; Guye, Maxime; Vilmen, Christophe; Le Fur, Yann; Bendahan, David; Gondin, Julien

2016-02-01

Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Potential therapeutic effects of branched-chain amino acids supplementation on resistance exercise-based muscle damage in humans

Directory of Open Access Journals (Sweden)

da Luz Claudia R

2011-12-01

Full Text Available Abstract Branched-chain amino acids (BCAA supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE-derived biochemical markers of muscle soreness (creatine kinase (CK, aldolase, myoglobin, soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality.

ATP economy of force maintenance in human tibialis anterior muscle

DEFF Research Database (Denmark)

Nakagawa, Yoshinao; Ratkevicius, Aivaras; Mizuno, Masao

2005-01-01

PURPOSE: The aim of this study was investigate ATP economy of force maintenance in the human tibialis anterior muscle during 60 s of anaerobic voluntary contraction at 50% of maximum voluntary contraction (MVC). METHODS: ATP turnover rate was evaluated using P magnetic resonance spectroscopy (P...... contraction. It averaged at 4.81 +/- 0.42 N.s.micromol-1, and correlated with the relative cross-sectional area of the muscle occupied by Type I fiber (r = 0.73, P contraction, subjects dropping in force showed lower ATP economy compared with those maintaining the force (3.......7 +/- 0.6 vs 5.3 +/- 0.6 N.s.micromol-1; P contraction could be due to an increase in the ATP economy of contracting muscle fibers offsetting the effects of increased temperature and low ATP economy...

Exercising with blocked muscle glycogenolysis

DEFF Research Database (Denmark)

Nielsen, Tue L; Pinós, Tomàs; Brull, Astrid

2018-01-01

BACKGROUND: McArdle disease (glycogen storage disease type V) is an inborn error of skeletal muscle metabolism, which affects glycogen phosphorylase (myophosphorylase) activity leading to an inability to break down glycogen. Patients with McArdle disease are exercise intolerant, as muscle glycogen......-derived glucose is unavailable during exercise. Metabolic adaptation to blocked muscle glycogenolysis occurs at rest in the McArdle mouse model, but only in highly glycolytic muscle. However, it is unknown what compensatory metabolic adaptations occur during exercise in McArdle disease. METHODS: In this study, 8......-week old McArdle and wild-type mice were exercised on a treadmill until exhausted. Dissected muscles were compared with non-exercised, age-matched McArdle and wild-type mice for histology and activation and expression of proteins involved in glucose uptake and glycogenolysis. RESULTS: Investigation...

Physical inactivity and muscle oxidative capacity in humans

DEFF Research Database (Denmark)

Gram, Martin; Dahl, Rannvá; Dela, Flemming

2014-01-01

Physical inactivity is associated with a high prevalence of type 2 diabetes and is an independent predictor of mortality. It is possible that the detrimental effects of physical inactivity are mediated through a lack of adequate muscle oxidative capacity. This short review will cover the present...... literature on the effects of different models of inactivity on muscle oxidative capacity in humans. Effects of physical inactivity include decreased mitochondrial content, decreased activity of oxidative enzymes, changes in markers of oxidative stress and a decreased expression of genes and contents...... of proteins related to oxidative phosphorylation. With such a substantial down-regulation, it is likely that a range of adenosine triphosphate (ATP)-dependent pathways such as calcium signalling, respiratory capacity and apoptosis are affected by physical inactivity. However, this has not been investigated...

Decreased thickness of the lower trapezius muscle in patients with unilateral neck pain.

Science.gov (United States)

Uthaikhup, Sureeporn; Pensri, Chalomjai; Kawsoiy, Kanokon

2016-09-01

Thickness of the lower trapezius muscle in patients with neck pain has not been established. We examined the thickness of the lower trapezius muscle in patients with and without unilateral neck pain. Twenty women with unilateral (right) neck pain and 20 matched controls participated in the study. Thickness of the lower trapezius muscles was measured bilaterally at rest (0 ° and 120 ° of shoulder abduction) and during contraction (120 ° of shoulder abduction) using ultrasound imaging. The neck pain group had smaller thickness of the lower trapezius muscle on the painful side compared with controls both at rest and during contraction (P  0.05). Patients with neck pain had smaller thickness of the lower trapezius muscle on the painful side compared with healthy controls. Muscle Nerve 54: 439-443, 2016. © 2015 Wiley Periodicals, Inc.

Influence of ER leak on resting cytoplasmic Ca2+ and receptor-mediated Ca2+ signalling in human macrophage.

Science.gov (United States)

Layhadi, Janice A; Fountain, Samuel J

2017-06-03

Mechanisms controlling endoplasmic reticulum (ER) Ca 2+ homeostasis are important regulators of resting cytoplasmic Ca 2+ concentration ([Ca 2+ ] cyto ) and receptor-mediated Ca 2+ signalling. Here we investigate channels responsible for ER Ca 2+ leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca 2+ we employ ionomycin action at the plasma membrane to stimulate ER Ca 2+ leak. Under these conditions ionomycin elevates [Ca 2+ ] cyto revealing a Ca 2+ leak response which is abolished by thapsigargin. IP 3 receptors (Xestospongin C, 2-APB), ryanodine receptors (dantrolene), and translocon (anisomycin) inhibition facilitated ER Ca 2+ leak in model macrophage, with translocon inhibition also reducing resting [Ca 2+ ] cyto . In primary macrophage, translocon inhibition blocks Ca 2+ leak but does not influence resting [Ca 2+ ] cyto . We identify a role for translocon-mediated ER Ca 2+ leak in receptor-mediated Ca 2+ signalling in both model and primary human macrophage, whereby the Ca 2+ response to ADP (P2Y receptor agonist) is augmented following anisomycin treatment. In conclusion, we demonstrate a role of ER Ca 2+ leak via the translocon in controlling resting cytoplasmic Ca 2+ in model macrophage and receptor-mediated Ca 2+ signalling in model macrophage and primary macrophage. Copyright © 2017 Elsevier Inc. All rights reserved.

Resting state brain networks in the prairie vole.

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Ortiz, Juan J; Portillo, Wendy; Paredes, Raul G; Young, Larry J; Alcauter, Sarael

2018-01-19

Resting state functional magnetic resonance imaging (rsfMRI) has shown the hierarchical organization of the human brain into large-scale complex networks, referred as resting state networks. This technique has turned into a promising translational research tool after the finding of similar resting state networks in non-human primates, rodents and other animal models of great value for neuroscience. Here, we demonstrate and characterize the presence of resting states networks in Microtus ochrogaster, the prairie vole, an extraordinary animal model to study complex human-like social behavior, with potential implications for the research of normal social development, addiction and neuropsychiatric disorders. Independent component analysis of rsfMRI data from isoflurane-anestethized prairie voles resulted in cortical and subcortical networks, including primary motor and sensory networks, but also included putative salience and default mode networks. We further discuss how future research could help to close the gap between the properties of the large scale functional organization and the underlying neurobiology of several aspects of social cognition. These results contribute to the evidence of preserved resting state brain networks across species and provide the foundations to explore the use of rsfMRI in the prairie vole for basic and translational research.

Rotator cuff tear state modulates self-renewal and differentiation capacity of human skeletal muscle progenitor cells.

Science.gov (United States)

Thomas, Kelsey A; Gibbons, Michael C; Lane, John G; Singh, Anshuman; Ward, Samuel R; Engler, Adam J

2017-08-01

Full thickness rotator cuff tendon (RCT) tears have long-term effects on RC muscle atrophy and fatty infiltration, with lasting damage even after surgical tendon repair. Skeletal muscle progenitor cells (SMPs) are critical for muscle repair in response to injury, but the inability of RC muscles to recover from chronic RCT tear indicates possible deficits in repair mechanisms. Here we investigated if muscle injury state was a crucial factor during human SMP expansion and differentiation ex vivo. SMPs were isolated from muscles in patients with no, partial-thickness (PT), or full-thickness (FT) RCT tears. Despite using growth factors, physiological niche stiffness, and muscle-mimetic extracellular matrix (ECM) proteins, we found that SMPs isolated from human RC muscle with RCT tears proliferated slower but fused into myosin heavy chain (MHC)-positive myotubes at higher rates than SMPs from untorn RCTs. Proteomic analysis of RC muscle tissue revealed shifts in muscle composition with pathology, as muscle from massive RCT tears had increased ECM deposition compared with no tear RC muscle. Together these data imply that the remodeled niche in a torn RCT primes SMPs not for expansion but for differentiation, thus limiting longer-term self-renewal necessary for regeneration after surgical repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1816-1823, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The NASA Bed Rest Project

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Rhodes, Bradley; Meck, Janice

2005-01-01

NASA s National Vision for Space Exploration includes human travel beyond low earth orbit and the ultimate safe return of the crews. Crucial to fulfilling the vision is the successful and timely development of countermeasures for the adverse physiological effects on human systems caused by long term exposure to the microgravity environment. Limited access to in-flight resources for the foreseeable future increases NASA s reliance on ground-based analogs to simulate these effects of microgravity. The primary analog for human based research will be head-down bed rest. By this approach NASA will be able to evaluate countermeasures in large sample sizes, perform preliminary evaluations of proposed in-flight protocols and assess the utility of individual or combined strategies before flight resources are requested. In response to this critical need, NASA has created the Bed Rest Project at the Johnson Space Center. The Project establishes the infrastructure and processes to provide a long term capability for standardized domestic bed rest studies and countermeasure development. The Bed Rest Project design takes a comprehensive, interdisciplinary, integrated approach that reduces the resource overhead of one investigator for one campaign. In addition to integrating studies operationally relevant for exploration, the Project addresses other new Vision objectives, namely: 1) interagency cooperation with the NIH allows for Clinical Research Center (CRC) facility sharing to the benefit of both agencies, 2) collaboration with our International Partners expands countermeasure development opportunities for foreign and domestic investigators as well as promotes consistency in approach and results, 3) to the greatest degree possible, the Project also advances research by clinicians and academia alike to encourage return to earth benefits. This paper will describe the Project s top level goals, organization and relationship to other Exploration Vision Projects, implementation

Motor units in the human medial gastrocnemius muscle are not spatially localized or functionally grouped.

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Héroux, Martin E; Brown, Harrison J; Inglis, J Timothy; Siegmund, Gunter P; Blouin, Jean-Sébastien

2015-08-15

Human medial gastrocnemius (MG) motor units (MUs) are thought to occupy small muscle territories or regions, with low-threshold units preferentially located distally. We used intramuscular recordings to measure the territory of muscle fibres from MG MUs and determine whether these MUs are grouped by recruitment threshold or joint action (ankle plantar flexion and knee flexion). The territory of MUs from the MG muscle varied from somewhat localized to highly distributed, with approximately half the MUs spanning at least half the length and width of the muscle. There was also no evidence of regional muscle activity based on MU recruitment thresholds or joint action. The CNS does not have the means to selectively activate regions of the MG muscle based on task requirements. Human medial gastrocnemius (MG) motor units (MUs) are thought to occupy small muscle territories, with low-threshold units preferentially located distally. In this study, subjects (n = 8) performed ramped and sustained isometric contractions (ankle plantar flexion and knee flexion; range: ∼1-40% maximal voluntary contraction) and we measured MU territory size with spike-triggered averages from fine-wire electrodes inserted along the length (seven electrodes) or across the width (five electrodes) of the MG muscle. Of 69 MUs identified along the length of the muscle, 32 spanned at least half the muscle length (≥ 6.9 cm), 11 of which spanned all recording sites (13.6-17.9 cm). Distal fibres had smaller pennation angles (P recruitment threshold or contraction type, nor was there a relationship between MU territory size and recruitment threshold (Spearman's rho = -0.20 and 0.13, P > 0.18). MUs in the human MG have larger territories than previously reported and are not localized based on recruitment threshold or joint action. This indicates that the CNS does not have the means to selectively activate regions of the MG muscle based on task requirements. © 2015 The Authors. The Journal of

Is Rest Really Rest? Resting State Functional Connectivity during Rest and Motor Task Paradigms.

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Jurkiewicz, Michael T; Crawley, Adrian P; Mikulis, David J

2018-04-18

Numerous studies have identified the default mode network (DMN) within the brain of healthy individuals, which has been attributed to the ongoing mental activity of the brain during the wakeful resting-state. While engaged during specific resting-state fMRI paradigms, it remains unclear as to whether traditional block-design simple movement fMRI experiments significantly influence the default mode network or other areas. Using blood-oxygen level dependent (BOLD) fMRI we characterized the pattern of functional connectivity in healthy subjects during a resting-state paradigm and compared this to the same resting-state analysis performed on motor task data residual time courses after regressing out the task paradigm. Using seed-voxel analysis to define the DMN, the executive control network (ECN), and sensorimotor, auditory and visual networks, the resting-state analysis of the residual time courses demonstrated reduced functional connectivity in the motor network and reduced connectivity between the insula and the ECN compared to the standard resting-state datasets. Overall, performance of simple self-directed motor tasks does little to change the resting-state functional connectivity across the brain, especially in non-motor areas. This would suggest that previously acquired fMRI studies incorporating simple block-design motor tasks could be mined retrospectively for assessment of the resting-state connectivity.

On the mechanism by which dietary nitrate improves human skeletal muscle function

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Charles eAffourtit

2015-07-01

Full Text Available Inorganic nitrate is present at high levels in beetroot and celery, and in green leafy vegetables such as spinach and lettuce. Though long believed inert, nitrate can be reduced to nitrite in the human mouth and, further, under hypoxia and/or low pH, to nitric oxide. Dietary nitrate has thus been associated favourably with nitric-oxide-regulated processes including blood flow and energy metabolism. Indeed, the therapeutic potential of dietary nitrate in cardiovascular disease and metabolic syndrome – both ageing-related medical disorders – has attracted considerable recent research interest. We and others have shown that dietary nitrate supplementation lowers the oxygen cost of human exercise, as less respiratory activity appears to be required for a set rate of skeletal muscle work. This striking observation predicts that nitrate benefits the energy metabolism of human muscle, increasing the efficiency of either mitochondrial ATP synthesis and/or of cellular ATP-consuming processes. In this mini-review, we evaluate experimental support for the dietary nitrate effects on muscle bioenergetics and we critically discuss the likelihood of nitric oxide as the molecular mediator of such effects.

Subcellular localization and mechanism of secretion of vascular endothelial growth factor in human skeletal muscle

DEFF Research Database (Denmark)

Høier, Birgitte; Prats Gavalda, Clara; Qvortrup, Klaus

2013-01-01

The subcellular distribution and secretion of vascular endothelial growth factor (VEGF) was examined in skeletal muscle of healthy humans. Skeletal muscle biopsies were obtained from m.v. lateralis before and after a 2 h bout of cycling exercise. VEGF localization was conducted on preparations...... regions and between the contractile elements within the muscle fibers; and in pericytes situated on the skeletal muscle capillaries. Quantitation of the subsarcolemmal density of VEGF vesicles, calculated on top of myonuclei, in the muscle fibers revealed a ∼50% increase (P...

FAK tyrosine phosphorylation is regulated by AMPK and controls metabolism in human skeletal muscle

DEFF Research Database (Denmark)

Lassiter, David G; Nylén, Carolina; Sjögren, Rasmus J O

2018-01-01

the FAK gene, PTK2. RESULTS: AMPK activation reduced tyrosine phosphorylation of FAK in skeletal muscle. AICAR reduced p-FAKY397in isolated human skeletal muscle and cultured myotubes. Insulin stimulation did not alter FAK phosphorylation. Serum starvation increased AMPK activation, as demonstrated...

Comparison of rhythmic masticatory muscle activity during non-rapid eye movement sleep in guinea pigs and humans.

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Kato, Takafumi; Toyota, Risa; Haraki, Shingo; Yano, Hiroyuki; Higashiyama, Makoto; Ueno, Yoshio; Yano, Hiroshi; Sato, Fumihiko; Yatani, Hirofumi; Yoshida, Atsushi

2017-09-27

Rhythmic masticatory muscle activity can be a normal variant of oromotor activity, which can be exaggerated in patients with sleep bruxism. However, few studies have tested the possibility in naturally sleeping animals to study the neurophysiological mechanisms of rhythmic masticatory muscle activity. This study aimed to investigate the similarity of cortical, cardiac and electromyographic manifestations of rhythmic masticatory muscle activity occurring during non-rapid eye movement sleep between guinea pigs and human subjects. Polysomnographic recordings were made in 30 freely moving guinea pigs and in eight healthy human subjects. Burst cycle length, duration and activity of rhythmic masticatory muscle activity were compared with those for chewing. The time between R-waves in the electrocardiogram (RR interval) and electroencephalogram power spectrum were calculated to assess time-course changes in cardiac and cortical activities in relation to rhythmic masticatory muscle activity. In animals, in comparison with chewing, rhythmic masticatory muscle activity had a lower burst activity, longer burst duration and longer cycle length (P motor activation in comparison to human subjects. © 2017 European Sleep Research Society.

Patterns of resting state connectivity in human primary visual cortical areas: a 7T fMRI study.

Science.gov (United States)

Raemaekers, Mathijs; Schellekens, Wouter; van Wezel, Richard J A; Petridou, Natalia; Kristo, Gert; Ramsey, Nick F

2014-01-01

The nature and origin of fMRI resting state fluctuations and connectivity are still not fully known. More detailed knowledge on the relationship between resting state patterns and brain function may help to elucidate this matter. We therefore performed an in depth study of how resting state fluctuations map to the well known architecture of the visual system. We investigated resting state connectivity at both a fine and large scale within and across visual areas V1, V2 and V3 in ten human subjects using a 7Tesla scanner. We found evidence for several coexisting and overlapping connectivity structures at different spatial scales. At the fine-scale level we found enhanced connectivity between the same topographic locations in the fieldmaps of V1, V2 and V3, enhanced connectivity to the contralateral functional homologue, and to a lesser extent enhanced connectivity between iso-eccentric locations within the same visual area. However, by far the largest proportion of the resting state fluctuations occurred within large-scale bilateral networks. These large-scale networks mapped to some extent onto the architecture of the visual system and could thereby obscure fine-scale connectivity. In fact, most of the fine-scale connectivity only became apparent after the large-scale network fluctuations were filtered from the timeseries. We conclude that fMRI resting state fluctuations in the visual cortex may in fact be a composite signal of different overlapping sources. Isolating the different sources could enhance correlations between BOLD and electrophysiological correlates of resting state activity. © 2013 Elsevier Inc. All rights reserved.

Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

DEFF Research Database (Denmark)

Bouzakri, Karim; Plomgaard, Peter; Berney, Thierry

2011-01-01

Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells.......Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells....

Molecular biology of human muscle disease

Energy Technology Data Exchange (ETDEWEB)

Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

1991-01-01

The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

Association between preterm labour and pelvic floor muscle function.

Science.gov (United States)

Aran, Turhan; Pekgöz, Ipek; Bozkaya, Hasan; Osmanagaoglu, Mehmet A

2018-03-23

We hypothesised that the pressure on the cervix increases with advancing gestation and it may lead to a cervical shortening and cause preterm labour in women with weak pelvic floor muscles. The aim of this prospective study was to measure vaginal resting pressure and pelvic floor muscle strength in the first trimester of pregnancy and to investigate their effects on labour. A study was conducted on the pregnant women with a low risk for preterm birth. The pelvic floor muscle strength and vaginal resting pressure were assessed in 320 pregnant women at their first trimester with a vaginal pressure measurement device. Fifty-two pregnant women were hospitalised for tocolytic therapy because of spontaneous preterm labour. Thirty-two of them (10.2%) had a preterm delivery despite the tocolytic therapy. Both the vaginal resting pressure (p = .009, 95%CI: 0.8; 5.9) and the pelvic floor muscle strength (p = .01, 95%CI: 3.5; 13.1) were significantly lower in the women with a preterm labour. Impact statement What is already known on this subject? The pelvic floor muscles have an essential role in continence and provide support to the pelvic organs. They also have an impact on labour. The pelvic floor muscles should distend to allow the passage of the foetus during labour. The rotation and flexion of the foetal head is due to the pelvic floor resistance. The effect of a vaginal birth on the pelvic floor's function is readily understood. On the other hand, the effect of the pelvic floor muscle function on labour is still controversial. What do the results of this study add? This prospective study showed that there is a negative association between the pelvic floor muscle strength and preterm labour. This is the first clinical study indicating that weak pelvic floor muscles may cause a preterm labour. What are the implications of these findings for clinical practice and/or further research? Pelvic floor physical therapy may be an alternative preventive strategy to reduce

Ultrasound evaluation of muscle thickness changes in the external oblique, internal oblique, and transversus abdominis muscles considering the influence of posture and muscle contraction.

Science.gov (United States)

Sugaya, Tomoaki; Abe, Yota; Sakamoto, Masaaki

2014-09-01

[Purpose] The aim of this study was to investigate muscle thickness changes in the external oblique (EO), internal oblique (IO), and transversus abdominis (TrA) muscles between the neutral position and trunk rotation, under a state of rest without voluntary contractions, and isometric contractions to both sides with resistance of 50% of the maximum trunk rotation strength. [Subjects] The subjects of this study were 21 healthy young men. [Methods] Muscle thickness changes in the EO, IO, and TrA in each position and state were evaluated by ultrasound. The range of motion at maximum trunk rotation and the maximum strength of trunk rotation were measured using a hand-held dynamometer. [Results] In the neutral position and at 50% trunk rotation to the right side, the thicknesses of the IO and TrA significantly increased with resistance. In both states, the thicknesses of the IO and TrA significantly increased at 50% trunk rotation to the right side. [Conclusion] The muscular contractions of the IO and TrA were stronger during ipsilateral rotation than in the neutral position and with resistance than at rest. Moreover, the muscular contraction was strongest in the resistive state during ipsilateral rotation.

Vascular Function and Regulation of Blood Flow in Resting and Contracting Skeletal Muscle

DEFF Research Database (Denmark)

Nyberg, Michael Permin

importance. The present work provides new insight in to vasodilator interactions important for exercise hyperemia and sheds light on mechanisms important for vascular function and regulation of skeletal muscle blood flow in essential hypertension (high blood pressure) and aging and identifies mechanisms......The precise matching of blood flow, oxygen delivery and metabolism is essential as it ensures that any increase in muscle work is precisely matched by increases in oxygen delivery. Therefore, understanding the control mechanisms of skeletal muscle blood flow regulation is of great biological...... in the regulation of exercise hyperemia. Furthermore, blood flow to contracting leg skeletal muscles is reduced both in essential hypertension and with aging. The potential difference in vasoactive system(s) responsible for the reduction in blood flow in the two conditions is in agreement with the suggestion...

Test-retest reliability of the soleus H-reflex excitability measured during human walking

DEFF Research Database (Denmark)

Simonsen, Erik B; Dyhre-Poulsen, Poul

2010-01-01

The purpose of the study was to investigate with what accuracy the soleus H-reflex modulation and excitability could be measured during human walking on two occasions separated by days. The maximal M-wave (Mmax) was measured at rest in the standing position. During treadmill walking every stimulus...... elicited an M-wave of 25+/-10% of Mmax in the soleus muscle and a supra-maximal stimulus elicited a maximal M-wave 60ms after the first stimulus. Both Mmax during rest and during walking were later used for normalization. When normalized to resting Mmax, the peak reflex amplitude during walking was 5...

Human skeletal muscle digitalis glycoside receptors (Na,K-ATPase)--importance during digitalization.

Science.gov (United States)

Schmidt, T A; Holm-Nielsen, P; Kjeldsen, K

1993-02-01

The aims of the present study were to evaluate in humans the putative importance of skeletal muscle digitalis glycoside receptors (Na,K-ATPase) in the volume of distribution of digoxin and to assess whether therapeutic digoxin exposure might cause digitalis receptor upregulation in skeletal muscle. Samples of the vastus lateralis were obtained postmortem from 11 long-term (9 months to 9 years) digitalized (125-187.5 micrograms daily) and eight undigitalized subjects. In intact samples from digitalized patients, vanadate-facilitated 3H-ouabain binding increased 15% (p 0.30) before and after washing in specific digoxin antibody fragments, respectively. Thus, the present study indicates a approximately 13% occupancy of skeletal muscle digitalis glycoside receptors with digoxin during digitalization. In light of the large skeletal muscle contribution to body mass, this indicates that the skeletal muscle Na,K-ATPase pool constitutes a major volume of distribution for digoxin during digitalization. The results gave no indication of skeletal muscle digitalis glycoside receptor upregulation in response to digoxin treatment. On the contrary, there was evidence of significantly lower (37%, p digitalized patients, which may be of importance for skeletal muscle incapacity in heart failure.

Human skeletal muscle-derived stem cells retain stem cell properties after expansion in myosphere culture

International Nuclear Information System (INIS)

Wei, Yan; Li, Yuan; Chen, Chao; Stoelzel, Katharina; Kaufmann, Andreas M.; Albers, Andreas E.

2011-01-01

Human skeletal muscle contains an accessible adult stem-cell compartment in which differentiated myofibers are maintained and replaced by a self-renewing stem cell pool. Previously, studies using mouse models have established a critical role for resident stem cells in skeletal muscle, but little is known about this paradigm in human muscle. Here, we report the reproducible isolation of a population of cells from human skeletal muscle that is able to proliferate for extended periods of time as floating clusters of rounded cells, termed 'myospheres' or myosphere-derived progenitor cells (MDPCs). The phenotypic characteristics and functional properties of these cells were determined using reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry and immunocytochemistry. Our results showed that these cells are clonogenic, express skeletal progenitor cell markers Pax7, ALDH1, Myod, and Desmin and the stem cell markers Nanog, Sox2, and Oct3/4 significantly elevated over controls. They could be maintained proliferatively active in vitro for more than 20 weeks and passaged at least 18 times, despite an average donor-age of 63 years. Individual clones (4.2%) derived from single cells were successfully expanded showing clonogenic potential and sustained proliferation of a subpopulation in the myospheres. Myosphere-derived cells were capable of spontaneous differentiation into myotubes in differentiation media and into other mesodermal cell lineages in induction media. We demonstrate here that direct culture and expansion of stem cells from human skeletal muscle is straightforward and reproducible with the appropriate technique. These cells may provide a viable resource of adult stem cells for future therapies of disease affecting skeletal muscle or mesenchymal lineage derived cell types.

Lactate oxidation in human skeletal muscle mitochondria

DEFF Research Database (Denmark)

Jacobs, Robert A; Meinild, Anne-Kristine; Nordsborg, Nikolai B

2013-01-01

of four separate and specific substrate titration protocols, the respirometric analysis revealed that mitochondria were capable of oxidizing lactate in the absence of exogenous LDH. The titration of lactate and NAD(+) into the respiration medium stimulated respiration (P = 0.003). The addition...... of exogenous LDH failed to increase lactate-stimulated respiration (P = 1.0). The results further demonstrate that human skeletal muscle mitochondria cannot directly oxidize lactate within the mitochondrial matrix. Alternately, these data support previous claims that lactate is converted to pyruvate within...

Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men

DEFF Research Database (Denmark)

Olesen, Jesper; Gliemann Hybholt, Lasse; Biensøe, Rasmus S

2014-01-01

Aim: To investigate the metabolic and anti-inflammatory effects of resveratrol alone and when combined with exercise training in skeletal muscle of aged human subjects. Material and Methods: Healthy physically inactive men (60-72 year old) were randomized into either 8 weeks of daily intake of 250...... mg resveratrol or placebo or into 8 weeks of high intensity exercise training with 250 mg resveratrol or placebo. Before and after the interventions, resting blood samples and muscle biopsies were obtained and a one-leg knee-extensor endurance exercise test (KEE) was performed. Results: Exercise...... with no significant additive or adverse effects of resveratrol on these parameters. Despite an overall ~25% reduction in total acetylation level in skeletal muscle with resveratrol, no exclusive resveratrol-mediated metabolic effects were observed on the investigated parameters. Notably however, resveratrol blunted...

Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Oezdemir, Mahir S; Reyngoudt, Harmen; Deene, Yves de; Sazak, Hakan S; Fieremans, Els; Delputte, Steven; D'Asseler, Yves; Derave, Wim; Lemahieu, Ignace; Achten, Eric

2007-01-01

Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pH i range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy ( 1 H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 ± 0.57/4.8 ± 1.59 mM (mean ± SD) for athletes and 2.58 ± 0.65/3.3 ± 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that 1 H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo

Effects of hypo- und hyperthyroidism on skeletal muscle metabolism

International Nuclear Information System (INIS)

Moka, D.; Theissen, P.; Linden, A.; Waters, W.; Schicha, H.

1991-01-01

31 P magnetic resonance spectroscopy allows non-invasive evaluation of phosphorus metabolism in man. The purpose of the present study was to assess the influence of hyper- and hypothyroidism on the metabolism of resting human skeletal muscle. The present data show that quantitative measurement of phosphate metabolism by NMR is possible as also demonstrated by other studies. Using a quantitative evaluation method with an external standard, significant differences in the levels of phosphocreatine, adenosintriphosphate, and phosphodiesters were found. In hypothyroid patients a TSH-dependent increase in phosphodiesters and a decrease in adenosintriphosphate and phosphocreatine was observed. In hyperthyroidism a similar decrease in adenosintriphosphate but a considerably higher decrease in phosphocreatine occurred. In the light of the results of other studies of muscle matabolism, these changes appear to be non-specific so that further studies are required to assess the clinical value of such measurements. (orig.) [de

Distinct migration and contact dynamics of resting and IL-2-activated human natural killer cells

Directory of Open Access Journals (Sweden)

Per Erik Olofsson

2014-03-01

Full Text Available Natural killer (NK cells serve as one of the first lines of defense against viral infections and transformed cells. NK cell cytotoxicity is not dependent on antigen presentation by target cells, but is dependent on integration of activating and inhibitory signals triggered by receptor–ligand interactions formed at a tight intercellular contact between the NK and target cell, i.e. the immune synapse. We have studied the single-cell migration behavior and target-cell contact dynamics of resting and IL-2-activated human peripheral blood NK cells. Small populations of NK cells and target cells were confined in microwells and imaged by fluorescence microscopy for >8 h. Only the IL-2-activated population of NK cells showed efficient cytotoxicity against the human embryonic kidney (HEK 293T target cells. We found that although the average migration speeds were comparable, activated NK cells showed significantly more dynamic migration behavior, with more frequent transitions between periods of low and high motility. Resting NK cells formed fewer and weaker contacts with target cells, which manifested as shorter conjugation times and in many cases a complete lack of post-conjugation attachment to target cells. Activated NK cells were approximately twice as big as the resting cells, displayed a more migratory phenotype, and were more likely to employ motile scanning of the target cell surface during conjugation. Taken together, our experiments quantify, at the single-cell level, how activation by IL-2 leads to altered NK cell cytotoxicity, migration behavior and contact dynamics.

Stress/Rest Tc-99m-MIBI SPECT in Comparison with Rest/Stress Rubidium - 82 PET

International Nuclear Information System (INIS)

Lee, D. S.; Kamg, K. W.; Lee, K. H.; Jeong, J. M.; Kwark, C. E.; Chung, J. K.; Lee, M.C.; Seo, J. D.; Koh, C. S.

1995-01-01

We compared stress/rest myocardial Tc-99m-MIBI tomographic image findings with rest/stress rubidium-82 tomographic images. In 23 patients with coronary artery disease (12 of them received bypass grafts before) and 6 normal subjects, rest rubidium PET study was performed, rubidium-82 and Tc-99m-MIBI were injected simultaneously to each patient after dipyridamole stress for rubidium PET and MIBI SPECT; and rest MIBI SPECT was performed 4 hours thereafter. We scored segmental decrease of rubidium, or MIBI uptakes into 5 grades for 29 segments from 3 short-axis, vertical and horizontal slices. Scores were summed for each major arterial territory. When more score than two grade-2's or one grade-3 was considered as the cue for significant stenosis for major arterial territories, 67% of 46 stenosed arteries were found with MIBI studies and 78% of them by rubidium studies. Fourteen among 28 grafted arterial territories of 12 post-CABG patients were found normal with both rubidium and MIBI. Segmental scores were concordant between rubidium and MIBI in 72% of 709-stress segments and in 80% of 825 rest segments. Stress rubidium segmental scores were less than stress MIBI scores in 9%, so were rest rubidium scores. Stress rubidium scores were more than stress MIBI scores in 20% of segments, and rest rubidium segmental scores were more than rest MIBI scores in 11%. Rank correlations (Spearman's rho's more than 0.7(stress) and 0.5(rest), slopes (MIBI/rubidium) around 0.7(stress) and 0.9(rest) suggested deeper and wider defects in stress with rubidium. Slope over 1 (MIBI/rubidium) with LAD segmental scores at rest and 7 territories which had much larger score with MIBI revealed exaggeration of rest defects with rest MIBI in same-day stress/rest study. Difference scores (stress-rest for each territory) suggesting ischemia were larger with rubidium (slope of MIBI/rubidium around 0.45). As has been implied by animal or separate-day- human studies, these segmental analyses with

Human lung mast cells modulate the functions of airway smooth muscle cells in asthma.

Science.gov (United States)

Alkhouri, H; Hollins, F; Moir, L M; Brightling, C E; Armour, C L; Hughes, J M

2011-09-01

Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction. To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays. Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation. Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma. © 2011 John Wiley & Sons A/S.

Changes in Cartilage Morphology of the Knee after 14-days of Bed Rest

Science.gov (United States)

Liphardt, A.-M.; Mündermann, A.; Koo, S.; Bäcker, N.; Andriacchi, T.; Zange, J.; Mester, J.; Heer, M.

Introduction While there are still many unanswered questions related to the effects of space flight and disuse on cartilage health and cartilage morphology the number of in vivo experiments in humans is small For muscle and bone tissue it is well known that unloading results in degeneration of those tissues Also for cartilage previous studies in patients suggest that unloading causes cartilage degeneration Studies using immobilization as a model of unloading help to investigate the importance of experiencing mechanical loads for the maintenance of healthy biological tissues The goal of our study was to investigate whether bed rest induced immobilization has a negative effect on articular cartilage in healthy subjects and if vibration training is a potential counter-measure for these negative effects Methods Eight male healthy subjects 78 1 pm 9 5 kg 179 pm 9 6 cm 26 pm 5 years performed a 14-day bed rest in 6 r -head down tilt HDT The study was designed in a cross-over-design where each subject received a training intervention vib in one phase and no intervention con in the other phase During the training intervention subjects trained 2 x 5-minutes per day at 20 Hz with 2 -- 4 mm amplitude on a vibration plate Galileo 900 Magnet resonance MR imaging of the right knee was performed to measure articular cartilage thickness MR-images 2 mm slice thickness 0 35 mm x 0 35 mm in-plane resolution 448 x 512 pixels were taken before and after bed rest to investigate the effects of bed rest