Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extent to which treatment with low doses of the nonfluorinated steroid methylprednisolone affects diaphragm contractility and morphology is unknown. In the present study, we compared the effects of equipotent doses of methylprednisolone and deflazacort, an oxazoline derivate of prednisolone with less systemic side-effects on bone structure and carbohydrate metabolism. Twenty six male adult rats were randomized to receive daily saline (control), methylprednisolone 0.4 mg.kg-1 or deflazacort 0.5 mg.kg-1 i.m. Contractile properties and histopathology were measured after a 6 week treatment period. During treatment, body weight increased in control and methylprednisolone-treated animals, but decreased by 4.2 +/- 1.1% (mean +/- SD) in the deflazacort group. Similarly, diaphragm mass in the deflazacort group was decreased compared to control and methylprednisolone groups. Twitch tension and twitch characteristics of isolated diaphragm bundles were similar in the three groups. Maximal tetanic tension was decreased in the deflazacort group. The force-frequency curve of the deflazacort bundles shifted downwards compared to control. Fatigue occurring during this protocol was greatest in the methylprednisolone- and deflazacort-treated animals. Microscopic examination revealed no gross abnormalities in the three groups. Histochemical analysis after staining for myosin adenosine triphosphatase (ATP-ase) showed that in the deflazacort group cross-sectional area of type I, IIa and IIb fibres were decreased. We conclude that low doses of methylprednisolone caused subtle and negligible changes in rat diaphragm contractile properties without affecting fibre dimensions, while deflazacort at an equipotent dose induced generalized fibre atrophy and changes in diaphragm contractility.
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PMID:Rat diaphragm contractility and histopathology are affected differently by low dose treatment with methylprednisolone and deflazacort. 765 57

1. The goal of this study was to characterize the fatigability, contractile relaxation properties, electrophysiological responses, and histochemical properties of the human paralyzed soleus muscle to determine its relative plasticity. 2. Acute (< 6 wk, n = 3) and chronic (> 1 yr, n = 10) paralyzed individuals had the tibial nerve activated with a 20-Hz square wave delivered for 330 ms every second for 4 min. The soleus muscle peak torque, one-half relaxation time (1/2RT), normalized maximum rate of relaxation (nMRR), and mass muscle action-potential amplitude (M wave) were computed every 30 s. A soleus muscle biopsy was evaluated for myosin adenosine triphosphatase enzyme (ATPase; pH 9.4, 4.6, and 4.2) and nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR). 3. In the chronically paralyzed group the torque was significantly reduced within 30 s of the fatigue protocol. The 1/2RT and nMRR were also significantly changed within 30 s, supporting that muscle relaxation was prolonged. No significant changes were present at comparable times during the same 4-min fatigue protocol applied to the acutely paralyzed soleus muscle. M-wave amplitude was significantly reduced in the chronic group, but only at 3 min of the fatigue protocol. Conversely, no significant changes occurred to the M waves of the acute group. 4. The correlation was high between torque and nMRR (r = 0.88-0.97) and torque and 1/2RT (r = 0.88-0.96) for each chronic subject. A close association was also found between 1/2RT and nMRR (r = 0.88-0.92) for each chronic subject. Because these variables changed minimally in the acutely paralyzed group, a lower correlation was present (r = 0.45-0.52). 5. Torque was weakly correlated to M-wave amplitude (r = 0.55) for the chronically paralyzed group. The greatest change in torque occurred at a time (0-65 s) when the least amount of change occurred in the M-wave amplitude, suggesting that the source of fatigue was within the contractile mechanism and not attributable to neuromuscular transmission compromise. 6. Despite a close association between torque and relaxation properties during fatigue of the chronically paralyzed soleus muscle, there was a significant dissociation after 5 min of recovery. Torque recovered to 60%, whereas the relaxation properties were consistently fully recovered. This suggests that the mechanism causing torque reduction covaried with the mechanism leading to prolonged relaxation during fatigue, but during recovery the two mechanisms no longer covaried. M-wave amplitude was also completely recovered at 5 min despite continued torque depression.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fatigability, relaxation properties, and electromyographic responses of the human paralyzed soleus muscle. 766 32

1. The effects of partial denervation on motor units of the fast twitch extensor digitorum longus (EDL) muscle of the rat were studied. 2. Partial denervation was performed by surgically removing 2-4 mm of the L4 ventral ramus in 3- and 18-day-old Wistar rats. Two to three months later, EMG activity, contractile properties and muscle fibre types were analysed. 3. After partial denervation the EDL muscle became significantly more active, particularly in the animals operated on at 3 days. The amount of activity during periods of rest was up to 4 times that of the control EDL muscle. 4. The maximum tetanic tension developed by the EDL muscles 2 months after partial denervation at 3 days was only 11 +/- 1.01% (S.E.M., n = 18) of the control. In animals operated on at 18 days this value was larger, i.e. 44 +/- 3.46% (S.E.M., n = 12). The low force output of animals operated on at 3 days was also reflected in the low mean motor unit (MU) force output which was only 69 +/- 5.82% (S.E.M., n = 17) of the contralateral control muscle. In contrast the force generated by MUs of rats operated on at 18 days was larger than that of control muscles, i.e. 151 +/- 13.05% (S.E.M., n = 11). The number of MUs was 6 +/- 0.32 (S.E.M., n = 19) in rats operated on at 3 days and 12 +/- 0.83 (S.E.M., n = 14) in rats operated on at 18 days. 5. The speed of contraction decreased and the resistance to fatigue increased. These changes were greater in animals operated on at 3 days. The proportion of muscle fibres reacting with antibody against slow myosin showed a significant increase, especially in the group of animals operated on at 3 days.
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PMID:The effect of partial denervation of developing rats fast muscles on their motor unit properties. 773 54

Biologists have long known that rates of adenosine triphosphate utilization and production need to be extremely closely balanced in all cells at all work rates. To put it in molecular rather than molar terms, in human muscle engaged in a 15-min work protocol, some 3.3 x 10(20) ATP molecules g-1 are used and resynthesized at close to 100 times the resting cycling rates before fatigue occurs. However, during this interval only a 20-25% decrease in the ATP pool is sustained. Review of recent studies as to how such remarkable regulatory precision is achieved suggests that in resting muscle, myosin behaves as a latent catalyst for which the full catalytic capacity is (a) realized with the arrival of its activator signal (Ca2+) and (b) attenuated with reaction products. These proactive controls, initiated at the onset of ATP utilization, set the required flux through ATP-producing pathways. For any given enzyme step in ATP-producing pathways, reaction velocity (upsilon) becomes the independent parameter, whereas substrate concentration ([s], the dependent parameter) must be adjusted accordingly. Because the dynamic range for muscles (change from resting to maximum ATP turnover rates) can exceed 100-fold, in many studies of working muscle the percentage change in ATP turnover rate usually greatly exceeds the percentage change in substrate concentrations. These kinds of observations are not easily explained by current metabolic regulation models, but are consistent with pathway enzymes behaving as latent catalysts in resting muscle. In this view, the unmasking of such latent catalytic potential is the main explanation for how large changes in upsilon can be achieved with modest (sometimes immeasurable) changes in [s]. In terms of the basic enzyme velocity equation, Vmax = kcat.e0 for pathways of ATP utilization and of ATP synthesis, the dominant (coarse level) regulation is achieved through e0 adjustments, whereas fine-tuning of flux is achieved by effective kcat adjustment.
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PMID:Solving the common problem: matching ATP synthesis to ATP demand during exercise. 780 35

The diaphragm is a vital respiratory muscle in the sleeping infant. Any changes in diaphragm fiber type number or size could represent either a primary developmental delay or a secondary reaction to increased workload, and could give a clue as to the pathogenesis of sudden infant death syndrome (SIDS). We therefore quantitated by point counting on ATPase histochemistry the numbers and areas of type 1 and 2 fibers in the diaphragm, external intercostal and psoas muscles of 37 SIDS and 20 control infants. The amount of slow, fast and fetal myosin in the diaphragm and psoas muscles was measured by electrophoresis to check the ATPase quantitation. There were fewer type 1 fibers in SIDS (median 30.0%) compared with control (median 40.0%) infants (p < 0.02), whereas the diameter of type 1 fibers in SIDS (median 33.9 microns) was larger than in control (median 30.3 microns) infants (p < 0.007). The total cross-sectional area occupied by type 1 and 2 fibers was similar in both groups. No changes were found in the external intercostal or psoas. The amount of slow and fast myosins correlated well with type 1 and type 2 fibers, respectively. The finding of fewer type 1 (fatigue-resistant) fibers of large diameter in SIDS diaphragms suggests that differences in muscle fiber types may predispose these infants to diaphragm fatigue and respiratory failure.
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PMID:Differences in diaphragm fiber types in SIDS infants. 781 77

Over the last 26 years diaphragm pacing has been used in over 400 adults and 70 children to support ventilation and oxygenation. Diaphragm pacing can be useful for conditions in which the brain stem respiratory centers provide little or no stimulation to the respiratory muscles, i.e. central hypoventilation syndrome, Arnold-Chiari malformation/brain stem dysfunction, and high quadriplegia. Because the pacing systems are so portable, the greatest advantages accrue to those patients who require ventilatory support both while awake and asleep. Infants and children require tracheostomy to avoid upper airway obstruction and bilateral pacing to meet higher metabolic demands. The stimulus parameters most appropriate for pediatric patients have been characterized as low stimulus frequency, short inspiratory time, and moderate respiratory rate. Use of similar stimulus parameters in an immature animal model has resulted in preservation of diaphragmatic structure and function but transformation of the diaphragm from a mixed muscle to one with a uniform population of type 1, fatigue-resistant fibers (physiologic, histochemical, myosin isoform, and ultrastructural evidence). In 33 pediatric patients, representing 96 patient-years of use, there were 26 failures of the pacing systems requiring removal and/or replacement of the internal components. Mean time to failure was 56 months. Of our 36 patients who had diaphragm pacing systems implanted, 26 are alive and 22 are currently using the pacing systems. wo recent advances may further improve the long-term outcome of patients using diaphragm pacing. Smaller, better encapsulated receivers may improve system longevity and a new stimulus electrode may reduce the risk of diaphragmatic damage.
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PMID:Diaphragm pacing: clinical and experimental results. 803 93

We analyzed the masticatory muscles (masseter, temporal, medial pterygoid and lateral pterygoid muscles) of Bovidae and Cervidae (Artiodactyla) for the histochemical characteristics of their fiber types. Analysis of muscle fiber types in the present study was based on the staining reaction for SDH, Sudan black B, alpha-GPDH, and myosin-ATPase after alkaline preincubations. Histochemical properties were found to contribute to masticatory function, including a slow-twitch fatigue resistant activity derived from the high percentage of red fibers, in spite of the differences in the distributions of fiber types in three portions (superficial, medial and profound portions) of each masticatory muscle. These results indicate a correlation between the histochemical profiles of individual masticatory muscles in these species and their functions during jaw movements.
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PMID:Differentiation of histochemical properties of masticatory muscles in Bovidae and Cervidae (Artiodactyla). 804 63

This study investigated the histochemical and morphometric properties of fibres in laryngeal, hyoid, tongue and pharyngeal muscles which contribute in maintaining patency of the upper airway. Muscle specimens from adult female goats were stained for nicotinamide adenine dinucleotide dehydrogenase-tetrazolium reductase and myosin adenosine triphosphatase activities, and the composition and size of the fibre types determined. These muscles contained types 1, 2A, 2B and 2C fibres with type 2 fibres predominating and the fibres possessed oxidative enzyme activity suggesting fast contraction speed and yet moderate resistance to fatigue. Abductor laryngeal muscles contained more type 1 fibres than the adductors. Among pharyngeal muscles fibre size and type 1 fibre composition increased progressively from the hyopharyngeus caudally. Upper airway muscles contained relatively small fibres (range of mean diameter: 25.7 to 46.1 microns) with the pharyngeal and lingualis proprius muscles containing the smallest fibres. These properties might influence the response of upper airway muscles to neuromuscular blocking drugs.
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PMID:Histochemical and morphometric properties of muscles of the upper airway of goats. 823 90

1. The muscles of the distal anterior compartment of the left hindlimb of rabbits were subjected to continuous indirect electrical stimulation at 10 Hz for periods of up to 12 weeks by means of an implantable stimulator. 2. The maximum shortening velocity (Vmax) and the velocity for maximum power production in single contractions (Vopt) were reduced to 42% and 32% of control values respectively after 12 weeks of stimulation. The rate of change of these parameters was greatest between the second and sixth week of stimulation. These changes, it is suggested, reflect the documented time course of the replacement of fast with slow isoforms of myosin. 3. The reductions in force production and speed of the stimulated muscles combined to produce a marked, progressive decline in the maximum power produced in single contractions. After 8 weeks of stimulation, the maximum power output had fallen to less than 10% of the control value. 4. The fatigue resistance of the stimulated and control muscles was tested over several hours of cyclical shortening contractions designed to elicit an initial power output of 10 W kg-1 with the muscles set to contract at Vopt. This level of work output represented about 1.6% (control) and 25% (12-week-stimulated) of the absolute maximum power output achieved during single contractions. 5. Despite the large reduction in the maximum power output of single contractions, the stimulated muscles showed less than 10% reduction in their power output during the fatigue tests over periods of up to 7 h. The control muscles showed a 70% reduction over the same period. There was no difference in the fatigue resistance under this protocol between muscles stimulated for 2 weeks and those stimulated for longer periods. Transformation of myosin isoforms, which is known to occur later than 2 weeks after the start of stimulation, is not necessary for the induction of this degree of fatigue resistance.
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PMID:Power production and working capacity of rabbit tibialis anterior muscles after chronic electrical stimulation at 10 Hz. 830 23

In the rat diaphragm muscle, the histochemical classification of type I, IIa, IIb, or IIx fibers was correlated with myosin heavy chain (MHC) immunoreactivity. Expression of MHC isoforms in single dissected fibers was also assessed electrophoretically. Most fibers (approximately 86%) expressed a single MHC isoform, and when present, coexpression of MHC-2X and MHC-2B isoforms was most prevalent. Type I and IIa fibers were the smallest, type IIb fibers were the largest, and type IIx fibers were intermediate. Succinate dehydrogenase (SDH) and calcium-activated myosin adenosinetriphosphatase (actomyosin ATPase) activities were measured with quantitative histochemical procedures. Type I and IIa fibers had the highest SDH activities, followed in rank order by type IIx and IIb fibers. Type I fibers had the lowest actomyosin ATPase activity, followed in rank order by type IIa, IIx, and IIb fibers. Across all fibers, there was an inverse relationship between fiber SDH activity and cross-sectional area and a positive correlation between fiber actomyosin ATPase activity and cross-sectional area. The SDH and actomyosin ATPase activities of muscle fibers were also inversely correlated. These phenotypic differences in SDH and ATPase activities may be important in determining the contractile and fatigue properties of different fiber types in the rat diaphragm muscle.
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PMID:SDH and actomyosin ATPase activities of different fiber types in rat diaphragm muscle. 859 23


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