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

We studied the relationship between contractile function and intracellular pH (pHi) in the isolated rat diaphragm when superfusate PCO2 was changed during hyperoxia or hypoxia. Superfused diaphragm strips were field stimulated at 0.5 Herz, and twitch tension (TT) was recorded. The pHi was calculated from the volume distribution of a weak acid, dimethyl-oxazolidinedione. In hyperoxia, hypercapnic acidosis (pH 7.06-6.63) depressed diaphragm pHi and TT, whereas hypocapnic alkalosis (pH 7.82-8.15) increased pHi but did not significantly affect TT. TT was maximum at physiological pHi (7.06), but in hyperoxic hypercapnic muscles substantial force was still generated at pHi values as low as 6.44. Hypoxia (PO2 30-38 mm Hg) markedly reduced TT; this effect was slightly exacerbated by hypercapnia and attenuated by hypocapnia. Hypoxia lowered pHi by about 0.2 units, which was insufficient to account for the hypoxic contractile failure. Knowledge of the hyperoxic muscle TT/pHi relationship suggests that, in other contexts, caution should be exercised in attributing severe muscle fatigue or force loss to modest falls in pHi.
 ...
PMID:The effect of pH and hypoxia on function and intracellular pH of the rat diaphragm. 210 18

We studied the effect of aminophylline on twitch tension (TT) and intracellular pH (pHi) in isolated rat diaphragm strips that were fatigued, hypercapnic, or hypoxic. Superfused muscles were directly stimulated at 0.5 Hz. The pHi was measured from distribution volumes of dimethyl-oxazolidinedione. Fatigue was induced by intermittent tetanic stimulation. Hypercapnia and hypoxia were produced by altering superfusate carbon dioxide tension (PCO2) or oxygen tension (PO2). Aminophylline (1.0 mmol.l-1) reversed the twitch decay seen during fatigue or hypercapnic acidosis, and caused partial recovery of twitch depression during hypoxia. Muscle fatigue was not due to an intracellular acidosis. Both hypercapnia and hypoxia lowered pHi. Aminophylline did not alter pHi in unstimulated muscles, but caused a significant fall in pHi in stimulated muscles that were fatigued or hypoxic. High dose aminophylline improved twitch tension in diaphragm strips that were fatigued, acidotic, or hypoxic. Twitch potentiation was not due to an intracellular alkalosis. Aminophylline lowered pHi in stimulated muscle, and thus, theoretically, could sometimes be harmful in the treatment of muscle fatigue.
 ...
PMID:The effect of aminophylline on function and intracellular pH of the rat diaphragm. 228 69

The relationship between intramuscular pH and the frequency components of the surface electromyographic (EMG) power spectrum from the vastus lateralis muscle was studied in eight healthy male subjects during brief dynamic exercise. The studies were carried out in placebo control and metabolic alkalosis induced by oral administration of NaHCO3. At the onset of exercise, blood pH was 0.08 units higher in alkalosis compared with placebo. Muscle lactate accumulation during exercise was higher in alkalosis (32 +/- 5 mmol/kg wet wt) than in placebo (17 +/- 4 mmol/kg wet wt), but no difference in intramuscular pH was found between the two conditions. The EMG power spectrum was shifted toward lower frequencies during fatigue in the control condition (10.1 +/- 0.9%), and these spectral shifts, evaluated from changes in the mean power frequency (MPF) of the EMG power spectrum, were further accentuated in alkalosis (19 +/- 2%). Although the changes in frequency components of EMG correlated with muscle lactate accumulation (r = 0.68, P less than 0.01), no direct relationship with muscle pH was observed. We conclude that alkalosis results in a greater reduction in MPF associated with a higher muscle lactate accumulation. However, the good correlation observed between the two variables is not likely causative, and a dissociation between intramuscular pH and the increase in the low-frequency content of EMG power spectrum appears during muscle fatigue.
 ...
PMID:Surface EMG power spectrum and intramuscular pH in human vastus lateralis muscle during dynamic exercise. 279 17

A patient with ectopic adrenocorticotrophic hormone (ACTH) production from a neuroendocrine tumour of the nasal roof is presented. By indirect immunoperoxidase techniques the tumour cells were shown to be distinctly positive for ACTH and beta-endorphin but negative for other peptides derived from pro-opiomelanocortin. Neither corticotropin releasing hormone (CRF) found in some tumours associated with ectopic Cushing's syndrome, nor gastrin immunoreactivity, which coexists with ACTH in normal rat pituitary and in rat and human gastrointestinal cells, were demonstrable in the tumour. A review of other, previously recognized locations of CRF/ACTH producing tumours is given to increase the awareness of the ectopic Cushing's syndrome, which may lack the classical features and is characterized by fulminant clinical course, extreme fatigue, weakness, pale facial swelling, oedema and hypokalaemic alkalosis.
 ...
PMID:Cushing's syndrome due to an ACTH-producing neuroendocrine tumour in the nasal roof. 298 19

The atrophy produced by endocrine disorders is primarily due to alterations in protein and carbohydrate metabolism. Type II muscle fibers are more severely affected than are Type I fibers. Steroid myopathy and the myopathy associated with excess ACTH have a typical pattern of proximal weakness affecting the legs more than the arms. Steroid myopathy is usually not apparent until other signs of glucocorticoid excess are present. Treatments of steroid myopathy are as follows: Lower the dose of steroid, use a nonfluorinated glucocorticoid, and exercise or physical therapy. Adrenal insufficiency produces generalized weakness, muscle cramping, and fatigue in 50 per cent of patients. Some patients also develop hyperkalemic paralysis. The treatment is hormone replacement. Thyrotoxicosis produces myopathy caused by net protein catabolism, accelerated basal metabolic rate and impaired carbohydrate metabolism. Shortening of contraction time may result from accelerated myosin ATPase activity and enhanced calcium uptake by the sarcoplasmic reticulum. Depolarization of the muscle fiber and impaired Na-K activity in muscle may predispose to thyrotoxic periodic paralysis. Neuromuscular presynaptic impairment may account for the worsening of myasthenia gravis by thyrotoxicosis. In hypothyroidism, impaired energy metabolism may limit force generation. Slow contraction and relaxation reflect reduction in myosin ATPase activity and impaired calcium uptake by the sarcoplasmic reticulum. Treatment for thyroid-associated muscle disorders is restoration of a euthyroid state. Muscle weakness associated with hypopituitarism is due to loss of thyroid and adrenal cortical hormones. Children require growth hormone for muscle development. T3 and growth hormone synergize to maintain normal protein synthesis. Primary and secondary hyperparathyroidism and osteomalacia are often associated with proximal weakness and fatigability. The myopathy improves with restoration of normal PTH levels and vitamin D replacement. Hypoparathyroidism and pseudohypothyroidism are associated with tetany. Tetany is worsened by alkalosis and is treated by calcium and magnesium replacement.
 ...
PMID:Endocrine myopathies. 306 2

In order to determine the influence of two artificially induced alkalotic states on the ability to perform maximal exercise, six male subjects (mean age, 22.0 years; mean height, 176.8 cm; mean weight, 69.1 kg; mean VO2 max, 3.83 l min-1) were studied during three experimental trials. The subjects performed six 60-s cycling bouts, at a work rate corresponding to 125% VO2 max, with 60 s recovery between work bouts; these regimens were performed 1 h after the ingestion of a solution containing either; I, placebo; II, NaHCO3 in a dosage of 0.15 g per kg body weight; or III, NaHCO3 0.30 g per kg body weight. The sixth work bout was continued until the pedal velocity dropped below 50 rev min-1. Total work done for the entire work period was calculated. Blood samples were taken from a forearm vein prior to the exercise bouts for analysis of pH and HCO3. The results showed a significant pre-exercise difference in pH and HCO3 for all conditions (P less than 0.01). In conditions where artificial alkalosis had been achieved prior to exercise there was significant increase in the work produced: I, 121.6 kJ; II, 133.1 kJ; III, 133.5 kJ (P less than 0.05). The time to fatigue in the six bout was also significantly increased; I, 74.7 s; II, 111.0 s; III, 106.0 p (P less than 0.05). There were no significant differences between conditions II and III. Thus augmentation of the bicarbonate reserves has a significant positive effect on the energy metabolism in interval-type exercise, leading to an increase in the work done and in the time to fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Maximal work production following two levels of artificially induced metabolic alkalosis. 373 82

The purpose of this investigation was to determine if the hyperventilatory response to fatiguing isometric exercise at sea level could predict resting ventilation and acute mountain sickness (AMS) at 4300 m altitude. Exercise consisted of four successive endurance handgrips held to complete fatigue at 40% of maximum isometric handgrip strength (MHS). There was no relationship between the magnitude or pattern of exercise-induced hyperventilation at sea level and the severity of AMS later at altitude. Sea level hyperventilatory response was not predictive of resting ventilation at altitude. Altitude exposure progressively increased both the incidence and magnitude of the hyperventilatory response to exercise and prolonged it for 60-90 s into the recovery period, providing support for the "central command" theory of ventilatory control during isometric exercise. MHS was significantly increased at altitude--by 11% on day 2 and 16% on day 6. Endurance times to fatigue were reduced, but not always significantly so. A follow-up study involving more practice at sea level demonstrated MHS to be significantly increased throughout an entire 18-d stay at 4300 m and for 3, but not 5, days after descent. Significant changes in endurance could not be demonstrated. Neither AMS nor changes in body weight or circulating norepinephrine levels can account for the temporal pattern of increased grip strength, but the respiratory alkalosis occurring at altitude appears to be a likely mechanism.
 ...
PMID:Respiratory response and muscle function during isometric handgrip exercise at high altitude. 381 31

The authors present a case of a 40-year-old female patient examined repeatedly in the course of 11 years and hospitalized on account of pain in the hypogastrium, subfebrile temperatures, watery diarrhoea, hypokaliaemic alkalosis, weakness, fatigue and loss of body weight. As to laboratory examinations hypokaliaemia, hyponatraemia, metabolic alkalosis, irregularly elevated CRP values and minor leucocytosis predominated. A weight loss of cca 8 kg along with a severe mineral deficiency and clinical symptomatology called for parenteral nutrition with a mean daily substitution of 240 mmol K and 200 mmol Na. Due to the clinical condition and non-specific results of graphic and histological examinations the possibility of a VIPoma was considered. This diagnosis was confirmed by laboratory examinations and clinically--after the onset of corticoid treatment marked improvement of the general condition occurred. Finally the authors discuss diagnostic and in particular therapeutic possibilities in this disease.
 ...
PMID:[A vasoactive-intestinal-polypeptide producing tumor (VIPoma) as an uncommon cause of life-threatening hypokalemia]. 748 36

Familial glucocorticoid resistance results from the partial inability of glucocorticoids to exert their effects on their target tissues throughout the organism. The condition is associated with compensatory elevations of circulating ACTH and cortisol, with the former causing excess abnormal secretion of steroids with mineralocorticoid and androgen activity. The manifestations of glucocorticoid resistance vary from asymptomatic to chronic fatigue, to varying degrees of hypertension and/or hypokalaemic alkalosis and hyperandrogenism. The latter can be manifest in women as acne, hirsutism, menstrual irregularity, oligoanovulation and infertility, in men as infertility, and in children as precocious puberty. Different molecular defects of the highly conserved glucocorticoid receptor gene, altering its concentration and functional characteristics, appear to cause the syndrome of familial glucocorticoid resistance. Depending on the molecular defect, this syndrome is transmitted by an autosomal dominant or recessive trait. There are recent suggestions that non-generalized forms of glucocorticoid resistance may exist, resulting in autoimmune-inflammatory phenomena or psychiatric manifestations.
 ...
PMID:Hormone-nuclear receptor interactions in health and disease. Glucocorticoid resistance. 798 Aug 39

Force development in skeletal muscle is driven by an increase in myoplasmic free [Ca2+]i ([Ca2+]i) due to Ca2+ release from the sarcoplasmic reticulum (SR). The magnitude of [Ca2+]i elevation during stimulation depends on: (a) the rate of Ca2+ release from the SR; (b) the rate of Ca2+ uptake by the SR; and (c) the myoplasmic Ca2+ buffering. We have used fluorescent Ca2+ indicators to measure [Ca2+]i in intact, single fibres from mouse and Xenopus muscles under conditions where one or more of the above factors are changed. The following interventions resulted in increased tetanic [Ca2+]i: beta-adrenergic stimulation, which potentiates the SR Ca2+ release; application of 2.5-di(tert-butyl)-1,4-benzohydroquinone, which inhibits SR Ca2+ pumps; application of caffeine, which facilitates SR Ca2+ release and inhibits SR Ca2+ uptake; early fatigue, where the rate of SR Ca2+ uptake is reduced; acidosis, which reduces both the myoplasmic Ca2+ buffering and the rate of SR Ca2+ uptake. Reduced tetanic [Ca2+]i was observed in late fatigue, due to reduced SR Ca2+ release, and in alkalosis, due to increased myoplasmic Ca2+ buffering. Force is monotonically related to [Ca2+]i but depends also on the myofibrillar Ca2+ sensitivity and the maximum force cross-bridges can produce. This is clearly illustrated by changes of intracellular pH where, despite a lower tetanic [Ca2+]i, tetanic force is higher in alkalosis than acidosis due to increases of myofibrillar Ca2+ sensitivity and maximum cross-bridge force.
 ...
PMID:Mechanisms underlying changes of tetanic [Ca2+]i and force in skeletal muscle. 872 1


1 2 3 Next >>