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 investigated the ionic changes in arterial (a) and femoral venous (fv) blood that accompany muscle fatigue with repeated maximal exercise. Measurements were made on separated plasma and hemolysed whole blood to quantify the relative contributions of plasma and erythrocytes to this acid-base challenge. Five healthy males performed four 30-s bouts of maximal isokinetic cycling exercise, with 4 min of rest between bouts, and recovery was followed for 90 min. In whole blood, maximal increases in [K+]a amounted to 10 +/- 2.0 meq/l and in [K+]fv to 7 +/- 4.3 meq/l and occurred at the end of bout 2. Whole blood lactate concentration ([Lac-]) peaked at 15.3 +/- 1.39 ([Lac-]a) and 16.7 +/- 1.59 meq/l ([Lac-]fv) at the end of bout 4. In plasma, peak [Lac-]a and [Lac-]fv were both 21 meq/l at the end of bout 4. Plasma [H+]a increased from 36 +/- 1.0 neq/l at rest to 44 +/- 2.9 neq/l at the end of the first bout of exercise; 80% of this increase was due to a 2.9 meq/l decrease in arterial strong ion difference ([SID]), and 20% was due to an increase in plasma protein ([Atot]a); a reduction in arterial PCO2 to 29 mmHg had an alkalinizing effect. In contrast, plasma [H+]fv increased from 39 +/- 0.5 neq/l at rest to 93 +/- 4.1 neq/l, with an increase in PfvCO2 to 97 +/- 7 mmHg contributing 75%, a decrease in [SID]fv 15%, and an increase in [Atot]fv 10% to the increase in [H+]fv. In later exercise bouts, the relative contributions of [SID]a, [Atot]a, and arterial PCO2 to plasma [H+]a were similar, but the contribution of [SID]fv to [H+]fv increased and that of femoral venous PCO2 decreased, with the contribution of [Atot]fv remaining unchanged (8-12%). During exercise and recovery, the changes in both arterial and femoral venous PCO2 and [K+] were more rapid than changes in [Lac-], and the time course of whole blood [K+] was slower than that of plasma [K+]. Erythrocytes may play an important role in regulating plasma [Lac-] and [K+] with intense exercise.
 ...
PMID:Blood ion regulation during repeated maximal exercise and recovery in humans. 173 31

Seven Arabian horses performed a standard incremental exercise test on a high-speed treadmill at 6% slope then were randomly assigned to two diets, a control diet of ground hay and concentrates and a similar diet with 10% added fat (by weight). Horses were sprint-trained 4 d/wk, and two additional exercise tests were performed at 5-wk intervals. Heart rates and rectal temperatures were monitored and venous blood samples were collected at rest and at each speed increment. Whole blood was analyzed for glucose, lactate, and hemoglobin concentrations, and plasma was analyzed for pH, pCO2, albumin, total protein, and sodium, potassium, and chloride concentrations. Bicarbonate concentration ([HCO3-]) and strong ion difference ([SID]) were calculated, and total weak acid ([Atot]) was estimated from total protein. During exercise, there were increases in plasma sodium and potassium concentrations (P < .001), whole blood lactate and glucose (P < .001), and hemoglobin concentrations (P < .01). There were decreases in plasma pH, [HCO3-], and chloride concentrations (P < .001). The decrease in plasma pH was associated with changes in [SID] and [Atot] that combined to offset a decrease in pCO2. After sprint training, heart rates at rest and during submaximal exercise were decreased (P < .01), whereas heart rates at the end of exercise were increased (P < .05). Sprint training also increased workrate and estimated oxygen consumption at a heart rate of 200 beats/min (P < .001). Training increased the duration of exercise and the speed attained at the end of exercise (P < .05). Training increased the blood hemoglobin response to exercise and decreased the pCO2 response (P < .01). There were diet x training interactions for pH, pCO2, and [SID] (P < .05). Horses consuming the high-fat diet had higher blood glucose during both standard exercise tests and higher lactate concentrations at fatigue (P < .05) during the last test. Fat adaptation involving sprint training of horses may influence glucolysis at the level of pyruvate during an incremental exercise test.
 ...
PMID:Acid-base variables during incremental exercise in sprint-trained horses fed a high-fat diet. 759 85

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.
 ...
PMID:Differences in diaphragm fiber types in SIDS infants. 781 77

Currently available as a dietary supplement, the pineal hormone melatonin is portrayed by the media as a formidable weapon against disease and aging. Accordingly, primary health care providers should be cognizant of which of its proposed uses are supported by biomedical research and which are, as yet, unproven. Melatonin entrains circadian rhythms and, thus, can treat jet lag, delayed sleep phase syndrome, and sleep disorders in the blind and in some neurologically impaired children. By virtue of its hypnotic effect, melatonin can mitigate insomnia in the elderly. Reductions in melatonin secretion have been associated with many disorders, including cardiovascular disease, Alzheimer's, diabetes, SIDS, and aging; however, melatonin's role in their etiology and/or pathophysiology is unproven. Preliminary studies suggest a possible adjuvant therapeutic role for melatonin in cancer therapy. Melatonin secretion is reduced by alcohol, caffeine, and some commonly prescribed drugs. Since tolerance, fatigue, and other side effects have been reported, melatonin use on consecutive nights should be avoided and only the lowest effective hypnotic dose should be taken.
 ...
PMID:Melatonin: media hype or therapeutic breakthrough? 905 17

1. This study investigated the effects of 7 weeks of sprint training on changes in electrolyte concentrations and acid-base status in arterial and femoral venous blood, during and following maximal exercise for 30 s on an isokinetic cycle ergometer. 2. Six healthy males performed maximal exercise, before and after training. Blood samples were drawn simultaneously from brachial arterial and femoral venous catheters, at rest, during the final 10 s of exercise and during 10 min of recovery, and analysed for whole blood and plasma ions and acid-base variables. 3. Maximal exercise performance was enhanced after training, with a 13% increase in total work output and a 14% less decline in power output during maximal cycling. 4. The acute changes in plasma volume, ions and acid-base variables during maximal exercise were similar to previous observations. Sprint training did not influence the decline in plasma volume during or following maximal exercise. After training, maximal exercise was accompanied by lower arterial and femoral venous plasma [K+] and [Na+] across all measurement times (P < 0.05). Arterial plasma lactate concentration ([Lac-]) was greater (P < 0.05), but femoral venous plasma [Lac-] was unchanged by training. 5. Net release into, or uptake of ions from plasma passing through the exercising muscle was assessed by arteriovenous concentration differences, corrected for fluid movements. K+ release into plasma during exercise, and a small net K+ uptake from plasma 1 min post-exercise (P < 0.05), were unchanged by training. A net Na+ loss from plasma during exercise (P < 0.05) tended to be reduced after training (P < 0.06). Release of Lac- into plasma during and after exercise (P < 0.05) was unchanged by training. 6. Arterial and venous plasma strong ion difference ([SID]; [SID] = [Na+] + [K+] - [Lac-] - [Cl-]) were lower after training (mean differences) by 2.7 and 1.8 mmol l-1, respectively (P < 0.05). Arterial and femoral venous CO2 tensions and arterial plasma [HCO3-] were lower after training (mean differences) by 1.7 mmHg, 4.5 mmHg and 1.2 mmol l-1, respectively (P < 0.05), with arterial plasma [H+] being greater after training by 2.2 nmol l-1 (P < 0.05). 7. The acute changes in whole blood volume and ion concentrations during maximal exercise were similar to previous observations: Arterial and femoral whole blood [K+] and [Cl-] were increased, whilst [Na+] was lower, across all observation times after training (P < 0.05). 8. Net uptake or release of ions by exercising muscle was assessed by arteriovenous whole blood concentration differences, corrected for fluid movements. A net K+ uptake by muscle occurred at all times, including exercise, but this was not significantly different after training. An increased net Na+ uptake by muscle occurred during exercise (P < 0.05) with greater Na+ uptake after training (P < 0.05). Net muscle Lac- release and Cl- uptake occurred at all times (P < 0.05) and were unchanged by training. 9. Sprint training improved muscle ion regulation, associated with increased intense exercise performance, at the expense of a greater systemic acidosis. Increased muscle Na+ and K+ uptake by muscle during the final seconds of exercise after training are consistent with a greater activation of the muscle Na(+) - K+ pump, reduced cellular K+ loss and the observed lesser rate of fatigue. The greater plasma acidosis found after sprint training was caused by a lower arterial plasma [SID] due to lower plasma [K+] and [Na+], and higher plasma [Lac-].
 ...
PMID:Sprint training enhances ionic regulation during intense exercise in men. 921 28

Increases in blood [H+] and lactic acid [La-] attend fatigue. We applied Stewart's physiological model of acid-base status and simple regressions to assess the importance of independent variables and [La-] on [H+] during repeated sprints. Eight well-conditioned Arabians performed 9 sprints. Plasma from jugular vein samples was analysed for pH, PCO2, Na+, K+ and Cl-. Plasma [La-] was calculated from blood [La-], plasma [H+] from pH, SID from Na+, K+, Cl- and La-, Atot from pH, PCO2 and SID. Peaks for SID, PCO2 and [H+] were reached at sprint 1, -2 and -3, respectively. At sprint 3, the 5.7 nmol/l peak in [H+] was partitioned into 2.3, 2.7 and 0.7 nmol/l for Atot, PCO2 and SID, respectively. From sprint 3 to sprint 9, increases in Atot and decreases in SID tended to increase [H+] but were counteracted by a steady decrease in PCO2 that determined the progressive decrease in [H+]. Therefore PCO2 was the dominant determinant of [H+] during 9 repeated sprints, and the expected major effect of [La-] was moderated in the SID by opposing increases in [Na+] and [K+]. In the work-adapted phase (sprints 3-9), decreasing [H+] was correlated positively with PCO2 (r = 0.997, P < 0.001) but negatively with La- (r = -0.986, P < 0.001). Respiration was therefore completely compensating for the effects of metabolism on [H+]. During the transition from rest to sprint 3 (peak plasma [H+]), increasing [H+] was highly correlated (r = 0.99, P = 0.011) with [La-] but no other variable. The empirical and physiological analyses were consistent with one another during the work-adapted phase, but emphasis was placed on [La-] by the regression analysis, in contrast to PCO2 by the Stewart analysis, during the rest-work transition.
 ...
PMID:Partition of plasma hydrogen ion concentration changes during repeated sprints. 1065 86

SIDS is almost invariably sleep-related. Viable syndrome aetiology must be compatible with its many epidemiologically diverse risk factors, each of which directly or indirectly associates with the creation of psychological and/or physiological infant stress, and the subsequent disruption of normal, contented sleep. During essential deep 'rebound' recovery sleep, arousal ability and upper airway muscle tone decrease further to that in normal sleep, with subsequent upper airway obstruction. When stress impact causes sufficient sleep disruption and physiological fatigue, a failure to arouse and so restore sufficient tone to overcome such obstruction results in sudden, unexpected death. SIDS has therefore many causes which share a final lethal mechanical pathway. Evidence is presented for obstructive apnoea during sleep as being the primary syndrome death mode, for sleep disruption, reduced arousal ability, and infant stress in SIDS, and for risk factor association with the creation of this stress. Specific infant vulnerability in the first 6 months of life to stress predominantly related to total dependency on a carer for gratification of need, and to obstructive sleep apnoea due to normal anatomical, physical, and respiratory immaturity, including rapid physiological fatigue, and peaks in sleep and thermal stress vulnerability, are discussed. Further reasons for the limited age period of SIDS, and for reduced neonatal risk, are given. Prone sleeping risk can relate to positional airway obstruction during normal sleep without prior infant stress. Much of SIDS aetiology appears to concern factors related to socio-economic deprivation and subsequent sub-optimal infant care.
 ...
PMID:Infant stress and sleep deprivation as an aetiological basis for the sudden infant death syndrome. 1117 74

Four basic control mechanisms of breathing (brainstem respiratory centre, peripheral and central chemoreceptors, intero- and exteroceptive reflexes and suprapontine influences), as well as their sleep-related disorders are analysed. A decrease in central chemoreceptor sensitivity to CO2 and an increase in upper airway resistance during sleep result in hypoventilation and mild hypoxaemia already in physiological conditions. Compensatory increase in ventilatory effort with synchronous inhibition of pharyngeal dilators during sleep reduces the upper airway lumen manifesting with snoring, upper airway resistance syndrome, and OSA. The resulting hypoxaemia may cause marked cardiovascular, neuro-psychic, endocrine-metabolic and behavioural disorders. The augmented ventilatory effort and hypoxaemia evoke reflex dilation of airways and arousal from sleep, stimulating the sympatho-adrenal system, which provokes autoresuscitation by gasping preventing fatal asphyxia. Failure of this autoresuscitation mechanism seems to cause SIDS. Elimination of voluntary breathing by sleep either in Ondine's curse induced by lesions of respiratory centre, or in congenital central hypoventilation syndrome caused by insufficient central chemoreceptors result in respiratory failure and death. Nocturnal attacks of bronchial and cardiac asthma, lung oedema and other consequences of pulmonary congestion are also discussed. The pathomechanism of extreme daytime sleepiness, chronic fatigue, and disorders of memory, cognitive and other brain functions, are also analysed. Severe cardiovascular consequences of SAS may manifest acutely as angina pectoris, myocardial infarction. dysrhythmias, transient ischaemic attacks and even stroke or sudden cardiac death. OSAS may result also in development of hypertension, central obesity, diabetes mellitus, erectile dysfunction, depression, and various behavioural disorders.
 ...
PMID:[Regulation of respiration and its sleep-related disorders]. 1244 39

Autoimmune dysfunction of certain vasoactive neuropeptides may be implicated in a range of disorders associated with fatigue like states (chronic fatigue syndrome, Gulf War syndrome) and even sudden infant death syndrome. These substances have neurotrophic, neuroregulatory, and neurotransmission functions, as well as that of immune modulators and hormones. They exert significant control over carbohydrate and lipid metabolism. The hypothesis is that because these substances have vital and indispensable roles in cellular processes, loss or compromise of these roles would lead to predictable and severe cellular and systemic effects. The important roles of certain VNs make them a vulnerable target for autoimmune dysfunction. They are known to be associated with heat shock proteins for intracellular functioning with which they may form immunostimulating complexes. While peptide-HSP complexes are a relatively new area for research, this paper asserts that attention could be focused on these substances and complexes in an effort to elucidate a number of perplexing fatigue-associated disorders.
 ...
PMID:Do vasoactive neuropeptides and heat shock proteins mediate fatigue-related autoimmune disorders? 1561 62

Vasoactive neuropeptides such as pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) have been implicated in a number of fatigue-related conditions. Associations of these vasoactive neuropeptides with heat shock proteins (hsps) and cytosine-guanosine dinucleotide (CpG) DNA fragments in autoimmune phenomena have been postulated to interfere with receptor signal activation for adenylate cyclase and other vital cellular processes. However, a specific mechanism for receptor dysfunction has not been explored to date. G protein-coupled receptors (GPCRs) constitute a high proportion of biological receptor mechanisms and serve a wide range of substances including nucleosides, nucleotides, catecholamines, calcium, histamine, serotonin and prostaglandins. They are complex transmembrane hepta-helical serpentine structures with specific binding capabilities resulting in conformational changes that activate cognate cyclic GMP (G proteins). GPCRs adapt to certain stimuli through desensitisation and changes in phosphorylation and are subject to distortions of signalling processes. Hence, these vital signalling structures are susceptible to impairment of function through a range of mechanisms. One of their vital functions is signalling through adenylate cyclase, a vital step in cyclic AMP metabolism. This step involves ATP metabolism and therefore is a crucial mediator of cellular energy pathways. Some GPCRs act to inhibit adenylate cyclase (Gi proteins). Also vasoactive neuropeptides, such as PACAP display a number of receptor isotypes including null variants. Overexpression of Gi proteins and null variant receptors may account for major disruptions of signal transduction and ATP/cAMP metabolism. This paper examines the possible role of GPCR dysfunction in contributing to fatigue-related vasoactive neuropeptide autoimmune disorders which may include chronic fatigue syndrome (CFS), Gulf War syndrome (GWS) and even sudden infant death syndrome (SIDS).
 ...
PMID:Are vasoactive neuropeptide autoimmune fatigue-related disorders mediated via G protein-coupled receptors? 1589 12


1 2 Next >>