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)

We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety-Schmidt-determined cerebral blood flow; n = 5) and the ammonia concentration in the cerebrospinal fluid (CSF; n = 8) at rest and immediately following prolonged exercise either with or without glucose supplementation. There was a net balance of ammonia across the brain at rest and at 30 min of exercise, whereas 3 h of exercise elicited an uptake of 3.7 +/- 1.3 micromol min(-1) (mean +/-s.e.m.) in the placebo trial and 2.5 +/- 1.0 micromol min(-1) in the glucose trial (P < 0.05 compared to rest, not different across trials). At rest, CSF ammonia was below the detection limit of 2 microm in all subjects, but it increased to 5.3 +/- 1.1 microm following exercise with glucose, and further to 16.1 +/- 3.3 microm after the placebo trial (P < 0.05). Correlations were established between both the cerebral uptake (r2 = 0.87; P < 0.05) and the CSF concentration (r2 = 0.72; P < 0.05) and the arterial ammonia level and, in addition, a weaker correlation (r2 = 0.37; P < 0.05) was established between perceived exertion and CSF ammonia at the end of exercise. The results let us suggest that during prolonged exercise the cerebral uptake and accumulation of ammonia may provoke fatigue, e.g. by affecting neurotransmitter metabolism.
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PMID:Cerebral ammonia uptake and accumulation during prolonged exercise in humans. 1561 Oct 36

Using either an ammoniacal route, the reaction between DyCl3, Na0, and HOR in liquid ammonia, or preferentially reacting Dy(N(SiMe3)2)3 with HOR in a solvent, we isolated a family of dysprosium alkoxides as [Dy(mu-ONep)2(ONep)]4 (1), (ONep)2Dy[(mu3-ONep)(mu-ONep)Dy(ONep)(THF)]2(mu-ONep) (2), (ONep)2Dy[(mu3-ONep)(mu-ONep)Dy(ONep)(py)]2(mu-ONep) (3), [Dy3(mu3-OBut)2(mu-OBut3(OBut)4(HOBut)2] (4), [Dy3(mu3-OBut)2(mu-OBut)3(OBut)4(THF)2] (5), [Dy3(mu3-OBut)2(mu-OBut)3(OBut)4(py)2] (6), (DMP)Dy(mu-DMP)4[Dy(DMP)2(NH3)]2 (7), [Dy(eta6-DMP)(DMP)2]2 (8), Dy(DMP)3(THF)3 (9), Dy(DMP)3(py)3 (10), Dy(DIP)3(NH3)2 (11), [Dy(eta6-DIP)(DIP)2]2 (12), Dy(DIP)3(THF)2 (13), Dy(DIP)3(py)3 (14), Dy(DBP)3(NH3) (15), Dy(DBP)3 (16), Dy(DBP)3(THF) (17), Dy(DBP)3(py)2 (18), [Dy(mu-TPS)(TPS2]2 (19), Dy(TPS)3(THF)3 (20), and Dy(TPS)3(py)3 (21), where ONep = OCH2CMe3, OBut) = OCMe3, DMP = OC6H3(Me)(2)-2,6, DIP = OC6H3(CHMe2)(2)-2,6, DBP = OC6H3(CMe3)(2)-2,6, TPS = OSi(C6H5)3, tol = toluene, THF = tetrahydrofuran, and py = pyridine. We were not able to obtain X-ray quality crystals of compounds 2, 8, and 9. The structures observed and data collected for the Dy compounds are consistent with those reported for its other congeners. A number of these precursors were used as Dy dopants in Pb(Zr0.3Ti0.7)O3 (PZT 30/70) thin films, with compound 12 yielding the highest-quality films. The resulting Pb0.94Dy0.04(Zr0.3Ti0.7)O3 [PDyZT (4/30/70)] had similar properties to PZT (30/70), but showed substantial resistance to polarization reversal fatigue.
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PMID:Synthesis and characterization of a family of structurally characterized dysprosium alkoxides for improved fatigue-resistance characteristics of PDyZT thin films. 1573 2

Autoimmune dysfunction of certain vasoactive neuropeptides (VNs) has been postulated as a contributing cause of sudden infant death syndrome (SIDS), chronic fatigue syndrome (CFS), Gulf War syndrome (GWS) and other fatigue-related disorders. This family of VNs includes pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and calcitonin gene related peptide (CGRP). The postulated mechanism is compromise of adenylate cyclase activation, a vital and unique step in cyclic AMP production from ATP, through autoimmune dysfunction of VNs, their receptors or their genes possibly involving cytosine-phosphate-guanine (CpG) fragments. CpG fragments are immunomodulatory dinucleotides serving as 'friend or foe' recognition systems to differentiate bacterial and viral (hypomethylated CpG) from mammalian (methylated CpG) DNA. However hypomethylation disorders affecting these fragments in mammals may convert them to dysfunctional states by promoting autoimmune inflammatory reactions. Epigenetic mechanisms acting on gene promoter regions may contribute to the development of VN autoimmune fatigue-related disorders through CpG fragments located in vital segments of VN/receptor genes by causing signalling defects with profound implications for VN function. Neurotransmitter dysfunction particularly glutamatergic transmission could also result with disruption of neuronal cellular biochemical functions such as ammonia regulation. Endosomal acidity and mitochondrial membrane potential modifiers such as chloroquine, together with immunoregulatory therapies, may have therapeutic implications in protecting against these apparent autoimmune disorders. This paper examines specific epigenetic and biochemical mechanisms possibly mediated by VN or receptor genes resulting in postulated VN autoimmune fatigue-related disorders. These mechanisms may have implications for treatment and prevention options for VN autoimmune disorders. VN autoimmune processes have implications for military medicine where radiological, chemical and biological agents may play an important role in pathogenesis.
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PMID:Does dysregulation of key epigenetic and biochemical pathways occur in postulated vasoactive neuropeptide autoimmune disorders? 1602 37

The clinical presentation of acute liver failure and hepatic encephalopathy (HE) in patients with cirrhosis differs significantly. The most serious neurological complication of acute liver failure is the development of devastating brain oedema. Therefore, intracranial pressure monitoring is urgently needed in these patients. Brain oedema is amplified by hypoglycemia, hypoxia and seizures, which are also frequent complications of acute liver failure. Therefore, these parameters must also be monitored. In contrast to acute liver failure in which cerebral dysfunction progresses rapidly, cognitive decline may be clinically undetectable for a long time in cirrhotic patients, until clinically overt symptoms such as psychomotor slowing, disorientation, confusion, extrapyramidal and cerebellar symptoms or a decrease in consciousness occur. Clinically, overt HE is preceded by minimal alterations of cerebral function that can only be detected by neuropsychological or neurophysiological measures, but which nevertheless interfere with the patient's daily living. Rapidly progressing spastic paraparesis (hepatic myelopathy) is a rare complication of cirrhosis. In contrast to HE, it does not respond to blood ammonia lowering therapies but must be considered as an indication for urgent liver transplantation. Cognitive dysfunction has recently been detected in hepatitis C virus (HCV)-infected patients with normal liver function. The patients presented with severe fatigue, cognitive dysfunction and mood disorders. Alterations in brain metabolites, as detected by magnetic resonance spectroscopy, indicated central nervous system alteration in these patients. In contrast to patients with HE, HCV-infected patients did not show motor symptoms or deficits in visual perception, but considerable deficits in attention and concentration ability.
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PMID:Neurological and neuropsychiatric syndromes associated with liver disease. 1625 35

In order to test the hypothesis that dietary restriction may have a negative influence on physiological and psychological adaptation to a judo competition, we examined the effects of weight loss induced by restricting energy and fluid intake on the physiology, psychology, and physical performance of judo athletes. Twenty male judoka were randomly assigned to one of two groups (Group A: called diet, n = 10; height 174.8 +/- 1.9 cm, body weight 75.9 +/- 3.1 kg; they were asked to lose approximately 5 % of their body weight through self-determined means during the week before the competition; Group B: called control, n = 10; height 176.4 +/- 1.1 cm, body weight 73.3 +/- 6.3 kg maintained their body weight during the week before the competition). A battery of tests was performed during a baseline period (T1), on the morning of a simulated competition (T2) and 10 min after the end of the competition (T3). The test battery included assessment for body composition, performance tests, evaluation of mood, determination of metabolic and hormonal responses. Dietary data were collected using a 7-day diet record. The nutrient analysis indicated that all the athletes followed a low carbohydrate diet whatever the period of the investigation. For the Group A, the food restriction (- 4 MJ per day) resulted in significant decreases of the body weight and altered the mood by increasing Fatigue, Tension and decreasing Vigour. Dietary restriction had also a significant influence on metabolic and endocrine parameters and was associated with poor performance. After the competition, significant decreases of the levels in testosterone, T/C ratio, alkali reserve, and free fatty acid were observed in both groups, whereas the plasma concentrations in insulin, ammonia, urea, and uric acid were increased. In conclusion, our results suggest that the combination of energy restriction and intense exercise training, which causes weight reduction before a competition, adversely affects the physiology and psychology of judo athletes and impairs physical performance before the competition. Our data are the first to demonstrate that a competition including five 5-min bouts induced the same changes of physiological and psychological variables and performance whatever the dietary intake (dietary restriction or not) during the seven days before the competition.
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PMID:Food restriction, performance, biochemical, psychological, and endocrine changes in judo athletes. 1638 36

This study investigated the influence of environmental heat stress on ammonia (NH3) accumulation in relation to nucleotide metabolism and fatigue during intermittent exercise. Eight males performed 40 min of intermittent exercise (15 s at 306+/-22 W alternating with 15 s of unloaded cycling) followed by five 15 s all-out sprints. Control trials were conducted in a 20 degrees C environment while heat stress trials were performed at an ambient temperature of 40 degrees C. Muscle biopsies and venous blood samples were obtained at rest, after 40 min of exercise and following the maximal sprints. Following exercise with heat stress, the core and muscle temperatures peaked at 39.5+/-0.2 and 40.2+/-0.2 degrees C to be approximately 1 degrees C higher (P<0.05) than the corresponding control values. Mean power output during the five maximal sprints was reduced from 618+/-12 W in control to 558+/-14 W during the heat stress trial (P<0.05). During the hot trial, plasma NH3 increased from 31+/-2 microM at rest to 93+/-6 at 40 min and 151+/-15 microM after the maximal sprints to be 34% higher than control (P<0.05). In contrast, plasma K+ and muscle H+ accumulation were lower (P<0.05) following the maximal sprints with heat stress compared to control, while muscle glycogen, CP, ATP and IMP levels were similar across trials. In conclusion, altered levels of "classical peripheral fatiguing agents" does apparently not explain the reduced capacity for performing repeated sprints following intermittent exercise in the heat, whereas the augmented systemic NH3 response may be a factor influencing fatigue during exercise with superimposed heat stress.
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PMID:Environmental heat stress, hyperammonemia and nucleotide metabolism during intermittent exercise. 1648 4

The purpose of this study was to examine the effects of fatigue on biomechanical indices of soccer kick performance. Ten male amateur soccer players performed maximal instep kicks prior to, in the middle and after the implementation of a 90 min intermittent exercise protocol. Three-dimensional data, ground reaction forces (GRFs) and segmental moments were measured during the kick while blood lactate and ammonia concentrations were monitored throughout the protocol. Analysis of variance designs with repeated measures indicated a significant increase in ammonia (P<0.01) and lactate levels (P<0.01) following fatigue. The GRFs and joint displacement curves during the kick remained unaltered after fatigue (P>0.01). However, post-fatigue maximum angular velocity of the shank, the net moments acting on the shank and the resultant joint moments were significantly lower compared with the corresponding pre-exercise values (P<0.01). The velocity of the ball was 24.69 m/s prior to the protocol and significantly decreased to 21.78 m/s after (P<0.01). Similarly, the ball/foot speed ratio significantly (P<0.01) declined from 1.40+/-0.12 (pre-fatigue) to 1.33+/-0.18 (post-fatigue). The present results suggest that an exercise protocol that simulates soccer game conditions results in significant impairment of soccer kick performance. This could be attributed to alterations of the function of the neuromuscular system and force generation capacity, which may have altered the mechanics of soccer kick performance.
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PMID:Effects of an intermittent exercise fatigue protocol on biomechanics of soccer kick performance. 1697 53

The crystal structure of the ammonia transport (Amt) protein AmtB at 1.4 Angstrom resolution revealed four ammonia/ammonium (NH(3)/NH(4)(+)) binding sites along the approximately 20 Angstrom narrow pore. It is an open question whether the bound NH(3)/NH(4)(+) are neutral (NH(3)) or cationic (NH(4)(+)). On the basis of the AmtB crystal structure, we calculated the pK(a) of these four NH(3)/NH(4)(+) by solving the Poisson-Boltzmann equation. Except for one NH(3)/NH(4)(+) binding site (Am1) at the entry point of the Amt pore, binding sites are occupied by NH(3) due to lack of energy contributions from solvation, eliminating an existence of charged form NH(4)(+) and, inevitably, its potential cation-pi interaction. The only two titratable residues in the pore, His168 and His318, are in the neutral charge state. The NH(4)(+) charge state at the Am1 site is stabilized by Ser219 functioning as an H-bond acceptor. However, when involving explicit crystal water nearby, the NH(3) charge state is stabilized by the reorientation of Ser219-OH group. This H-bond donor Ser219 significantly decreases the pK(a) of NH(3)/ NH(4)(+) at the Am1 site to approximately 1. The flip/flop H-bond of Ser219 may play a dual role first in binding and subsequently in deprotonating NH(4)(+), which is a prerequisite to conduct NH(3) through the Amt pore across the membrane.
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PMID:Protonation states of ammonia/ammonium in the hydrophobic pore of ammonia transporter protein AmtB. 1726 3

During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by (133)Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries, a approximately 25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O(2) supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O(2) enhances cerebral oxygenation and work capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exercise are of importance for the development of so-called central fatigue. During prolonged exercise, the perceived exertion is related to accumulation of ammonia in the brain, and data support the theory that glycogen depletion in astrocytes limits the ability of the brain to accelerate its metabolism during activation. The release of interleukin-6 from the brain when exercise is prolonged may represent a signaling pathway in matching the metabolic response of the brain. Preliminary data suggest a coupling between the circulatory and metabolic perturbations in the brain during strenuous exercise and the ability of the brain to access slow-twitch muscle fiber populations.
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PMID:Cerebral blood flow and metabolism during exercise: implications for fatigue. 1796 75

Blood ammonia concentration increases during endurance exercise and has been proposed as a cause for both peripheral and central fatigue. We examined the impact of glutamine and (or) carbohydrate supplementation on ammonemia in high-level runners. Fifteen men in pre-competitive training ran 120 min (approximately 34 km) outdoors on 4 occasions. On the first day, the 15 athletes ran without the use of supplements and blood samples were taken every 30 min. After that, each day for 4 d before the next 3 exercise trials, we supplemented the athletes' normal diets in bolus with carbohydrate (1 g.kg(-1).d(-1)), glutamine (70 mg.kg(-1).d(-1)), or a combination of both in a double-blind study. Blood ammonia level was determined before the run and every 30 min during the run. During the control trial ammonia increased progressively to approximately 70% above rest concentration. Following supplementation, independent of treatment, ammonia was not different (p>0.05) for the first 60 min, but for the second hour it was lower than in the control (p<0.05). Supplementation in high-level, endurance athletes reduced the accumulation of blood ammonia during prolonged, strenuous exercise in a field situation.
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PMID:Glutamine and carbohydrate supplements reduce ammonemia increase during endurance field exercise. 1805 93


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