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)

Patients with chronic hepatitis C virus (HCV) infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. Several studies have shown that patients exhibit low quality-of-life scores that are independent of disease severity. We therefore considered whether HCV infection has a direct effect on the central nervous system, resulting in cognitive and cerebral metabolite abnormalities. Twenty-seven viremic patients with biopsy-proven mild hepatitis due to HCV and 16 patients with cleared HCV were tested with a computer-based cognitive assessment battery and also completed depression, fatigue, and quality-of-life questionnaires. The HCV-infected patients were impaired on more cognitive tasks than the HCV-cleared group (mean [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P =.02). A factor analysis showed impairments in power of concentration and speed of working memory, independent of a history of intravenous drug usage (IVDU), depression, fatigue, or symptom severity. A subgroup of 17 HCV-infected patients also underwent cerebral proton magnetic resonance spectroscopy (1H MRS). The choline/creatine ratio was elevated in the basal ganglia and white matter in this group. Patients who were impaired on 2 or more tasks in the battery had a higher mean choline/creatine ratio compared with the unimpaired patients. In conclusion, these preliminary results demonstrate cognitive impairment that is unaccounted for by depression, fatigue, or a history of IVDU in patients with histologically mild HCV infection. The findings on MRS suggest that a biological cause underlies this abnormality.
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PMID:Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease. 1182 20

Fatigue is a common symptom of neurological diseases that affect basal ganglia function. We used proton magnetic resonance spectroscopy ((1)H MRS) to study the metabolic functions of the basal ganglia in chronic fatigue syndrome (CFS) to test the hypothesis that fatigue in CFS may have a neurogenic component. (1)H MRS of left basal ganglia was carried out in eight non-psychiatric patients with CFS and their results were compared to age- and sex-matched healthy asymptomatic healthy controls. A highly significant increase in the spectra from choline-containing compounds was seen in the CFS patient group (p < 0.001). In the absence of regional structural or inflammatory pathology, increased choline resonance in CFS may be an indicator of higher cell membrane turnover due to gliosis or altered intramembrane signalling.
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PMID:Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. 1259 34

Traditional control theories of muscle O2 consumption are based on an "inertial" feedback system operating through features of the ATP splitting (e.g., [ADP] feedback, where brackets denote concentration). More recently, however, it has been suggested that feedforward mechanisms (with respect to ATP utilization) may play an important role by controlling the rate of substrate provision to the electron transport chain. This has been achieved by activation of the pyruvate dehydrogenase complex via dichloroacetate (DCA) infusion before exercise. To investigate these suggestions, six men performed repeated, high-intensity, constant-load quadriceps exercise in the bore of an magnetic resonance spectrometer with each of prior DCA or saline control intravenous infusions. O2 uptake (Vo2) was measured breath by breath (by use of a turbine and mass spectrometer) simultaneously with intramuscular phosphocreatine (PCr) concentration ([PCr]), [Pi], [ATP], and pH (by 31P-MRS) and arterialized-venous blood sampling. DCA had no effect on the time constant (tau) of either Vo2 increase or PCr breakdown [tauVo2 45.5 +/- 7.9 vs. 44.3 +/- 8.2 s (means +/- SD; control vs. DCA); tauPCr 44.8 +/- 6.6 vs. 46.4 +/- 7.5 s; with 95% confidence intervals averaging < +/-2 s]. DCA, however, resulted in significant (P < 0.05) reductions in 1). end-exercise [lactate] (-1.0 +/- 0.9 mM), intramuscular acidification (pH, +0.08 +/- 0.06 units), and [Pi] (-1.7 +/- 2.1 mM); 2). the amplitude of the fundamental components for [PCr] (-1.9 +/- 1.6 mM) and Vo2 (-0.1 +/- 0.07 l/min, or 8%); and 3). the amplitude of the Vo2 slow component. Thus, although the DCA infusion lessened the buildup of potential fatigue metabolites and reduced both the aerobic and anaerobic components of the energy transfer during exercise, it did not enhance either tauVo2 or tau[PCr], suggesting that feedback, rather than feedforward, control mechanisms dominate during high-intensity exercise.
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PMID:Effects of dichloroacetate on VO2 and intramuscular 31P metabolite kinetics during high-intensity exercise in humans. 1275 81

Muscle fatigue, which is defined as the decline in muscle performance during exercise, may occur at different sites along the pathway from the central nervous system through to the intramuscular contractile machinery. Historically, both impairment of neuromuscular transmission and peripheral alterations within the muscle have been proposed to be involved in the development of fatigue. However, according to the more recent studies, muscle energetics would have a key role in this process. Intramyoplasmic accumulation of inorganic phosphate (P(i)) and limitation in ATP availability are frequently proposed as the causative factors of fatigue development. Although attractive, these hypotheses have been elaborated on the basis of experimental results obtained in vitro and their physiological relevance has never been clearly demonstrated in vivo. In that context, non-invasive methods such as 31-phosphorus magnetic resonance spectroscopy ((31)P MRS) and electromyographic (EMG) recordings have been employed to understand both metabolic and electrical aspects of muscle fatigue under physiological condition. The main results of these studies are reviewed in the present paper.
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PMID:Non-invasive investigations of muscular fatigue: metabolic and electromyographic components. 1465 76

Fatigue and impairment mobility are frequent problems in multiple sclerosis (MS). Despite its enormous potential, in vivo (1)H MRS of skeletal muscles for MS patients is a largely unexplored field. One fundamental question remains unanswered: whether MS can cause observable proton metabolite changes. High quality two-dimensional in vivo (1)H MRS reveals that the spectral pattern of total creatine (tCr) and trimethyl ammonium (TMA) of soleus muscles of MS patients can be distinctively different from that of healthy volunteers, and in vivo (1)H MRS of skeletal muscles has a potential to become a useful tool in MS study.
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PMID:Spectral pattern of total creatine and trimethyl ammonium in multiple sclerosis. 1506 40

Investigations of back muscle fatigue are important for understanding the role of muscle strain in the development of low back pain. The aim of this contribution is to review the two main techniques used for in vivo investigations of metabolic and electrophysiological changes, namely magnetic resonance phosphorous spectroscopy ((31)P MRS) and surface electromyography (SEMG), and to report some of our recent results on simultaneous measurements using these techniques during isometric back-muscle contraction in volunteers. Since it appears that electrophysiological and metabolic factors are simultaneously involved in the processes of fatigue and muscle recovery during load application, simultaneous acquisition of complete information is quite promising for obtaining new insights into the metabolic origin of electrophysiological changes or vice versa. Performing these measurements simultaneously, however, is more intricate owing to the occurrence of signal artifacts caused by mutual signal interferences of both techniques. Besides these mutual disturbances, further experimental difficulties are related to spatial limitations within the bore of clinical whole-body high-field magnetic resonance (MR) systems (1.5 T) and the sensitivity of MR measurements to motion-induced artifacts. Our own experimental results are presented, and problems that occur using both techniques simultaneously, as well as possibilities to resolve them, are discussed. The results shed light on the interrelation of electrophysiological and metabolic changes during fatigue of the back muscle while performing an exercise.
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PMID:Investigations of back muscle fatigue by simultaneous 31P MRS and surface EMG measurements. 1715 65

Carnosine (beta-alanyl-l-histidine) is present in high concentrations in human skeletal muscle. The ingestion of beta-alanine, the rate-limiting precursor of carnosine, has been shown to elevate the muscle carnosine content. We aimed to investigate, using proton magnetic resonance spectroscopy (proton MRS), whether oral supplementation with beta-alanine during 4 wk would elevate the calf muscle carnosine content and affect exercise performance in 400-m sprint-trained competitive athletes. Fifteen male athletes participated in a placebo-controlled, double-blind study and were supplemented orally for 4 wk with either 4.8 g/day beta-alanine or placebo. Muscle carnosine concentration was quantified in soleus and gastrocnemius by proton MRS. Performance was evaluated by isokinetic testing during five bouts of 30 maximal voluntary knee extensions, by endurance during isometric contraction at 45% maximal voluntary contraction, and by the indoor 400-m running time. beta-Alanine supplementation significantly increased the carnosine content in both the soleus (+47%) and gastrocnemius (+37%). In placebo, carnosine remained stable in soleus, while a small and significant increase of +16% occurred in gastrocnemius. Dynamic knee extension torque during the fourth and fifth bout was significantly improved with beta-alanine but not with placebo. Isometric endurance and 400-m race time were not affected by treatment. In conclusion, 1) proton MRS can be used to noninvasively quantify human muscle carnosine content; 2) muscle carnosine is increased by oral beta-alanine supplementation in sprint-trained athletes; 3) carnosine loading slightly but significantly attenuated fatigue in repeated bouts of exhaustive dynamic contractions; and 4) the increase in muscle carnosine did not improve isometric endurance or 400-m race time.
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PMID:beta-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. 1769 Jan 98

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 pHi 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 (1H 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 1H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo.
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PMID:Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy. 1802 75

Metabolism of the colonic mucosa of patients with ulcerative colitis (UC; n=31) and Crohn's disease (CD; n=26) and normal mucosa (control, n=26) was investigated using in vitro high-resolution proton magnetic resonance spectroscopy. Of the 31 UC patients, 20 were in the active phase and 11 were in the remission phase of the disease. Out of 26 CD patients, 20 were in the active phase, while 6 were in the remission phase of the disease. Twenty-nine metabolites were assigned unambiguously in the perchloric acid extract of colonic mucosa. In the active phase of UC and CD, significantly lower (P<or=.05) concentration of amino acids (isoleucine, leucine, valine, alanine, glutamate and glutamine), membrane components (choline, glycerophosphorylcholine and myo-inositol), lactate and succinate were observed compared to normal mucosa of controls. Patients in the active phase of UC and CD also showed increased level of alpha-glucose compared to normal mucosa. Altered level of metabolites indicates decreased protein and carbohydrate metabolism, thereby decreased energy status and deterioration of mucosa integrity during chronic inflammation. In the remission phase of UC and CD, the concentration of most of the metabolites was similar to controls except for lower values of lactate, glycerophosphorylcholine and myo-inositol in UC and Lac in CD. Formate was significantly lower in patients with the active phase of UC compared to patients with the active phase of CD, suggesting the potential of in vitro MRS in the differentiation of these two diseases.
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PMID:Metabolism of the colonic mucosa in patients with inflammatory bowel diseases: an in vitro proton magnetic resonance spectroscopy study. 1859 42

Although citrulline malate (CM; CAS 54940-97-5, Stimol) is used against fatigue states, its anti-asthenic effect remains poorly documented. The objective of this double-blind study was to evaluate the effect of oral ingestion of CM on a rat model of asthenia, using in situ (31)Phosphorus magnetic resonance spectroscopy ((31)P-MRS). Muscle weakness was induced by intraperitoneal injections of Klebsiella pneumoniae endotoxin (lipopolysaccharides at 3 mg/kg) at t(0) and t(0)+24 h. For each animal, muscle function was investigated strictly non-invasively before (t(0)-24 h) and during (t(0)+48 h) endotoxemia, through a standardized rest-stimulation-recovery protocol. The transcutaneous electrical stimulation protocol consisted of 5.7 min of repeated isometric contractions at a frequency of 3.3 Hz, and force production was measured with an ergometer. CM supplementation in endotoxemic animals prevented the basal phosphocreatine/ATP ratio reduction and normalized the intracellular pH (pH(i)) time-course during muscular activity as a sign of an effect at the muscle energetics level. In addition, CM treatment avoided the endotoxemia-induced decline in developed force. These results demonstrate the efficiency of CM for limiting skeletal muscle dysfunction in rats treated with bacterial endotoxin.
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PMID:Beneficial effects of citrulline malate on skeletal muscle function in endotoxemic rat. 1903 44


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