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)

Rabbits were immunized versus either an acetylcholinesterase- or a cholinergic receptor-rich fraction isolated from the electric organ of Torpedo marmorata. In both groups of animals we obtained a production of specific antibodies detected by immunodiffusion without cross reaction for the two antigens. Only rabbits immunized with the receptor-rich fraction developed a progressive flaccid paralysis, which affected first the leg muscles, progressively the neck muscles and eventually the respiratory muscles. The paralysis lasted in several animals up to 20 days. Eserine reversed the paralysis only in the first days but was ineffective in the "chronic" stage of the disease. In these animals high frequency stimulation of sciatic nerve induced a rapid failure of the responses of the anterior tibialis muscle while the muscle responded normally to a direct stimulation. A period of rest allowed a complete recovery of the muscle from fatigue. Tetani did not evoke the post-tetanic potentiation. Abnormalities, such as lymphocytic infiltration, fibers atrophy and necrosis, smearing and widening of Z line were sometimes present in muscles of Cho-R-immunized rabbits. In ACh-E immunized animals the neuromuscular transmission and the muscle morphology were similar to that of normal animals. Glycogen, ATP, cytochrome C oxidase, phosphorylases and acetylcholinesterase did not change significantly in the muscles of the immunized animals, while a large increase of cholineacetyltransferase activity was present. Red blood cell acetylcholinesterase showed a particularly high activity in ACh-E-immunized animals. The autoimmune paralysis induced in Cho-R-immunized rabbits may be a useful experimental model for further studies on human myasthenia gravis.
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PMID:Immunization of rabbits with secific components of postsynaptic membrane. Acetylcholinesterase and cholinergic receptor. 18 67

In rats with third-degree burns, the blood glucose level increased remarkably, with a concomitant suppression of insulin secretion from the pancreas after an oral glucose load. The energy charge (ATP + 1/2 ADP/ATP + ADP + AMP) levels of the kidney decreased to 0.659 as compared with 0.858 of controls at 8 hr after the burn (p less than 0.001). The phosphorylative activity of the kidney mitochondria fell to one third of controls at 8 hr after the burn (p less than 0.001), and that of heart mitochondria decreased to approximately 70% (p less than 0.005); the fall in liver and brain was less remarkable. The decrease in mitochondrial phosphorylative activity was accompanied by a reduction in the respiratory control ratio, P/O ratio, and state 3 respiration. The concentrations of cytochrome a(+a3) in the kidney mitochondria decreased to 69.9% of controls at 8 hr after the burn (p less than 0.001), those of cytochrome b to 82.6%, and those of cytochrome c + c1 to 75.3% (p less than 0.001). The decreased energy charge and oxidative phosphorylation of the kidney in burned rats were remarkably restored by subcutaneous administration of insulin. It is suggested that a reduction in insulin secretion from the pancreas may play an important role in initiating an impairment of adenine nucleotide and mitochondrial metabolism of the kidney.
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PMID:Changes in adenine nucleotide and mitochondrial metabolism of the kidney of burned rats and their relation to insulin. 89 1

A thirty-two year old female had chronic progressive external ophthalmoplegia (CPEO), exertional fatigue, dysarthria, dysphagia, and bilateral hearing impairment. Histochemical stains, obtained from the right vastus lateralis, showed ragged-red fibers and wide-spread abnormalities in the number, size, and the structure of mitochondria under electronomicroscopic examination. A biochemical analysis showed a low activity of NADH-cytochrome C reductase, NADH dehydrogenase and a normal activity of succinate cytochrome C reductase and cytochrome C oxidase. This data suggests a specific defect in the NADH dehydrogenase of complex I (NADH CoQ reductase). We believe that this is the first biochemically defined mitochondrial myopathy reported in Taiwan and provides additional evidence for the existence of biochemical heterogeneity in mitochondrial disorders of CPEO.
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PMID:Chronic progressive external ophthalmoplegia with NADH-CoQ reductase deficiency: report of a case. 132 93

In principle, target inactivation analysis provides a means of determining the molecular weights (Mr) and states of aggregation of proteins in native environments where they are functionally active. We applied this irradiation technique to the rat liver microsomal membrane proteins: cytochrome b5, epoxide hydrolase, flavin-containing monooxygenase, NADH-ferricyanide reductase, NADPH-cytochrome P-450 reductase, and seven different forms of cytochrome P-450. Catalytic activities, spectral analysis of prosthetic groups, and sodium dodecyl sulfate-polyacrylamide electrophoresis/peroxidase-coupled immunoblotting were used to estimate apparent Mr values in rat liver microsomal membranes. Except in one case (cytochrome P-450PCN-E), the estimated Mr corresponded most closely to that of a monomer. Purified cytochrome P-450PB-B, NADPH-cytochrome P-450 reductase and epoxide hydrolase were also subjected to target inactivation analysis, and the results also suggested monomeric structures for all three proteins under these conditions. However, previous hydrodynamic and gel-exclusion results clearly indicate that all three of these proteins are oligomeric under these conditions. The discrepancy between target inactivation Mr estimates and hydrodynamic results is attributed to a lack of energy transfer between monomeric units. Thus, while P-450PCN-E may be oligomeric in microsomal membranes, target inactivation analysis does not appear to give conclusive results regarding the states of aggregation of these microsomal proteins.
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PMID:Target inactivation analysis applied to determination of molecular weights of rat liver proteins in the purified state and in microsomal membranes. 311 94

In the cirrhotic rat liver induced by phenobarbitone and carbon tetrachloride, adenylate energy charge, mitochondrial oxidative phosphorylation, and respiratory enzyme concentrations were studied along with serum albumin concentrations. Cytochrome a (+a3) concentrations of the liver increased with the severity of cirrhosis and were negatively correlated with the ATP-synthesizing ability per unit of cytochrome a (+a3). These changes were associated with the decrease in hepatic energy charge. Such decreased energy charge may be responsible for the decreased serum albumin level in the cirrhotic rat. It is suggested that such falls in hepatic energy charge may be one of the most important factors contributing to the decreased functional reserve of cirrhotic patients.
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PMID:Adenylate energy charge and cytochrome a (+a3) in the cirrhotic rat liver. 609 79

Temporal and site correlation of local cerebral blood flow (1-CBF), tissue redox state, energy metabolism, tissue pH, and cerebral electrophysiological activity in induced cerebral ischemia was performed in rats in an effort to obtain helpful clues for the management of occlusive cerebrovascular disease. CBF decreased acutely in both the embolized and nonembolized hemispheres but returned toward normal in 5 minutes. However, total cerebral oxidative metabolism remained depressed throughout the 30-minute observation period despite improved perfusion. The change in CBF correlated with the development and resolution of tissue acidosis, which was maximal 3 minutes after embolization but became alkaline after 30 minutes, possibly due to accumulation of sodium lactate. Oxidized form of nicotinamide-adenine dinucleotide and cytochrome a,a3 quickly became reduced in the ischemic core, but a tardyspontaneous postischemic tissue perfusion resulted in their hyperoxidation. The CBF-metabolism uncoupling as well as postischemic hyperoxidation of the electron transport system, which is associated with accumulation of pyruvate and lactate, probably resulted from stagnation of electron flow at the entrance to the mitochondrial respiratory processes. Seizures could not account for these results, as paroxysmal changes in the EEG usually appeared only in the nonembolized hemisphere and were not dependent upon lack of energy. These studies confirm that metabolic failure may persist in ischemic tissue despite adequate reperfusion, which may, in fact, contribute to tissue damage through hyperoxidation.
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PMID:The dissociation of cerebral blood flow, metabolism, and function in the early stages of developing cerebral infarction. 743 71

Mitochondrial cytopathies are due to genetic anomalies in the oxidative phosphorylation enzymes (excepting Krebs cycle, pyruvate and certain other mitochondrial enzymes). Recently discovered, these diseases have a characteristic heterogeneous clinical expression because of the ubiquitous nature of this intracellular organelle. We observed a case in a 16-year-old girl who had cytochrome C oxidase deficiency. The child was born to non-consanguinous parents and had a healthy brother. The first manifestation of the disease was a systolic murmur heard at the age of 4 years. Progressively, exertion dyspnoea, lipothymia with cyanose led to the first echocardiography at 8 years revealing non-obstructive cardiomyopathy. Functional inadaptation of cardiac performance worsened requiring various symptomatic treatments. At the age of 16, the symptomatology included lower limb fatigue and the diagnosis of a metabolic disease was entertained. Phosphorylase A and B activity and phosphokinase activity were normal. High lactic acid levels after exertion suggested a mitochondrial enzyme deficiency. The diagnosis of cytochrome C oxidase deficiency was confirmed by spectrophotometric and polarographic assay of mitochondria from a peripheral muscle biopsy. Treatment with riboflavin, ascorbic acid, factor P, menadione, carnitine and iron sulfate has currently provided some symptomatic improvement. In patients with unexplained cardiomyopathy, the diagnosis of mitochondrial cytopathy should be entertained if oxidoreduction potentials (lactate/pyruvate ratio) are perturbed. The diagnosis is confirmed by enzyme studies of fresh muscle mitochondria. Currently therapeutic prospects are at best very poor. Genetic counselling may be advisable.
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PMID:[Hypertrophic cardiomyopathy caused by cytochrome-oxidase deficiency]. 782 67

Congestive heart failure is often associated with skeletal muscle abnormalities that contribute to early fatigue and acidosis. Up to the present time, however, the mechanisms responsible for these changes are unclear. Myocardial infarctions were produced by coronary ligation in adult Sprague-Dawley rats. At 20 weeks, 10 control rats, and 15 animals with heart failure [defined by elevated LVEDP (26.1 +/- 3.1 v 2.5 +/- 0.5 mmHg) and RV hypertrophy (300 +/- 21 g v 158 +/- 9 mg)] underwent in vivo measurements of total body, and soleus total protein and myosin heavy chain (MHC) synthesis by [3H]leucine constant infusion. Soleus muscle was also analysed for protein content, and MHC isoenzyme content by SDS-PAGE. Northern blotting also was used to determine levels of the mRNA's encoding type I, IIa, IIb, and IIx MHC, alpha-skeletal actin, COX III, SDH and GAPDH. Soleus muscles in heart failure rats were smaller than controls (112 +/- 6 v 126 +/- 5 mg) and the degree of atrophy was significant when corrected for body mass (0.38 +/- 0.02 v 0.46 +/- 0.02 mg/g. P = 0.007). Although there was no significant difference in plasma leucine flux (an index of whole-body protein synthesis), soleus muscle total and MHC synthesis was reduced in heart failure animals. Whereas the Type I MHC isoenzyme (beta MHC) was the only MHC detected in the soleus of control animals, type II MHC isoenzyme comprised 11.8 +/- 3.1% of the MHC in the heart failure group. Furthermore, steady-state mRNA levels encoding beta MHC were significantly depressed in the heart failure rats, where those encoding Types IIb and IIx MHC were increased. Steady-state mRNA levels of alpha-skeletal actin, cytochrome C oxidase (COX III) and succinate dehydrogenase (SDH) were also significantly depressed. This animal model of chronic heart failure is associated with quantitative and qualitative alterations in skeletal muscle gene expression that are similar to those reported in skeletal muscle of patients with chronic heart failure. The altered phenotype and impaired metabolic capacity may contribute to exercise intolerance in CHF.
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PMID:Alterations in skeletal muscle gene expression in the rat with chronic congestive heart failure. 887 78

The effects of chronic, around the clock, low-frequency electrostimulation on the respiratory chain activity and cytochrome content of freshly isolated mitochondria were evaluated in rabbit skeletal muscle before and after 30 days of continuous or cyclical electrostimulation using a totally implantable system and a training programme now used in humans. The respiratory activity measured in state III increased strongly after electrostimulation. The efficiency of the respiratory chain increased significantly after electrostimulation but the activity of complex [(reduced nicotinamide adenine dinucleotide dehydrogenase) did not increase. The amount of cytochromes a and a3, b562, and c and c1 increased clearly after electrostimulation. The respiratory activity rate of mitochondria obtained after continuous electrostimulation was apparently higher than after cyclical electrostimulation. Chronic uninterrupted low-frequency electrostimulation, using a clinical training programme, induces an increase in mitochondrial respiratory chain activity in purified mitochondria of skeletal muscle. These changes are the basis of induced resistance to fatigue in fast-to-slow muscle conversion by chronic electrostimulation.
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PMID:Fast-to-slow muscle conversion by chronic electrostimulation: effects on mitochondrial respiratory chain function with possible implications for the gracilis neosphincter procedure. 911 26

A 54-year-old male liver transplant patient received mibefradil, a novel T-type calcium channel blocker, as antihypertensive treatment while he was on tacrolimus. He subsequently developed dizziness and fatigue of gradual onset as well as shoulder muscle ache. In addition, reversible impairment of renal function occurred with an increase in creatinine and potassium levels. Monitoring of tacrolimus levels, which had been in the desired range (5-8 ng/ml) until recently, revealed an increase to toxic level of 54 ng/ml. After discontinuation of mibefradil, tacrolimus levels returned to the normal range and all symptoms and clinical changes were reversible. Mibefradil and tacrolimus both are metabolized through the cytochrome--P-450 pathway. We suspect that drug interaction due to competitive inhibition of tacrolimus metabolism by mibefradil was responsible for these toxic effects. Therefore, special caution is recommended when administering tacrolimus with other drugs that carry the potential for pharmakokinetic interaction.
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PMID:Tacrolimus toxicity due to drug interaction with mibefradil in a patient after liver transplantation. 1054 98


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