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)

Varying reactions of the vegetative nerve system to various point combinations (for example: vomiting, dizziness, diarrhea, urge to urinate, fatigue or drowsiness, headache), especially to the needling of Tai Chong (Li 3), induced us to perform biochemical studies before and after acupuncture treatment. A group of children and a group of adults were studied. The material studied was urine and blood; from the children, urine only. The following were determined in the urine: indolacetic acid, 5-hydroxy-indol-3-acetic acid, homovanillic acid, and vanillic-mandelic acid; in the blood, tyrosine and tryptophan (free and bound). Individual points with wide influence (He Gu = LI 4; Zu San Li = St 36; Tai Chong = Li 3) and their combination with generally effective points were tested. The needling of Tai Chong especially showed a clear increase in indolamine metabolism. Isolated increases in metabolites of catecholamine metabolism could be correlated with the patient's increased physical activity after acupuncture. Noteworthy is the observation that no significant chemical reactions were evident if local reactions to the needling no longer appeared at the end of a series of acupuncture treatments.
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PMID:Manipulation of neurotransmitters by acupuncture (?) (A preliminary communication). 23 99

The anti-convulsive action of dipropyl acetic acid (Convulex) was tested in 21 patients with grandmal seizures (GM) and/or temporal lobe attacks (TL), or with Jacksonian epilepsy. Patients were chosen according to a negative selection system. Results showed that in GM and TL seizures, Convulex constitutes an important addition to the battery of anticonvulsives available today. Action was more potent in GM than in TL attacks. Toxic effects are slight. Treatment had to be discontinued in two patients -- once because of cerebellar symptoms and once because of crowded incidence of seizures. In two cases the patients gained weight. Occasional gastrointestinal complaints disappeared when antacids were administered. No changes were observed with reference to blood count, or to hepatic or renal function. Fatigue set in only when treatment was combined with barbiturates and disappeared again when pre-medication was reduced. Five patients showed an improved state of mind (activation and better communication with others); this psychological action may be considered an additional advantage. Since the action of barbiturates and hydantoins is potentiated by Convulex, pre-medication may be reduced --provided Convulex therapy alone does not seem adequate. Hence, trial treatment with Convulex may also be recommended in those patients who are successfully controlled with barbiturates and hydantoins,but whose daily work schedule is impaired due to fatigue.
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PMID:[The effect of dipropyl acetic acid (Convules) in epileptic adults with a high frequency of seizures]. 82 58

In both trained and untrained rats, exercise increased the plasma concentration ratio of aromatic amino acids to branched-chain amino acids which might favour entry of the aromatic amino acids into the brain. Exercise in trained rats did not change the brain concentration of 5-hydroxytryptamine but increased that of 5-hydroxyindole acetic acid. Exercise in the untrained rat increased the concentration of brain tryptophan and that of 5-hydroxytryptamine but that of 5-hydroxyindole acetic acid was unchanged. The increased concentration of 5-hydroxytryptamine in untrained rats might be involved in central fatigue.
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PMID:Effect of sustained exercise on concentrations of plasma aromatic and branched-chain amino acids and brain amines. 242 44

We have conducted a Phase I and pharmacological study of flavone acetic acid, one of a series of novel flavonoids. The drug was administered i.v. weekly for 4 weeks, with a 2-week rest and then repeated. Flavone acetic acid was given initially in a 1-h infusion, but at the 3900-mg/m2 dose level, the infusion time was lengthened to 3 h. A total of 31 patients were treated with 9 different dose levels, ranging from 330 to 6400 mg/m2. Dose-limiting toxicity was acute hypotension that began after about one-third of each drug dose had been infused and rarely lasted more than a few minutes after the infusion was discontinued. In addition, subjective fatigue and asthenia causing unacceptable patient discomfort was dose limiting. A significant side effect noted that was not dose limiting was diarrhea during the infusion. This drug exhibited nonlinear pharmacokinetic behavior. Plasma levels exceeded 300 micrograms/ml during the infusion at the maximally tolerated dose. After the infusion ended the principal half-life was about 2 h. In 24-h urine collections 27% of the flavone acetic acid dose was recovered as intact drug and an additional 37% was recovered as a metabolite. The maximally tolerated dose determined in this study is 6400 mg/m2 given i.v. over 3 h.
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PMID:Phase I and clinical pharmacology study of intravenous flavone acetic acid (NSC 347512). 316 43

Pharmacological properties of "Reiousan", a crude drug preparation consisting of bezoar and ginseng, were studied. The hypotensive effect on spontaneously hypertensive rat, inhibition of platelet aggregation, acetic acid-induced writhing, stress ulcer, CCl4 and d-galactosamine-induced hepatic injury, and facilitation of recovery from neuroparalysis and muscular fatigue, protective effect on anoxic brain damages, antipyretic effect, and facilitation of learning in aged mice were observed after administration of "Reiousan". It was suggested that bezoar and ginseng act synergistically in causing the hypotensive effect, acetic acid-induced writhing and drug-induced hepatic injury, and protection from anoxic brain damages and muscular fatigue.
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PMID:[Pharmacological studies of "reiousan" which contains bezoar and ginseng]. 337 97

A single-dose, double-blind study included a total of 196 patients with neurologic pain. The subjects were subdivided into five groups and treated with alpha-methyl-4-(2-thienylcarbonyl) benzene acetic acid (suprofen, Suprol) 400 mg; suprofen 200 mg acetylsalicylic acid (ASA) 650 mg; ASA 650 plus codeine 60 mg; and placebo. The population was homogeneous as to age, sex, and body weight. About 95% of the patients rated the intensity of pain severe prior to treatment. The clinical effect was appreciated by investigator and patients after up to 6 h following administration of the single dose. It was demonstrated that the active substances all were significantly superior to placebo in all criteria tested. Statistical analysis of the parameters investigated revealed the following order of effectiveness of the test medications: Suprofen 400 and 200, respectively, = ASA 650 + codeine 60 greater than ASA 650 greater than placebo. The final overall patients appreciation of effectiveness showed good to very good results in 97.4% of the patients on suprofen 400; 65% of those on suprofen 200; 72.5% of those on ASA 650 + codeine 60; 13.5% of those on ASA 650; and 7.5% of those on placebo. During the treatment 26 patients experienced adverse reactions; of these, 18 subjects on ASA 650 + codeine 60 complained of fatigue or somnolence as the side effect experienced most frequently.
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PMID:[Experience with suprofen for acute and chronic pain in neurologic practice]. 635 9

Discussion focuses on 3 of the most promising lines of current contraceptive research -- gossypol, vaccines, and GnRH analogues, considering both the scientific principles behind their development and the ethical implications of their future application. 1) Chinese scientists confirmed the antispermatogenic effects of cotton seed oil in animal experiments; in 1971 the active agent was identifed as gossypol. The 1st clinical trials were initiated in 1972 and thus far more than 8000 volunteers have been treated with a variety of gossypol preparations including native gossypol, gossypol acetic acid, and gossypol formic acid. The conventional contraceptive regime involves a loading dose of 20mg/day for 60-75 days followed by a maintenance dose of 50 mg/week. An undisclosed number of pregnancies have occurred. Reversibility seems to be a major problem since around 10% of men remain infertile after the cessation of gossypol intake. Other hazards of gossypol ingestion include fatigue, gastrointestinal disorders, decreased libido, dizziness, and in 0.75% of cases hypokalaemic paralysis. The question arises as to whether it is right that 8000 Chinese men have been administered gossypol while ignorance concerning the toxicity and effectiveness of this compound prohibits its approval by any other government west of the Himalayas. 2) The development of a contraceptive vaccine would be appropriate to the needs of the Third World, the population of which will have doubled in 34 years to 6.6 billion. The advantages of vaccines are that they can be administered by paramedical personnel, they should provide a long-lasting protection against pregnancy, and they can take advantage of the service infrastructure existing in most developing countries for the administration of vaccines against disease. The zona pellucida and human chorionic gonadotropin (hCG) are not the only candidates for an antifertility vaccine but they are the most promising. A 3rd but less attractive possibility is to immunize against sperm antigens. Possibly the most feasible sperm antigen for contraceptive development is a specific lactate dehydrogenase, isozyme, LDH-X. Both gossypol and vaccines will most likely find their ultimate application in developing countries where factors such as cost, ease of administration, and duration of action are paramount. 3) Progress has also recently been made with an alternative method more oriented toward the Western market. This approach involves the chronic administration of powerful analogues of the hypothalamic releasing hormone, GnRH, modified to contain a D-aminoacid in position 6 and, in some formulations, an ethylamide group in position 10 to prolong the half-life of the agonist "in vivo." Recent clinical trials have noted some variability in the responsiveness of individuals to chronic treatment with GnRH analogues, administered in the form of a nasal spray. The optimum protocol for administering GnRH has yet to be determined.
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PMID:New techniques in contraception: gossypol, vaccines and GnRH analogues. 636 84

1. In the cat anaesthetized with sodium pentobarbitone, electrical activity was recorded from single unmyelinated sensory fibres innervating the cornea. 2. Based on their response to mechanical (calibrated aesthesiometer), chemical (10 mM acetic acid or 616 mM NaCl) and thermal (cooling from 35 to 5 degrees C; heating to 51 degrees C) stimuli, corneal unmyelinated fibres were classified as polymodal (71%) or 'cold' nociceptors (29%). 3. Polymodal units responded to mechanical indentation of the cornea and developed fatigue after repeated stimulation. They were excited by temperatures over 37 degrees C and exhibited sensitization to repeated heating. 4. Corneal polymodal units were also activated by topical application of 10 mM acetic acid and hypertonic NaCl (616 mM). Capsaicin (0.33 mM) elicited a discharge of impulses that was followed by inactivation to mechanical, chemical and thermal stimuli. 5. 'Cold' nociceptors had small receptive fields, preferentially located at the periphery of the cornea. They were excited by small temperature decreases of the corneal surface in a range between 30 and 8 degrees C, but were not responsive to noxious heat. 6. 'Cold' nociceptors encoded temperature changes between 35 and 23 degrees C. The discharge was proportional to the velocity of the temperature drop; sustained temperatures were not signalled by changes in static frequency values. 'Cold' nociceptive fibres responded to hypertonic NaCl (616 mM) and weakly to 10 mM acetic acid. Capsaicin (0.33 mM) first excited and then inactivated 'cold' nociceptors. 7. Thermoreceptive fibres were found in the episclera. They fired in bursts and responded to small temperature decreases, but were insensitive to irritant chemical and capsaicin.
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PMID:Response of sensory units with unmyelinated fibres to mechanical, thermal and chemical stimulation of the cat's cornea. 825 27

Pharmacological manipulation of brain serotonergic [5-hydroxytryptamine (5-HT)] activity affects run time to exhaustion in the rat. These effects may be mediated by neurochemical, hormonal, or substrate mechanisms. Groups of rats were decapitated during rest, after 1 h of treadmill running (20 m/min, 5% grade), and at exhaustion. Immediately before exercise rats were injected intraperitoneally with 1 mg/kg of quipazine dimaleate (QD; a 5-HT agonist), 1.5 mg/kg of LY 53857 (LY; a 5-HT antagonist), or the vehicle (V; 0.9% saline). LY increased and QD decreased time to exhaustion (approximately 28 and 32%, respectively; P < 0.05). At fatigue, QD animals had greater plasma glucose, liver glycogen, and muscle glycogen concentrations but lower plasma free fatty acid concentration than did V and LY animals (P < 0.05). In general, plasma corticosterone and catecholamine levels during exercise in QD and LY rats were similar to those in V rats. Brain 5-HT and 5-hydroxyindole-3-acetic acid concentrations were higher at 1 h of exercise than at rest (P < 0.05), and the latter increased even further at fatigue in the midbrain and striatum (P < 0.05). Brain dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were higher at 1 h of exercise (P < 0.05) but were similar to resting levels at fatigue. QD appeared to block the increase in DA and DOPAC at 1 h of exercise, and LY prevented the decrease in DA and DOPAC at fatigue (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. 836

An earlier study conducted by the authors indicated that body potassium levels were partially maintained in male langur monkeys treated with gossypol acetic acid (5 mg) and potassium salt supplementation. The present study sought to confirm the persistence of hypokalemia at two higher dosage levels (7.5 and 10 mg/animal/day) and assess the role of exogenous potassium salt (0.50 and 0.75 mg/animal/day) in preventing gossypol-induced hypokalemia. The two dosages of highly purified gossypol acetic acid were administered alone and in combination with potassium chloride for 180 days. All regimens produced severe oligospermia and azoospermia. However, monkeys who received gossypol alone showed significant potassium deficiency with signs of fatigue at both doses. On the other hand, animals receiving gossypol acetic acid and potassium salt supplementation showed normal serum potassium with a less significant increase in urine potassium level during treatment. Also noted was a gradual but significant elevation in the activity of serum transaminases. All parameters returned to normal 150-180 days after treatment termination. The hypokalemic effect documented in this study with gossypol alone may be due to renal leakage and gastrointestinal disturbances.
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PMID:Gossypol-induced hypokalemia and role of exogenous potassium salt supplementation when used as an antispermatogenic agent in male langur monkey. 940 7


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