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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies were designed to determine whether the previously demonstrated [24] enhancement of neuromuscular function by MSH/ACTH 4-10 is due to peptide action on the neurogenic and/or myogenic elements involved. The nerve muscle unit studied incorporated the sciatic nerve and its branches, and the extensors digitorum longus and brevis in the hypophysectomized rat, in situ. Parameters investigated included muscle action potentials (MAP) and muscle contractions (MC) during 30 min of stimulation (supramaximal, 10/sec; 0.05 msec duration). Resting membrane potentials and miniature endplate potential (mepp) characteristics were investigated in situ at neuromuscular junctions in the extensor digitorum brevis. Hypophysectomy results in markedly deleterious changes in neuromuscular function which can be partially alleviated by the administration of ACTH 4-10 (0.01 microgram/kg). This dosage increases MAP and MC amplitudes and reduces fatigue. Higher dosages (1.0 microgram/kg) have a depressing effect on these parameters. The facilitatory actions of ACTH 4-10 are abolished when the muscle is stimulated directly or stimulated through the peripheral stump of the cut nerve. ACTH 4-10 increases mepp frequency (a presynaptic event) but does not affect postsynaptic characteristics as measured by the resting membrane potential. These results indicate that MSH/ACTH 4-10 influences skeletal muscle function through a neurotropic action mediated by spinal motoneurons. Changes in the central excitatory state of higher motor centers are possibly involved.
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PMID:Neurotropic action of MSH/ACTH 4-10 on neuromuscular function in hypophysectomized rats. 626 56

The adrenocorticotropin fragment ACTH/MSH 4--10 (0.1 ug/kg IP) effectively modulates the neuromuscular responses of 9 to 15 day old rats. Muscle (extensor digitorum longus) contraction amplitude is increased, fatigue is delayed and muscle half-relaxation time is shortened during 20 min of continuous in situ stimulation of a branch of the deep peroneal nerve (square wave shocks 10 Hz, duration 0.5 msec, strength supermaximal). No effect on contraction time is seen. There is no facilitation or change in any contraction parameter in rats older than two weeks (16 to 40 days) indicating that these older animals, like normal adult rats, are unaffected by the peptide. Immature rats, however, are even more sensitive than hypophysectomized adult rats [29] to the ameliorative action of ACTH/MSH 4-10. This early sensitivity to ACTH/MSH 4--10 corresponds to important developmental changes occurring in nerve and muscle during the most critical period in postnatal development, the first two weeks.
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PMID:Neuromuscular response of the immature rat of ACTH/MSH 4--10. 627 Jun 35

The effects of the ACTH 1-17 analogue (100 micrograms i.m.) as a function both of time of day (7.00, 14.00 and 21.00 h) and season (winter versus summer) were determined on a set of physiological variables: urinary 17-hydroxycorticosteroids, oral temperature, grip strength (right and left hands), peak expiratory flow and self - rated fatigue. Six young healthy males took part in the study in January-February 1980 and June-July 1981. They were synchronized with a diurnal activity from 7.00 to midnight and a nocturnal rest. Urine was collected every 3 to 4 hours, at fixed clock hours over 72 h (winter) and 48 h (summer). There was a one week interval between each ACTH test or placebo control. Variables were measured according to the same schedule. 24 h urinary 17-OHCS excretion was maximum for ACTH injected at 7.00 in winter and 14.00 in summer, and the minimum occurred after ACTH given at 21.00. The highest peak of urinary 17-OHCS was found after ACTH at 7.00 both in winter and in summer. It is likely that the maximal stimulation of glucocorticoid secretion occurs when ACTH is administered around the beginning of the activity span. Both in winter and summer the injection of ACTH at 7.00 was followed by the greatest decrease in self-rated fatigue (24 h mean) and the largest increase (24 h mean) both in grip strength and peak expiratory flow (bronchial patency) in comparison with other times of ACTH administration (14.00 and 21.00 h).
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PMID:Circadian and seasonal changes in ACTH-induced effects in healthy young men. 631 51

A certain number of HIV-infected patients (about 17% in our series) manifest symptoms of cortisol resistance--weakness, weight loss, hypertension, chronic fatigue and intense mucocutaneous melanosis--symptoms which are also typical of Addison's disease. The diagnosis of cortisol resistance is determined through the increased plasma and urinary cortisol values and limited increases in ACTH values. Compared with patients with primary glucocorticoid resistance, AIDS patients have no symptoms of mineral-corticoid or androgen excess, only of glucocorticoid deficiency at target tissues. Mononuclear leukocytes from these patients show receptor changes which consist of an increased receptor number and decreased receptor affinity for glucocorticoids. They also show defective glucocorticoid-induced inhibition of [3H]thymidine incorporation. Glucocorticoid-resistant AIDS patients have a characteristic persistent increase in interferon-alpha production. The inverse correlation between plasma values of interferon-alpha and the receptor affinity for glucocorticoids clearly suggests that interferon production is regulated by the glucocorticoid receptor: the smaller the glucocorticoid effect on lymphocyte cells is, the greater interferon production is. Owing to the antiviral effect of interferon-alpha, it is possible that glucocorticoid-resistant AIDS patients have greater defences against viral infection than other AIDS patients. As interferon-alpha is melanogenetic, its increased production may also explain the intense skin pigmentation found in patients with the glucocorticoid-resistance syndrome.
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PMID:The syndrome of acquired glucocorticoid resistance in HIV infection. 781 Dec 21

Familial glucocorticoid resistance (FGR) is a rare hereditary disorder characterized by hypercortisolism and the absence of stigmata of Cushing's syndrome. The inability of glucocorticoids to exert their effects on target tissues is compensated for by increases in circulating corticotropin (ACTH) and cortisol, the former causing excess secretion of both adrenal androgens and adrenal steroid-biosynthesis intermediates with salt-retaining activity. There is considerable variability in the clinical presentations of FGR ranging from asymptomatic, to isolated chronic fatigue and to hypertension with or without hypokalemic alkalosis or to hyperandrogenism, or both. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men it may lead to infertility and in children to precocious puberty. The reported molecular defects in FGR, such as point mutations and a microdeletion of the glucocorticoid receptor (GR) gene, cause partial resistance by, respectively, compromising the function of the GR or decreasing its intracellular concentration in glucocorticoid target tissues. Complete glucocorticoid resistance is believed to be incompatible with life in humans. Hence, the glucocorticoid resistance cases reported have been partial and of variable degree. The extreme variability in the clinical manifestations of the disorder can, additionally, be explained by differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps by different biochemical defects of the glucocorticoid receptor, causing selective resistance of certain glucocorticoid responses in specific tissues. Isolated tissue-resistance from a somatic mutation of the GR in a corticotropinoma from a patient with Nelson's syndrome was also found, suggesting that this may be a mechanism of tumorigenesis. There is additional evidence that defects of GR function can appear surreptitiously in a variety of clinical conditions, suggesting that glucocorticoid resistance in humans may be involved in the pathogenesis and/or clinical picture of a plethora of disease states, of which FGR is the archetype.
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PMID:Glucocorticosteroid resistance in humans. Elucidation of the molecular mechanisms and implications for pathophysiology. 782 90

Familial glucocorticoid resistance results from the partial inability of glucocorticoids to exert their effects on their target tissues throughout the organism. The condition is associated with compensatory elevations of circulating ACTH and cortisol, with the former causing excess abnormal secretion of steroids with mineralocorticoid and androgen activity. The manifestations of glucocorticoid resistance vary from asymptomatic to chronic fatigue, to varying degrees of hypertension and/or hypokalaemic alkalosis and hyperandrogenism. The latter can be manifest in women as acne, hirsutism, menstrual irregularity, oligoanovulation and infertility, in men as infertility, and in children as precocious puberty. Different molecular defects of the highly conserved glucocorticoid receptor gene, altering its concentration and functional characteristics, appear to cause the syndrome of familial glucocorticoid resistance. Depending on the molecular defect, this syndrome is transmitted by an autosomal dominant or recessive trait. There are recent suggestions that non-generalized forms of glucocorticoid resistance may exist, resulting in autoimmune-inflammatory phenomena or psychiatric manifestations.
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PMID:Hormone-nuclear receptor interactions in health and disease. Glucocorticoid resistance. 798 Aug 39

Tourette's syndrome (TS) is a complex inherited neuropsychiatric disorder that is characterized by multiple motor and phonic tics. Stress-related fluctuations in symptom severity and medication responsiveness are common, and patients often report that tics are worsened by fatigue, emotional trauma, and anxiety. We examined the effects of lumbar puncture (LP) stress on plasma adrenocorticotropin (ACTH) and cortisol, urinary catecholamines, and self- and clinician ratings of anxiety in 13 medication-free TS patients and 10 normal controls, ages 17 to 41 years. The TS patients secreted significantly more ACTH than the normal controls in response to the stress of the lumbar puncture. Compared to the controls the TS patients had significantly greater postLP mean and postLP peak ACTH levels. The TS patients also excreted significantly more norepinephrine in the 20 hr preceding the lumbar puncture and reported higher levels of anxiety before and during the procedure than the controls. In addition, urinary norepinephrine excretion of the TS patients was significantly correlated with clinician ratings of tic severity. The results were not related to current levels of depression and anxiety. Taken together, these findings suggest that a subset of TS patients may be characterized by heightened reactivity of the hypothalamic-pituitary-adrenal axis and related noradrenergic sympathetic systems.
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PMID:Enhanced stress responsivity of Tourette syndrome patients undergoing lumbar puncture. 808 Sep 1

A case of systemic lupus erythematosus (SLE) complicated with hypopituitarism after steroid pulse therapy is reported. A 46-years-old-female with a history of SLE starting in 1975 was admitted to our hospital in February 1991 for lupus nephritis. Steroid pulse therapy, 1000 mg methyl-prednisolone for 3 successive days as one therapy unit, was administered. Proteinuria improved remarkably, however, general fatigue and headache appeared 2 weeks after initiation of therapy. Endocrinological examination revealed hypopituitarism including the levels of TSH, FSH, GH and ACTH. The secretion of FSH and LH gradually improved after replacement therapy of dried thyroid. MRI examination of the brain revealed an empty sella. It is known that pituitary tumor, cerebrovascular accident and autoimmune lymphocytic hypophysitis cause hypopituitarism. In this case, it is unlikely that the pulse therapy may be responsible for the infarction of the anterior pituitary artery furthermore, there has been no articles describing such incidence after steroid pulse therapy. This case may be indicative of a very rare case in which the empty sella might have been exacerbated by the pulse therapy in the causation of hypopituitarism.
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PMID:[Hypopituitarism associated with empty sella after steroid pulse therapy in a patient with SLE]. 814 29

We reported a case of Addison's disease, caused by adrenal tuberculosis. The patient was female, seventy four years old. She complained cough and body weight loss. She complained cough from June, 1989, but her home doctor didn't take care of her symptoms. September 1989, she felt appetite loss, and easy fatigue, so her home doctor suspected her disease as pulmonary tuberculosis, so he introduced our hospital, and she admitted. When she admitted, her chest roentogenogram revealed bIII2. Sputum smear examinations were negative. Laboratory data on admission, we observed slightly eosinophilia, severe iron deficiency anemia, and accenturation of blood sedimentation rate. Immediately after admission, she complained nausea, vomiting, coldness, and powerless. On 25 days after admission, she lost her senses suddenly, and her blood pressure fell 5 days after, she fell in shock state, too. We found out her blood sugar data was 29. After blood examinations, we found out that ACTH was high, cortisole, 17-KS, 17-OHCS were low. So we thought she got acute hypoadrenocorticism. We found her abdominal CT revealed calcification in her right adrenal gland. We diagnosed her disease as Addison's disease caused by adrenal tuberculosis so we began to give prednisolone, 7.5 mg per day. After giving, her state made better. We thought her disease as Addison's disease caused by adrenal tuberculosis, revealed acute hypoadrenocorticism.
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PMID:[A case of Addison's disease caused by adrenal tuberculosis, and revealed acute hypoadrenocorticism]. 826 25

In an acute trial, three different dosages (60, 300, and 600 micrograms) of the endocrinologically inert but behaviorally active corticotropin 4-9 (ACTH4-9) fragment ebiratide were given to three patients with clinically probable Alzheimer's disease and five patients with a major depressive episode who were psychomotorly retarded. The drug was given intravenously in a double-blind, placebo-controlled, crossover design, and cognitive as well as psychopathologic assessments were carried out predrug and postdrug treatment. In summary, no adverse effect of the ACTH fragment was detected. In this explorative study, none of the patients improved cognitively, as measured by neuropsychologic testing. However, all patients, regardless of underlying disorder, reported a decrease of the feeling of tiredness or loss of energy, respectively. They felt more vigorous and alert. This occurred after any of the three doses of ACTH4-9, but not after placebo. In concert with reports from other studies, it is concluded that the ACTH4-9 fragment ebiratide may have activating properties in humans. However, given acutely, it does not seem to have antidementia or antidepressive efficacy.
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PMID:Behavioral effects of a synthetic corticotropin 4-9 analog in patients with depression and patients with Alzheimer's disease. 839 47


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