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)

The clinical examinations covered 1710 women. The investigations were performed on 199 women with symptoms of menopause, who were selected and divided into two groups. The first control group (I) included 80 women employed in the Industrial Clothing Factory "Dana" in Szczecin, without contact with carbon disulphide. The second study group (II) comprised 119 women employed in the Synthetic Fibres Factory "Chemitex-Wiskord" and exposed chronically to carbon disulphide in concentration of 9.36-23.4 mg/m3. The microclimate conditions of the production halls in both groups were similar (Tab. 1). Menopause was present in 16.59% of women in the population chronically exposed to carbon disulphide, as compared with 8.05% in the normal population. Mean age at menopause in women of the first group was 48.1 years and 43.9 years in the second group. In the studied group of menopausal women retrospective estimation of menopausal and gestational cycles shows statistically significant increase in abortion and disorders of menstrual cycles (p < 0.001) (Tab. 2). The women chronically exposed to CS2 had significantly more frequently headaches, weight gain and loss of libido (p < 0.001). In the normal group fatigue, palpitations and hot flushes were found significantly more often (p < 0.001) (Tab. 4). The serum concentrations of estrone (p < 0.01), estradiol, progesterone, 17-hydroxyprogesterone were significantly decreased in women chronically exposed to CS2 (p < 0.001). No significant differences in the level of FSH or LH were noted between both groups (Tab. 3). The daily excretion of adrenaline and noradrenaline in urine concentrations of dopamine in plasma of women chronically exposed to CS2, was significantly lower (p < 0.001), but the serum concentrations of serotonin (Tab. 5), testosterone, dehydroepiandrosterone sulphate (DHAS) and prolactin in plasma were significantly higher (p < 0.001). No difference concerning the level in serum of dehydroepiandrosterone and beta-endorfine was found (Tab. 6). Significant negative linear correlations between serotonin and FSH (r = -0.45; p < 0.001), serotonin and daily excretion of adrenaline (r = -0.43; p < 0.01) or noradrenaline (r = -0.58; p < 0.001) were disclosed in the exposed group. In this group a positive correlation was noted between the concentration of serotonin and prolactin (r = 0.45; p < 0.001).
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PMID:[The effect of carbon disulphide on menopause, concentration of monoamines, gonadotropins, estrogens and androgens in women]. 947 21

This study investigated whether drug therapy explains why the concentration of arterial plasma catecholamines in patients who have received an orthotopic heart transplant (OHT) or coronary bypass and graft (CABG) is greater than in those with heart failure (HF). The results suggest that the differences in plasma catecholamine concentrations in these groups of patients could not be attributed to administration of any of the drugs studied here. An additional finding is that the use of aspirin is associated with a higher concentration of plasma noradrenaline, but not adrenaline. Patients who were taking aspirin also had a more positive mood, as rated by the Profile of Mood States; this was mainly because they had a lower fatigue score than did patients who were not taking this drug. In contrast, several agents (warfarin, Ca2+-channel blockers and 'mixed cardiac' drugs), which had no effects on catecholamine overspill, were linked with negative mood; this was expressed consistently as a higher tension score. These findings suggest that drugs which are administered for their effects in the periphery could also influence patients' psychological status. With the possible exception of aspirin, this does not involve changes in spillover of catecholamines in the periphery.
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PMID:Plasma catecholamines, pharmacotherapy and mood of subjects with cardiovascular disorder. 1051 81

We are the first to report clinical characteristics and circulatory and catecholamine responses to postural change in 44 children with instantaneous orthostatic hypotension (INOH). The symptoms include chronic fatigue, orthostatic dizziness, weakness, sleep disturbance, syncope or near syncope, headache, and loss of appetite. We divided the patients into two groups: group I (30 patients) had either a recovery time for mean arterial pressure of >25 s or a recovery time of >20 s with a 60% or greater decrease in mean arterial pressure at the initial decrease; group II (14 patients) had a prolonged reduction in systolic arterial pressure of > 15% during the later stage of standing (3-7 min) in addition to the criteria for group I. INOH was characterized by a marked reduction in blood pressure at the initial decrease (mean, -55/-27 mm Hg systolic/diastolic). Delayed recovery time of >60 s was found in 21 of 44 patients and orthostatic tachycardia (>35 beats per minute) in 20 of 44. Plasma noradrenaline responses were significantly lower in group I and II than in controls at 1 min of standing and were lower in group II at 5 min of standing. These results suggest that mechanisms responsible for INOH may depend on insufficient sympathetic activation during standing, possibly due to centrally mediated sympathetic inhibition, thus causing impairment of quality of life including school absenteeism. INOH is an important pathologic condition in children with complaints of orthostatic intolerance and can be an unrecognized cause of chronic fatigue. This condition can be identified by using a noninvasive beat-to-beat continuous blood pressure monitoring system.
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PMID:Instantaneous orthostatic hypotension in children and adolescents: a new entity of orthostatic intolerance. 1059 25

The lack of energy conservation in brown adipose tissue mitochondria when prepared by conventional methods was established in the 1960s and was correlated with the thermogenic function of the tissue. In order to observe energy conservation, two requirements had to be met: the removal of the endogenous fatty acids and the addition of a purine nucleotide. These two factors have been the essential tools that led to the discovery of the energy dissipation pathway, the uncoupling protein UCP1. The activity is regulated by these two ligands. Purine nucleotides bind from the cytosolic side of the protein and inhibit transport. Fatty acids act as seconds messengers of noradrenaline and increase the proton conductance. This review presents a historical perspective of the steps that led to the discovery of UCP1, its regulation, and our current view on its mechanism of transport.
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PMID:A history of the first uncoupling protein, UCP1. 1065 69

Sibutramine and Orlistat are suitable "supporting drugs" for use in patients trying to lose weight. Orlistat reduces the absorption of fat from the intestine by about one-third. Over the long term too, the weight loss achieved under Orlistat (9%) has been greater than that seen under placebo (6.5%). Increased fat losses via the stools are associated with side effects and abandonment of treatment. Sibutramine inhibits the uptake of serotonin and noradrenaline in the synaptic gap, thus enhancing the CNS effects of these two transmitters, and prolonging the sensation of satiety. The most common side effects of sibutramine are dry mouth, headache and fatigue. The effects of sibutramine on weight reduction are similar to those of orlistat. For both drugs, the indications have been defined, and in the case of sibutramine, interactions with other medications have to be taken into account.
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PMID:[How safe are the new obesity drugs? Indications and contraindications of orlistat and sibutramine]. 1072 44

The aim of the present study was to characterise the quantitative sweating response of the horse to beta2-adrenergic stimulation. The sweating responses of 6 horses to the randomised infusion of 8 different adrenaline concentrations (0.025, 0.05, 0.075, 0.1, 0.2, 0.4, 1.0 or 2.0 microg/kg bwt/min), was investigated. Sweating rate (SR) and skin temperature (TSK) on the neck (N) and gluteal region (G), and plasma adrenaline and noradrenaline concentrations were measured. Peak SR was approximately 15 (N) and approximately 9 g/m2/min (G) during infusion of both 1.0 and 2.0 microg/kg bwt/min adrenaline. Sweat produced per nmol/l plasma adrenaline peaked during the infusion of 0.075 microg/kg bwt/min adrenaline. Higher adrenaline infusion concentrations resulted in a progressive decrease in the amount of sweat produced per nmol/l plasma adrenaline and a plateau of 6 g/m2/(nmol/l) plasma adrenaline was reached for infusions between 1.0 and 2.0 microg/kg bwt/min. Peak SR were far lower than we have previously reported during exercise. There was no evidence of sweat gland fatigue or vasoconstriction during infusion, suggesting saturation of sweat gland beta2 receptors. We conclude that sweating in the horse is under dual control from a combination of hormonal and neural mechanisms.
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PMID:Quantification of the response of equine apocrine sweat glands to beta2-adrenergic stimulation. 1172 33

To evaluate whether occasional strong physical activity at moderate altitude for several consecutive days is acceptable in untrained middle-aged people, 10 men (age range, 46-59 years) underwent physical examinations before (control day, D0), during (D1-D8), and after 1 wk of leisure alpine skiing. With respect to D0, the resting concentration of plasma noradrenaline (NOR) increased transiently (p < 0.01) on D2 and then increased to a maximal value from D6-D8 (p < 0.01). There was no significant change in the concentration of adrenaline. Although maximal voluntary contraction of knee extensors diminished on D3 (P < 0.05), that of the digit flexors did not change. Heart rate (HR) and blood pressure at rest in the evening were always higher than control values except on D4 (forced rest). After the stay, there was a reduction in sympathetic activity. This was reflected by a return of NOR to its control value, a decrease in resting HR (64.2 [11.4] beats per minute [bpm]: control: 71.1 [10.1] bpm, P < 0.02), a tendency for triglyceride and insulin resistance to decrease, and a significant increase in alipoprotein A1/alipoprotein A2 (P < 0.01). Our results show that despite signs of fatigue on D3, the effects of physical activity that is relatively intense (HR > 70% maximal HR) together with mild hypoxia are well tolerated by untrained middle-aged men and that the controlled practice of downhill skiing may be accepted into a program to lower cardiovascular risk factors.
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PMID:Physiological effects of downhill skiing at moderate altitude in untrained middle-aged men. 1199 Jan 14

Norepinephrine (NE), a vital neurotransmitter in both the central and peripheral nervous systems, is synthesized by dopamine beta-hydroxylase (DBH) through the oxidation of dopamine (DA) to NE. DBH deficiency is a congenital disorder characterized by severe orthostatic hypotension, ptosis, and retrograde ejaculation. Biochemical features of the syndrome include elevated levels of dopamine, undetectable levels of DBH, undetectable tissue and circulating levels of NE and epinephrine. Molecular genetic analysis studies suggested that DBH deficiency is a Mendelian recessive disorder attributable to heterogenous mutations at the DBH locus. DBH deficiency has been treated effectively with L-threo-3,4-dihydroxyphenylserine (DOPS). DOPS is converted directly to NE through decarboxylation by L-aromatic amino acid decarboxylase (AADC), thereby bypassing DBH. Orthostatic intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, syncope, and postural tachycardia. Biochemical features may include plasma NE concentration that is disproportionately high in relation to sympathetic outflow, decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists. A subset of OI patients has pathophysiologic features that have been associated with a genetic polymorphism. The coding mutation, A457P, occurs in one of the alleles of norepinephrine transporter gene of a proband with OI and her family. Alpha-methyl dopa, beta blockers and clonidine, a partial agonist of alpha2-adrenoceptor that acts centrally to reduce sympathetic outflow and lower blood pressure, have been effective in the treatment of this condition. The identification of the genetic polymorphisms involved in the synthesis, transport, storage, and metabolism of the catecholamines may provide new insights into the diagnosis and management of autonomic, cardiovascular, endocrine and psychiatric disorders.
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PMID:The broader view: catecholamine abnormalities. 1210 62

Fibromyalgia is a chronic pain disorder of which other clinical features, such as persistent fatigue and disordered sleep, may be a secondary consequence. The initial pharmacological approach to treating the disorder is the management of the pain. Tricyclic antidepressants are the most effective drugs in use so far, especially when administered in combination with other therapies (e.g., selective serotonin re-uptake inhibitors), which suggests modulation of the neurotransmitters serotonin and noradrenaline. The effectiveness of amitriptyline and related tricyclic antidepressants, however, is consistent with the involvement of mechanisms, such as potassium channel modulation and NMDA receptor antagonism, in addition to or in place of the modulation of monoamine neurotransmitters. Investigation of the importance of each of the pharmacological properties of amitriptyline and related molecules in the management of fibromyalgia could provide clues for the rational design of new drugs.
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PMID:Tricyclic antidepressants and fibromyalgia: what is the mechanism of action? 1238 4

The purpose of this study was to compare the sympathoadrenergic and metabolic responses following 30 s of maximal high intensity cycle ergometry exercise when cradle resistive forces were derived from total-body mass (TBM) or fat-free mass (FFM). Increases in peak power output (PPO) and pedal velocity were recorded when resistive forces reflected FFM (953 +/- 114 W vs 1020 +/- 134 W; 134 +/- 8 rpm vs 141 +/- 7 rpm ; P < 0.05). No differences were observed between mean power output (MPO), fatigue index (FI%), work done (WD) or heart rate (HR) when the TBM and FFM protocols were compared. There were no differences between the TBM and FFM protocols for adrenaline (A), noradrenaline (NA) or blood lactate concentrations ([La-]B) recorded at rest, immediately post or 24 h post exercise. However, increases in blood concentrations of A and NA (P < 0.05) were recorded for both the TBM and FFM protocol immediately post exercise. Significant correlations (P < 0.05) were recorded between PPOs, immediate post- exercise NA and [La-]B for both the TBM and FFM protocols. [La-]B levels were also significantly elevated (P < 0.01) immediately post exercise for both the TBM and FFM protocols. The results from this study suggest that greater peak power outputs are obtainable with no subsequent differences in neurophysiological or metabolic stress as determined by plasma A, NA and [La-]B concentrations when resistive forces reflect FFM and not TBM during loading procedures. The findings also indicate that immediate post exercise concentrations return to resting levels 24 h post exercise.
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PMID:Catecholamine responses to high intensity cycle ergometer exercise: body mass or body composition? 1464 73


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