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)

Protein kinase C (PKC) has a critical role in several signal transduction pathways, and is involved in renal cancer pathogenesis. Bryostatin-1 modulates PKC activity and has antitumour effects in preclinical studies. We conducted a multicentre phase II clinical trial in patients with advanced renal cancer to determine the response rate, immunomodulatory activity and toxicity of bryostatin-1 given as a continuous 24 h infusion weekly for 3 out of 4 weeks at a dose of 25 mug m(-2). In all, 16 patients were recruited (11 males and five females). The median age was 59 years (range 44-68). Patients had been treated previously with nephrectomy (8) and/or interferon therapy (9) and/or hormone therapy (4) and/or radiotherapy (6). Eight, five and three patients had performance statuses of 0, 1 and 2, respectively. A total of 181 infusions were administered with a median of 12 infusions per patient (range 1-29). Disease response was evaluable in 13 patients. Three patients achieved stable disease lasting for 10.5, 8 and 5.5 months, respectively. No complete responses or partial responses were seen. Myalgia, fatigue, nausea, headache, vomiting, anorexia, anaemia and lymphopenia were the commonly reported side effects. Assessment of biological activity of bryostatin-1 was carried out using the whole-blood cytokine release assay in six patients, two of whom had a rise in IL-6 levels 24 h after initiating bryostatin-1 therapy compared to pretreatment values. However, the IL-6 level was found to be significantly lower at day 28 compared to the pretreatment level in all six patients analysed.
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PMID:A multicentre phase II trial of bryostatin-1 in patients with advanced renal cancer. 1456 10

Cancer-related fatigue (CRF) is a prevalent and distressing symptom experienced by patients during cancer therapy. One proposed mechanism for the development of fatigue is the increased secretion of proinflammatory cytokines and/or the development of anemia. The major purpose of this pilot study was to investigate the levels of fatigue and cytokines during radiation therapy and determine whether there was a correlation between the two. A secondary purpose was to explore the relationships among hemoglobin values, cytokines, and fatigue. Participants included 15 women diagnosed with uterine cancer, who received curative external radiation therapy. Fatigue was assessed by a self-report instrument (Multidimensional Fatigue Inventory [MFI-20]) and hemoglobin and cytokines (Il-1, Il-6, and TNF-alpha) were measured before, during, and after radiotherapy. The degree of fatigue increased during radiotherapy without a significant change in IL-1, IL-6, or TNF-alpha levels. There was no significant correlation between changes in general fatigue and the changes in IL-1 and TNF-alpha. There was a significant negative correlation between the change in IL-6 and general fatigue. The hemoglobin levels did decrease significantly during radiotherapy, but there was no significant correlation between general fatigue and hemoglobin after 3 weeks of therapy or after the completion of therapy. In conclusion, pelvic radiotherapy in women with uterine cancer is associated with increased fatigue. There were no significant relationships between anemia or cytokine levels and fatigue. The pathogenesis of fatigue during radiation therapy remains to be elucidated.
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PMID:Levels of fatigue compared to levels of cytokines and hemoglobin during pelvic radiotherapy: a pilot study. 1473 21

The aim of the study was to characterise the profile and clinical correlates (arthritis, rash, and fatigue) of cytokines, chemokines, and other mediators in symptomatic acute parvovirus B19 infection. Serum was examined from cases of acute B19 infection (as defined by serum anti-B19 IgM positivity) (n = 84), and in normal persons (n = 43) for B19 markers (serum B19 antibodies and DNA), rheumatoid factor (RF), and antinuclear antibody (ANA). A panel of cytokines/chemokines was measured in duplicate using the Bioplex Protein Array system (BioRad Hemel Hempstead, UK). These included interleukin-1 beta (IL-1 beta), IL-4, IL-5, IL-6, IL-8, IL-13, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), macrophage chemoattractant protein-1 (MCP-1), granulocyte-monocyte colony stimulating factor (GM-CSF), transforming growth factor-beta1 (TGF-beta 1), endothelin-1 (ET-1), and neopterin. Acute symptomatic infection was characterised by specific IgG positivity (83%), serum B19 DNA positivity (96%), and raised levels of IL-4, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, GM-CSF, TGF-beta 1, and ET-1. Patients with acute B19-associated arthritis were found to have lower levels of IL-6, TNF-alpha, and GM-CSF than patients without arthritis, while those with rash had lower levels of TGF-beta 1. It is concluded that cytokine levels following acute symptomatic infection with parvovirus B19 indicate a state of immune activation. The profile of circulating mediators may provide insights into the possible pathogenesis of particular clinical manifestations of this infection.
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PMID:Circulating cytokines and chemokines in acute symptomatic parvovirus B19 infection: negative association between levels of pro-inflammatory cytokines and development of B19-associated arthritis. 1525 81

Mental fatigue, with decreased concentration capacity, is common in neuroinflammatory and neurodegenerative diseases, often appearing prior to other major mental or physical neurological symptoms. Mental fatigue also makes rehabilitation more difficult after a stroke, brain trauma, meningitis or encephalitis. As increased levels of proinflammatory cytokines are reported in these disorders, we wanted to explore whether or not proinflammatory cytokines could induce mental fatigue, and if so, by what mechanisms.It is well known that proinflammatory cytokines are increased in major depression, "sickness behavior" and sleep deprivation, which are all disorders associated with mental fatigue. Furthermore, an influence by specific proinflammatory cytokines, such as interleukin (IL)-1, on learning and memory capacities has been observed in several experimental systems. As glutamate signaling is crucial for information intake and processing within the brain, and due to the pivotal role for glutamate in brain metabolism, dynamic alterations in glutamate transmission could be of pathophysiological importance in mental fatigue. Based on this literature and observations from our own laboratory and others on the role of astroglial cells in the fine-tuning of glutamate neurotransmission we present the hypothesis that the proinflammatory cytokines tumor necrosis factor-alpha, IL-1beta and IL-6 could be involved in the pathophysiology of mental fatigue through their ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons, thereby attenuating glutamate transmission. To test whether our hypothesis is valid or not, brain imaging techniques should be applied with the ability to register, over time and with increasing cognitive loading, the extracellular concentrations of glutamate and potassium (K+) in humans suffering from mental fatigue. At present, this is not possible for technical reasons. Therefore, more knowledge of neuronal-glial signaling in in vitro systems and animal experiments is important.In summary, we provide a hypothetic explanation for a general neurobiological mechanism, at the cellular level, behind one of our most common symptoms during neuroinflammation and other long-term disorders of brain function. Understanding pathophysiological mechanisms of mental fatigue could result in better treatment.
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PMID:On the potential role of glutamate transport in mental fatigue. 1552 5

Aramid fibers from aromatic polyamide group are plastic materials with high mechanical resistance to breaking, small elongation and low mass. They have obtained numerous technical usage for products carrying high mechanical forces and resistance to consumption. Application of aramid in alloplasty would satisfy the grafts with high mechanical resistance. However, the biological influence and biostability of aramid is unknown and univocal. Research of the degree of biocompatibility of aramid fibres in comparison with commonly used polyester fibres with known and accepted biological reaction was the purpose of the study. The research included in the first phase: physicochemic properties, hemolytic action, cytotoxity degree, intracutaneous reactivity of aqueous extracts, in the second phase: estimation of tissue reaction after implantation the early and distant period, estimation of systemic and local induction of proinflammatory cytokines IL-1beta ad IL-6 after implantation. In physicochemic studies of aqueous extracts from fibers proper electric conductivity and dry residue were determined. The research of toxic action was carried out on frozen sperm of a bull estimating the survival time of sperm cells in the tested aqueous extracts. The estimation of hemolytic was conducted on human erythrocytes according to the method based on photometric measurement of blood supernatant and aqueous extracts. The research of irritating action measured with the changes of colour and size reaction after intracutaneous injection of aqueous extracts was carried out on rabbits. The research of the local reaction of soft tissue after implanting of aramid and polyester fibers into back muscles and into the peritoneal cavity was carried on 90 rats. Estimation was performed in early period, that is to 90th, and distant period, that is to the 360th day after implantation. The estimation of the local reaction of cartilaginous tissue was performed on 24 rabbits after implantation on 60, 90, 180, 270 and 360 days of aramid and polyester fibers into xiphoid process of sternum. The quantitative microscopic estimation of the local reaction of tissue after implantation of fibers was performed using punctual estimation of tissue reaction. The research of proinflammatory cytokines IL-1beta and IL-6 induction after implantation of aramid and fibers into peritoneal cavity was performed on 85 mice Balb/c. the level IL-1beta and IL-6 was determined in the serum of peripheral blood of mouse and in peritoneal fluid in 3rd, 7th, 14th and 21st day after implantation. The results were compared with control of operative and spontaneous production of proinflammatory cytokines in non-operated animals. A rubber medical drain constituted the control of the tested cytokines induction. The determinations were made with ELISA method. The tests of resistance to biocorrosion in electronic scanning microscope were performed after implantation of fibers into peritoneal cavity of rats for 180 and 360 days. Biostability of mechanical properties of fibers after remaining for 360 days in the application of the tested breaking force in the knot and in the dynamic system of cyclic strain of fibers (with strength 20N and 1Hz). In the tests of aqueous extracts from fibers comparative pH (aramid--6.42 and polyester 6.35), four-time higher proper electric conductivity (aramid 45.5; polyester 11.0) and five-time higher-dry mass of residue after vaporization of extracts from aramid fibers in comparison with polyester fibers (aramid--10.4 mg, polyester--2.1 mg) were observed. In biological tests of aqueous extracts toxic, hemolytic or irritating action was not observed. The local reaction soft tissues after implantation of aramid and polyester fibers was similar. Macroscopically it was characterized with producing on the third day thin, transparent membrane which in distant period, was whitish, thicker and strongly connected with the implanted fibers and surrounding tissues. In the microscopic tests the reaction was characterized with a short-lasting exudative phase less intense around the aramid fibers and a proliferating phase led to producing a capsule from newly created areolar tissue sharply separated from muscles undergoing collagenization in the cicatrization phase. The produced connective tissue capsule from the side of the graft both around aramid and polyester had the cellular character with the presence of single giant multinucleated cells till the 360th day after implantation. From the side of the muscles the connective tissue streak had more dense character and in distant period consisted mainly of collagenous fibers with hyalinization features. The reaction of cartilaginous tissue after implantation both kinds of fibers from the 90th to the 360th day was similar. It was characterized with producing cartilaginous tissue and locally fibrous tissue with a large amount of intercellular substance. Connective tissue showed hyalinization features and was transformed into cartilaginous tissue. According to the punctual estimation of reaction the tested fibers caused minimal reaction. In the testes of level of proinflammatory cytokines IL-1beta and IL-6 their constant presence on the low level in the serum of mouse blood and in the peritoneal fluid was observed. aramid fibers did not induce an increase of the level IL-1beta and IL-6, whereas polyester fibers in the 3rd day after surgery stimulated locally their moderate increase. The influence of surgery on the local induction IL-1beta and IL-6 was statistically essential in the 3rd day. The rubber medical drain was strong inductor of mediators of inflammation IL-1beta and IL-6. In physiocomechanical fatigue-testing and in SEM in the period to 360th day after implantation, biocorrosion of aramid and polyester fibers was not observed. The value of breaking force of aramid fibers was twice higher and the resistance to cyclic fatigue was over two hundred times higher in comparison to polyester fibers. Those differences were statistically significant (p < 0.001). On the basis of the performed tests it is possible observed that aramid fibers cause minimal tissue reaction compared with the observed one around polyester fibers, they do not cause local nor systemic stimulation of proinflammatory cytokines IL-1beta and IL-6. aramid fibers show essentially higher statistic and dynamic mechanical resistance in comparison with polyester fibers; they not undergo biocorosion and they can be useful to increase mechanical resistance of medical materials or as independent biomaterial resistant to high mechanical forces.
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PMID:[Estimation of biocompatibility of fibers with large mechanical resistance]. 1563 Nov 54

The progressive deterioration in nutrition status frequently seen in cancer patients is often referred to as cancer cachexia. Unlike starvation, in which fat stores from adipose are depleted and protein is spared from skeletal muscle, neither fat nor protein is spared in cachexia. Cachexia affects nearly half of cancer patients, causing the clinical manifestations of anorexia, muscle wasting, weight loss, early satiety, fatigue, and impaired immune response. Cachexia does not only impede the response to chemotherapy but also is a major cause of morbidity and mortality. According to clinical studies, increasing caloric intake does not necessarily reverse cachexia. The pathophysiology of cachexia involves more complex mechanisms than simply caloric deficiency. The process appears to be mediated by circulating catabolic factors, either secreted by the tumor alone or in concert with host-derived factors, such as tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-1 and IL-6), interferon (IFN-y), and leukemia inhibitory factor (LIF). The successful reversal of this process will require in-depth knowledge of the mechanisms involved, which will then enable the development of effective pharmacologic interventions that may not only improve quality of life, but more importantly, improve survival among cancer patients.
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PMID:The cancer cachexia syndrome: a review of metabolic and clinical manifestations. 1620 77

To the ill patient with diabetes, the behavioral symptoms of sickness such as fatigue and apathy are debilitating and can prevent recuperation. Here we report that peripherally administered insulin-like growth factor 1 (IGF-1) attenuates LPS-dependent depression of social exploration (sickness) in nondiabetic (db/+) but not in diabetic (db/db) mice. We show that the insulin/IGF-1 mimetic vanadyl sulfate (VS) is effective at augmenting recovery from sickness in both db/+ and db/db mice. Specifically, peak illness was reached at 2 h for both VS and control animals injected with LPS, and VS mice recovered 50% faster than non-VS-treated animals. Examination of the mechanism of VS action in db/+ mice showed that VS paradoxically augmented peritoneal macrophage responsivity to LPS, increasing both peritoneal and ex vivo macrophage production of IL-1beta and IL-6 but not TNF-alpha. The effects of VS in promoting recovery from sickness were not restricted to LPS, because they were also observed after direct administration of IL-1beta. To explore the possibility that VS impairs immune-to-brain communication via vagal afferents, the vagally mediated satiety-inducing effects of cholecystokinin 8 were tested in db/+ mice. Cholecystokinin decreased food intake in saline-injected mice but not in VS-treated mice. VS also inhibited LPS-dependent up-regulation of IL-1beta and IL-6 mRNA in the brain, while increasing by 50% the cerebral expression of transcripts of the specific antagonist of IL-1 receptors IL-1RA and IL-1R2. Taken together, these data indicate that VS improves recovery from LPS-induced sickness by blocking vagally mediated immune-to-brain signaling and by up-regulating brain expression of IL-1beta antagonists.
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PMID:Inhibition of vagally mediated immune-to-brain signaling by vanadyl sulfate speeds recovery from sickness. 1621 19

An 80-year-old man presented to the internist with fever, fatigue and leukocytosis up to 66.8 x 10(3)/microl. Although a chronic myelogenous leukemia was initially suspected, he was diagnosed as metastatic bone marrow tumor with bone marrow necrosis from primary prostate cancer on the basis of the clinical and pathological findings. The serum concentrations of IL-6 and TNF-alpha were mildly elevated to 65.0 pg/ml and, 54.0 pg/ml respectively. It is probable that these humoral factors were partially responsible for the leukemoid reaction although other factors induced by the bone marrow necrosis with bone marrow metastasis of prostate cancer are also likely involved.
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PMID:Leukemoid reaction in association with bone marrow necrosis due to metastatic prostate cancer. 1629 25

Many cancer patients receiving chemotherapy experience fatigue, disturbed circadian rhythms, anorexia and a variety of dyspeptic symptoms including nausea. There is no animal model for this 'chemotherapy-related malaise' so we investigated the behavioural and molecular effects of a potent chemotherapeutic agent, cisplatin (CP, 6 mg/kg, i.p.) in rats. Dark-phase horizontal locomotor activity declined post-CP reaching a nadir on day 3 (P < 0.001), before recovering after 7 days. CP's effect was most marked in the late part (05.00-07.00) of the dark-phase. Food intake reached a nadir (P > 0.001) at 2 days, coincident with an increase in gastric contents (cisplatin 9.04+/-0.8 vs. saline 2.32+/-0.3 g; P < 0.001). No changes occurred in hypothalamic mRNA expression for AGRP, NPY, HCRT, CRH, IL-1, IL-6, TNFalpha, ABCG1, SLC6A4, PPIA and HPRT mRNA but tryptophan hydroxylase (TPH) mRNA was decreased (47%, P < 0.05) at day 21 post-CP. This shows that despite marked behavioural effects of cisplatin, only a discrete change (TPH) was found in hypothalamic mRNA expression and that occurred when the animals' behaviour had recovered. Findings are discussed in relation to the neuropharmacology of chemotherapy-induced malaise.
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PMID:Behavioural and hypothalamic molecular effects of the anti-cancer agent cisplatin in the rat: A model of chemotherapy-related malaise? 1644 63

Cytokines are glycoproteins that serve as chemical messengers between cells. They assist in the regulation of cell growth and repair and also have immune modulating properties. Cytokines play a role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress and aching. A review of the fibromyalgia literature and related studies suggest that IL-1, IL-6 and IL-8 are dysregulated in the syndrome. Therapies directed against these cytokines may be of potential importance in the management of fibromyalgia.
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PMID:Is there a role for cytokine based therapies in fibromyalgia. 1645 20


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