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)

In the adolescent population, fatigue is associated with somatic complaints, unrefreshing sleep, cognitive disturbances and symptoms of depression and anxiety. This pattern of symptoms resembles the one described in chronic fatigue syndrome (CFS). Since immunological alterations have been reported in CFS patients, we wondered whether also severely fatigued girls from a healthy population would show comparable alterations in psychological and immunological parameters. We tested this hypothesis in a longitudinal design, allowing a reliable assessment of the participants' characteristic immune status. Groups of severely fatigued (N=67) and non-fatigued (N=61) participants were selected. Severely fatigued girls reported more depressive symptoms, anxiety, reduced sleep quality, and somatic and CFS-related symptoms than non-fatigued participants across three measurements during one year (T1: spring, T2: autumn, T3: spring). In contrast, no group differences in mitogen-induced cytokine production or T-cell proliferation in vitro or in leukocyte subset counts were observed. Although absolute cytokine production and cell counts were affected by seasonal variation, the within-subject values, relatively to the rest of the participants, were fairly stable. Data from a small group of CFS patients (N=11) showed similarities in self-reported complaints between CFS patients and fatigued participants. Interestingly, CFS patients showed a distinct immune profile when compared to the severely fatigued or non-fatigued participants, i.e. increased levels of anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points analyzed. These results show that, although overlap in symptomatology between the general population and patients with CFS was observed, only CFS patients show a skewing of the cytokine balance towards an anti-inflammatory profile.
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PMID:Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents. 1754 55

It has been suggested that dysregulation of immune-to-brain communication plays a role in the biopsychological process underlying medically unexplained symptoms (MUS). Immune and non-immune stressors can both be involved in the activation of the central sickness-behavioural-system leading to complaints like malaise, pain and fatigue. We hypothesized increased pro-inflammatory and/or reduced anti-inflammatory cytokine activity to exist in MUS patients. Twenty-seven participants (4 male; 23 female) with heterogeneous MUS were compared with 27 healthy controls (6 male; 21 females). Blood samples were analysed for leukocyte subset cell counts, in vitro T-cell mitogen-stimulated cytokine production (IL-2, IL-4, IL-5, IL-6, IL-10, TNF-alpha and IFN-gamma) and in vitro monocyte cytokine release (IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha) in response to increasing concentrations of LPS. No significant group differences were found for any of the cytokines measured. One unexpected exception was an elevation in the number of circulating B and NK-cells in participants high on MUS. Nonetheless, no support was found for the hypothesized immunological dysregulation in peripheral blood leukocyte function of MUS patients.
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PMID:Heterogeneous medically unexplained symptoms and immune function. 1755 64

Chi-Shie-Shuang-Bu-An-Shen-Tang (CST), a traditional Chinese medicine, has long been used to stabilize one's spirit and treatment of body weakness caused by fatigue. In order to understand whether the CST possess the immunological function and effect of thermal processing on its activities, sterilized (SCST) and nonsterilized CST (NCST) extracts were orally administrated to BABL/c mice for 1 or 3 weeks as drinking water. The results showed that CST extract after sterilization at 121 degrees C for 15 min had higher immunological activities than nonsterilized CST. SCST revealed mitogenic effects on splenocyte stimulated by concanavalin A (Con A) and mediated the changes of total serum antibodies; production of IgG increased and IgE reduced. Among cytokines, secretion of IFN-gamma increased and IL-5 decreased, which fit in with the Th1 cell profile, however cytolytic activity of natural killer cells did not show any significant difference. Furthermore, the population of CD4(+) T cells in the mice spleen increased after oral administration of SCST for 3 weeks. These results suggest that SCST had the immunomodulatory effects which drove CD4(+) T cells into Th1 cells and had potential benefit to cope with CD4(+) T lymphopenia condition.
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PMID:Immunomodulatory effects of a traditional Chinese medicine, Chi-Shie-Shuang-Bu-An-Shen-Tang, on BALB/c mice. 1768 44

Idiopathic inflammatory myopathies (IIMs) are heterogeneous rheumatic disorders of unknown cause characterized by muscle weakness, inflammatory cell infiltrates, and major histocompatibility complex (MHC) class I expression on muscle fibers. The nonhistone nuclear protein alarmin high-mobility group box 1 protein (HMGB1) has been detected extranuclearly in muscle biopsies from patients with IIMs. We hypothesize that HMGB1 has a central role in the cause of muscle weakness, particularly in the early phases of IIMs. Experiments were performed on skeletal muscle fibers isolated from adult mice, which were exposed to recombinant interferon (IFN)-gamma or HMGB1. The myoplasmic free [Ca(2+)] was measured. Stimulation with IFN-gamma resulted in increased HMGB1 expression in muscle nuclei and the myoplasm. Exposure to HMGB1 induced a reversible up-regulation of MHC class I in the muscle fibers. However, HMGB1 exposure caused an irreversible decrease in Ca(2+) release from the sarcoplasmic reticulum during fatigue, induced by repeated tetanic contractions. HMGB1 and MHC class I were frequently colocalized in the myoplasm of muscle fibers in muscle biopsies from patients with early IIMs. However, HMGB1-expressing fibers outnumbered fibers expressing MHC class I. Our data indicate that HMGB1 could be an early inducer of skeletal muscle dysfunction in IIMs.
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PMID:Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional aspects in skeletal muscles of idiopathic inflammatory myopathies. 1983 64

Our preclinical work showed a dramatic synergy between interleukin-12 (IL-12) and trastuzumab for stimulation of natural killer cell cytokine secretion. We aimed to determine the safety profile of IL-12 when given in combination with trastuzumab and paclitaxel to patients with metastatic HER2-overexpressing cancers. Paclitaxel was given i.v. at 175 mg/m(2) every 3 weeks. Trastuzumab was given on day 1 each week (4 mg/kg initially and 2 mg/kg thereafter) in combination with injections of IL-12 on days 2 and 5 starting in cycle 2. This trial accrued 21 patients with metastatic HER2-positive tumors (breast, 7; colon, 6; esophagus, 4; stomach, 2; pancreas, 1; thyroid, 1). The IL-12 component was dose-escalated in cohorts of three patients. The dose-limiting toxicity was grade 3 fatigue at the 300 ng/kg dose level in two patients. The recommended phase II dose was 200 ng/kg administered s.c. There was one complete response in a patient with breast cancer, partial responses in 4 patients (breast, 2; esophageal, 2), and stabilization of disease lasting 3 months or greater (SD) in 6 other patients. All but one response occurred in patients with HER2 3+ disease. Two SD patients completed 1 year of therapy. Ten patients had progressive disease. There was increased activation of extracellular signal-regulated kinase in peripheral blood mononuclear cells and increased levels of IFN-gamma and several chemokines in patients with clinical benefit (complete response, partial response, or SD), but not in patients with progressive disease. IL-12 in combination with trastuzumab and paclitaxel therefore exhibits an acceptable toxicity profile and has activity in patients with HER2-overexpressing cancers.
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PMID:A phase I trial of paclitaxel and trastuzumab in combination with interleukin-12 in patients with HER2/neu-expressing malignancies. 1988 43

Ultra-high molecular weight polyethylene (UHMWPE) has been the most commonly used bearing material in total joint arthroplasty. Wear and oxidation fatigue resistance of UHMWPE are regarded as two important properties to extend the longevity of knee prostheses. The present study investigated the accelerated ageing of UHMWPE in hydrogen peroxide highly oxidative chemical environment. The sliced samples of UHMWPE were oxidized in a hydrogen peroxide solution for 120 days with their total level of oxidation (Iox) characterized by Fourier Transformed Infrared Spectroscopy (FTIR). The potential inflammatory response, cell viability and biocompatibility of such oxidized UHMWPE systems were assessed by a novel biological in vitro assay based on the secretion of nitric oxide (NO) by activated murine macrophages with gamma interferon (IFN-gamma) cytokine and lipopolysaccharide (LPS). Furthermore, macrophage morphologies in contact with UHMWPE oxidized surfaces were analyzed by cell spreading-adhesion procedure using scanning electron microscopy (SEM). The results have given significant evidence that the longer the period of accelerated aging of UHMWPE the higher was the macrophage inflammatory equivalent response based on NO secretion analysis.
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PMID:Macrophage Response to UHMWPE Submitted to Accelerated Ageing in Hydrogen Peroxide. 2072 21


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