Arthritis research & therapy
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Arthritis Res. Ther. · Jan 2005
Comparative StudyCatabolic stress induces expression of hypoxia-inducible factor (HIF)-1 alpha in articular chondrocytes: involvement of HIF-1 alpha in the pathogenesis of osteoarthritis.
Transcription factor hypoxia-inducible factor (HIF)-1 protein accumulates and activates the transcription of genes that are of fundamental importance for oxygen homeostasis - including genes involved in energy metabolism, angiogenesis, vasomotor control, apoptosis, proliferation, and matrix production - under hypoxic conditions. We speculated that HIF-1alpha may have an important role in chondrocyte viability as a cell survival factor during the progression of osteoarthritis (OA). The expression of HIF-1alpha mRNA in human OA cartilage samples was analyzed by real-time PCR. ⋯ Our findings in human OA cartilage show that HIF-1alpha expression in OA cartilage is associated with the progression of articular cartilage degeneration. Catabolic-stresses, IL-1beta, and oxidative stress induce the expression of HIF-1alpha in chondrocytes. Our results suggest an important role of stress-induced HIF-1alpha in the maintenance of chondrocyte viability in OA articular cartilage.
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Arthritis Res. Ther. · Jan 2005
Comparative StudyNatural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome.
Macrophage activation syndrome (MAS) has been reported in association with many rheumatic diseases, most commonly in systemic juvenile rheumatoid arthritis (sJRA). Clinically, MAS is similar to hemophagocytic lymphohistiocytosis (HLH), a genetic disorder with absent or depressed natural killer (NK) function. We have previously reported that, as in HLH, patients with MAS have profoundly decreased NK activity, suggesting that this abnormality might be relevant to the pathogenesis of the syndrome. ⋯ There was a profound decrease in the proportion of circulating CD56bright NK cells in three sJRA patients, a pattern similar to that previously observed in MAS and HLH. In conclusion, a subgroup of patients with JRA who have not yet had an episode of MAS showed decreased NK function and an absence of circulating CD56bright population, similar to the abnormalities observed in patients with MAS and HLH. This phenomenon was particularly common in the systemic form of JRA, a clinical entity strongly associated with MAS.
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Arthritis Res. Ther. · Jan 2005
Comparative StudyHypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents.
In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latter, rather than the pain, might explain the HPA results. ⋯ After adjusting for levels of psychological distress, the association between chronic widespread pain and post-stress cortisol scores remained, albeit slightly attenuated. This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group. Although some aspects of the altered function are related to the psychosocial factors measured, we conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress.
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Arthritis Res. Ther. · Jan 2005
CommentOpioids for non-operable osteoarthritis and soft-tissue rheumatism.
Reviews of oral opioid trials have shown that many side-effects need to be considered when treating patients with non-operable osteoarthritis and soft-tissue problems. European and American guidelines recommend their use with or without paracetamol. The controversy surrounding the use of non-steroidal anti-inflammatory drugs/cyclo-oxygenase-2 inhibitors is limiting physician and patient choices. There is a great need for alternative medication or ways of using current compounds.
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Arthritis Res. Ther. · Jan 2005
ReviewPrevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids.
Adverse events of opioids may restrict their use in non-cancer pain. Analysis of the incidence of common adverse events in trials conducted in non-cancer pain has usually been limited to opioids used to treat severe pain according to the WHO three-step ladder. To examine the incidence of common adverse events of opioids in non-cancer pain, a systematic review and meta-analysis of information from randomised trials of all opioids in non-cancer pain was undertaken. ⋯ A substantial proportion of patients on opioids (22%) withdrew because of adverse events. Because most trials were short, less than four weeks, and because few titrated the dose, these results have limited applicability to longer-term use of opioids in clinical practice. Suggestions for improved studies are made.