Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatigue, a complex symptom, significantly affects the quality of life in many patients with systemic lupus erythematosus (SLE). To understand this phenomenon, 23 patients with SLE and fatigue were studied. Standardized tests of depression (NIMH), fatigue, exercise tolerance (ETT) on a bicycle ergometer, and SLE activity were obtained. At baseline, SLE patients had significantly lower maximum oxygen consumption (VO2 max) than normals (p less than 0.005). Adjusted for age and sex, SLE patients perform at 54% of their expected maximum VO2, which is similar to published data from patients with rheumatoid arthritis. Depression by NIMH was not correlated with VO2 max or length of time on ETT. Fatigue measured by Profile of Mood States (POMS) was correlated with ETT time (r = 0.476, p less than 0.025) and with VO2 max (r = -0.402, p less than 0.07). After an 8-week aerobic conditioning programme the experimental group increased their aerobic capacity by 19% in contrast to 8% in controls. This change correlated with decreased fatigue as measured by visual analogue scales. Exercise did not exacerbate disease, and only two of 16 experimental subjects experienced transient joint symptoms during exercise.
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PMID:Effects of aerobic conditioning in lupus fatigue: a pilot study. 259 Aug 2

Free oxygen radicals are involved in many pathological conditions and particularly in the inflammation which characterizes rheumatic disorders. Tiopronin (Acadione), a new basic treatment for rheumatoid arthritis, and sodium 3-aurothio-2-hydroxypropane-1-sulfonate (Allochrysine), the reference treatment for the disease, have been tested in vitro for their ability to regulate the free radicals produced by inflammatory murine macrophages or granulocytes. The production of free radicals was measured using the technique of luminol-dependent chemoluminescence. Results show that tiopronin causes dose-dependent inhibition of chemoluminescence whereas, under the same experimental conditions, sodium 3-aurothio-2-hydroxypropane-1-sulfonate leads to a stimulation in production of the radicals. Taking into consideration the deleterious effects of free radicals in rheumatic disorders, inhibition of the radicals may be considered as forming part of tiopronin's mode of action.
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PMID:[Inhibitory action of tiopronin on free radicals]. 274 Aug 3

Alteration of IgG by oxygen-derived free radicals has been implicated in an in vivo process which renders IgG autoantigenic and leads to the production of rheumatoid factor (RF) and the perpetuation of inflammation, as in rheumatoid arthritis (RA). In this study the impact of UV irradiation on IgG was investigated as well as the ability of RF to bind to UV-altered gamma globulin. Inhibition studies of the binding of 125I aggregated human gamma globulin (AHG) to RF-coated sepharose beads show that UV-irradiated IgG is able to bind RF to the same extent as AHG. Binding studies to 125I-C1q proved that UV-irradiated IgG could bind the first complement component, but also that the complement system could be activated as illustrated by the C3a generation. These results support the hypothesis that free radical damage to gamma globulins plays a role in the chronicity of the inflammatory reaction in RA.
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PMID:Possible role of free radical altered IgG in the etiopathogenesis of rheumatoid arthritis. 277 83

The initial and end parts of the ventricular complex of the ECG and the roentgenopneumopolygraphy data were assayed in 22 patients with rheumatoid arthritis before and after inhalation of the gaseous hypoxic mixture (GGS-10) consisting of 90% of nitrogen and 10% of oxygen. After the inhalation of the mixture the area of the ST-T segment significantly increased as compared with the initial data, mainly in the AVR, V2 and V5 leads of the ECG. In addition, individual features of the changes in respiratory pulmonary function were discovered, which directly correlated with the disease stage.
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PMID:[Myocardial reaction and lung ventilation response to inhalation of the gaseous hypoxic mixture GGS-10 in patients with rheumatoid arthritis]. 278 93

Peripheral blood monocytes (PBMo) and synovial fluid macrophages (SFMO) of patients with rheumatoid arthritis (RA), HLA B27-positive reactive oligoarthritis and controls were investigated for their capacity to generate superoxide anions (O2-) upon stimulation with phorbolmyristoacetate (PMA) in a cytochrome c (cyt c) microassay. PBMo of RA patients, patients with reactive arthritis and controls did not reveal any significant differences and also treatment of RA patients with gold salts or immunosuppressive therapy had no effect on the oxidative burst in PBMo. In contrast, in SFMO of RA patients treated only with nonsteroidal anti-inflammatory drugs (NSAID) we found significantly enhanced O2- release, compared with PBMo of the same group. Treatment with gold salts had no effect on this enhanced oxidative response, whereas immunosuppressive therapy with azathioprin or corticosteroids significantly reduced the O2- release of SFMO. In patients suffering from reactive arthritis we did not find significant differences between SFMO and PBMo. The O2- release of SFMO of this group was significantly reduced, when compared to that of SFMO of RA patients, treated with NSAID. These results indicated that SFMO but not PBMo in RA in cyt c microassay produce increased levels of activated oxygen species. In comparison to PBMo, SFMO of patients suffering from reactive arthritis do not show such an increased oxidative burst. These findings suggest that in RA, activated oxygen species have a local destructive effect in inflamed joints. This seems to be caused by activation of catalytic enzymes and complement components, as well as induction of release of interleukins or prostaglandins, contributing to the augmentation of the chronic inflammatory process.
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PMID:Superoxide anion production by monocytes and synovial fluid macrophages of patients with chronic inflammatory joint disorders. 282 1

In the sera and synovial fluid of patients with rheumatoid arthritis, part of the IgG fraction is found in an aggregated and fluorescent form. Oxygen-free radicals have been implicated in this denaturation, although the precise radical species responsible is unknown. In this work, oxygen-free radicals generated radiolytically were allowed to attack polyclonal IgG in solution. OH radicals induced aggregation of the monomer and a new fluorescence appeared in the visible region (Ex 360 nm, Em 454 nm). The superoxide radical anion was found to be inert in both these respects, whilst peroxy radicals induced autofluorescence without concomitant aggregation. The results suggest that OH.and/or peroxy radical attack may be an in vivo mechanism for IgG denaturation.
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PMID:Oxygen radical induced alterations in polyclonal IgG. 283 12

Convincing evidence is presented that oxygen free radicals are involved in the pathogenesis of rheumatoid arthritis (RA). Superoxide is produced by polymorphonuclear leucocytes (PMN) in synovial fluid and by macrophages in the synovial membrane. Tissue damage typical for free radical attack is detected in RA. No absolute deficiency of protective factors is found in RA compared to controls, but the available protection is insufficient to cope with all radicals formed. The toxicity of superoxide is increased by iron. It is doubtful whether a low molecular weight iron pool is present. Superoxide is able to release iron from ferritin, providing a suitable source of iron, for the formation of hydroxyl radicals. This new pathogenetic mechanism stimulates to the application of iron chelators in the treatment of RA. Preliminary results with desferrioxamine were disappointing because of serious side-effects. Hopefully in the future intra-articular injection of iron chelators with better pharmacodynamics will be possible. The interaction of free radicals and ferritin is probably also involved in the pathogenesis of other inflammatory diseases such as systemic lupus erythematosus, hepatitis, and haemochromatosus.
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PMID:Superoxide dependent iron release from ferritin in inflammatory diseases. 283 31

There is evidence for both oxygen-centred free radicals and products of complement activation acting as mediators of inflammation. Evidence for the generation and reaction of free radicals at sites of inflammation can only be indirect and circumstantial due to their very transient nature. Evidence for complement activation in several inflammatory conditions, including rheumatoid arthritis is strong. These mediator classes individually possess a range of potential proinflammatory activities. Their effects may be linked through the formation of immune complexes and the activation of polymorphonuclear leukocytes. Their actions will also be linked with and modulated by the activities of other mediators mentioned only briefly in this chapter. The relative importance of the different mediators in any particular inflammatory condition is difficult to ascertain. The importance of free radicals and complement will be better understood when drugs specifically and unequivocally aimed at their control are identified. This potential for therapeutic advances in the treatment of inflammatory disorders has yet to be realized.
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PMID:Free radicals, immunoglobulins and complement as mediators of inflammation. 284 97

Intracellular thiols (LSH), superoxide dismutase (SOD) and plasma thiols (PSH) are thought to have an important role in the protection of tissues from damage by oxygen-derived free radicals. The change in the levels of activity of these substances in patients with active rheumatoid arthritis treated with sulphasalazine for 6 months was assessed in 22 patients. Over this time there was a marked improvement in disease activity. This was accompanied by an early increase in red cell LSH and decrease in SOD, although by 6 months these changes had completely reversed. In addition the negative correlation between these indices at week 0 had disappeared by week 6. Over the 6 months there was a steady rise in PSH. The change in PSH is slow and is thus more likely to reflect a change in the disease process rather than an active role for the thiol, but the early changes in intracellular parameters may be of importance in the action of this drug. These changes are similar to changes found with other second-line drugs. It is also of interest that a drug which does not itself possess a thiol group is capable of altering the thiol status of cells.
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PMID:Alteration of thiol and superoxide dismutase status in rheumatoid arthritis treated with sulphasalazine. 222 14

A microassay was developed for the estimation of macrophage (M phi)-activation by released activated oxygen. From peripheral blood or synovia M phi are isolated. O-2 which is released by activated M phi is photometrically detected by cytochrome c reduction. Differences in O-2-production do not exist between monocytes of rheumatoid arthritis patients and controls. In contrast synovial M phi from rheumatoid arthritis patients show increased levels of O-2-production.
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PMID:[Detection of macrophage activity in the blood and synovia of chronic polyarthritis patients using an activated oxygen microassay]. 298 9


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