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)

A 64-year-old woman with a 15-years-history of rheumatoid arthritis developed generalized hemorrhagic diathesis. Routine coagulation tests revealed a slightly diminished platelet count only. Platelet aggregation in vitro induced by ADP, collagen, thrombin, arachidonic acid and ristocetin were reduced. The patient's plasma aggregating activity was significantly diminished which was due to a decrease of the intraplatelet nucleotide pool. The number of mepacrine labelled bodies as well as dense bodies in electron microscopy was below the normal values as well. Moreover, the intraplatelet concentration of cyclooxygenase--malonylodialdehyde (MDA) and lipoxygenase pathway products were lowered. Total platelet immunoglobulin G and M contents were significantly increased. The platelet survival time (in vitro aspirin method) was slightly shortened. Finally the diagnosis of delta-acquired platelet storage pool deficiency (delta-SPD) was established and possibilities of treatment were discussed.
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PMID:[Acquired platelet storage pool deficiency in rheumatoid arthritis]. 178 43

Fish oil is rich in the polyunsaturated N-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic acids (DCHA). EPA competes with arachidonic acid (AA) for metabolism by the cyclooxygenase and lipoxygenase pathways. Selective metabolites derived from EPA have reduced biological activities as compared with the AA-derived counterparts. Dietary supplementation with EPA led to incorporation of EPA into membrane phospholipids, an inhibition of 5-lipoxygenase pathway activity, and a reduction of the elaboration of platelet-activating factor. Neutrophil chemotaxis and the capacity of these cells to adhere to endothelial cells are substantially attenuated. This suggests that EPA has anti-inflammatory potential. Clinical trials in rheumatoid arthritis, psoriasis, atopic dermatitis, and bronchial asthma have shown beneficial effects. Whether the benefit obtained clinically is sufficient to replace or significantly reduce any clinical condition remains to be answered.
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PMID:Effects of dietary fish oil lipids on allergic and inflammatory diseases. 195 66

SK&F 86002, a mixed cyclooxygenase-lipoxygenase inhibitor, was examined for its effects on helper T cell functions. The drug was found to inhibit concanavalin A-induced mitogenesis of splenic T cells (IC50 = 13 microns), the mixed lymphocyte response (IC50 = 16 microM), and proliferation of antigen specific T cells (cloned line, IC50 = 11 microM; uncloned line, IC50 = 13 microM). In contrast, another mixed cycloxygenase-lipoxygenase inhibitor, BW775c, did not have such effects at non-cytotoxic levels. These T cell functions are believed to be dependent on the effects of elaborated IL-1. SK&F 86002 has been shown to inhibit the production of mature IL-1 (IC50 = 1 microM), possibly accounting for the anti-inflammatory effects of the drug in rheumatoid arthritis models. In an in vivo model of contact sensitivity, SK&F 86002 was able to inhibit mouse footpad swelling, demonstrating additional anti-inflammatory activity. As an inhibitor of IL-1 synthesis or release, SK&F 86002 may be useful for the treatment of T cell-dependent inflammation.
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PMID:The effect of dual inhibitor, SK&F 86002, on helper T cell functions. 214 Oct 33

Leukotriene B4 (LTB4) is an activator of white blood cells (WBC) and it has been suggested that its inhibition may be useful in rheumatoid arthritis (RA). Its production by peripheral WBC has not yet been investigated. We measured LTB4 production in 105 patients with RA and compared it with 59 matched controls. C-reactive protein (CRP) and ESR were measured in 90 patients and correlated with LTB4 values. Ten millilitres of blood were drawn. Separation was undertaken to obtain polymorphonuclear leukocytes (PMN) which were stimulated with calcium ionophore, and the supernatant was frozen for radioimmunoassay of LTB4. Results show that RA patients produce significantly higher levels of LTB4. It has been suggested that blockage of the cyclo-oxygenase enzyme by non-steroid anti-inflammatory drugs (NSAID) leads to increased production of LT via the lipoxygenase enzyme. Twenty-one patients not taking NSAID were compared with 84 on therapy. There was no significant difference. A linear regression was used to obtain Pearson's correlation coefficients. With LTB4 and CRP, r = 0.3 (p less than 0.003). With LTB4 and ESR, r = 0.25 (p less than 0.02). Low but significant correlations with CRP and ESR were obtained.
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PMID:Leukotriene b4 production by peripheral blood neutrophils in rheumatoid arthritis. 255 71

This study examines the interrelationship between arachidonic acid (AA) metabolism and chemotactic potential of human peripheral blood neutrophils from both normal donors and patients with rheumatoid arthritis (RA). We demonstrate that there is a significant inverse relationship between the neutrophil's metabolic capability to produce [3H]LTB4 in response to ionophore A23187 stimulation versus the cell's chemotactic potential to optimal concentrations (i.e., 20 nM) of the chemotactic peptide f-Met-Leu-Phe as determined by leading front (r = 0.567, p = 0.009), mean depth (r = 0.458, p = 0.042), and population ratio (r = 0.471, p = 0.036) analyses. Subsequent Percoll density gradient studies revealed several RA neutrophil subpopulations exhibiting significantly enhanced (p less than 0.05) [3H] AA metabolism over corresponding density normal cells. Based on these results, we speculate that RA peripheral blood neutrophils have been "processed" to become less chemotactically-responsive yet more metabolically-active cells, and that the increased ability to produce LTB4 through both increased phospholipase A2 and lipoxygenase activities are part of the increased metabolic capabilities of the cell.
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PMID:Alterations in arachidonic acid metabolism and chemotactic response in polymorphonuclear leukocytes from patients with rheumatoid arthritis. 255 30

Effects of E-5110, a novel non-steroidal antiinflammatory drug, on interleukin-1 (IL-1) generation from human monocytes were studied in vitro. E-5110 reduced the amounts of extra- and intracellular IL-1 activity induced by lipopolysaccharide (LPS, 1 micrograms/ml) in a dose-dependent manner (1-10 microM). E-5110 also inhibited the IL-1 generation induced by antigen-antibody complexes, opsonized zymosan and silica particles. It was suggested that the inhibition of IL-1 generation by E-5110 was independent of the inhibitory effects on arachidonate cyclooxygenase and/or lipoxygenase because indomethacin, piroxicam, BW755C and AA861 had no effects on IL-1 generation. Hydrocortisone (IC50:0.084 microM), aurothioglucose (11.5 microM) and lobenzarit (75.0 microM), which are clinically effective antirheumatic drugs, also inhibited IL-1 generation, like E-5110 (1.21 microM). It is expected that E-5110 will be superior to classical non-steroidal antiinflammatory drugs in medical treatment of rheumatoid arthritis.
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PMID:Inhibitory effects of E-5110 on interleukin-1 generation from human monocytes. 280 17

In rheumatoid arthritis (RA) benefit from non-steroidal anti-inflammatory drugs (NSAIDs) is mediated through inhibition of the cyclo-oxygenase enzyme, thereby decreasing production of the 2 series prostaglandins (PGs). The lipoxygenase enzyme is intact, however, allowing leucotriene (LT) production, e.g., LTB4 (an inflammatory mediator). Treatment with evening primrose oil (EPO) which contains gamma-linolenic acid (GLA) leads to production of the 1 series PGs, e.g., PGE1, which has less inflammatory effects. Also LT production is inhibited. Eicosapentaenoic acid (EPA, fish oil) treatment provides a substrate for PGs and LTs, which are also less inflammatory. In this study 16 patients with RA were given 540 mg GLA/day (EPO), 15 patients 240 mg EPA and 450 mg GLA/day (EPO/fish oil), and 18 patients an inert oil (placebo). The aim of this study was to determine if EPO or EPO/fish oil could replace NSAID treatment in RA. The initial 12 month treatment period was followed by three months of placebo for all groups. Results at 12 months showed a significant subjective improvement for EPO and EPO/fish oil compared with placebo. In addition, by 12 months the patients receiving EPO and EPO/fish oil had significantly reduced their NSAIDs. After 3 months of placebo those receiving active treatment had relapsed. Despite the decrease in NSAIDs, measures of disease activity did not worsen. It is suggested that EPO and EPO/fish oil produce a subjective improvement and allow some patients to reduce or stop treatment with NSAIDs. There is, however, no evidence that they act as disease modifying agents.
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PMID:Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. 283 84

This review considers recent pharmacological and biochemical studies of sulphasalazine and its colonic metabolites, 5-aminosalicylic acid and sulphapyridine, in relation to the use of the parent drug for the treatment of ulcerative colitis and, more recently, rheumatoid arthritis. Several factors make it difficult to analyse the mode of action of sulphasalazine, such as the aetiology and variable course of the conditions it is used to treat, lack of suitable animal models, and the question of which moiety of the drug is active. An important feature of the pharmacokinetics of the drug after oral administration is the significance of the azo cleavage of sulphasalazine due to bacterial action. The effects of sulphasalazine on the metabolism of arachidonic acid to prostaglandins and leukotrienes have been widely studied because of the evidence that these substances are formed in increased amounts in inflammatory bowel diseases. The effects are complex, but it appears that sulphasalazine and 5-aminosalicylic acid are weak and very weak inhibitors, respectively, of both cyclo-oxygenase- and lipoxygenase-dependent pathways. The overall pharmacological profile may favour a more marked inhibition of the lipoxygenase pathway because of the additional ability of 5-aminosalicylic acid to enhance prostanoid production and of sulphasalazine to inhibit prostaglandin inactivation. Drugs with selective lipoxygenase inhibitory actions in the colon should thus be sought so as not to compromise the prostaglandin pathway. Other properties of sulphasalazine, including its immunosuppressive, antifolate, lymphocyte inhibitory and leucocyte modulatory actions, are also discussed in the context of the therapeutic uses of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological and biochemical actions of sulphasalazine. 287 50

Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAID) that has been used in 120 countries since its introduction in Japan in 1974. It is currently the eighth largest-selling drug and the most frequently used NSAID in the world. Diclofenac, a phenylacetic acid derivative, is a potent inhibitor of cyclooxygenase enzyme activity, and may also interact with the lipoxygenase enzyme pathway, and with the release and reuptake of arachidonic acid. Diclofenac is almost completely absorbed, highly protein-bound, penetrates well into synovial fluid, and is extensively metabolized. Comparative studies have shown that diclofenac is at least equivalent in efficacy to aspirin and other NSAID when used for the treatment of rheumatic diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Diclofenac also possesses potent analgesic properties. Clinical trials suggest that diclofenac has a favorable side-effect profile, excellent patient tolerability, and a lower patient dropout rate when compared with aspirin and other NSAID.
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PMID:Review of diclofenac and evaluation of its place in therapy as a nonsteroidal antiinflammatory agent. 306 24

Timegadine is a tri-substituted guanidine derivative which inhibits both arachidonate cyclo-oxygenase and lipoxygenase activity. In a 24-week randomized double-blind controlled trial, timegadine 500 mg/day was compared with naproxen 750 mg/day in two groups of 20 patients with active rheumatoid arthritis. In the timegadine group, significant improvements were seen in both biochemical and clinical markers of disease activity, i.e. ESR, serum IgG and IgM, leukocyte and platelet counts, duration of morning stiffness, Ritchie index, number of swollen joints, pain, and general condition. In the naproxen group, only the Ritchie index improved. Differences between treatments, when present, were always in favour of timegadine. Serum alkaline phosphatase rose during the first 8 weeks of treatment in the timegadine group. A transient rise was also seen in the naproxen group. The side effects reported were mainly gastrointestinal and allergic, the latter being more frequently found in the timegadine group. Timegadine is superior to naproxen in controlling disease activity in rheumatoid arthritis, and appears to possess disease-modifying properties.
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PMID:Timegadine: more than a non-steroidal for the treatment of rheumatoid arthritis. A controlled, double-blind study. 329 Oct 99


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