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)

The use of salicylates in rheumatic diseases has been established for over 100 years. The more recent recognition of their modification of platelet and endothelial cell function has lead to their use in other areas of medicine. Aspirin (acetylsalicylic acid) is still the most commonly used salicylate. After oral administration as an aqueous solution aspirin is rapidly absorbed at the low pH of the stomach millieu. Less rapid absorption is observed with other formulations due to the rate limiting step of tablet disintegration - this latter factor being maximal in alkaline pH. The rate of aspirin absorption is dependent not only on the formulation but also on the rate of gastric emptying. Aspirin absorption follows first-order kinetics with an absorption half-life ranging from 5 to 16 minutes. Hydrolysis of aspirin to salicylic acid by nonspecific esterases occurs in the liver and, to a lesser extent, the stomach so that only 68% of the dose reaches the systemic circulation as aspirin. Both aspirin and salicylic acid are bound to serum albumin (aspirin being capable of irreversibly acetylating many proteins), and both are distributed in the synovial cavity, central nervous system, and saliva. The serum half-life of aspirin is approximately 20 minutes. The fall in aspirin concentration is associated with a rapid rise in salicylic acid concentration. Salicylic acid is renally excreted in part unchanged and the rate of elimination is influenced by urinary pH, the presence of organic acids, and the urinary flow rate. Metabolism of salicylic acid occurs through glucuronide formation (to produce salicyluric acid), and salicyl phenolic glucoronide), conjugation with glycine (to produce salicyluric acid), and oxidation to gentisic acid. The rate of formation of salicyl phenolic glucuronide and salicyluric acid are easily saturated at low salicylic acid concentrations and their formation is described by Michaelis-Menten kinetics. The other metabolic products follow first-order kinetics. The serum half-life of salicylic acid is dose-dependent; thus, the larger the dose employed, the longer it will take to reach steady-state. There is also evidence that enzyme induction of salicyluric acid formation occurs. No significant differences exist between the pharmacokinetics of the salicylates in the elderly or in children when compared with young adults. Apart from differences in free versus albumin-bound salicylate in various disease states and physiological conditions associated with low serum albumin, pharmacokinetic parameters in patients with rheumatoid arthritis, osteoarthritis, chronic renal failure or liver disease are essentially the same.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of the salicylates. 388 90

The clarification of turbid AA-amyloid-fibril-containing agarose gels by serum has been ascribed to degradation of the fibrils and designated as 'amyloid degrading factor'. In the present study, sera of 32 healthy blood donors and 32 patients with rheumatoid arthritis all showed 'degrading factor activity' against both AA amyloid fibrils and a non-fibrillar reticulin preparation of normal liver in an agarose plate assay. AL amyloid fibrils were not affected. The 'degrading activity' of serum was correlated with the serum albumin concentration, and the effect was also given by purified human and bovine serum albumin, although it was not seen with other serum proteins. The 'degrading activity' of serum against AA amyloid and reticulin was significantly correlated: both substrates showed low levels in a chronic disease such as rheumatoid arthritis, and reticulin inhibited 'degrading activity' against AA amyloid and vice versa. These results suggest the same process involves both substrates. 'Degrading activity' was also given by EDTA and a specific calcium chelator, and was inhibited by calcium and magnesium. An enzyme inhibitor showed only partial inhibition of the 'degrading activity' of serum, purified albumin, and EDTA. These results suggest that serum 'degrading factor activity' is a non-specific calcium-mediated effect against AA amyloid and reticulin preparations dispersed in agarose. It may represent a change in the degree of aggregation of these proteins rather than being an effect of proteolytic degradation. This confirms the conclusions of other workers that amyloid 'degrading factor activity' is an phenomenon in vitro of doubtful pathophysiological significance.
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PMID:Amyloid 'degrading factor activity': a non-specific calcium-mediated effect. 391 27

Long-term therapy of D-penicillamine (D-Pen) for rheumatoid arthritis (RA) is associated with a fall in rheumatoid factor, but many patients develop autoantibodies. In vitro binding of D-Pen to human peripheral blood monocytes was examined in 37 patients with RA and 75 healthy subjects. Mononuclear cells were reacted with D-Pen coupled to a fluorescein isothiocyanate-bovine serum albumin (BSA) conjugate in the presence of sodium azide and BSA, and analyzed by flow cytometry. Patients showed significantly higher D-Pen binding to monocytes than did healthy subjects. The proportion of monocytes binding D-Pen increased with age in the patients but not in healthy subjects. None of 6 patients who had D-Pen-induced autoimmune side effects was associated with increased D-Pen binding though patients with therapeutic responses showed high D-Pen binding. These results suggest that D-Pen binding to monocytes may be important in mediating therapy and inducing autoimmune side effects.
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PMID:Increased binding of D-penicillamine to monocytes in rheumatoid arthritis. 394 34

Isopycnic ultracentrifugation is frequently applied for preparative isolation of macromolecules. Using bovine serum albumin (BSA)-anti-BSA antibody complexes as a model system, isopycnic banding of complexes was observed in CsCl, Nycodenz, and sucrose gradients. In CsCl gradients, free antigen or antibody could not be separated from the immune complexes. Variations in antigen to antibody ratio from equivalence and in the amount of complement present during complex formation resulted in zone broadening and banding at slightly lower densities in Nycodenz. This was not observed in sucrose. Serum immune complexes were isolated from patients with rheumatoid arthritis or ankylosing spondylitis. Banding of in vivo-formed immune complexes was observed more frequently in sucrose than in Nycodenz.
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PMID:Isopycnic ultracentrifugation of immune complexes. 396 36

Serum selenium concentrations were measured in 87 patients with rheumatoid arthritis. The serum selenium levels of the whole group of patients was significantly reduced (70.2 +/- 13.3 micrograms/l, p less than 0.001) when compared with the reference material (79.8 +/- 10.6 micrograms/l). However, the reduction was not equally pronounced in three groups of patients representing different courses of the disease. One group with an active, disabling disease of long duration had a very reduced serum selenium level (63.7 +/- 14.1 micrograms/l, p less than 0.001). Another group, with a protracted but mild disease had a slightly reduced level (74.1 +/- 10.8 micrograms/l, p less than 0.01), and a group with mild disease of short duration had a slightly but not significantly reduced selenium level (75.9 +/- 10.8 micrograms/l, p less than 0.1). Significant correlation was found between serum selenium and the number of joints with limitation of motion, number of joints with active arthritis, haemoglobin concentration and IgG concentration. No correlation was found between serum selenium and disease duration, morning stiffness, ESR, C-reactive protein, rheumatoid factor titre, serum albumin, IgM and IgA. Selenium is part of the enzyme glutathione peroxidase that catabolizes peroxides which are suggested to be actively involved in inflammation. A low selenium level may thus be a further factor in the pathogenesis of rheumatoid arthritis.
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PMID:Low selenium level in severe rheumatoid arthritis. 400 93

The effect of heat-aggregated human gamma globulin (aggFII) on the induction of in vitro lymphocyte transformation, measured by the uptake of tritiated thymidine into newly synthesized DNA, was studied with peripheral blood lymphocytes derived from 12 patients with rheumatoid arthritis (RA), six with ankylosing spondylitis (AS), two with systemic lupus erythematosus (SLE), and seven normal subjects. It was found that 200 mug aggFII induced significant transformation of the lymphocytes of eight patients with RA, five with AS, one with SLE, and one normal subject. Neither deaggregated FII nor heat-aggregated human serum albumin induced significant transformation of the lymphocytes of any subject tested. A source of complement appeared necessary to support aggFII-induced blastogenesis, since enhanced transformation occurred only in the presence of fresh plasma. Heat-inactivated plasma and fetal calf serum (FCS), and FCS devoid of hemolytic complement, failed to support enhanced blastogenesis in the presence of aggFII. Since substrates similar to those employed in these studies are present in vivo in the rheumatoid joint, it is suggested that aggFII may enhance intra-articular lymphocyte transformation in subjects with RA.
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PMID:Enhancement of human lymphocyte transformation by aggregated human gamma globulin. 413 Nov 62

"Capillary permeability" to serum albumin has been measured in patients with collagen vascular diseases by a method which compares the dilution of intravenously injected (131)I-human serum albumin and (51)Cr-R.B.C.s. The results indicate an increased capillary permeability comparable to that which occurs in patients with extensive inflammatory skin disease. We suggest that this increased capillary permeability may be the cause of the episodes of oedema which occur in patients with collagen vascular diseases such as disseminated lupus erythematosus, systemic sclerosis, dermatomyositis, polyarteritis nodosa, and rheumatoid arthritis. "Spontaneous periodic oedema" may be the presenting feature of collagen vascular disease and is due to increased capillary permeability.
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PMID:"Capillary permeability" in patients with collagen vascular diseases. 440 Dec 48

Antibodies to the (PGA) prostaglandin A were produced in rabbits immunized with a conjugate of PGE2 covalently linked to (BSA) bovine serum albumin by reaction with carbodiimide reagent. A radioimmunoassay was developed using dextran-coated charcoal to separate the free from antibody bound PGA1-3H. The sensitivity of the method was found to be 100 picograms/ml of plasma. Ethyl acetate was used for extraction of plasma and the various classes of PGs were separated by silicic acid column chromatography. Recovery of PGA1-3H throughout the entire procedure was 65-75%. The antibody showed progressively decreasing affinity to PGA2, PGA1, PGE2, PGE1, PGB2, and PGF2alpha, respectively. The mean plasma PGA level in adult males (N=13) was found to be 1.39 + or - 0.55 ng/ml, and 1.62 + or - 0.52 ng/ml in adult females (N=7). Corresponding plasma and serum samples were found to give essentially similar results. Plasma PGA levels in adult males treated with indomethacin for rheumatoid arthritis were 0.18 + or - 0.15 ng/ml (P 0.001 in comparison with the normal adult males). This method is sufficiently sensitive, precise, and rapid to allow the routine estimation of the PGAs in biological samples.
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PMID:Radioimmunoassay of the A prostaglandins. 466 56

The metabolism of radioiodinated IgG was studied in a series of 42 patients with connective tissue diseases (16 systemic lupus erythematosus, nine rheumatoid arthritis, five polymyositis, five vasculitis, and seven miscellaneous diagnoses). Fractional catabolic rates were increased and survival half-lives were shortened in all diagnostic categories indicating hypercatabolism of IgG. This hypercatabolism was masked by increased IgG synthesis, resulting in elevated serum concentrations of IgG in patients with systemic lupus erythematosus and rheumatoid arthritis and in generally normal concentrations in the others. The metabolism of iodinated IgM was also studied in eight patients with systemic lupus erythematosus, in seven with rheumatoid arthritis, and in 12 controls. The fractional catabolic rates were normal in both groups of patients. Serum concentrations of both IgM and IgA were moderately elevated in all diagnostic categories. Serum albumin metabolism was entirely normal in the nine subjects studied who were not receiving corticosteroids; in three who were receiving them, moderate hypercatabolism was observed. The hypercatabolism of IgG could not be accounted for by factors previously known to alter IgG metabolism. It was not observed in 15 patients with other chronic, inflammatory diseases and was not explained by concomitant administration of adrenal corticosteroids to some patients. Identical results were obtained whether the IgG was obtained from a patient himself or from a normal donor, demonstrating that the hypercatabolism is a host defect and not an abnormality of the protein. Thus, patients with connective tissue disease of several different diagnostic categories have been shown to have an unexplained immunoglobulin abnormality: they catabolize normal IgG at an accelerated rate.
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PMID:Hypercatabolism of normal IgG; an unexplained immunoglobulin abnormality in the connective tissue diseases. 541 73

The rate of formation of tissue fluid for a given increase of venous pressure and for a known volume of tissue has been measured in the forearm. There is a significant increase in this figure in rheumatoid arthritis and a still greater increase in patients who develop recurrent oedema. This increase could not be attributed to steroid or phenylbutazone therapy, nor to a fall in the serum albumin. The results imply that there is some generalized abnormality in capillary function in rheumatoid disease and that this change is not limited to the joints.
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PMID:Oedema in rheumatoid arthritis: changes in the coefficient of capillary filtration. 557 91


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