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

A mixture of histidine, cystine, and copper mimicked gold thiomalate, N-ethylmaleimide, and p-chloro-mercuribenzoic acid in inhibiting sulfhydryl-disulfide interchange-mediated denaturation of human gamma globulin, bovine serum albumin, and diluted human serum. Measurable inhibitory effects were obtained with a mixture of physiologic concentrations of L-histidine, L-cystine, and copper. This work suggests a mechanism by which the hypohistidinemia of rheumatoid arthritis could contribute to the pathogenesis of the disease.
 ...
PMID:Inhibition of denaturation of human gamma globulin by a mixture of L-histidine, L-cystine, and copper, and its clinical implication in rheumatoid arthritis. 5

The immune complex-induced reversed passive Arthus (RPA) reaction in the rabbit has been investigated as a screening test for detecting anti-inflammatory agents potentially more effective in the treatment of rheumatoid arthritis than those presently available. RPA lesions, characterized by edema, erythema, and hemorrhage, were elicited by intravenous injections of bovine serum albumin (BSA) followed by intradermal injections of rabbit anti-BSA antiserum. The anti-edema activities of compounds (mg quantities required for testing) were evaluated after their administration by the intradermal route (compounds admixed with antiserum) as well as by the intraperitoneal route. Of 14 reference anti-inflammatory agents tested by the intradermal screening procedure, only aurothioglucose and chloroquine were inactive. Other pharmacologically active compounds (e.g. antihistamines, anti-complement agents, cytotoxic-immunosuppressives) were also evaluated after their intradermal administration. Protoporphyrin, phloretin, and hexadimethrine bromide (Polybrene) were active. When whole antiserum, or the antibody fraction of the serum, was used to eliminate nonspecific edema, intraperitoneally administered reference agents were found to be effective in the RPA test.
 ...
PMID:Use of the reversed passive Arthus reaction as a test for anti-inflammatory agents. 12 39

Antigen-induced arthritis was developed in mice as a model of human rheumatoid arthritis by using methylated bovine serum albumin (mBSA) as antigen. It was found that most strains were susceptible, whereas CBA mice were resistant. We therefore investigated the humoral and cell-mediated immune responses to mBSA in resistant mice (CBA) and susceptible mice (exemplified by C57BL) to determine whether these were associated with susceptibility to arthritis. The resistant strain (CBA) differed from the suceptible strains in the following respects. First, there was a lower humoral immune response to mBSA as measured by passive hemagglutination, but this could be overcome by a larger immunogenic dose. Secondly, there were differences in response to low doses of DNP-mBSA after mBSA carrier preimmunization. Thirdly, there were striking differences in delayed-type hypersensitivity (DTH) to mBSA as determined by a radioisotopic assay in vivo; the response of CBA mice occurred early, at 5 days, declined quickly, and was weaker, whereas that of C57BL mice developed later and was long sustained. Genetic studies of the DTH response with hybrids and backcrosses showed an oligogenic control of immune responsiveness, with one gene being linked to the H-2b allele of the susceptible C57BL mice, and another being independent of the H-2 complex. Our findings indicate that in mice, susceptibility to antigen-induced arthritis with mBSA correlates with a higher responder state to this antigen, and that T cells are the major if not the only determinant of the high responder state.
 ...
PMID:Studies on antigen-induced arthritis in mice. II. Immunologic correlates of arthritis susceptibility in mice. 30 Jul 52

When correction was made for hypoalbuminaemia, 23 of 50 ambulant patients with definite or classical rheumatoid arthritis were found to have hypercalcaemia. When these 23 patients were studied 6 months later, 7 had hypercalcaemia as defined by the correction factor for a low serum albumin level, and 6 of these patients had raised serum ionised calcium concentrations. Biochemical studies in the 23 patients indicated evidence of hyperparathyroidism, namely, hypophosphataemia, increased serum alkaline phosphatase, hyperchloraemia, and reduced tubular reabsorption of calcium. However, serum immunoreactive parathyroid hormone concentrations were normal. Only one patient had an abnormally low serum 25-hydroxy-vitamin D result: this patient had a high level of urinary D-glucaric acid and was receiving phenobarbitone for treatment of epilepsy. The biochemical features suggestive of parathyroid overactivity were particularly found in patients with raised serum calcium levels. The cause of hypercalcaemia in rheumatoid arthritis remains to be explained.
 ...
PMID:Hypercalcaemia in rheumatoid arthritis: investigation of its causes and implications. 51 39

The effects of varying intra-articular (ia) doses of bovine serum albumin (BSA) antigen on immune synovitis in rabbits have been investigated. Chronic synovitis, characterized by mononuclear cell infiltration in synovial tissues, was induced by a single ia challenge with BSA in sensitized rabbits. However, cartilage and bone erosions and pannus formation were rarely observed. By varying the number and magnitude of the BSA challenges, lesions with different characteristics were observed at different times of analysis of joint pathology. In 3- to 10-week studies, multiple ia challenges with BSA produced lesions characterized by severe cartilage and bone changes; polymorphonuclear leukocyte (PMN) exudates; and mononuclear cells and, sometimes, PMNs in synovial tissues. Substantial increases in knee widths and synovial tissue weights also observed. By increasing the frequency of ia injections, more severe changes were produced more rapidly, so that within a 3-week period, the animals also experienced pain and were unable to fully extend their antigen-challenged knees. Some of the lesions observed in immune synovis resembled those in rheumatoid arthritis (RA). However, the presence of large numbers of PMNs in synovial tissue under certain conditions suggests some possible differences between the pathogenesis of experimental synovitis and RA.
 ...
PMID:Immune synovitis in rabbits. Effects of differing schedules for intra-articular challenge with antigen. 64 28

Serum protein and immunoglobulin concentrations, rheumatoid factor (RF) titers, and erythrocyte sedimentation rates (ESR) from 18 patients with active rheumatoid arthritis (RA) who were being treated with gold sodium thiomalate (Myochrysine) and monitored clinically were measured serially. Serum antiepithelial antibody (AEA) titers from 10 patients with pemphigus who were similarly treated were measured at frequent intervals. Statistically significant reductions of alpha2, gamma, and total globulins, IgG, IgA, and IgM, ESR, and RF, and AEA titers were found after 3 to 6 months of gold treatment. Serum albumin levels rose significantly, but alpha1, beta-globulin, and total protein did not change. A temporal relationship between the alteration of these serological tests and the clinical response to treatment was noted, but the magnitude of protein change did not correlate with the degree of clinical improvement within a given patient. These findings indicate that gold treatment influences serum protein and antibody concentrations in two diseases having diverse target organs and different etiologies. The question of whether gold compounds exert an immunosuppressive action, or whether the serologic changes are a secondary phenomenon reflecting amelioration of disease activity, is unresolved.
 ...
PMID:The influence of chrysotherapy on serum protein and immunoglobulin levels, rheumatoid factor, and antiepithelial antibody titers. 81 42

Salicylates form the basis of drug treatment in rheumatoid arthritis. Despite their use for many decades, there is considerable confusion about what constitutes a regime which will ensure anti-inflammatory properties. We have found that blood vessels in the proposed therapeutic range can be maintained overnight on a four times daily dose regime, using either soluble aspirin (in the form of "Disprin") or aloxiprin ("Palaprin Forte"), and on a 12 hourly regine using an aspirin-sustained release aspirin combination ("BiPrin"). Because of variation in the levels reached using a fixed dosage schedule, treatment should be individualised. No correlation was found between dosage levels and either disease activity or serum albumin levels. No significant alteration in free or total salicylate levels was found following the addition of indomethacin to therapy.
 ...
PMID:Salicylate therapy and drug interaction in rheumatoid arthritis. 106 85

Only some of the areas of drug interactions of relevance to those treating rheumatic diseases have been mentioned and there are still enormous gaps in our knowledge. It is likely that some potential areas of danger have been over-emphasised, being based on speculation rather than real data or purely animal experiments using non-clinical doses of drugs. We are learning how certain drugs can stimulate or inhibit the metabolism of other drugs through effects on liver enzymes systems. For example, the metabolism of corticosteroids is induced by phenylbutazone (and also by phenobarbital and phenytoin). The patient with active rheumatoid arthritis with a low serum albumin would be unusually susceptible to changes induced by combinations of highly protein-bound anti-inflammatory drugs. Finally, although drug interactions are responsible for adverse effects it has been suggested that a more frequent cause of therapeutic failure is not drug interactions but the increase in the number of drug defaulters when more than one drug is prescribed.
 ...
PMID:Drug interactions in the management of rheumatoid arthritis. 107 Sep 94

A retrospective study is reported of 160 patients with definite or classical rheumatoid arthritis, in which changes in haemoglobin concentration were analysed against changes in various routine clinical and laboratory indices of disease activity over a period of time. Although statistically significant correlations were found between haemoglobin concentrations and the articular index of joint tenderness, serum albumin concentration, and erythrocyte sedimentation rate at one point in time, significant relationships in changes in haemoglobin concentration were only found with changes in the latter two laboratory indices. The significant correlations were weak and less important than the cumulative effect of unknown variables in determining haemoglobin level. The study shows that the routine clinical and laboratory parameters of disease activity in rheumatoid arthritis are of no value in predicting the haemoglobin concentration.
 ...
PMID:Relationship between haemoglobin and the other clinical and laboratory parameters in rheumatoid arthritis. 113 63

The use of multiple drugs in treating rheumatoid arthritis is based on the assumption that their effects are additive. Sometimes the results are unexpected or the added drug may confer no additional benefit to the patient whilst leaving him more liable to undesirable side-effects. Some form of polypharmacy may be necessitated by the different pharmacological properties of our drugs. Certain drugs have been judged on their steroid-sparing effects allowing lower doses to be used and thereby reducing the toxicity of corticosteroids. It is likely that some potential areas of danger from interacting drugs have been over-emphasized, being based on speculative rather than real data or purely on animal experiments using non-clinical doses. The patient with active RA with a low serum albumin would be unusually susceptible to changes induced by combinations of strongly bound anti-inflammatory drugs. He would also be highly susceptible to side-effects, as has been shown with prednisone. Side-effects here are doubled when the patients serum albumin is below 2.5g/100ml(lewis et al.1971). I believe we should continue to ask ourselves whether by subtracting one or more drugs from the patients cocktail we may not produce a most welcome benefit for both patient and doctor and, I suppose we could even add, the hard-pressed tax payer.
 ...
PMID:Samuel Hyde lecture. Polypharmacy in rheumatoid arthritis--help or hindrance? 126 8


1 2 3 4 5 6 7 8 9 10 Next >>