Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic hemochromatosis in young adults has been increasingly recognized over the last three decades. Younger patients with hemochromatosis frequently have presenting problems other than diabetes, cirrhosis, and hyperpigmentation. A young woman with idiopathic hemochromatosis is described. Arthritis and secondary amenorrhea developed at age 20, and liver biopsy showed hemochromatosis at age 29. Further work-up revealed that the amenorrhea was due to underproduction of pituitary gonadotropins. The patient was treated with phlebotomy. Estrogen and progesterone replacement was begun because of severe osteoporosis. Serum iron studies may be useful in young patients with unexplained amenorrhea and/or arthropathy.
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PMID:Idiopathic hemochromatosis presenting as amenorrhea and arthritis. 357 42

The degrees of anaemia and microcytosis in 100 patients with juvenile chronic arthritis (JCA) were analysed according to the pattern of disease and its activity. Microcytosis was common (40% of patients had a mean corpuscular volume (MCV) of less than 75 fl), sometimes severe (MCV less than 65 fl in 14 patients), and closely correlated with the severity of the anaemia. The degrees of microcytosis and anaemia were both directly related to disease activity as measured by the ESR, and were most severe in cases with the systemic form of JCA. In 50 patients iron status was assessed. The serum iron concentration was directly related to the MCV, whereas the serum ferritin was inversely related to MCV and haemoglobin concentration and directly related to the ESR. Bone marrow iron stores were normal or increased in 6 patients with severe microcytic anaemia. These data suggest that the anaemia of JCA is typically microcytic, and that this microcytosis is associated with the disturbance of iron metabolism seen in the 'anaemia of chronic disorders' rather than overall depletion of body iron.
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PMID:Microcytic anaemia in juvenile chronic arthritis. 358 90

Iron mobilized from ferritin is able to convert superoxide and hydrogen peroxide, which are produced in large amounts in rheumatoid arthritis (RA), to the extremely toxic hydroxyl radical. We have found that synovial fluid ferritin is increased significantly in RA patients compared with levels in controls. The high synovial fluid:serum ferritin ratio is compatible with the hypothesis that synovial fluid ferritin is derived from the synovial membrane. We found no difference in ferritin concentrations in the synovial membranes of RA patients compared with those of controls. Quantitative data on the amount of iron bound to ferritin showed that the level was 2.9 times higher in RA synovial membranes than in those of controls. Moreover, RA synovial fluid contained considerable amounts of iron bound to ferritin. Calculation of the iron saturation of ferritin revealed that RA synovial membranes contained a mean of 2,210 moles of iron per mole of ferritin: a significant elevation when compared with the mean value of 1,500 moles found in the synovial membranes of the controls. The decreased saturation of ferritin in RA synovial fluid, compared with that in the synovial membrane, could be caused by an uncompensated release of iron from ferritin, which has been induced by superoxide that is produced by stimulated granulocytes. The results demonstrate that in the joints of RA patients, sufficient ferritin loaded with iron is available to stimulate oxygen free radical damage.
Arthritis Rheum 1986 Oct
PMID:Intraarticular ferritin-bound iron in rheumatoid arthritis. A factor that increases oxygen free radical-induced tissue destruction. 376 55

A detailed ultrastructural study was made of the synovial iron deposits in cases of haemophilic synovitis (HS), pigmented villonodular synovitis (PVNS), rheumatoid arthritis (RA), osteoarthritis (OA), seronegative inflammatory arthritis (SNA), and in controls, to investigate the relationship between iron deposits and tissue damage. Iron was seen by electron microscopy in about 75% of synovial lining cells in HS and PVNS but only in about 25% of synovial cells from cases of RA and SNA. In cases of OA and in controls iron deposits were scarce. The iron was usually deposited within pleomorphic siderosomes and in HS was most common in type A synovial cells. In contrast, deposits in all other cases were more common in type B cells, which were frequently the predominant cell type, and siderosomes were smaller, more homogeneous, and were more common in deeper synovial tissue. Considerable tissue damage was noted in the vicinity of iron rich siderosomes in synovial A cells from cases of HS, but such deposits in B cells in the synovium from the other cases had relatively little effect. We discuss the possibility that such differences directly reflect the differing functions of type A and B synovial cells, and particularly their relative ability to produce metabolically active oxygen metabolites with tissue destructive potential in the presence of iron.
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PMID:Relationship between iron deposits and tissue damage in the synovium: an ultrastructural study. 395 54

Current medical management programs for established joint diseases in hemophiliacs are unsatisfactory and do not modify the eventual outcome. D-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in a rabbit model of hemarthroses-induced arthritis and in four hemophiliacs with chronic synovitis. The animals had intra-articular injections of citrate (left knees) and autologous citrated whole blood (right knees). Eight weeks later, the rabbits were divided into two groups: no treatment and D-penicillamine (50 mg/kg/day, IM) until sacrificed at 6 months. The saline-injected joints showed no inflammation and no iron deposition. The blood-injected knees showed iron deposition in both groups, the D-penicillamine animals had marked suppression of chronic inflammation. Of the four patients treated, three had clinical responses (reduction in synovial thickness, reduction in number of bleeds in the affected joint). One patient, who did not respond, developed mild-moderate proteinuria. Those patients who responded received between 5.3 and 7.1 mg/kg/day of the drug. Mild abnormalities in platelet aggregation were seen in the responders. This preliminary study suggests that D-penicillamine is beneficial in the chronic synovitis/arthritis induced by hemarthroses. Further trials are recommended.
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PMID:Treatment of hemophilic arthritis with D-penicillamine: a preliminary report. 401 26

Seventeen patients with early rheumatoid synovitis underwent synovial biopsy to assess the interrelationship between both ferritin (the intracellular iron storage protein) and Perls' positive iron (ferric iron in loose combination with protein), on the activity and course of rheumatoid disease. The amount of ferritin was associated to a significant degree with the activity of the disease at the time of biopsy, but showed no relation to the way the disease progressed over the following year. In contrast, the amount of Perls' iron bore no relation to the activity of the disease at biopsy, but its presence was associated with persistent disease. It is argued that this association is direct, that ferritin production may fail in a population of synovial macrophages, and that Perls' ferric iron may either be reduced to the ferrous form and promote the formation of toxic free radical species, or stimulate collagenase and prostaglandin release from synovial macrophages.
Arthritis Rheum 1984 May
PMID:The effect of synovial iron on the progression of rheumatoid disease. A histologic assessment of patients with early rheumatoid synovitis. 620 3

Synthetic triclinic calcium pyrophosphate dihydrate crystals, uniformly labeled with 85Sr and 45Ca, were injected into the knee joints of 2 normal adult rabbits and 2 rabbits previously injected repeatedly with autologous blood. The "half clearance time" of the injected crystal mass was 20.4 and 19 days from control joints, nearly identical to previously reported values in 6 rabbits (19.1 +/- 1.4), and 28.8 and 34 days from the joints injected with blood, a significant difference (P less than 0.05). Iron stains showed hemosiderin granules in the superficial synovium in these joints. Electron microscopy showed crystals with a molar calcium/phosphorus ratio of 1.0 and particles containing iron within synovial cells. We hypothesize that the decreased clearance rate from hemosiderotic synovium is due to inhibition of one or more intracellular pyrophosphatases by iron.
Arthritis Rheum 1981 May
PMID:Clearance of calcium pyrophosphate dihydrate crystals in vivo. III. Effects of synovial hemosiderosis. 626 91

Serum copper, iron and ceruloplasmin concentrations were determined in 45 subjects (22 males and 23 females, medium age 50.3, range 25-76) diagnosed as psoriatic arthritic patients (20 with poliarticular, 12 with mono-oligoarticular and 13 with spondyloarticular form), in 63 patients (30 males and 33 females, medium age 32.4, range 10-78) with psoriasis, and in 60 blood donors (32 women and 28 men) as reference group. Mean serum copper, iron and ceruloplasmin was significantly increased (p less than .001) in psoriatic arthritis as compared with controls or subjects with psoriasis alone. The number of synovial joints affected was significantly correlated to changes in these serum parameters. Indeed, serum copper, iron and ceruloplasmin were found to be significantly different from that of normals in the polyarticular subgroup (p less than .001), while only copper and ceruloplasmin were different in the mono-oligoarticular form (p less than .001 and p less than .01 respectively). No significant changes were found in a spondyloarticular subgroup. In the polyarticular subgroup a direct correlation was found between another disease activity marker (e.g. ESR) and serum changes in iron, ceruloplasmin and copper (p less than .001). Our data indicate that psoriatic arthritis is a multifaceted disease: the polyarticular form behaves like seronegative rheumatoid arthritis, while the monoarticular forms shows a lesser involvement of serum iron; spondylitic arthritis does not show any significant change in serum copper, ceruloplasmin and iron concentrations.
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PMID:Supportive laboratory findings in psoriatic arthritis. 646 61

After administration of D-penicillamine to patients with rheumatoid arthritis, measurements of serum level and urinary excretion showed half-life times of 1.6 hours in the rapid phase and 4-6 days in the slow phase. The latter evidence suggests that tissue pooling occurs. With a dosage of 750 mg/day, basic serum levels of 100 microM are gradually reached. Serum D-penicillamine levels were shown to be the same for patients who responded well to treatment, those who did not respond, and for patients who had adverse side effects as well as those who had none. Intestinal resorption decreased when D-penicillamine was taken close to meals and was greatly reduced by iron preparations.
Arthritis Rheum 1984 Dec
PMID:D-penicillamine in patients with rheumatoid arthritis. Serum levels, pharmacokinetic aspects, and correlation with clinical course and side effects. 650 61

Both severe and marginal copper deficiency were produced in male Sprague Dawley rats prior to induction of adjuvant arthritis. Degree of copper deficiency was confirmed by analysis of plasma, liver, and brain samples prior to adjuvant injection. Incidence of adjuvant arthritis was the same in both copper deficient and control animals although the severity was slightly but not statistically less in the former. However, recovery from foot edema was impaired in copper-deficient animals, while marginally copper-deficient animals recovered at the same rate as did controls. Plasma copper concentration increased in response to the injection of adjuvant and the increase was directly related to dietary copper content. Plasma zinc concentration was decreased in arthritic animals and the decrease was inversely correlated to paw edema. Liver copper, zinc, and iron concentrations in arthritic animals remained unchanged or increased slightly in comparison to the corresponding non-injected controls. Copper-deficient rats were immunosuppressed as demonstrated by impaired responsiveness to the T-cell dependent contact sensitizing agent oxazolone and diminished capacity to respond to the T-cell independent antigen Type III pneumococcal polysaccharide. Although a statistical difference in paw volumes was not found for group of animals fed diets differing in copper content, it is postulated that copper deficiency may alter the severity and kinetics of adjuvant arthritis by impairing aspects of the immune response and the tissue repair processes subsequent to injury.
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PMID:Effect of nutritional copper deficiency on adjuvant arthritis and immunocompetence in the rat. 660 63


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