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)

Rats injected with peptidoglycan-polysaccharide polymers derived from group A streptococcal cell walls (PG-APS) develop a chronic, remittant, erosive synovitis. Spleen cells from injected rats failed to proliferate when stimulated in vitro by Con A or PHA, unless nylon wool adherent cells were first removed. The suppression could also be reversed by removing phagocytic cells which had ingested carbonyl iron. Cells from control rats were suppressed in vitro by co-culture with unfractionated or nylon wool-adherent cells from PG-APS injected rats, and the suppressor activity was still expressed after exposure of the suppressor cells to 3,000 rad of irradiation. Addition of catalase and indomethacin to cultures only partially reversed the suppression. T lymphocytes from rats given a single arthropathic dose of PG-APS remained suppressed for at least 86 days after injection. Cells from rats given a low, non-arthropathic dose of PG-APS did not become suppressed. Cells from the Buffalo rat, which is resistant to development of PG-APS-induced chronic arthritis, showed less suppression than cells from the susceptible Lewis and Sprague-Dawley rat strains.
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PMID:Immunosuppressive macrophages induced by arthropathic peptidoglycan-polysaccharide polymers from bacterial cell walls. 306 53

The metabolic disorder, alkaptonuria, is distinguished by elevated serum levels of 2,5-dihydroxyphenylacetic acid (homogentisic acid), pigmentation of cartilage and connective tissue and, ultimately, the development of inflammatory arthritis. Oxygen radical generation during homogentisic acid autoxidation was characterized in vitro to assess the likelihood that oxygen radicals act as molecular agents of alkaptonuric arthritis in vivo. For homogentisic acid autoxidized at physiological pH and above, yielding superoxide (O2-)2 and hydrogen peroxide (H2O2), the homogentisic acid autoxidation rate was oxygen dependent, proportional to homogentisic acid concentration, temperature dependent and pH dependent. Formation of the oxidized product, benzoquinoneacetic acid was inhibited by the reducing agents, NADH, reduced glutathione, and ascorbic acid and accelerated by SOD and manganese-pyrophosphate. Manganese stimulated autoxidation was suppressed by diethylenetriaminepentaacetic acid (DTPA). Homogentisic acid autoxidation stimulated a rapid cooxidation of ascorbic acid at pH 7.45. Hydrogen peroxide was among the products of cooxidation. The combination of homogentisic acid and Fe3+-EDTA stimulated hydroxyl radical (OH.) formation estimated by salicylate hydroxylation. Ferric iron was required for the reaction and Fe3+-EDTA was a better catalyst than either free Fe3+ or Fe3+-DTPA. SOD accelerated OH. production by homogentisic acid as did H2O2, and catalase reversed much of the stimulation by SOD. Catalase alone, and the hydroxyl radical scavengers, thiourea and sodium formate, suppressed salicylate hydroxylation. Homogentisic acid and Fe3+-EDTA also stimulated the degradation of hyaluronic acid, the chief viscous element of synovial fluid. Hyaluronic acid depolymerization was time dependent and proportional to the homogentisic acid concentration up to 100 microM. The level of degradation observed was comparable to that obtained with ascorbic acid at equivalent concentrations. The hydroxyl radical was an active intermediate in depolymerization. Thus, catalase and the hydroxyl radical scavengers, thiourea and dimethyl sulfoxide, almost completely suppressed the depolymerization reaction. The ability of homogentisic acid to generate O2-, H2O2 and OH. through autoxidation and the degradation of hyaluronic acid by homogentisic acid-mediated by OH. production suggests that oxygen radicals play a significant role in the etiology of alkaptonuric arthritis.
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PMID:Homogentisic acid autoxidation and oxygen radical generation: implications for the etiology of alkaptonuric arthritis. 312 48

Rats with adjuvant-induced arthritis (AA) were used to determine whether chronic systemic paw inflammation was accompanied by appearance of the acute phase response, an increase in splenic interleukin-1 (IL-1) production, and a reduction of nonhelper T cells in the spleen and peripheral blood. Two weeks after injection of adjuvant, the rats developed significant (P less than or equal to 0.01) swelling of the noninjected paw indicative of systemic inflammation. The rats with AA also exhibited signs of the acute phase response, as measured by a significant increase in plasma C-reactive protein (138% above normal) and a significant decrease in plasma albumin (47% below normal), zinc (30% below normal), and iron (58% below normal). IL-1 production from spleen cells of rats with AA was increased 115% compared with normals. Results from immunofluorescence studies with W3/25 and OX8 antibodies to distinguish rat T-helper-inducer (TH) spleen cells from suppressor-cytotoxic (nonhelper T) spleen cells indicated no significant difference between the percentage of OX8+ cells in spleens of arthritic rats compared with OX8+ cells in spleens of normal rats. The W3/25+-to-OX8+ ratio of 1.6 +/- 0.2 for normal rat spleen cells (33% to 21%) was not significantly different from the arthritic rat ratio of 1.9 +/- 0.1 (36% to 19%). When the phenotypes of peripheral blood mononuclear cells were analyzed, the normal animals possessed a greater percentage of W3/25+(TH) cells than did rats with AA. Normal blood mononuclear cell samples were composed of 51% +/- 3% W3/25+ cells and 22% +/- 2% OX8+ cells, and the samples from rats with AA contained 43% +/- 4% W3/25+ cells and 24% +/- 3% OX8+ cells. Thus, the helper-to-nonhelper ratio was higher for normal rats (2.3 +/- 0.1) than for arthritic rats (1.8 +/- 0.2). The data indicated that the appearance of the acute phase response and the abnormally high rate of splenic IL-1 production in the rats with AA did not stem from a subnormal percentage of OX8+ nonhelper T cells in the spleen or peripheral blood.
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PMID:Examination of interleukin-1 activity, the acute phase response, and leukocyte subpopulations in rats with adjuvant-induced arthritis. 312 93

The purpose of the paper was to determine whether two clinically active antirheumatic compounds, cyclosporin-A (CS-A) and methotrexate (MTX) were efficacious in the treatment of adjuvant arthritis (AA) in rats, as measured by reduction of paw inflammation, lymphocyte activating factor (LAF) activity and the acute phase response. Parameters of the acute phase response consisted of plasma fibronectin (Fn), C-reactive protein (CRP), albumin and iron. Rats injected with Freund's complete adjuvant on day 1, developed systemic arthritis, which was quantitated by measuring non-injected paw swelling on day 17. When compared to normal animals, AA rats had significantly (P less than or equal to 0.01) increased: (1) splenic LAF activity (100% increase), (2) plasma Fn (58%), and (3) CRP (122%), as well as abnormally reduced levels of: (1) plasma albumin (53% reduction), and (2) iron (54%). Orally dosing AA rats from days 3 to 17 with the immunoregulatory drugs, CS-A (3 and 5 mg/kg) or MTX (0.5 and 1 mg/kg), significantly (P less than or equal to 0.01) reduced paw inflammation (100% reduction), increased final body wt 40-50 g over arthritic controls and decreased LAF activity from splenic leukocytes. The acute phase response, often associated with a high degree of LAF activity, was significantly (P less than or equal to 0.01) decreased by dosing with CS-A (3 and 5 mg/kg) and MTX (0.5 and 1 mg/kg). The inhibition of the acute phase response was measured by reduction of high plasma Fn levels (42-79% decrease) and CRP levels (57-100% decrease) as well as elevation of subnormal levels of plasma albumin (57-101% increase) and iron (40-114% increase). Dosing with the nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin (50 and 100 mg/kg) or phenylbutazone (10 and 30 mg/kg), significantly inhibited paw inflammation (29-85%), but did not decrease the high rate of splenic LAF activity, nor did aspirin (55, 100 and 200 mg/kg) or phenylbutazone (1, 10 and 30 mg/kg) alter the acute phase response in AA rats, as measured by levels of plasma Fn, CRP, albumin and iron. Since CS-A and MTX have been reported to be effective in the treatment of RA, their activity in the LAF, Fn, CRP, albumin and iron assays of the AA rat suggests that these immunological and serological parameters may be useful in identifying potential antirheumatic drugs and distinguishing them from standard NSAIDs.
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PMID:Alteration of interleukin-1 production and the acute phase response following medication of adjuvant arthritic rats with cyclosporin-A or methotrexate. 314 80

In a sequential study the pathogenesis of chronic polyarthritis occurring spontaneously in MRL mice was analysed by light microscopy. A total of 128 MRL mice of both substrains (MRL/Mp-lpr/lpr and +/+) and different age groups was studied. In 50 lpr/lpr mice, tinctorial and histochemical methods were applied for the identification of fibrin/fibrinoid, iron compounds, amyloid, and proteoglycan. The earliest lesions seen in mice of substrain lpr/lpr at the age of 2 months were proliferation of synovial lining cells and loss of tinctorially demonstrable proteoglycan in the articular cartilage. Beginning at 3 months, severe joint destruction associated with pannus formation was encountered usually in knee, carpal and tarsal joints. Besides inflammatory processes in tendons, nerves and musculature fibrinoid-necrotising panarteritis occurred in the intra- and extraarticular tissue. Furthermore, fibrin-containing exudations and deposits of fibrinoid material, occurred in the synovium of large joints and in the periarticular connective tissue of phalangeal joints. The occurrence of these morphological changes, destructive arthritis, vasculitis and periarticular inflammatory changes, was, at the age of 3 months, associated with a highly significant increase of circulating immune complexes. In mice of substrain +/+ aged 1 year and older, arthritic changes with synovial lining cell proliferation, cartilage destruction and inflammatory periarticular lesions developed.
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PMID:[Pathogenesis of spontaneous chronic polyarthritis in MRL mice]. 318 80

In summary, the work reviewed in the present paper indicates that 1. Iron and the iron-binding proteins can act as regulators of immune function, and not only as a result of a nutritional dependence of lymphoid cells on transferrin and transferrin-iron. Subsets of cells of the immune system respond differently to increases in iron concentration in vitro and in vivo. 2. Macrophages and lymphocytes differ in the H and L subunit content of the ferritins synthesized in response to increases in iron concentration in vitro. 3. NK activity by adherent and nonadherent cells differ in their susceptibility to the enhancing effect of lactoferrin in vitro. 4. Responses to mitogen stimulation by PHA and Con A are diminished, while the PWM response remains unaffected by exposure to acidic ferritins or by increasing concentrations of iron in vitro and in vivo. 5. Pretreatment of effector but not target cells with iron results in diminished responses in the MLR, an effect that appears to be related to the HLA-A locus. 6. In situ hybridization studies indicate that transferrin is synthesized by a specific subset of the T lymphocytes. 7. Transient increases in serum iron concentration above the full saturation of transferrin, reproducing the clinical situation frequently seen in hereditary hemochromatosis, are followed by a series of cellular changes in the synovium that can be correlated to changes in the course of an experimental model of arthritis in the rat.
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PMID:Iron, iron-binding proteins and immune system cells. 329 85

We observed a consistent sequence of activation changes in rat knee synovia following a single intravenous injection of sterile ferric citrate at a dosage sufficient to cause a transient saturation of transferrin. The initial alteration, appreciated 2 hours postinjection, consisted of an expansion in the lumen of synovial lining and subsynovial tissue due to the hypervascularity and increased cellularity was noted, along with peaks in the mitotic activity of synovial cells (fourfold over baseline) and pinocytosis by endothelial cells. During the period of 8-24 hours, mature collagen appeared in the space between pericyte layers and between pericytes and endothelial cells, and 2-9-fold increases in ferritin +, W3/13+, W3/25+, Ox8+, and Ox26+ mononuclear cells occurred. In contrast to the action on synovial fibroblasts, iron injection did not affect the mitotic activity of fibroblasts within the serosa of the small intestine. These findings demonstrate that, under experimental conditions, iron can readily induce changes in the synovium that are reminiscent of early events occurring in response to antigen.
Arthritis Rheum 1988 May
PMID:Activation of rat synovium by iron. 337 69

The level of haemoglobin, serum iron, total iron binding capacity and ferritin were measured in patients with rheumatological conditions who were anaemic at the time of upper gastrointestinal endoscopy. These parameters were similar in patients with or without lesions of their upper gastrointestinal tract, and in patients with a positive or negative faecal occult blood result. Lesions of the upper gastrointestinal tract were not more frequent in patients with a microcytic anaemia when compared to those with a normocytic anaemia, nor were they found more frequently in patients with a positive faecal occult blood test. Lesions visible at upper gastrointestinal endoscopy are not an important cause of microcytic anaemia in patients with arthritis. The finding that patients with normocytic anaemia are more likely to proceed to lower bowel examination than patients with microcytic anaemia is a reflection of the difficulty in interpretation of these simple haematological tests and showed they were unhelpful in determining which patients warrant investigation of the lower bowel. The frequency of further investigation of the lower bowel was significantly reduced by a positive endoscopy report, irrespective of the nature of the lesion, but was not significantly increased by finding faecal occult blood. We suggest that patients with arthritis selected for investigation of possible gastrointestinal blood loss should follow an organized plan of investigation that includes examination of both upper and lower bowel, and which should proceed uninfluenced by pro tem results. Unfortunately the selection of patients for such further investigation is hampered by a lack of simple discriminatory tests.
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PMID:Anaemia in patients with arthritis: are simple investigations helpful? 291 44

A 56-year-old man, who had previously been treated for arthritis of the hands, was admitted to the hospital because of abdominal pain and fever. Physical examination, laboratory tests and liver biopsy led to the diagnosis of hemochromatosis. The patient's brother, who had also been treated for arthritis, was then found to have hemochromatosis. The patient's five children appeared to be well, but serum iron studies and HLA typing showed that four were affected with hemochromatosis.
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PMID:Hemochromatosis in a family. 350

The carrageenin rat paw edema was dose-dependently inhibited by i.v. and i.m. administration of desferrioxamine, a specific iron chelating agent. Therefore, iron-catalyzed formation of free radicals might be involved in this acute inflammatory reaction. In contrast, no antiinflammatory activity of desferrioxamine could be seen in rat adjuvant arthritis, a model of subacute and chronic inflammation.
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PMID:Influence of the iron chelating agent desferrioxamine on two rat inflammatory models. 350 37


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