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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydrogen peroxide is receiving increasing attention as a mediator of tissue damage during inflammation. To evaluate its destructive potential in vivo, we devised a model in which hydrogen peroxide is, initially, the sole mediator of tissue damage. Glucose oxidase, which was made cationic to obtain good retention in tissue, was injected intraarticularly in mouse knee joints. This enzyme produces hydrogen peroxide, using endogenous glucose as a substrate. The local production of hydrogen peroxide induced drastic vascular damage, as measured by 99mTc uptake and leakage of 125I-albumin. The chondrocyte proteoglycan synthesis was severely inhibited, as measured by 35SO4 incorporation. Histologic examination showed impressive inflammatory and degenerative changes, including periarticular infiltration, chondrocyte death, subchondral erosions, and muscle necrosis. Intraarticular administration of catalase could inhibit these vascular effects and cartilage damage. Systemic administration of ebselen, a synthetic glutathione peroxidase-like compound, provided partial protection. Indomethacin and piroxicam were not effective in the acute phase. We think this model is useful both for testing drugs that are purported to act as scavengers of hydrogen peroxide and for studying chronic destructive processes.
Arthritis Rheum 1986 Apr
PMID:An experimental model for hydrogen peroxide-induced tissue damage. Effects of a single inflammatory mediator on (peri)articular tissues. 370 31

SA96 in combination with indomethacin or prednisolone was investigated for their effects on the adjuvant arthritis in Lewis rats. SA96 given orally at a dose of 10 mg/kg inhibited the inflammation of adjuvant treated foot and untreated foot and the increase of serum Cu concentration which followed the development of adjuvant arthritis, but 2 mg/kg had no effect. Indomethacin given orally at a dose of 0.1 mg/kg or prednisolone given orally at a dose of 0.4 mg/kg also inhibited the adjuvant arthritis. Prednisolone suppressed the decrease of A/G ratio. Indomethacin and prednisolone, however, had no effects on the increase of serum Cu concentration. SA96 at a dose of 10 mg/kg in combination with indomethacin was more effective than the treatment of each drug alone on inflammation of adjuvant treated and untreated foot, serum Cu concentration, erythrocyte sedimentation rate and A/G ratio. The combination of SA96 at a dose of 2 mg/kg or 10 mg/kg with prednisolone had similar synergistic effects towards the adjuvant arthritis in rats.
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PMID:[Pharmacological studies of N-(2-mercapto-2-methylpropanoyl)-L-cysteine (SA96). V. Effects of SA96 in combination with indomethacin or prednisolone on adjuvant arthritis in rats]. 387 26

Indomethacin is a potent prostaglandin synthesis inhibitor, which is widely used in treating arthritis and other inflammatory conditions. This study investigated the effect of physiological levels of indomethacin on synthesis of the antiplatelet substance prostacyclin, by human vascular endothelial cells in culture. The nature of the inhibition and its reversibility following removal of indomethacin were characterized. Almost complete inhibition of prostacyclin synthesis was obtained at concentrations of 5.6 microM indomethacin, which were within physiological blood levels (1.4-16.8 microM) attained during routine indomethacin therapy. Inhibition was essentially irreversible for all exposure periods in excess of one minute. Following inactivation by brief (5 minute) exposure to indomethacin, partial recovery of prostacyclin synthesis to between 45% and 60% of control values was attained 24 hours after indomethacin removal. Prolonged (24 hours) exposure of cells to indomethacin did not further impair subsequent recovery of prostacyclin synthesis and did not affect cell viability. Recovery of enzyme was much more rapid in confluent quiescent monolayers of endothelial cells than in dividing cultures. The results indicate that continuous or intermittent exposure to indomethacin may significantly impair vascular prostacyclin synthesis in vascular endothelium, but that substantial recovery may occur within 24 hours of drug removal.
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PMID:Recovery of prostacyclin synthesis in human vascular endothelial cells following intermittent or continuous exposure to indomethacin. 389 46

Indomethacin given continuously in the drinking water (20 micrograms/ml) to BALB/cAn pi mice during the latent period of pristane-induced plasmacytoma development dramatically reduced the plasmacytoma incidence from 34.9 to 2.2%. Additionally, indomethacin given from day 0 to 120 or begun as late as 60 d after a single injection of 1.0 ml pristane was also highly effective in reducing the development of plasmacytomas. Indomethacin treatment did not prevent the formation of a peritoneal inflammatory exudate or peritoneal oil granulomatous tissue, although it had a mild inhibitory effect on the intensity of the cellular inflammation, particularly after extensive treatment of greater than 100 d. Indomethacin treatment reduced the incidence of arthritis by 50%. A major effect of indomethacin treatment was a reduction in the appearance of microscopic plasmacytomas that appear in the oil granuloma before plasmacytomas can be detected by routine sampling of the peritoneal exudate. Between days 116 and 181, 16 of 20 mice given 0.5 ml pristane were found to have foci of plasmacytoma cells, while only 2 of 20 indomethacin-treated mice had foci-containing plasmacytoma cells. The number of mice with microscopic foci in the pristane-treated group greatly exceeded the expected incidence of plasmacytomas (22%) at this dose of pristane. The growth of primary plasmacytomas in transplant that is dependent on the pristane-conditioned peritoneal environment was not inhibited by indomethacin treatment. The role of indomethacin in inhibiting plasmacytoma development was not established; two possibilities are that it inhibits production of mutagenic and tissue destructive oxidants by inflammatory cells, and it inhibits prostaglandin synthesis and intracellular production of oxidant biproducts.
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PMID:Inhibition of plasmacytoma development in BALB/c mice by indomethacin. 398 72

1 Old English (OE) rabbits produced more severe monoarticular arthritis (MAA) after sensitization and intra-articular challenge with ovalbumin than did either New Zealand White (NZW) or Dutch rabbits. NZW rabbits were better responders than Dutch rabbits.2 The swelling of the joint in all three strains of rabbits was triphasic. There was an initial acute swelling which appeared to peak at 2-4 days after challenge. This was followed by a decrease in joint size, and then a secondary increase in size beginning 1-2 weeks after challenge.3 An investigation of MAA in OE rabbits showed that there was an increase in E-type prostaglandins, total leucocyte counts and free acid phosphatase activity in the synovial fluid of the challenged joints at 6 h, 19 h, 47 h, 7 days and 46 days following challenge. There were also histopathological changes at these times. In addition, there was an increase in the surface temperature of both the challenged and non-challenged knees, and a rise in the body temperature.4 Prostaglandin levels peaked at 19 h and were equivalent to 19 ng E(2) per joint. In a separate experiment, the prostaglandin present at 18 h was shown to be mainly E(1). Maximum levels of prostaglandin appeared to coincide with maximum joint temperature, but preceded maximum joint swelling and a significant rise in both the number of inflammatory cells and the free acid phosphatase activity in the synovial fluid, all of which occurred at 47 hours.5 Indomethacin, 7.5 mg/kg orally twice daily, almost completely inhibited the increase in prostaglandin levels in the challenged joints and produced a moderate reduction in joint swelling. It also reduced the increased surface temperature of both knee joints and the raised body temperature. However, indomethacin had no effect on the number of leucocytes present, the free acid phosphatase levels, or the histopathological changes in the joint.6 The mean plasma level of indomethacin ranged from 0.5 to 3 mug/ml at the time when the animals were killed.7 Lysosomal enzymes may be more important than prostaglandins in rabbit MAA, and the lack of effect of indomethacin on joint histopathology may be due to its inability to prevent the release of these enzymes.
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PMID:The role of prostaglandins in rabbit monoarticular arthritis. 444 95

1. The amounts of latent and active collagenase and of collagenase inhibitor (TIMP) produced by two normal, three rheumatoid and two osteoarthritic synovial specimens in culture were compared. Normal synovia produced TIMP, but little latent enzyme. Rheumatoid synovia produced higher levels of total collagenase activity than normal, of which up to 50% in one sample was present in the medium in an active form, whereas no specific inhibitory activity due to TIMP was detectable. The amounts of collagenase and TIMP produced by osteoarthritic synovia were more variable and appeared to reflect the degree of inflammation in the tissue at the time of initiating the cultures. 2. Concentrations of TIMP were usually higher in the culture media of normal, rheumatoid and osteoarthritic synovia when hydrocortisone was present. Correspondingly, amounts of total collagenase were reduced. Production of prostaglandin E (PGE) were inhibited in a dose-dependent manner by hydrocortisone. 3. Indomethacin had no consistent effect on the production of TIMP by rheumatoid and osteoarthritic synovia, although it tended to depress production of collagenase. The production of TIMP by normal synovia was depressed by indomethacin. No PGE was detectable in the media when indomethacin was present. 4. These results are consistent with those from previous animal studies, and we conclude that the balance between production of collagenase and TIMP may be critical in determining the extent of the destructive processes in arthritis. The ability of hydrocortisone to suppress production of collagenase and to increase free TIMP concentration, as well as to inhibit synthesis of prostaglandin, may explain in part how the drug exerts its therapeutic effects in patients with rheumatoid arthritis.
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PMID:Production of collagenase and inhibitor (TIMP) by normal, rheumatoid and osteoarthritic synovium in vitro: effects of hydrocortisone and indomethacin. 627 49

The present study, using 14C-DMSO, established the systemic and local load and distribution of topically applied DMSO in adjuvant arthritic rats. Under equivalent conditions, the antiinflammatory effects (systemic and local) of topical DMSO treatments were compared with a topical treatment of a control vehicle or of indomethacin, a known effective antiinflammatory agent. No significant systemic or local antiinflammatory effect of topical DMSO was seen in the adjuvant arthritic rats. Indomethacin, applied topically, had a significant systemic antiinflammatory effect; however, no significant local antiinflammatory effect of indomethacin was observed.
Arthritis Rheum 1983 Jul
PMID:Penetration and effect of topically applied dimethylsulfoxide or indomethacin on adjuvant arthritis in the rat. 687 Sep 68

Indomethacin increases plasma lithium levels. A patient taking lithium for manic-depressive illness became delirious after indomethacin was initiated for arthritis. The probable mechanism of this interaction is the inhibition of prostaglandin synthesis by indomethacin, resulting in renal vasoconstriction and decreased renal excretion of lithium. When indomethacin is administered in addition to lithium, there is a risk of potentially fatal lithium toxicity.
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PMID:Indomethacin-induced lithium toxicity. 688 Oct 8

We reported in our previous paper that TN-762, a potent inhibitor of prostaglandin biosynthesis, has marked inhibitory activity on acute experimental inflammation. In this paper, the anti-inflammatory, analgesic, and antipyretic activities of TN-762 were assessed in animal models, and compared with those of indomethacin, ketoprofen and ibuprofen. TN-762 inhibited the sustained paw edema induced by mustard in rats during administration for 3 days, but after final administration, the inhibitory activity was decreased rapidly and was less then that of ketoprofen and indomethacin. TN-762 also inhibited the proliferation of granuloma induced by means of cotton pellet and granuloma pouch methods, and the adjuvant arthritis in rats. The inhibitory activity of the compound on inflammatory proliferation was more potent than that of ibuprofen, but slightly less than that of ketoprofen and less than about 1/10 times that of indomethacin. Indomethacin markedly inhibited the body weight gain at a high dose, while TN-762 did not affect it. Therefore, TN-762 was proven to have an inhibitory effect on subacute and chronic inflammation at low doses without toxic effects, but the compound appeared to have a less of an inhibitory effect on secondary or late stages of inflammation than on primary stage inflammation. TN-762 inhibited the acute paw edema induced by nystatin, and the inhibitory activity was the same as that of ketoprofen and indomethacin. The pathogenesis of nystatin edema has been considered to be due to lysosomal labilization. This result suggests that TN-762 has a potent membrane stabilizing action which is considered to be one of the necessary mechanisms in anti-inflammatory action. On the other hand, TN-762 showed the same potent analgesic effect as ketoprofen and indomethacin as observed by the acetic acid writhing and modified Haffner's methods in mice and by the Randall-Selitto's method in rats. However the antipyretic effect of TN-762 was significantly less than that of ketoprofen and indomethacin.
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PMID:[Anti-inflammatory, analgesic and antipyretic activities of alpha-(p-thenoylphenyl)-propionic acid (TN-762) (author's transl)]. 697 98

Benoxaprofen, a new nonsteroidal anti-inflammatory agent recently marketed as an an antirheumatic drug, has been reported to suppress leucocyte migration into inflammatory sites, possibly by its reported inhibition of leukotriene synthesis. Benoxaprofen is also a weak to moderate inhibitor of prostaglandin synthesis. The effect of benoxaprofen was examined on adjuvant-induced arthritis in rats by radiographic assessment of bone damage. The effect of benoxaprofen was compared to other nonsteroidal anti-inflammatory agents, considered to act primarily by the inhibition of synthesis and/or release of prostaglandins. Drugs were administered from the 15th to the 30th day after induction of the adjuvant disease ('established adjuvant'). Radiographs of adjuvant rats showed extensive bone damage that was markedly suppressed by 30-40 mg/kg of benoxaprofen. Benoxaprofen exerted a dose-related inhibition of bone damage. There was less suppression of bone damage by comparable doses of phenylbutazone, oxyphenbutazone, ibuprofen, fenbufen, naproxen, tolectin and sulindac. Indomethacin, piroxicam and flurbiprofen were nearly as effective but only in doses that produced adverse effects or death in rats. Benoxaprofen may modify the progression of the experimental arthritic disease through a suppression of leucocyte migration.
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PMID:Comparative effects of benoxaprofen and other anti-inflammatory drugs on bone damage in the adjuvant arthritic rat. 713 58


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