allopurinol and Arthritis--Rheumatoid

Rapid and effective suppression of inflammation is a primary goal in the treatment of rheumatic diseases. However, the therapeutic effect of most medications may be slow to manifest, in the order of weeks or months in the case of DMARDs. Monitoring of drug concentrations allows the possibility of appropriate dose adjustment or changes in medication to achieve more rapid or better outcomes. We review the evidence for drug concentration monitoring. Despite the theoretical utility for monitoring of MTX polyglutamate concentrations in red blood cells in patients with RA, studies have not shown a clear association between concentrations and either efficacy or toxicity and routine measurement is not yet recommended. Small studies associating disease control with concentrations of anti-TNF therapies and anti-drug antibodies suggest that routine monitoring may be useful in the future. However, the data are not yet sufficient for this recommendation. With the use of allopurinol in gout, there is a putative therapeutic range for the active metabolite oxypurinol; however, adjusting the allopurinol dose to achieve a target urate concentration is likely to be most effective, and measuring oxypurinol may be best suited to assessing drug adherence. Although measuring thiopurine metabolite concentrations with AZA therapy has been shown to be useful in IBD, studies in rheumatic diseases have so far failed to confirm a useful association between concentrations and disease control or drug toxicity. Whole blood concentrations of HCQ have been associated with disease control in SLE and future studies may be able to determine a therapeutic range.

Topics: Allopurinol; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Monitoring; Gout Suppressants; Humans; Methotrexate; Rheumatic Diseases; Tumor Necrosis Factor-alpha

Gout is a group of diseases characterized by arthritis and results from a disturbance of urate metabolism with the deposition of monosodium urate crystals in the joints and soft tissues. Often, but not invariably, the serum urate levels are elevated as a result of overproduction or underexcretion of uric acid. Clinical manifestations include acute and chronic arthritis, tophaceous deposits, interstitial renal disease, and uric acid nephrolithiasis. The diagnosis is based on the identification of uric acid crystals in joints, tissues, or body fluids. Acute episodes are treated with colchicine, NSAIDs, or steroids. Long-term management includes treatment with uricosuric agents or xanthine oxidase inhibitors.

Topics: Adult; Age Factors; Arthritis, Gouty; Arthritis, Rheumatoid; Colchicine; Diagnosis, Differential; Female; Gout; Gout Suppressants; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Osteoarthritis; Prevalence; Sex Factors; Tomography, X-Ray Computed; Uricosuric Agents; Xanthine Oxidase

Topics: Animals; Arthritis, Rheumatoid; Bone Resorption; Humans; Inflammation; Models, Chemical; Nitrate Reductase; Nitrate Reductases; Nitrite Reductases; Synovial Membrane; Xanthine Oxidase

Rheumatic diseases are prevalent in the elderly population, resulting in high morbidity caused mainly by lack of mobility. Consequently, the use of antirheumatic drugs in older persons is extensive. This review outlines some of the hazards encountered in the use of antirheumatic drugs in the elderly. Analgesics such as propoxyphene and acetaminophen are useful adjuncts to the treatment of arthritic pain, but propoxyphene has been associated with respiratory depression, and renal clearance of acetaminophen is reduced in elderly subjects. Salicylates may cause deafness, and like the other nonsteroidal anti-inflammatory drugs, may cause salt and water retention resulting in congestive cardiac failure. Phenylbutazone should not be used because of the risk of blood dyscrasia, and indomethacin has been reported as interfering with the antihypertensive effect of beta-blockers. Chloroquine levels may be raised in patients with impaired renal function, and there is increased risk of retinal damage with the drug in elderly subjects. Injectable gold compounds and penicillamine are not contraindicated in the elderly, because they are just as efficacious as in younger persons for the treatment of rheumatoid arthritis. Toxicity due to gold compound is not increased in the elderly, but skin rashes and abnormalities of taste do occur more commonly in elderly patients treated with penicillamine. Corticosteroids do not affect disease progression and therefore should be used only in acute severe disease for short periods of time. As in the younger population, treatment of gout in the elderly is dependent on renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Cortex Hormones; Age Factors; Aged; Allopurinol; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthritis, Rheumatoid; Chloroquine; Female; Gold; Gout; Humans; Male; Methotrexate; Middle Aged; Osteoarthritis; Penicillamine; Probenecid

Topics: Allopurinol; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Gold; Gout; Humans; Lupus Erythematosus, Systemic; Osteoarthritis; Penicillamine; Rheumatic Diseases; Salicylates; Spondylitis, Ankylosing; Vasculitis

Topics: Allopurinol; Arthritis; Arthritis, Rheumatoid; Diagnosis, Differential; Female; Humans; Immunoglobulin A; Immunoglobulin M; Male; Nails, Malformed; Prognosis; Psoriasis; Radiography; Spondylitis, Ankylosing

Topics: Adrenocorticotropic Hormone; Allopurinol; Analgesics; Arthritis, Juvenile; Arthritis, Rheumatoid; Colchicine; Diagnosis, Differential; Gold; Gout; Humans; Phenylbutazone; Probenecid; Prognosis; Rheumatic Diseases; Rheumatic Fever

Topics: Alkylating Agents; Allopurinol; Analgesics; Anti-Inflammatory Agents; Antimalarials; Antimetabolites; Arthritis, Rheumatoid; Arthroplasty; Aspirin; Gold; Gout; Humans; Immunosuppressive Agents; Indomethacin; Phenacetin; Polymyalgia Rheumatica; Prednisolone; Prednisone; Rheumatic Fever; Synovitis

The effect of the free radical scavengers allopurinol (50 milligrams) and dimethyl sulfoxide (DMSO) (500 milligrams), taken orally four times a day, on the clinical outcome of hematemesis resulting from nonsteroidal anti-inflammatory drugs (NSAID) induced erosive gastritis was examined in a prospective randomized double-blinded controlled trial. In 180 fully evaluable patients with osteoarthritis or rheumatoid arthritis, administration of allopurinol (n = 63) or DMSO (n = 58) enabled significantly (p < 0.01) larger numbers of patients to remain hemodynamically stable with no rebleed relative to those in the control group (n = 59). The results of endoscopic examination 48 hours after admission demonstrated that gastric erosions were still present in significantly more patients in the control group (p < 0.01; n = 20; 50 percent) than in the allopurinol (n = 5; 9 percent) or DMSO (n = 4; 7 percent) groups. The radical scavengers also reduced the number of patients requiring blood transfusion because of a rebleed or continued bleeding and emergency operation relative to control values. It is, thus, construed that oxygen derived free radicals mediate the mechanism of NSAID induced erosive gastritis. Scavenging these radicals impairs the gastritis, stimulates healing and protects against the complications of its hemorrhagic episodes.

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dimethyl Sulfoxide; Double-Blind Method; Female; Free Radical Scavengers; Gastritis; Hematemesis; Humans; Male; Middle Aged; Osteoarthritis; Prospective Studies; Treatment Outcome

Topics: Allopurinol; Arthritis, Rheumatoid; Azathioprine; Blood Cells; Capsules; Clinical Trials as Topic; Eye Diseases; Female; Gastrointestinal Diseases; Gout; Humans; Indomethacin; Lupus Erythematosus, Systemic; Male; Middle Aged; Rheumatic Diseases; Scleroderma, Systemic; Spondylitis, Ankylosing; Suppositories

Topics: Acute Kidney Injury; Adult; Aged; Allopurinol; Arthritis, Rheumatoid; Clinical Trials as Topic; Duodenal Ulcer; Enzyme Therapy; Female; Gout; Humans; Male; Middle Aged; Psoriasis; Sulfinpyrazone; Uric Acid; Xanthine Oxidase

Musculoskeletal disorders are one of the most common reasons military servicemen seek medical care during their line of duty. This study aims to review the clinical profile and outcomes of military personnel with inflammatory arthritis (IA) referred to a specialist rheumatology center in Singapore.. Consecutive new case referrals from the Singapore Armed Forces medical centers during the study period January 1, 2010, to December 31, 2019, were retrospectively studied.. There were 123 referrals, comprising 112 (91.1%) males, with the majority being Chinese (110, 89.4%). The mean age was 25.5 ± 11.1 years. The most common diagnoses were gout (including chronic tophaceous gout; 34, 27.6%), spondyloarthritis (18, 14.6%), palindromic rheumatism (8, 6.5%), rheumatoid arthritis (4, 3.3%), and juvenile idiopathic arthritis (4, 3.3%). Among servicemen with gout, all were male, the majority (31, 91.3%) were Chinese, and mean age was 34.1 ± 8.8 years. Mean body mass index (BMI) was 27.5 ± 3.9 kg/m2, of which 41.2% had moderate-risk and 47.1% high-risk BMI for cardiovascular disease and diabetes mellitus (DM). Comorbidities included hyperlipidemia (14), hypertension (6), and type 2 DM (3). Urate lowering therapy was initiated in 27 (79.4%) patients, comprising allopurinol (85.2%), probenecid (11.1%), and their combination (3.7%). One patient developed allopurinol-induced hepatitis; none had severe cutaneous adverse reactions. Among the remaining patients with IA, conventional synthetic disease-modifying antirheumatic drugs (DMARDs) used were sulfasalazine (8), methotrexate (4), hydroxychloroquine (4), and leflunomide (2). Biologic DMARDs used in five patients comprised adalimumab (3) and golimumab (2).. Servicemen with IA and good functional status can still be physically fit and deployable into certain combat and service support vocations. This will optimize manpower resources in military organizations with a shrinking young workforce.

Topics: Adolescent; Adult; Allopurinol; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Gout; Humans; Male; Military Personnel; Retrospective Studies; Rheumatology; Singapore; Young Adult

Inconclusive findings about infection risks, importantly the use of immunosuppressive medications in patients who have undergone large-joint total joint arthroplasty, challenge efforts to provide evidence-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a post-operative infection in patients undergoing TJA of a large joint (total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty) by identifying clinical and demographic factors, including the use of high-risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses [i.e., rheumatoid arthritis (RA), osteoarthritis (OA), gout, obesity, and diabetes mellitus] that are linked to infection status, controlling for length of follow-up.. A retrospective, case-control study (N = 2212) using de-identified patient health claims information from a commercially insured, U.S. dataset representing 15 million patients annually (from January 1, 2007 to December 31, 2009) was conducted. Descriptive statistics, t-test, chi-square test, Fisher's exact test, and multivariate logistic regression were used.. Male gender (OR = 1.42, p < 0.001), diagnosis of RA (OR = 1.47, p = 0.031), diabetes mellitus (OR = 1.38, p = 0.001), obesity (OR = 1.66, p < 0.001) or gout (OR = 1.95, p = 0.001), and a prescription for prednisone (OR = 1.59, p < 0.001) predicted a post-operative infection following total joint arthroplasty. Persons with post-operative joint infections were significantly more likely to be prescribed allopurinol (p = 0.002) and colchicine (p = 0.006); no significant difference was found for the use of specific disease-modifying anti-rheumatic drugs and TNF-α inhibitors.. High-risk, post-operative joint infection groups were identified allowing for precautionary clinical measures to be taken.

Topics: Aged; Allopurinol; Arthritis, Rheumatoid; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Shoulder; Case-Control Studies; Comorbidity; Diabetes Mellitus; Female; Glucocorticoids; Gout; Gout Suppressants; HIV Infections; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Logistic Models; Lupus Erythematosus, Systemic; Male; Middle Aged; Multivariate Analysis; Neoplasms; Obesity; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prednisone; Prosthesis-Related Infections; Retrospective Studies; Risk Factors; Sex Factors; Shoulder Joint; Surgical Wound Infection

This report describes the clinical, biochemical and molecular data of a 78-year-old patient with xanthine dehydrogenase deficiency presenting as rheumatoid arthritis.. Xanthinuria type I is a rare disorder of purine metabolism caused by xanthine dehydrogenase (XDH) deficiency; fewer than 150 cases have been described in the literature so far.. We describe the clinical history and urine and serum findings of a 78-year-old patient with isolated XDH deficiency presenting as rheumatoid arthritis. The diagnosis was confirmed by mutation analysis.. The patient suffered from arthral symptoms and nephrocalcinosis. Very low concentrations of uric acid were observed in her serum and urine. The allopurinol loading test indicated her xanthinuria to be type I. Analysis of genomic DNA revealed novel heterozygous deletion in exon 8 (g.27073delC, p.214QfsX4) and previously published heterozygous nucleotide missense transition in exon 25 (g.64772-C>T, p.T910M).. Hereditary xanthinuria is a rare disorder, but it also needs to be considered in patients not originating from Mediterranean countries or the Near or Middle East. Urate concentration in serum and urine may provide an initial indication of XDH deficiency before high-performance liquid chromatography (HPLC) analysis is performed. The key to identifying the disorder is a greater awareness of XDH deficiency amongst primary care physicians, nephrologists, and urologists, but also rheumatologists. The diagnosis and therapeutic management requires a multidisciplinary approach.

Topics: Aged; Allopurinol; Arthritis, Rheumatoid; Biomarkers; Chromatography, High Pressure Liquid; DNA Mutational Analysis; Exons; Female; Genetic Predisposition to Disease; Genetic Testing; Heterozygote; Humans; Metabolism, Inborn Errors; Mutation, Missense; Nephrocalcinosis; Phenotype; Predictive Value of Tests; Sequence Deletion; Uric Acid; Xanthine Dehydrogenase

Topics: Aged; Allopurinol; Arthritis, Rheumatoid; Female; Gout; Gout Suppressants; Hand Joints; Humans; Radiography; Toe Joint

In order to further understand and assess the validity of herbal medicine, we investigated the potential inhibitory effect of various extracts from Fraxinus angustifolia and Pistacia lentiscus, two plants used traditionally in Algeria against several inflammatory diseases such as rheumatism, arthritis, and gout, on purified bovine milk xanthine oxidase (XO) activity. The total phenolic contents of the leaves and bark of F. angustifolia and the leaves and seeds of P. lentiscus were estimated. P. lentiscus aqueous fractions from hexane and chloroform extractions and F. angustifolia aqueous fraction from ethyl acetate extraction inhibited XO activity by 72.74 +/- 2.63% (50% inhibitory concentration [IC(50)] = 27.52 microg/mL), 68.97 +/- 3.89% (IC(50) = 42.46 microg/mL) and 53.92 +/- 3.17% (IC(50) = 58.84 mmicroug/mL), respectively, at 100 microg/mL, compared to that of reference drug, allopurinol (98.18% [IC(50) = 6.34 microg/mL]). Moreover, at a concentration of 50 microg/mL, both P. lentiscus extracts showed inhibition rates higher than 50%. F. angustifolia leaf extracts showed only mild inhibition. Lineweaver-Burk analysis showed that the inhibitory activity exerted by F. angustifolia bark aqueous extract and P. lentiscus aqueous extracts is of mixed type, whereas the leaf extracts from F. angustifolia inhibited XO noncompetitively. Positive correlations were established between XO inhibition and total phenols (r = 0.89) and flavonoids (r = 0.93) for P. lentiscus and with total phenols (r = 0.72) and tannins (r = 0.54) for F. angustifolia. Our findings suggest that the therapeutic use of these plants may be due to the observed XO inhibition, thereby supporting their use in traditional folk medicine against inflammatory-related diseases, in particular, gout.

Topics: Algeria; Animals; Arthritis, Rheumatoid; Cattle; Down-Regulation; Enzyme Inhibitors; Fraxinus; Gout; Humans; Kinetics; Milk; Pistacia; Plant Extracts; Xanthine Oxidase

To enable clinicians to initiate appropriate steps for long-term management of gout, including controlling acute exacerbations and pain and sustaining target serum uric acid (SUA) levels to control hyperuricemia as the underlying metabolic disorder.. Incorporation of pertinent rheumatology and primary care literature seeking a comprehensive overview about the disease state of gout and its symptoms, comorbidities, and impact on quality of life, with a key focus on the role of serum uric acid, evidence-based approaches to long-term management of gout, and the importance of a functioning clinician-patient relationship.. Gout is increasingly recognized as a prevalent chronic disease state requiring appropriate long-term management while controlling for risk factors and comorbid conditions. Effective treatment options can help gout patients achieve therapeutic SUA targets to control gout flares and prevent potentially destructive disease manifestations. Patient education is an important element in achieving treatment goals and ensuring adherence.. Effective treatment plans for any gout patient must be guided by a long-term approach that focuses on sustained control of hyperuricemia, while providing continuous control of chronic disease. Patient education can be a key element in this process.

Topics: Acute Disease; Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Arthritis, Rheumatoid; Chronic Disease; Colchicine; Comorbidity; Disease Progression; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Patient Education as Topic; Quality of Life; Risk Factors; Thiazoles; Uric Acid; Uricosuric Agents; Xanthine Oxidase

To search whether xanthine oxido-reductase (XOR) present in the synovium is also liberated, to determine its activity in synovial fluid and to establish a possible relationship between XOR levels in rheumatoid arthritis (RA) and non-RA patients.. This study was carried out in the Laboratory of Immunology, University Ferhat Abbas, Setif, Algeria from 2001-2008. This study is a retrospective controlled study matching cases with RA to non rheumatoid joint inflammations. Synovial fluid (SF) samples were collected with consent of the patients, at Setif University Hospital, from adults suffering from RA (n=36) or only with joint inflammations (n=52). After its detection in SF with indirect enzyme-linked immunosorbent assay (ELISA) and dot-immunobinding, using anti-bovine XOR as first antibodies, XOR was assayed with capture ELISA.. Xanthine oxidoreductase is found in all studied SF. Capture ELISA showed levels up to 0.762 and 0.143 mg/mL in SF of RA and other joint inflammations patients, respectively. In most cases, more than 50% of synovial XOR is present as oxidase form. Positive correlation was observed between enzyme level and the disease severity since RA patients had a significantly high enzyme amount compared to patients with other less severe arthritic pathologies.. These results suggest that the enzyme could well be involved in joint inflammation probably by producing reactive oxygen species.

Topics: Adult; Arthritis; Arthritis, Rheumatoid; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoblotting; Male; Middle Aged; Osteoarthritis; Prognosis; Retrospective Studies; Severity of Illness Index; Synovial Fluid; Xanthine Oxidase

To study anti-bovine milk xanthine oxidoreductase XOR antibody levels in synovial fluid as well as in serum of patients suffering from rheumatoid affections to assess a possible correlation between antibody titres and severity of disease.. Sera and synovial fluids were collected from volunteer donors at Setif University Hospital, Setif, Algeria from 2001--2007 with the consent of patients. Human IgG and IgM levels of free and bound anti-bovine milk XOR antibodies were determined using bovine XOR as antigen, with enzyme-linked immunosorbent assay ELISA.. Serum IgG anti-bovine milk XOR titres in 30 healthy normal subjects 2.74+/-2.31 microgram/mL are in agreement with that reported in the literature. Immunoglobulin G and IgM anti-bovine milk XOR antibody titres were found to be significantly higher in serum from patients with rheumatoid arthritis RA, and latex positives subjects. Synovial IgM antibody titres to bovine XOR were found to be significantly higher in rheumatoid arthritis patients compared to patients with other joint inflammations.. In rheumatoid arthritis patients, high concentrations of antibodies against XOR were noticed. These antibodies may play a major role in RA by inhibiting both xanthine and NADH oxidase activities of XOR. They may also play a key role in eliminating XOR from serum and synovial fluid positive role but unfortunately, immune complex formation could also activate complement and participate in self maintenance of inflammation.

Topics: Adult; Animals; Antibodies; Arthritis; Arthritis, Rheumatoid; Cattle; Humans; Milk; Synovial Fluid; Xanthine Oxidase

The thioredoxin/thioredoxin reductase system is strongly induced in patients with rheumatoid arthritis (RA). We have investigated the impact on TR activity of doses of superoxide anion generated by the hypoxanthine (HX)/xanthine oxidase (XO) system and by hydrogen peroxide, H(2)O(2), for various times and compared the findings with synoviocytes obtained from osteoarthritis (OA) patients. At baseline, TR activity in RA cells was significantly higher than in OA cells (2.31 +/- 0.65 versus 0.74 +/- 0.43 mUnit/mg protein, p < 0.01). HX/XO and H(2)O(2) in RA cells decreased TR activity, which was found to be unchanged in OA cells. H(2)O(2) and superoxide anion caused a time-dependent accumulation of oxidized TR and induced the formation of carbonyl groups in TR protein in RA cells rather than OA cells, and oxidized the selenocysteine of the active site. The oxidation in TR protein was irreversible in RA cells but not in OA cells. In conclusion, we report that the oxidative aggression generates modifications in the redox status of the active site of the TR and induces an alteration of the Trx/TR system, concomitant with those of the other antioxidant systems that could explain the causes of oxidative stress related to RA disease.

Topics: Antioxidants; Arthritis, Rheumatoid; Female; Humans; Hydrogen Peroxide; Hypoxanthine; Immunoblotting; Immunoprecipitation; Male; Middle Aged; Oxidants; Oxidation-Reduction; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Superoxides; Synovial Membrane; Thioredoxin-Disulfide Reductase; Thioredoxins; Xanthine Oxidase

To find the antiinflammtory constituents of Acanthopanax chiisanensis (Araliaceae) leaves, phytochemical isolation procedures were performed by activity-guided fractionation in carrageenan- and Freund's complete adjuvant (FCA) reagent-induced rat models, respectively. In the two assay system, the MeOH extract (100 and 250 mg/kg, p.o.) showed significant antiinflammtory effects. Since BuOH extract among the fractionated extracts exhibited the most potent effect, it was subjected to column chromatography to yield a main triterpene glycoside, chiisanoside (1). This compound was hydrolyzed in alkaline solution to find the biological activity of produced aglycone, chiisanogenin (1a). Oral treatment with compounds 1 and 1a produced significant antiinflammtory effects at 10 and 30 mg/kg dose, and 1a was more potent than 1. The antiiflammtory effects of the two compounds were supported by the reduction of carrageenan-induced lipid peroxidation and hydroxy radical in serum. Furthermore, treatment with 1 and 1a significantly reduced rheumatoid arthritis (RA) and C-reactive protein (CRP) factors in the rat induced by Freund's complete adjuvant reagent. Compounds, 1 and 1a, inhibited xanthine oxidase activity and increased superoxide dismutase (SOD), glutathione peroxidase and catalase indicating that both compounds scavenged reactive oxygen species (ROS).

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Edema; Eleutherococcus; Enzyme Inhibitors; Male; Phytotherapy; Plant Leaves; Rats; Rats, Sprague-Dawley; Xanthine Oxidase

Bridelia ferruginea Benth. (Euphorbiaceae) is a subtropical medicinal plant widely used in traditional African medicine against various diseases, including rheumatic pains. Seven of its constituents (3-O-methylquercetin (1), 3,7,3',4'-tetra-O-methylquercetin (rutisin, 2), myricetin (3), 3',4',5'-tri-O-methylmyricetin (ferrugin, 4), 3,3',4',5'-tetra-O-methylmyricetin (5), quercetin 3-O-glucoside (6), and a biflavanol gallocatechin-[4'-O-7]-epigallocatechin (7)) have been evaluated in-vitro in the xanthine-xanthine oxidase enzymatic system for inhibition of xanthine oxidase and radical scavenging activity. Results indicated that compounds 1, 3, 4 and 6 exhibited, at different levels, xanthine oxidase inhibiting and superoxide scavenging activity at micromolar concentrations, whereas compound 7 showed scavenging activity only. Compounds 2 and 5 were inactive in both cases. Study of the structure-activity relationship demonstrated that for flavonoids the xanthine oxidase inhibitory activity was reduced by methylation of the hydroxyl functionality at C-3 and in rings A and B. These results may partly explain and support the use of B. ferruginea stem bark for the treatment of rheumatic pains in traditional medicine.

Topics: Arthritis, Rheumatoid; Free Radical Scavengers; Humans; Medicine, African Traditional; Phenols; Plant Extracts; Plants, Medicinal; Xanthine Oxidase

It has been suggested that enzymatic and/or non-enzymatic antioxidant systems are impaired in rheumatoid arthritis (RA) and hence patients are exposed to oxidant stress. This study aimed to establish whether this is really the case. Fasting blood samples were obtained from 24 patients with rheumatoid arthritis and 20 controls. The activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) enzymes and malondialdehyde (MDA), oxidant resistant (OR) and non-enzymatic superoxide radical scavenger activity (NSSA) values were measured in both groups. Patients with RA had higher SOD and XO activities and MDA levels than did the controls. However, NSSA and OR levels were found to be decreased, and CAT and GSH-Px activities unchanged in the study group. Results suggest that excessive free radical production through the xanthine-xanthine oxidase system is the primary factor in rheumatoid arthritis, rather than an impaired antioxidant system. The therapeutic use of XO enzyme inhibitors and some antioxidants can be beneficial in this regard.

Topics: Adult; Aged; Analysis of Variance; Antioxidants; Arthritis, Rheumatoid; Catalase; Erythrocytes; Female; Free Radical Scavengers; Free Radicals; Glutathione Peroxidase; Humans; Male; Malondialdehyde; Middle Aged; Oxidants; Oxidative Stress; Superoxide Dismutase; Xanthine Oxidase

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Arthritis, Rheumatoid; Biopsy; Colchicine; Diagnosis, Differential; Female; Gout; Gout Suppressants; Humans; Synovial Fluid; Uric Acid

To apply an electron spin resonance (ESR) spectroscopic technique as a means of determining the oxidising capacity of reactive oxygen species produced during hypoxia and reoxygenation of diseased human synovial tissue.. Twenty four specimens of fresh synovial tissue were obtained from patients undergoing primary total knee joint replacement and graded according to the degree of inflammation present. Tissue samples were subjected to an ex vivo hypoxia-reoxygenation cycle in the presence of the nitroso based spin trap, 3,5-dibromo-4-nitrosobenzene sulphonate. The degree of oxidation of the spin trap to a stable free radical was determined and followed with time. Control samples were subjected to hypoxia only.. The results indicate that the oxidising capacity of reactive oxygen species produced by human synovial tissue varies with the degree of inflammation present. Only the more inflamed specimens, from both rheumatoid arthritis and osteoarthritis patients, demonstrated increased production of reactive oxygen species when subjected to a hypoxia-reoxygenation cycle. This change was reduced by both competitive and non-competitive inhibitors of the endothelial based enzyme xanthine oxidase. The relative concentration of reactive oxygen species generated by the synovial tissue samples correlated with the mean capillary density of the specimens.. This study supports the hypothesis of movement induced hypoxicreperfusion injury of the chronically inflamed joint by demonstrating the generation of reactive oxygen species within inflamed human synovium following an ex vivo hypoxia-reoxygenation cycle. Evidence is presented that the microvascular endothelial based enzyme xanthine oxidase is the predominant source of ESR detectable oxidising species in inflamed synovial specimens exposed to hypoxia-reoxygenation.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Culture Techniques; Electron Spin Resonance Spectroscopy; Humans; Knee Joint; Middle Aged; Osteoarthritis; Oxypurinol; Reactive Oxygen Species; Reperfusion Injury; Synovial Membrane; Thiazoles; Xanthine Oxidase

Treatment of rabbit synovial fibroblasts with active oxygen (AO) released by xanthine/xanthine oxidase resulted in an induction of procollagenase in these cells in concentrations ranging from 12.5 micrograms/ml xanthine plus 0.0025 U/ml xanthine oxidase to 50 micrograms/ml xanthine plus 0.01 U/ml xanthine oxidase. Preceding this there was an accumulation of poly(ADP-ribose) for the same concentration range of xanthine/xanthine oxidase. Furthermore, it was found that AO caused activation of the latent procollagenase to the active enzyme in concentrations ranging from 0.1 micrograms/ml xanthine plus 0.00002 U/ml xanthine oxidase to 1 microgram/ml xanthine plus 0.0002 U/ml xanthine oxidase. It is suggested that poly(ADP-ribosyl)ation participates in the induction of procollagenase by relaxing chromatin. Furthermore, it is proposed that AO activates latent procollagenase under physiological conditions.

Topics: Animals; Arthritis, Rheumatoid; Cells, Cultured; Collagenases; Dose-Response Relationship, Drug; Enzyme Precursors; Extracellular Matrix; Fibroblasts; Interleukin-1; Models, Biological; Poly Adenosine Diphosphate Ribose; Rabbits; Reactive Oxygen Species; Synovial Membrane; Xanthine; Xanthine Oxidase; Xanthines

We suggest that crystals, when introduced into an organism, may behave as conventional antigens, mediating the production of specific antibodies. These antibodies would bear an imprint of the crystal surface and may consequently behave as a nucleating matrix in a new crystallization event. Thus, they would behave as catalytic antibodies. We show that IgG antibodies isolated from patients suffering from gout, a joint disease caused by crystals of monosodium urate monohydrate (MSUM), accelerate the appearance of new crystals of MSUM from a supersaturated solution of the salt in vitro. The same effect is not observed for IgG antibodies isolated from the joint fluids of patients with other joint diseases, such as pseudogout, rheumatoid arthritis, or osteoarthritis. Furthermore, IgG antibodies obtained from rabbits injected subcutaneously with crystals of MSUM, were also nucleating towards MSUM crystals.

Topics: Allopurinol; Animals; Antibody Formation; Arthritis, Rheumatoid; Crystallography; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Gout; Humans; Immunoglobulin G; Osteoarthritis; Rabbits; Synovial Fluid; Uric Acid

The effect of 5 days treatment with allopurinol (300 mg) on the pharmacokinetics of indomethacin at steady-state was investigated in eight patients. Allopurinol produced no significant effect on the indomethacin serum concentration-time curve. Allopurinol did not alter significantly the amounts of indomethacin excreted in the urine within 8 h. However, the urinary ratio of N-deschlorobenzoylindomethacin to indomethacin was reduced significantly by allopurinol administration (P less than 0.05).

Topics: Adult; Allopurinol; Arthritis, Rheumatoid; Biotransformation; Humans; Indomethacin; Middle Aged; Osteoarthritis

Topics: Allopurinol; Arthritis, Rheumatoid; Azathioprine; Drug Therapy, Combination; Humans; Liver

It is postulated that the mobile inflamed joint may be subject to cyclical ischaemic reperfusion injury. Xanthine oxidoreductase is an enzyme thought to contribute to oxidative reperfusion injury, and the detection of this activity in human synovium is described. Three normal and five rheumatoid tissues were assayed with a carbon-14 radioassay detecting the conversion of [14C]xanthine to [14C]uric acid. Rheumatoid synovia contained 0.67-305 microU/g tissue (n = 5), while normal synovia contained 1.2-5.0 microU/g tissue (n = 3).

Topics: Allopurinol; Arthritis, Rheumatoid; Humans; NAD; Synovial Membrane; Xanthine Oxidase

Interleukin-1 (Il-1)-like activity in biological fluids was measured by their ability to rectify the Il-1-dependent lymphokine production of highly purified T lymphocytes to a recall antigen. Il-1-like activity was found in 9 of 11 synovial fluid (SF) specimens from patients with rheumatoid arthritis (RA) but only in 2 of 11 paired RA sera. In traumatic synovitis, low Il-1-like activity was recorded in 5 of 9 SF specimens, and a similar low activity was found in sera of 4 of these patients. The Il-1-like activity was partly absorbed by an anti-Il-1 antibody. The presence of Il-1 in the SF of patients with RA suggests in vivo activation of monocytes/macrophages.

Topics: Adsorption; Adult; Aged; Allopurinol; Arthritis, Rheumatoid; Female; Humans; Interleukin-1; Lipoproteins, HDL; Macrophages; Male; Middle Aged; Monocytes; Synovial Fluid; Synovitis; Wounds and Injuries

Rheumatoid arthritis and gout are both common rheumatic diseases, but their coincidence is rare. We report the case of a 67-year-old Caucasian woman with rheumatoid arthritis who later developed tophaceous gout. The tophi disappeared with remarkable rapidity on treatment with allopurinol.

Topics: Aged; Allopurinol; Arthritis, Rheumatoid; Female; Gout; Humans

Topics: Acute Disease; Allopurinol; Arthritis, Rheumatoid; Colchicine; Diagnosis, Differential; Gout; Humans; Probenecid; Uremia; Uric Acid; Uricosuric Agents

Topics: Allopurinol; Arthritis, Rheumatoid; Gout; Humans; Male; Middle Aged

Topics: Adrenocorticotropic Hormone; Adult; Allopurinol; Arthritis, Rheumatoid; Colchicine; Diagnosis, Differential; Gout; Humans; Indomethacin; Male; Middle Aged; Phenylbutazone; Uricosuric Agents

Topics: Allopurinol; Arthritis, Rheumatoid; Aspirin; Cartilage; Chloroquine; Colchicine; Factor VIII; Glucuronidase; Hot Temperature; Humans; Immunoglobulin G; Indomethacin; Iodine Radioisotopes; L-Lactate Dehydrogenase; Methylprednisolone; Neutrophils; Peptide Hydrolases; Probenecid; Protein Denaturation; Sulfur Radioisotopes; Synovial Fluid; Triamcinolone Acetonide; Vinblastine

Topics: Allopurinol; Arthritis, Rheumatoid; Chondrocalcinosis; Colchicine; Diagnosis, Differential; Gout; Humans; Long-Term Care; Oxyphenbutazone; Phenylbutazone; Uric Acid

Topics: Allopurinol; Arthritis, Rheumatoid; Benzofurans; Diagnosis, Differential; Gout; Humans; Ketones; Psoriasis; Rheumatic Fever; Uric Acid

Topics: Allopurinol; Arthritis; Arthritis, Rheumatoid; Ohio; Rheumatic Diseases; Societies, Medical

Topics: Alkaline Phosphatase; Allopurinol; Arthritis, Rheumatoid; Blood Cell Count; Blood Protein Electrophoresis; Bone Marrow Examination; Creatinine; Erythrocytes; Feces; Gout; Humans; Iron; Iron Isotopes; Liver; Radiography; Sacrum; Spleen; Transaminases; Uric Acid

Topics: Adult; Aged; Allopurinol; Arthritis, Rheumatoid; Female; Gout; Humans; Kidney Calculi; Male; Middle Aged; Uric Acid