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PubMed1994

Treatment of psoriatic arthritis with auranofin and gold sodium thiomalate.

Forty-two patients with psoriatic arthritis were included in a multicenter, double-blind trial comparing auranofin and gold sodium thiomalate (GST) for 6 months, followed by a 6-month open treatment. Fifty-two percent of the patients on auranofin and 33% on GST were able to complete the 1-year course of therapy. As a result of the study we conclude that both gold compounds are effective agents in the treatment of psoriatic arthritis. Degree of improvement of arthritis was better in the GST group, but the number of improved patients was greater in the auranofin group. Two patients on auranofin were withdrawn for side effects (one diarrhoea, one worsening of psoriasis) and 5 on GST (rash 2, total loss of appetite 1, exacerbation of psoriasis 2). Comparing the side effects of both compounds, auranofin is less likely to aggravate the psoriatic condition or result in withdrawal of patients for adverse reactions.

Adult↗
PubMed1979

Gold excretion and retention during auranofin treatment: a preliminary report.

Auranofin, an oral gold compound, was administered to 12 patients with rheumatoid arthritis using 2 dosage schedules (3 mg or 1 mg twice daily for 8 weeks, and then once daily for 18 weeks). In addition to outpatient clinic monitoring, all patients were admitted to a metabolic ward for 3 days for collection of 24 hr daily urine and feces. Gold content of excreta was determined by atomic absorption spectroscopy. Seventy-three per cent of the administered gold was recovered in the urine and feces of patients receiving 3 mg b.i.d., and all the gold was recovered in those taking 1 mg b.i.d. Ninety-five per cent of the recovered gold was in the feces and 5% was in the urine. These findings contrast with those observed during intramuscular (gold sodium thiomalate) chrysotherapy: 40% of the injected dose was recovered, 70% in urine, 30% in feces. Less tissue gold retention occurred with oral gold than with parenteral therapy. Following 20 weeks of auranofin (6 mg/day) chrysotherapy approximately 66 mg of gold was retained. By comparison, 300 mg of gold was retained after injectable gold sodium thiomalate treatment. The significance of these findings is discussed.

Adult↗
PubMed2001

Gold as an oral corticosteroid sparing agent in stable asthma.

BACKGROUND: Patients with chronic severe asthma are often dependent on the long term prescription of oral corticosteroids. The use of steroids is associated with serious side effects. Physicians treating such patients continue to search for alternative therapies that reduce the need for chronic dosing with oral steroids. Gold compounds are immunosuppressive agents and have benefits in the treatment of a number of inflammatory disorders. They have therefore been identified as an potentially useful agents in the treatment of chronic severe asthma both in terms of possible efficacy and as steroid sparing agents. OBJECTIVES: The objective of this review was to assess the effects of adding gold to oral steroids in the treatment of chronic steroid dependent asthmatics. SEARCH STRATEGY: The Cochrane Airways Group trials register and reference lists of identified articles were searched. SELECTION CRITERIA: Randomised trials looking at the addition of gold compared to placebo in adult steroid dependent asthmatics. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Three trials fulfilled the criteria for inclusion in the review and a total of 376 patients were recruited into these studies. Data from 311 patients could be analysed. There was a small but significant treatment effect for gold in terms of steroid dose reduction (Peto Odds Ratio 0.51, 95% confidence intervals 0.31,0.83). No meta-analysis could be done for measures of lung function although overall there were few changes suggesting a positive benefit for gold. There were trends suggestive of adverse effects but no significant changes for gold treated patients with respect to proteinuria (Peto Odds Ratio 1.4, 95% confidence intervals 0.6, 3.3) dermatitis/eczema Peto Odds Ratio 2.1, 95% confidence intervals 0.9, 4.7). REVIEWER'S CONCLUSIONS: The changes seen in these trials are small and probably of limited clinical significance. Given the side effects of gold and necessity for monitoring the use of gold as a steroid sparing agent in asthma cannot be recommended.

Adrenal Cortex Hormones↗
PubMed1988

Rheumatoid arthritis: a pharmacologic overview.

Numerous drugs are available for the treatment of rheumatoid arthritis. The nonsteroidal anti-inflammatory drugs differ in structure and pharmacokinetics, and they rarely act synergistically. The disease-modifying antirheumatic drugs include gold compounds, penicillamine, hydroxychloroquine and sulfasalazine. Useful immunosuppressive and cytotoxic agents include methotrexate, azathioprine and cyclophosphamide. Costicosteroids find their greatest use in short courses.

Adrenal Cortex Hormones↗
PubMed1983

Auranofin: experience to date.

Auranofin, an oral gold-containing medication for the treatment of rheumatoid arthritis, has unique chemical, pharmacologic, and kinetic characteristics. Clinical improvement is achieved with lower blood gold levels than with parenteral gold compounds. More than 3,000 patients with rheumatoid arthritis in 27 countries have been treated with auranofin to date. In many patients, experience with auranofin extends beyond three years, and in some it exceeds four years. Available information indicates that auranofin (3 mg twice a day) is superior to placebo therapy, with similar efficacy and greater safety than gold sodium thiomalate.

Animals↗
PubMedDate not supplied

Intracellular accumulation and cytotoxic effect of (8-thiotheophyllinate) (triphenylphosphine) gold(I) in Friend leukemia cells.

Following continuous exposure to tTAuP in medium containing 10% fetal calf serum (FCS), cells resistant to doxorubicin (DOX-RFLC) were 3 fold more resistant to tTAuP than its sensitive counterpart (FLC). Moreover, FLC were 100 fold more sensitive to tTAuP when the cells were grown in the absence of FCS but in the presence of synthetic medium (BMS). When the cytotoxic effect was measured after short-term exposure (60 min) followed by 72 hr incubation in drug-free medium, unexpectedly, DOX-RFLC were 8 fold more sensitive [ID50 = 1.5 microM] than FLC [ID50 = 12 microM] to tTAuP. When FLC were exposed 60 min at different temperatures (4, 25 or 37 degrees C) to tTAuP prior to 72 hr incubation in drug free medium, the ID50 was achieved at 20, 13 and 3 microM respectively). In contrast, when DOX-RFLC were treated in similar conditions, the cytotoxic activity of tTAuP did not vary following exposure at 4, 25 or 37 degrees C. Although the mechanism of action of gold compounds is still unknown we have assumed that tTAuP cytotoxicity is related to the ease with which it is accumulated. This assumption was supported by the analysis of tTAuP incorporation by SXRF. The results reported here show that tTAuP accumulates rapidly in the cell and is distributed in the cytoplasmic and the nuclear fractions. It is suggested that accumulation is mediated by passive diffusion. However, the detection of gold binding to DNA in complexes resistant to solvent treatments suggests that interaction with macromolecules can be mediated by the formation of covalently bound complexes.

Animals↗
PubMed1987

Benign lymphoplasia of the earlobes induced by gold earrings: immunohistologic study on the cellular infiltrates.

We report three patients with peculiar nodules of the earlobes that developed a few months after the wearing of pierced-type gold earrings. Biopsy specimens showed dense infiltration of lymphoid cells in the dermis and subcutaneous tissue associated with the formation of lymphoid follicles. The clinical and histologic pictures were similar to those of lymphocytoma cutis. Immunohistologically, the nodular lesions were characterized by the proliferation of T cells, mainly suppressor/cytotoxic T cells, and the presence of histiocytic cells displaying Leu-3a antigens on the surface. Patch tests of aqueous gold compound induced a strong skin reaction. A histologic study of the patch test reaction sites revealed a picture of ordinary allergic contact dermatitis showing that T cells, including both helper and suppressor T cells, invaded the spongiotic epidermis and the papillary dermis. Eosinophils and a few Langerhans cells were also present in the dermal infiltrates. These findings suggest that pierced-type gold earrings induced a long-term dermal response that resulted in producing benign lymphoplasia in the sensitized individuals.

Adult↗
PubMed1975

The influence of chrysotherapy on serum protein and immunoglobulin levels, rheumatoid factor, and antiepithelial antibody titers.

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.

Aged↗
PubMed1985

Monocytes and granulocytes in rheumatoid arthritis (RA): phagocytic activity and superoxide anion production.

It is suggested by many tests that phagocytic cells were implied in inflammation which occurred during rheumatoid arthritis (RA). Further, three subject populations were selected for this study: Rheumatoid arthritis patients diagnosed according to American Rheumatism Association criteria (ARA mean = 6) and treated with gold compounds. Control subjects treated with the same non-steroidal anti-inflammatory drug (NSAID), diclofenac (75 mg per day). Normal subjects without disease or treatment. Blood granulocytes and monocytes were separately tested for ingestion of three different particle species (opsonized zymosan, immunoglobulin G sheep red cells, glutaraldehyde-treated sheep red cells) and stimulation of superoxide anion production by these particles. All phagocytic cells in RA patients have normal phagocytic response and superoxide anion production. Autologous serum does not inhibit the activity of these cells. In addition the NSAID (diclofenac) does not act upon phagocytosis and oxidative burst of control cells.

Adolescent↗
PubMed1983

Auranofin (SK + F 39162) induced enterocolitis in rheumatoid arthritis. A case report.

A case of gold-induced enterocolitis in a 69-year-old female with rheumatoid arthritis who had received the new gold compound by oral administration (Auranofin (AF) for 4 weeks) is reported. Mild diarrhoea is a commonly described side effect accompanying AF, but in this case a severe colitis developed. The course of this case is very similar to those reported regarding Myochrysin. The pathogenesis is discussed. It might be a direct toxic effect on the mucosa of the bowel, evidenced by the relatively high excretion of oral gold with faeces.

Administration, Oral↗
PubMed1979

Cellular antiproliferative action exerted by auranofin.

Auranofin (AF) is a new orally absorbed coordinated gold compound currently undergoing Phase I studies for its use in the treatment of rheumatoid arthritis. Our investigations with RAJI lymphoma, HeLa carcinoma, and EBV-transformed cells indicate AF exerts an inhibitory effect on DNA, RNA, and protein synthesis as assessed by 3H-thymidine, 3H-uridine, and 3H-leucine uptake, respectively. A rapid and persistent dose dependent inhibition of 3H-thymidine uptake was observed at gold concentrations of 50-100 microgram/dl while all parameters were inhibited after a 24 hr exposure to 100 microgram/dl. Reductions in viability and surface morphological changes were also observed. These results suggest AF exerts a significant inhibitory effect on essential biological processes and functions.

Aurothioglucose↗
PubMed1999

Metals and kidney autoimmunity.

The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease of the kidney and other tissues. Gold compounds, currently used in the treatment of patients with progressive polyarticular rheumatoid arthritis, can cause a nephrotic syndrome. Similarly, an immune-mediated membranous nephropathy frequently occurred when drugs containing mercury were commonly used. Recent epidemiologic studies have shown that occupational exposure to mercury does not usually result in autoimmunity. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals. Laboratory investigations have confirmed that the administration of gold or mercury to experimental animals leads to autoimmune disease quite similar to that observed in human subjects exposed to these metals. In addition, studies of inbred mice and rats have revealed that a few strains are susceptible to the autoimmune effects of gold and mercury, whereas the majority of inbred strains are resistant. These findings have emphasized the importance of genetic (immunogenetic and pharmacogenetic) factors in the induction of metal-associated autoimmunity. (italic)In vitro(/italic) and (italic)in vivo(/italic) research of autoimmune disease caused by mercury and gold has already yielded valuable information and answered a number of important questions. At the same time it has raised new issues about possible immunostimulatory or immunosuppressive mechanisms of xenobiotic activity. Thus it is evident that investigations of metal-induced renal autoimmunity have the potential to produce new knowledge with relevance to autoimmune disease caused by xenobiotics in general as well as to idiopathic autoimmunity.

Animals↗
PubMed1988

Breath pentane excretion as a marker of disease activity in rheumatoid arthritis.

Activated inflammatory cells are capable of stimulating lipid peroxidation. In 27 patients with rheumatoid arthritis, we measured the pulmonary excretion of pentane, a product released during lipid peroxidation. We found highly significant correlations between pentane excretion and both joint inflammation (r = 0.88, p less than 0.001) and the erythrocyte sedimentation rate (r = 0.80, p less than 0.001). Patients treated with gold compounds or D-penicillamine excreted diminished amounts of pentane. The data suggest that lipid peroxidation may be related in part to the mechanism of injury in rheumatoid arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Inhibitory effects of gold sodium thiomalate on the proliferation and interferon-gamma induced HLA-DR expression in human endothelial cells.

Our study was undertaken to investigate the effects of gold sodium thiomalate (GSTM) on the proliferation and HLA-DR antigen expression of human umbilical vein endothelial cells (EC). The proliferation of the EC was determined by 3H-thymidine incorporation into the EC. The expression of HLA-DR antigen on the surface of the EC was detected by an indirect immunofluorescent method using a fluorescent flow cytometer. When GSTM was added at the start of the EC culture, GSTM at a low concentration could inhibit the proliferative response of the EC to endothelial cell growth supplement. Furthermore, when the EC were cultured with recombinant interferon-gamma (rIFN-gamma) and GSTM, GSTM was also able to suppress the HLA-DR antigen expression on the surface of EC induced by rIFN-gamma. On the time-kinetic study of the effects of GSTM on the HLA-DR antigen expression induced by rIFN-gamma, the pretreatment of GSTM was able to suppress the HLA-DR antigen expression, whereas GSTM did not affect the HLA-DR antigen expression already induced by rIFN-gamma. Our findings suggest that the therapeutic effects of gold compounds in patients with rheumatoid arthritis may be attributed to the interference of the proliferation and HLA-DR antigen expression of the EC.

Antigens, Surface↗
PubMed1984

Inhibition of polyclonally induced immunoglobulin secretion by aurothiomalate.

The influence of sodium aurothiomalate on the secretion of immunoglobulins by normal human lymphocytes in vitro was investigated by means of a reverse hemolytic plaque forming cell (PFC) assay. Aurothiomalate inhibited the PFC response induced by pokeweed mitogen (PWM) and by Epstein-Barr virus (EBV) in a dose dependent manner. The inhibition was irreversible, as pre-incubation for 2 h with the drug followed by extensive washing and further culture in gold salt-free medium still caused an inhibition of the PFC response to PWM and to EBV. Cell proliferation was not significantly affected, suggesting that the inhibition of PFC formation was not due to cytotoxicity. Pre-incubation of monocytes/macrophages (Mø's), T lymphocytes and B lymphocytes with the gold compound prior to culture with PWM showed that Mø's and B cells were highly sensitive, whereas T lymphocytes were resistant to the drug. The findings indicate that aurothiomalate inhibits the polyclonally induced PFC response by interfering with accessory Mø function and by affecting the B lymphocyte itself.

B-Lymphocytes↗
PubMed1992

Role of glutathione peroxidase in rheumatoid arthritis: analysis of enzyme activity and DNA polymorphism.

Aberrant expression of the antioxidant enzyme glutathione peroxidase (GPx) could contribute to the etiology of rheumatoid arthritis (RA). However, previous enzyme activity studies examining this relationship were inconclusive. Indirect evidence for this relationship derives from the known efficacy of gold therapy in RA, since gold compounds specifically inhibit GPx. The hypothesis that variants of GPx are associated with RA was examined by two approaches: enzyme activity analysis and restriction fragment length polymorphism (RFLP) association analysis. No significant difference was found in whole blood GPx activity between 28 RA patients and 36 controls. GPx activity appeared to be independent of sex, race, or type of drug treatment. However, a statistically significant difference was found with respect to treatment responsiveness. RA patients classified as good responders to gold therapy, but who were no longer taking gold, had a significantly higher GPx activity compared to both the controls and good responders currently on gold therapy. Aberrantly high GPx activity could contribute to RA by generating excess oxidized glutathione, a potent collagenase activator. Gold therapy would reduce GPx activity to normal levels. The restriction enzyme Pvu II in conjunction with a GPx gene probe identified a useful RFLP (Al, 22 kbp; A2, 15 kbp) with allelic frequencies of A1 and A2 equal to 0.11 and 0.89, respectively, in the control population. No statistically significant association, however, could be demonstrated between this allelic variant of the GPx gene and RA.

Adult↗
PubMed1984

Pemphigus vulgaris: results of treatment with gold as a steroid-sparing agent in a series of thirteen patients.

Between 1974 and 1981, thirteen patients with pemphigus vulgaris were treated with prednisone supplemented by gold salts. Therapy resulted in excellent responses in eleven of the thirteen, with complete remission in seven. At a mean follow-up of 48.8 months, five patients still had complete remission and required no further treatment. Treatment of pemphigus vulgaris initially with prednisone followed by gold compounds is recommended as an important modality with relatively low morbidity and may permit lower effective doses of corticosteroids to be employed, occasionally even permitting their complete withdrawal.

Adult↗
PubMed1983

Practices, strategies, and motivations in treatment of rheumatoid arthritis.

National Analysts conducted primary research with rheumatologists--specifically, two panel discussions, 25 in-depth telephone interviews, and a mail survey of conference (Auranofin Symposium and Workshop) participants--to examine current treatment practices and to probe the rationale and motivations underlying treatment strategies in rheumatoid arthritis. The research identified important areas of consensus in drug perceptions, therapeutic approaches, and disagreements. Physicians differ regarding the minimum time they wait after diagnosing rheumatoid arthritis before initiating remittive therapy, some beginning immediately and others waiting six months or longer. Younger physicians are quicker to initiate remittive treatment than their older colleagues, but both younger and older practitioners are initiating remittive therapy earlier than in the past. Some noteworthy differences between hospital-based and office-based practitioners were discerned with respect to factors that figure in their decisions to initiate remittive therapy. Differences were also found among physicians in the way they pose drug options to their patients; "authoritarian," "libertarian," and "guided democracy" were names given to the three styles identified. In general, however, physicians report that patients are more directly involved in treatment selection than previously, a trend that may in part be due to the use of more aggressive treatment strategies than in the past and a desire to share the psychologic burden of those decisions. Findings suggest that gold compounds will continue to be a mainstay first-line disease-modifying agent in the treatment of rheumatoid arthritis but that there may be less reluctance to use other agents as physicians become increasingly familiar and comfortable with alternative options, especially penicillamine and immunosuppressive agents.

Adult↗