Gold metabolism in patients with rheumatoid arthritis treated with gold compounds—reinvestigated

Mascarenhas, Bento R.; Granda, J. L.; Freyberg, R. H.

doi:10.1002/art.1780150410

Cited by 113 publications

(68 citation statements)

References 15 publications

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“…Small amounts of gold were seen in association with garnmaglobulins. Calculations using this technique produce results similar to those reported by others, ie, at these concentrations up to 95% of gold is bound to serum albumin (10)(11)(12).…”

Section: Protein-binding Studiessupporting

confidence: 85%

Interaction of D‐Penicillamine with Gold Salts

Davis

Barraclough

1977

Arthritis & Rheumatism

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Serum and urinary gold levels were monitored in 18 patients previously treated with gold salts for rheumatoid arthritis and the effects of D-peniCihnine studied. There was no statistically significant change in urinary gold levels on D-penicillamine therapy although there were some individual variations. Serum gold levels fell during D-penicillamine therapy but the rates of fall did not differ from those seen in patients not treated. In vitro studies on protein binding of gold salts suggest that a high affinity exists between gold salts and albumin with low levels of unbound gold even at concentrations far exceeding those seen in vivo. These preliminary results Suggest that at therapeutic levels only small amounts of gold are available for chelation by penicillamine. It is concluded that penicilldmine at low dosage is an unreliable chelator of gold salts in vivo and its use in the management of gold toxicity remains speculative.Both gold salts and D-penicillamine suppress disease activity in rheumatoid arthritis (RA) (1,2). The property of penicillamine by which this is mediated is not known, but this compound is a chelating agent and will influence the mobilization and excretion of heavy metals, particularly copper (3). Penicillamine will chelate with gold, although the evidence for this is based mainly on studies in experimental animals (4-6). Much of the supporting clinical data is based on individual case reports (7,8) and only a few studies have reported experience with larger numbers of patients (4). Despite this, it is widely accepted that D-penicillamine may be of value in the chelation of gold salts and its use has been advocated in the management of patients with adverse reactions to chrysotherapy.It is our clinical practice to institute D-penicillamine therapy in patients with rheumatoid arthritis after gold therapy if an adverse reaction to gold salts occurs or if gold therapy fails to ameliorate disease a c h y . In view of the chelating properties of D-penicillamine, it is of potential importance to know its effect on the mobilization and excretion of gold salts in patients who had previously received gold therapy. This is particularly relevant in patients who had discontinued chrysotherapy because of an adverse reaction, since significant

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Section: Protein-binding Studiessupporting

confidence: 85%

Interaction of D‐Penicillamine with Gold Salts

Davis

Barraclough

1977

Arthritis & Rheumatism

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“…In other experiments, control cultures were performed with thiomalate (Sigma, St. Louis, MO), using 12.5 pg/ml and 25 pg/ml, which represent the proportion of thiomalate in 33 pg/ml and 66 &mi, respectively, of GST. A GST concentration of 10 pg/ml was chosen to represent a serum GST concentration readily achievable during routine chrysotherapy (35). Concentrations of 33 pg/ml and 66 pg/ml of GST reflect concentrations attainable in RA synovial tissues (36,37) and are lower than levels found in synovial macrophages exposed to long-term chrysotherapy (38).…”

Section: Methodsmentioning

confidence: 99%

Alterations in macrophage collagenase secretion induced by gold sodium thiomalate

Spalding

Darby

Heck

1986

Arthritis & Rheumatism

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The effects of gold sodium thiomalate (GST) on the production of specific collagenase by thioglycolateelicited macrophages was investigated. Our studies demonstrated that GST administration can significantly decrease collagenase production in a dose-dependent manner. These effects were observed with levels of GST attainable in serum or synovial tissue during routine chrysotherapy. In addition, GST altered lysozyme secretion by activated macrophages in a pattern distinct from that of collagenase alteration. These effects of enzyme secretion were not secondary effects of GST on viability, general protein secretion, or the specific assay procedures utilized, and were not attributable to the thiomalate moiety. Thus, GST may exert its therapeutic effect in rheumatoid arthritis through interference with the production of degradative proteolytic enzymes, which are important effector molecules mediating tissue destruction.In 1934, Forestier presented a report which summarized the favorable results he found after 6 years of treating more than 550 rheumatoid arthritis (RA) patients with gold salts (1). Since that time, chrysotherapy has been recognized as an important

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“…The concentrations that were used (Traber et al 1999) were clinically relevant as they were similar to the concentration of gold in the synovium and blood of patients on chrysotherapy (Mascarenhas et al 1972;Yoshida et al 1998;Stern et al 2005).…”

Section: Gold(i) Compoundsmentioning

confidence: 99%

HIV therapeutic possibilities of gold compounds

2010

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Highly active antiretroviral therapy (HAART) has resulted in decreased mortality and morbidity from the acquired immune deficiency syndrome caused by the human immunodeficiency virus (HIV). Drug resistance and toxicity of HAART has led to the search for novel inhibitors of HIV infection. Gold-based compounds have shown promising activity against a wide range of clinical conditions and microorganism infections including HIV-1. A typical example is auranofin which resulted in an elevated CD4? T-cell count in an HIV patient being treated for psoriatic arthritis. In addition, reports exist on gold-based inhibitors of reverse transcriptase (RT), protease (PR) and viral entry of host cells. These and other characteristics of goldbased HIV drugs are reviewed here.

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Gold metabolism in patients with rheumatoid arthritis treated with gold compounds—reinvestigated

Cited by 113 publications

References 15 publications

Interaction of D‐Penicillamine with Gold Salts

Interaction of D‐Penicillamine with Gold Salts

Alterations in macrophage collagenase secretion induced by gold sodium thiomalate

HIV therapeutic possibilities of gold compounds

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