Free thiomalate is measureable in the plasma and urine of patients with rheumatoid arthritis receiving sodium aurothiomalate (Myocrisin). Plasma concentrations and urinary excretion of free thiomalate were measured in 8 patients by high-performance liquid chromatography and electrochemical detection. After an initial intramuscular dose of 20 mg sodium aurothiomalate, free thiomalate was detecte...

The excretory fate and plasma level of thiomalate were studied after intramuscular administration of auro-14C-thiomalate to 3 patients with rheumatoid arthritis. The gold and the thiomalate parts separated in vivo, and the free thiomalate was excreted in the urine, rapidly at first and then slowly. After one day about 60% of the 14C-label had been recovered in the urine. The plasma level also d...

Endothelial adhesion molecules play an important role in the tissue recruitment of leukocytes in inflammatory conditions such as rheumatoid arthritis. We have investigated the effect of the antirheumatic drug gold sodium thiomalate on adhesion molecule protein and mRNA expression in cultured human endothelial cells. Gold sodium thiomalate inhibited cytokine (TNF, IL-1, IL-4)-stimulated expressi...

Cultured human epithelial cells (HE), grown as monolayers, acquired resistance to otherwise lethal concentrations (300 mumol/l, culture medium) of sodium aurothiomalate during five months' exposure to stepwise increased concentrations of the drug. The resistance acquired was shown by exposure to drug concentrations ranging from 25 to 300 mumol/, resulting in 100% of the resistant cells (HeMyo) ...

Human synovial cells from cases of rheumatoid and osteoarthritis were cultured and at their 3-5 passages, were treated with gold thiomalate. At early-log phase gold thiomalate arrested the proliferation of cells. However, at confluent state shere was a slight proliferation of synovial cells. This was followed by an increase in prolyl hydroxylase, collagen and protein synthesis, indicating that ...

Clinical formulations of the antiarthritic drug aurothiomalate sometimes contain phenylmercury(ll) compounds as antimicrobial preservative agents and, in the presence of para-chloromercuri-benzoate, aurothiomalate is a potent inhibitor of collagenase. By (1)H NMR spectroscopy, para-hydroxymercuribenzoate and para-hydroxymercuriphenylsulphonate were shown to react with aurothiomalate by complexi...

We have previously shown that cells with a high content of the gold-binding protein metallothionein (MT) are resistant to the growth inhibitory effects of gold(III) chloride and auranofin. To investigate whether MT confers resistance to sodium aurothiomalate two cell lines of cultured human epithelial (HE) cells were used; the parental cell line (HE) and a substrain (HE100) containing high leve...

Sixteen patients with seropositive rheumatoid arthritis were treated with 20 mg disodium aurothiomalate (Myocrisin) weekly for six months. Disease activity was assessed before and after treatment. Plasma profiles and urinary excretion of free thiomalate were measured in all patients after the initial injection and again at six months in the 12 patients remaining on therapy. No difference was fo...

Several HMGB1-specific antagonists have provided beneficial results in multiple models of inflammatory disease-preclinical trials including arthritis. Since no HMGB1-specific targeted therapy has yet reached the clinic, we have performed in vitro studies to investigate whether any of a selection of well-established antirheumatic drugs inhibit HMGB1 release as part of its mode of action. Freshly...