Disease relevance of Monomercaptosuccinic acid

• The relative risk of proteinuria during treatment with aurothiomalate is increased 32 times in patients who are HLA-DRw3 positive [1].
• Patients with RA who develop dermatitis following treatment with sodium aurothiomalate [gold(I)] have T cells which proliferate in an HLA-DR-restricted manner in response to HAuCl4 [gold(III)] [2].
• Two patients developed a Guillain-Barre-like syndrome and a third suffered neuropathy and myokymia during therapy with sodium aurothiomalate [3].
• The relationship between adverse reactions to chrysotherapy and specific IgE antibodies to sodium aurothiomalate (auIgE) was studied in 67 patients with rheumatoid arthritis (62) or psoriatic arthritis (5) [4].
• Sodium aurothiomalate, at concentrations of 10 to 150 microgram/ml of culture, inhibited rat lymphocyte stimulation by Mycoplasma pulmonis mitogen in a dose-dependent manner [5].

High impact information on Monomercaptosuccinic acid

• HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis [1].
• The antirheumatic drug disodium aurothiomalate inhibits CD4+ T cell recognition of peptides containing two or more cysteine residues [6].
• To determine the effects of aurothioglucose, aurothiomalate, and auranofin on basal and forskolin-activated adenylyl cyclase activity in human total lymphocyte membranes, and in membranes of T and B lymphocyte subsets [7].
• In addition, a gold salt currently used for therapy of chronic inflammation, auranofin, induced hsp and inhibited IL-1 beta biosynthesis, whereas a second salt, sodium aurothiomalate, did neither [8].
• We have also observed the selective inhibition of chemotactic responsiveness of human blood monocytes by a clinically useful antirheumatic drug, sodium aurothiomalate [9].

Chemical compound and disease context of Monomercaptosuccinic acid

• Nineteen of 24 patients in whom proteinuria developed were positive for HLA-B8 and HLA-DRW3 antigens; 14 of 15 episodes of aurothiomalate-induced proteinura and nine of 13 episodes of penicillamine-induced proteinura occurred in patients with these antigens [1].
• 2 NaAuCl4, aurothioglucose, aurothiomalate, auranofin and chloro-triethyl phosphine) gold all inhibited the trypsin-like neutral protease on the surfaces of Ehrlich ascites tumour cell membranes equally well [10].
• Measurement of 'free' gold in patients receiving disodium aurothiomalate and the association of high free to total gold levels with toxicity [11].
• In a prospective study of 45 patients with rheumatoid arthritis mucocutaneous symptoms and signs were evaluated before and during treatment with intramuscular sodium aurothiomalate (Myocrisin) [12].
• BACKGROUND: Sodium aurothiomalate has been reported to have in vitro activity against Helicobacter pylori [13].

Biological context of Monomercaptosuccinic acid

• Paradoxical derepression of collagenase gene expression by the antirheumatic gold compound aurothiomalate [14].
• We report that aurothiomalate negatively modulates glucocorticoid hormone action; it represses the ligand- and DNA-binding activities and the transactivation function of the glucocorticoid receptor [15].
• Sodium aurothiomalate produced dose-related reductions in chemotaxis in normal subjects and in patients who had a good clinical response to gold therapy, while patients who had failed to respond to gold showed a minimal nondose dependent reduction [16].
• The present studies have shown that gold complexes [auranofin (AF), aurothiomalate (Autm), aurocyanide (Au(CN)2-)] have contrasting effects on the membrane potential of 3,3'-dipentyloxacarbocyanine [di-O-C5(3)] loaded PMN [17].
• In these studies, the Cys2His2 zinc finger was chosen as a model for understanding how the gold (I) (Au1+) drug, aurothiomalate (AuTM), interacts mechanistically with the Zn2+ coordination sphere [18].

Anatomical context of Monomercaptosuccinic acid

• Intramuscular injection of sodium aurothiomalate (Myochrysine) produced lysosomes (aurosomes) of a characteristic morphology distinct and different from other lysosomes [19].
• Intramuscularly injected sodium aurothiomalate in immature rabbits leads to the production of aurosomes in the articular cartilage chondrocytes and synovial intimal cells and subsynovial macrophages [19].
• Renal tubular dysfunction was induced in Hartley guinea pigs by injection of sodium aurothiomalate (gold) as manifested by excretion of tubular basement membrane (TBM) antigen and renal tubular epithelial (RTE) antigen in urine and tubular proteinuria [20].
• Chemotactic and phagocytic analysis of leucocytes in the exudate showed that there was a significant suppression of the neutrophil activities in all the mice treated with sodium aurothiomalate [21].
• Action of sodium aurothiomalate on erythrocyte membrane [22].

Associations of Monomercaptosuccinic acid with other chemical compounds

• We identified aurothioglucose (ATG), a gold compound used clinically to treat rheumatoid arthritis, and the related compound, aurothiomalate (ATM), as potent inhibitors of PKCiota-Par6 interactions in vitro (IC(50) approximately 1 micromol/L) [23].
• Zinc ions antagonize the inhibitory effect of aurothiomalate on glucocorticoid receptor function at physiological concentrations [15].
• Two meta-analyses showed that methotrexate is among the most efficacious of slow-acting antirheumatic agents, together with parenteral gold (sodium aurothiomalate), penicillamine and sulfasalazine [24].
• Monocyte superoxide anion production in rheumatoid arthritis: preliminary evidence for enhanced rates of superoxide anion production by monocytes from patients receiving penicillamine, sodium aurothiomalate and corticosteroids [25].
• Although thiomalate penetrates cellular membranes slowly in vitro. the compound is found in all organs, mostly in the liver and the kidneys, after administration of aurothiomalate [26].

Gene context of Monomercaptosuccinic acid

• The in vivo effect of triethylphosphine gold (auranofin), sodium aurothiomalate and azathioprine on natural killer cell activity of patients with rheumatoid arthritis [27].
• Sodium aurothiomalate inhibits T cell responses to interleukin-2 [28].
• The drugs sodium aurothiomalate, D-penicillamine and sulphasalazine were all able to modulate IL-8 mRNA synthesis in and protein secretion from endothelial cells [29].
• RESULTS: IL-1 beta and TNF-alpha caused a prominent PMN-mediated 51Cr release that was dose-dependently reduced when auranofin (AF) or gold sodium aurothiomalate (GSTM) were added to PMN and HUVEC in the assay system [30].
• We studied the effects in vitro of sodium aurothiomalate (GSTM) on the production of, and response to, a monocyte supernatant with interleukin-1 (IL-1)-like activity [31].

Analytical, diagnostic and therapeutic context of Monomercaptosuccinic acid

• In a double-blind study, patients were randomly selected for treatment using conventional doses (CD; 50 mg) or high doses (HD; 150 mg) of sodium aurothiomalate given weekly by injection [32].
• The cytosolic gold concentration and the association of 199Au with cytosolic proteins after gel filtration were similar in both cell lines after sodium aurothiomalate exposure to the exponentially growing cells [33].
• It is therefore concluded that the significant reduction in the number of exudate leucocytes at the carrageenan induced inflammatory site after treatment with sodium aurothiomalate is most likely due to the direct action of gold on the functional activities of circulating neutrophils [21].
• It is shown that sodium aurothiomalate does not act as an antipyretic after intravenous injection of two pyrogens into rabbits [34].
• Inefficacy led to cessation of treatment in 14 patients receiving auranofin, 27 receiving placebo, and one receiving sodium aurothiomalate [35].

References