Clinical response and serum gold levels in chrysotherapy. Lack of correlation.

Gerber, Robert C.; Paulus, Harold E.; Bluestone, Rodney; Pearson, Carl M.

doi:10.1136/ard.31.4.308

Cited by 70 publications

(31 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…T h e benefits of such manipulation are unproven and the techniques of measurement are expensive and lend themselves to considerable variability in uncontrolled settings. Our study could not define significant correlations between weekly serum stable gold concentrations and clinical course and toxicity, confirming several previous reports (14)(15)(16). Therefore, the current results fail to support the use of serum gold concentrations to monitor gold treatment.…”

Section: Recent Reports Reflect Current Interest Insupporting

confidence: 67%

“…Investigators have sought to correlate serum and plasma gold concentrations with the clinical course of RA in an effort to obtain a test with prognosticative value and thereby enhance and perpetuate the therapeutic benefits of gold and reduce the incidence and severity of gold toxicity (12)(13)(14)(15)(16)(17). T h e results of these studies have been conflicting, however, and are responsible in part for stimulating this study.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pharmacodynamics of ¹⁹⁷Au and ¹⁹⁵Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion

Gottlieb¹,

Smith²,

Smith³

1974

Arthritis & Rheumatism

View full text Add to dashboard Cite

The relationships between serum stable gold (IS7Au) concentration and serum and whole blood radioactive gold (IS5Au) disappearance curves to clinical course and gold excretion are analyzed in this prospective clinical-metabolic study of 18 patients with active rheumatoid arthritis (RA). Patients received a standard course of Myochrysine (' O' Au aurothiomalate), were given lD5Au labeled aurothiomalate to monitor current dose dynamics, and clinically evaluated at regular intervals. Stable and radiogold concentrations in blood were measured serially on an outpatient basis and during periods of hospitalization using neutron activation anallysis and standard radiometric techniques. Serum concentrations of both isotopes failed to correlate with clinical course and toxicity. Serum radiogold disappearance curves were similar in patients who received radioactive gold on two or more occasions, despite changes in clinical course. Whole blood radiogold disappearance curves however were significantly different in most and least improved patients. These findings, and others reported herein, suggest that a) the probable interstitial or intracellular mechanism(s) of action of gold on the inflammatory process are not dependent upon serum gold concentrations and b) they raise the possibility that whole blood radiogold disappearance curves would provide a means of selecting those patients who will derive maximum therapeutic benefit from chrysotherapy.

show abstract

Section: Recent Reports Reflect Current Interest Insupporting

confidence: 67%

mentioning

confidence: 99%

Pharmacodynamics of ¹⁹⁷Au and ¹⁹⁵Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion

Gottlieb¹,

Smith²,

Smith³

1974

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…Elevations in nail gold concentration were minor and irregular during gold treatment. Mean nail gold concentrations were 0.87 and 0.98 pg/g for gold-toxic patients and 1.03 and 0.74 pg/g for nontoxic patients at 6 and 12 months, respectively.…”

Section: Resultsmentioning

confidence: 95%

Gold concentrations in hair, nail, and skin during chrysotherapy

Gottlieb

Smith

Penneys

et al. 1974

Arthritis & Rheumatism

View full text Add to dashboard Cite

Serial hair and nail specimens were obtained from 18 patients with rheumatoid arthritis receiving chrysotherapy. Punch biopsies of skin lesions and normal-appearing skin from 4 other patients with gold dermatitis, and serial skin biopsies from 4 additional patients were obtained at intervals during chrysotherapy. Gold content was measured in these samples using neutron activation analysis. Small quantities of gold were found in hair (mean = 0.30 pg/g), nail (mean = 0.17 pg/g), and skin (mean = 0.03 pg/g) prior to chrysotherapy, with two-to fivefold increases after 3-12 months of treatment. Compared to those from patients who did not develop gold toxicity, gold concentrations in all three tissues were similar in patients who developed gold toxicity. Gold levels were identical in skin lesions and normal-appearing skin of patients with gold dermatitis. These findings indicate that gold has little affinity for keratinous tissues, and that determination of gold content in these tissues is not helpful in differentiating gold-toxic from nontoxic patients.Recent studies (1,2) have confirmed earlier reports (3) of the efficacy of gold compounds in the treatment of rheumatoid arthritis (RA). Although gold compounds

show abstract

“…pounds. It is generally accepted that serum gold levels attained in GST-treated patients tend to be in the range of 2-5 /Ag/ml (38)(39)(40)(41)(42)(43), which is equivalent to the gold in 4-10 tg/ml GST. It has also been reported that the blood concentration range of AUR gold is 0.3-1.0 ,ug/ml (44).…”

Section: Methodsmentioning

confidence: 99%

Immunomodulatory effects of therapeutic gold compounds. Gold sodium thiomalate inhibits the activity of T cell protein kinase C.

Hashimoto¹,

Whitehurst²,

Matsubara³

et al. 1992

J. Clin. Invest.

View full text Add to dashboard Cite

Previous studies have shown that the gold compounds, gold sodium thiomalate (GST) and auranofin (AUR), which are effective in the treatment of rheumatoid arthritis, inhibit functional activities ofa variety ofcells, but the biochemical basis of their effect is unknown. In the current studies, human T cell proliferation and interleukin 2 production by Jurkat cells were inhibited by GST or AUR at pharmacologically relevant concentrations. Because it has been documented that protein kinase C (PKC) is involved in T cell activation, the capacity of gold compounds to inhibit PKC partially purified from Jurkat cells was assayed in vitro. GST was found to inhibit PKC in a dose-dependent manner, but AUR caused no significant inhibition of PKC at pharmacologically relevant concentrations. The inhibitory effect of GST on PKC was abolished by 2-mercaptoethanol. To investigate the effect of GST on the regulation of PKC in vivo, the levels of PKC activity in Jurkat cells were examined. Cytosolic PKC activity decreased slowly in a concentration-and time-dependent manner as a result of incubation of Jurkat cells with GST. To ascertain whether GST inhibited PKC translocation and down-regulation, PKC activities associated with the membrane and cytosolic fractions were evaluated after phorbol myristate acetate (PMA) stimulation of GST incubated Jurkat cells. Translocation of PKC was markedly inhibited by pretreatment ofJurkat cells with GST for 3 d, but the capacity of PMA to down-regulate PKC activity in Jurkat cells was not altered by GST preincubation. The functional impact of GST-mediated downregulation of PKC in Jurkat cells was examined by analyzing PMA-stimulated phosphorylation of CD3. Although GST preincubated Jurkat cells exhibited an increased density of CD3, PMA-stimulated phosphorylation of the y chain ofCD3 was markedly inhibited. Specificity for the inhibitory effect of GST on PKC was suggested by the finding that GST did not alter the mitogen-induced increases in inositol trisphosphate levels in Jurkat cells. Finally, the mechanism of the GST-induced inhibition of PKC was examined in detail, using purified PKC subspecies from rat brain. GST inhibited type II PKC more effectively than type III PKC, and also inhibited the enzymatic activity of the isolated catalytic fragment of PKC. The inhibitory effect ofGST on PKC activity

show abstract

Clinical response and serum gold levels in chrysotherapy. Lack of correlation.

Cited by 70 publications

References 7 publications

Pharmacodynamics of ¹⁹⁷Au and ¹⁹⁵Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion

Pharmacodynamics of ¹⁹⁷Au and ¹⁹⁵Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion

Gold concentrations in hair, nail, and skin during chrysotherapy

Immunomodulatory effects of therapeutic gold compounds. Gold sodium thiomalate inhibits the activity of T cell protein kinase C.

Contact Info

Product

Resources

About

Clinical response and serum gold levels in chrysotherapy. Lack of correlation.

Cited by 70 publications

References 7 publications

Pharmacodynamics of 197Au and 195Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion

Pharmacodynamics of 197Au and 195Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion

Gold concentrations in hair, nail, and skin during chrysotherapy

Immunomodulatory effects of therapeutic gold compounds. Gold sodium thiomalate inhibits the activity of T cell protein kinase C.

Contact Info

Product

Resources

About

Pharmacodynamics of ¹⁹⁷Au and ¹⁹⁵Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion

Pharmacodynamics of ¹⁹⁷Au and ¹⁹⁵Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion