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Clinical Rheumatology Sep 1986Radiographic films of 40 patients participating in a single centre patient blind study of auranofin versus aurothioglucose were evaluated in a random order by one... (Clinical Trial)
Clinical Trial Comparative Study
Radiographic films of 40 patients participating in a single centre patient blind study of auranofin versus aurothioglucose were evaluated in a random order by one reader. The two treatment groups were comparable with respect to number of erosions and total radiographic score at the start of the study. Only in the auranofin-treated patients was a statistically significant increase in the mean number of new erosions (p less than 0.001 at 6 months and p less than 0.01 at 12 months treatment, paired t-test) as well as in the total radiographic score (p less than 0.01 at 6 and 12 months treatment, paired t-test) observed. Results of this study confirm that parenteral gold compounds do retard radiographic progression of joint destruction in the treatment of rheumatoid arthritis. The effects on radiographic progression shown in this study are in agreement with other reports which, based on clinical and biochemical parameters, have shown that auranofin is somewhat less effective than the injectible gold salts.
Topics: Adult; Aged; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Clinical Trials as Topic; Drug Administration Schedule; Female; Gold; Humans; Male; Middle Aged; Radiography; Random Allocation; Time Factors
PubMed: 3096626
DOI: 10.1007/BF02054254 -
Drugs May 1984Auranofin is the first orally active gold compound for the treatment of rheumatoid arthritis. Like other chrysotherapeutic agents, its exact mechanism of action is... (Clinical Trial)
Clinical Trial Comparative Study Review
Auranofin is the first orally active gold compound for the treatment of rheumatoid arthritis. Like other chrysotherapeutic agents, its exact mechanism of action is unknown, but it probably acts via immunological mechanisms and alteration of lysosomal enzyme activity. Although long term clinical experience with auranofin is limited, its efficacy appears to approach that of sodium aurothiomalate. Further comparative studies with aurothioglucose, hydroxychloroquine and D-penicillamine are required before definitive statements can be made regarding the relative efficacy of auranofin and these agents. While patients have demonstrated clinical remission of rheumatoid arthritis in response to auranofin therapy, radiological studies have been inconclusive regarding its effect on the occurrence or progression of erosive lesions. Auranofin is relatively well tolerated in most patients, but diarrhoea, skin rash, and pruritus are sometimes troublesome, and thrombocytopenia and proteinuria are potentially serious side effects which may occur during therapy. Whereas mucocutaneous side effects are more frequent with injectable gold compounds, gastrointestinal reactions are the most common adverse effect seen with auranofin. The frequency of side effects has been similar with auranofin and sodium aurothiomalate, but they are generally less severe with auranofin. While some of the side effects are controlled by a reduction in dosage, temporary or permanent withdrawal of auranofin may be necessary. Auranofin is clearly a useful addition to the limited list of agents with disease-modifying potential presently available for the treatment of rheumatoid arthritis. It will doubtless generate much interest as its final place in therapy becomes better defined through additional well-designed studies and wider clinical experience.
Topics: Absorption; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Clinical Trials as Topic; Diarrhea; Dose-Response Relationship, Drug; Female; Gold; Gold Sodium Thiomalate; Humans; Immunity, Cellular; In Vitro Techniques; Kinetics; Male; Mice; Middle Aged; Pregnancy; Rats; Reproduction; Tissue Distribution
PubMed: 6426923
DOI: 10.2165/00003495-198427050-00002 -
Biological Trace Element Research 1993Experiments were conducted to determine whether the increased glutathione S-transferase (GSH-T) activity associated with selenium (Se) deficiency is necessarily related...
Experiments were conducted to determine whether the increased glutathione S-transferase (GSH-T) activity associated with selenium (Se) deficiency is necessarily related to losses in the activity of Se-dependent glutathione peroxidase (SeGSHpx) in chicks. Nutritional Se status was altered in two ways: by treatment with an antagonist of Se utilization, aurothioglucose (AuTG), and by feeding diets containing excess Se. Chicks given AuTG (10-30 mg AU/kg, sc) had growth rates and hepatic GSH concentrations that were comparable to those of saline-treated controls; however, their plasma GSH levels exceeded those of either Se-deficient (6-fold) or -adequate (3-fold) saline-treated chicks. Hepatic SeGSHpx activities of AuTG-treated chicks were half those of controls under conditions of Se-adequacy; however, this effect was not detected when Se was deficient. Hepatic GSH-TCDNB (assayed with 1-chloro-2,4-dinitrobenzene) activities of AuTG-treated chicks were significantly greater than those of controls when Se was deficient (i.e., when SeGSHpx activity was 12% of the Se-adequate level); however, deprivation of Se did not affect GSH-TCDNB activity in the absence of AuTG. Chicks fed excess Se (6-20 ppm as Na2SeO3) in diets containing either low (2 IU/kg) or adequate (100 IU/kg) VE, showed hepatic GSH-TCDNB activities and GSH concentrations greater than those of Se-adequate (0.2 ppm Se) chicks by 100% and 40%, respectively. That increased hepatic GSH-TCDNB activity can occur because of either AuTG or excess Se status under conditions wherein SeGSHpx activity is not affected indicates that the transferase response is not directly related to changes in the peroxidase.
Topics: Animals; Aurothioglucose; Body Weight; Chickens; Diet; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Liver; Male; Selenium
PubMed: 7688530
DOI: 10.1007/BF02783792 -
Annals of the Rheumatic Diseases Feb 1985The question 'Does the use of second-line therapy confer long-term benefit on outcome measures in rheumatoid arthritis?' remains unanswered. The major obstacle which... (Clinical Trial)
Clinical Trial Review
The question 'Does the use of second-line therapy confer long-term benefit on outcome measures in rheumatoid arthritis?' remains unanswered. The major obstacle which prevents collection of the necessary data is the lack of a suitable control group. In this report experience with three 'second-line placebo groups' is described, and previous studies in the literature which incorporated a placebo group are reviewed. In the absence of concurrent corticosteroid therapy very few patients remain on placebo second-line medication after one year. Those that do, appear to have milder disease and are not representative of the group as a whole. Data on outcome measures need to be collected over two to five years, but the answer to the question which is posed does not depend upon larger and larger placebo groups which constitute increasing bias. To define the extent of benefit offered by the more powerful therapeutic agents a novel approach in regard to drug assessment will be required.
Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Azathioprine; Clinical Trials as Topic; Cyclophosphamide; Gold Sodium Thiomalate; Humans; Ketotifen; Levamisole; Penicillamine; Placebos; Prognosis; Sulfasalazine
PubMed: 2858180
DOI: 10.1136/ard.44.2.134 -
[Auranofin and aurothiomalate sodium: a comparative review (and II) Efficacy, tolerance and safety].Medicina Clinica Jun 1985
Clinical Trial Comparative Study Review
Topics: Anemia; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Clinical Trials as Topic; Diarrhea; Drug Eruptions; Drug Tolerance; Gold; Gold Sodium Thiomalate; Humans; Leukopenia; Penicillamine
PubMed: 3160899
DOI: No ID Found -
Medicina Clinica May 1985
Comparative Study Review
Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Chemical Phenomena; Chemistry; Gold; Gold Sodium Thiomalate; Humans; Rats
PubMed: 3928990
DOI: No ID Found -
Gut Jan 1986Gastrointestinal function was assessed in six patients with rheumatoid arthritis who had developed diarrhoea on treatment with Auranofin. With the administration of...
Gastrointestinal function was assessed in six patients with rheumatoid arthritis who had developed diarrhoea on treatment with Auranofin. With the administration of Auranofin whole gut transit time decreased markedly (to 50% or less of control values) in five of six patients. The speed of passage of intestinal contents through the colon was certainly increased but attempts to assess transit through the upper gastrointestinal tract failed because the breath hydrogen method gave inconclusive results. There was no evidence of colitis and in all cases biopsy of the rectal mucosa appeared normal by light microscopy. In the five patients with rapid intestinal transit faecal weight increased more than two-fold (range +44 to +335%) although in only three cases were the changes sufficient to cause an increased frequency of bowel action. Overall the concentration of sodium in faecal water increased three-fold (mean values rose from 10.6 to 38.3 mmol/l). There were no significant changes in the concentrations of either potassium or chloride but bicarbonate was reduced. Faecal pH fell from a mean value of 7.5 (range 6.8-7.9) to a mean value of 6.4 (range 6.0-7.4). In the three patients who developed overt diarrhoea and in two others taking Auranofin the intestinal uptake of 51Cr-EDTA was increased on average three-fold and there was a similar change in the ratio of the absorption of lactulose/mannitol. The mean clearance of alpha-1-antitrypsin from the circulation into the gastrointestinal tract was doubled. These data indicate an increase in intestinal permeability. In contrast the absorption of vitamin B12 was unaffected and there was no significant change in the excretion of faecal fat although one patient developed mild steatorrhoea. Thus in a selected group of subjects with rheumatoid arthritis the administration of Auranofin caused diarrhoea in association with a reversible defect in intestinal permeability but without significant change in the absorption of nutrients.
Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Diarrhea; Feces; Female; Gold; Humans; Intestinal Absorption; Intestinal Mucosa; Intestines; Middle Aged; Permeability
PubMed: 3081411
DOI: 10.1136/gut.27.1.59 -
Molecules (Basel, Switzerland) Jul 2015The mammalian thioredoxin reductases (TrxRs) are a family of selenium-containing pyridine nucleotide disulfide oxidoreductases playing a central role in cellular redox... (Review)
Review
The mammalian thioredoxin reductases (TrxRs) are a family of selenium-containing pyridine nucleotide disulfide oxidoreductases playing a central role in cellular redox homeostasis and signaling pathways. Recently, these selenoproteins have emerged as promising therapeutic targets for anticancer drug development, often being overexpressed in tumor cells and contributing to drug resistance. Herein, we summarize the current knowledge on metal- and semimetal-containing molecules capable of hampering mammalian TrxRs, with an emphasis on compounds reported in the last decade.
Topics: Animals; Antineoplastic Agents; Auranofin; Aurothioglucose; Enzyme Inhibitors; Humans; Isoenzymes; Models, Molecular; Neoplasm Proteins; Neoplasms; Organoplatinum Compounds; Oxidative Stress; Phosphines; Ruthenium Compounds; Thioredoxin-Disulfide Reductase
PubMed: 26184149
DOI: 10.3390/molecules200712732 -
British Medical Journal (Clinical... Sep 1987
Topics: Arthritis, Rheumatoid; Aurothioglucose; Gold; Gold Sodium Thiomalate; Humans; Proteinuria
PubMed: 3119018
DOI: 10.1136/bmj.295.6601.739 -
The Journal of Rheumatology. Supplement 1981Drugs like penicillamine act slowly, benefit extraarticular features of the disease as well as the joints, reduce erythrocyte sedimentation rate and rheumatoid factor... (Comparative Study)
Comparative Study
Drugs like penicillamine act slowly, benefit extraarticular features of the disease as well as the joints, reduce erythrocyte sedimentation rate and rheumatoid factor titer and may slow the progression of radiographic changes and alter the outcome of the disease. Their action is to some extent disease-dependent. The 1st choice of drugs of this type is now penicillamine. It compares favourably with other drugs of the same type including gold, azathioprine and levamisole. A number of compounds in the development stage offer potential advantages over currently available drugs of this class. A compound which was safe enough to be recommended for widespread use would take over the role of first-line treatment of rheumatoid arthritis.
Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Dapsone; Humans; Levamisole; Penicillamine; Phosphines; Sulfhydryl Compounds
PubMed: 6785437
DOI: No ID Found