A 12-month comparative trial of auranofin and D-penicillamine in rheumatoid arthritis.

The oral gold salt auranofin, 6 mg per day, was compared with oral d-penicillamine, 500 mg per day, in a single-blind trial in 40 patients suffering with definite or classic rheumatoid arthritis. The patients were randomly allocated into the two therapeutic regimens (19 patients auranofin; 21 patients d-penicillamine) and monitored at a minimum of four-week intervals during the first year of treatment. Significant diminution in rheumatoid disease activity, as assessed by numerous clinical and laboratory parameters, was observed in both the auranofin- and penicillamine-treated groups. No significant differences existed for these parameters between the two groups, either initially or at the end of the trial period. Ten patients were lost from the trial over the 52-week period. Three subjects were withdrawn from the auranofin-treated group (increasing severity of rheumatoid arthritis at four weeks; severe diarrhea at four weeks; probable drug-related erosive gastritis at 40 weeks). Seven subjects were permanently withdrawn from the penicillamine-treated group (four, skin rashes four to eight weeks; one, heavy proteinuria at 24 weeks; one, therapeutic failure at 32 weeks; one, compliance failure at eight weeks), and treatment was temporarily withheld in three further patients because of thrombocytopenia (two) and proteinuria (one). We conclude that both drugs are effective in rheumatoid arthritis and that the lesser toxicity with auranofin will make it a valuable addition to our therapeutic armamentarium.

Studies in rapidly labelled ribonucleic acid in cell fractions and in tumour tissues.

1. Twenty minutes after injection of [(3)H]orotic acid into rats the rapidly labelled RNA from the liver is mainly associated with the nuclear fraction and little with the ribosomal cytoplasmic fraction. 2. The thermal denaturation of RNA from the fractions was not as reversible as that of the RNA extracted from whole liver. 3. Rapidly labelled RNA is synthesized by cells from a transplantable hepatoma when incubated in the presence of [(3)H]uridine and, after extraction and centrifugation, the label is present in three main fractions: one which sediments to the bottom of a gradient and is associated with DNA, a second which sediments to the heavy side of the 28s RNA, and a third which has a peak of activity between 28s RNA and 18s RNA and is associated with DNA. 4. After labelling and extraction of the RNA from Ehrlich ascites cells the distribution of radioactive components is similar to that of the material from the hepatoma cells. 5. The difference between the tumour cells and liver is due to some extent to the method of homogenizing the tissues and the nature of the components is discussed.

Rapidly labelled ribonucleic acid from rat liver. Studies in the attachment to ribosomes and stimulation of the incorporation of amino acids into polypeptides in cell-free systems.

1. Rapidly labelled RNA from rat liver, either as a complex with DNA (m-RNA-DNA) or with ribosomal RNA (m-RNA-RNA) binds to ribosomes in the polysome region. No binding could be demonstrated with ribosomal RNA or native DNA from Bacillus subtilis. 2. With ribosomes from rat liver, Escherichia coli or hepatoma the m-RNA-DNA stimulated incorporation of amino acids with rat-liver ribosomes only, whereas the m-RNA-RNA complex was effective with ribosomes from E. coli or the hepatoma. 3. Polyuridylic acid was effective as messenger RNA with all three ribosomes but much greater stimulation was obtained with ribosomes from E. coli and the hepatoma. 4. The degree of incorporation of phenylalanine with polyuridylic acid and ribosomes from a hepatoma was decreased by about 50% when ribosomal RNA was present.