Seven rats were trained on Fixed Ratio 20 and two on Fixed Ratio 12 Escape Schedules until a stable baseline was established. Five of the subjects were administered gold thioglucose, three received gold thiomalate, and one was injected with gold, gold thioglucose, and gold thiomalate, allowing for an intrasubject comparison. Colloidal gold appeared to suppress response rate for one or two sessions, while gold thioglucose and gold thiomalate suppressed normal response rates from several to a number of sessions. This response rate suppression was often followed by gradual recovery, although in several subjects recovery of response rate could not be achieved prior to termination of the experiments. The drop in response rate was more consistent for the gold thiomalate-treated subjects than for the gold thioglucose group. A toxic effect of the injected compounds was manifest as a loss of weight, which was regularly associated with a drop in response rate. This weight reduction was greatest in the gold thiomalate-injected animals, indicating that gold thiomalate is probably more toxic than gold thioglucose to rats. Tolerance was developed for gold thioglucose and gold thiomalate, as indicated by smaller response rate decrements after repeated injections of the compound. As a consequence of repeated drug administrations, the animals demonstrated that they could tolerate a 1 milligram per gram of body weight dose of gold thioglucose if the dosage was increased gradually from a low-dosage initial injection. This dosage of 1 milligram per gram of body weight is double the amount required to produce demonstrable hypothalamic lesions in the rat. Previous investigations have failed to demonstrate this degree of tolerance in rats, primarily because the animals did not have the opportunity to adapt themselves to this treatment. Decrease in spontaneous activity on a balance beam apparatus was observed in several rats following administration of the larger gold thioglucose dosages (i.e., 0.5 milligrams per gram of body weight to 1.0 milligram per gram of body weight), as well as following the administration of gold thiomalate. Dosages of 20 milligrams to 50 milligrams of gold chloride were lethal to two rats. The heavy dosage of gold thioglucose administered to the female rat subjects at Utah State University (i.e., up to 1 mg per gram of body weight), although potentially producing extensive hypothalamic lesions, did not produce demonstrable hyperphagia or obesity, probably due to the anorexia and hypophagia associated with liver and kidney damage,which could counteract the hyperphagia expected to be associated with the extensive hypothalamic lesions produced at dosages over 0.5 milligram per gram of body weight following gold thioglucose administration.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

The effects of gold sodium thiomalate (GST) on murine spleen cells were investigated using in vitro mitogen blastogenesis techniques. Addition of GST to intact spleen cells resulted in a decreased blastogenic response to the T cell mitogen, concanavalin A (Con A). Thymidine uptake of spleen cells depleted of macrophages and cultured with Con A and GST demonstrated biphasic effects. At 2.5 pg Con A/ml, blastogenesis of macrophage depleted spleen cells was inhibited to a lesser degree than intact spleen cells; whereas, at 0.5 pg Con A/ml, the macrophage depleted spleen cells were inhibited to a greater degree than the intact spleen cells. Addition of GST at intervals ranging from 0 to 48 hours indicated that inhibition occurred within 36 hours following mitogen stimulation. These results suggest that GST inhibits early events of lymphocyte activation by direct interaction with lymphocytes.

Balb/c normal mice were used to study the effects of gold sodium thiomalate (GST) on intact, nonadherent, and adherent mononuclear spleen cells. The three populations were tested for the following aspects: in vitro effects of GST on the mitogen-triggered DNA synthesis; intracellular levels of cyclic AMP; and chemotaxis ability. These studies showed that GST inhibited the proliferative responses of all three populations as the concentration of GST increased. Cyclic AMP levels in the nonadherent population increased as the GST concentration increased. GST had a biphasic effect on the adherent population. At concentrations of 5 and 10 jag/ml, GST suppressed the cyclic AMP levels, and at concentration of 50 pg/ml it enhanced the cyclic AMP levels. GST had no effect on the cyclic AMP levels in the intact mononuclear spleen cells. GST appeared to have an inhibitory effect on the chemotaxis ability of all three populations of spleen cells.