Jack Schubert

Tissue distribution of monomeric and polymeric plutonium as modified by a chelating agent.

Mice injected with a polymeric (colloidal) solution of plutonium retained more of the radioelement in the liver and spleen and less in the bone than did mice injected with a monomeric plutonium solution. After daily diethylenetriaminepentaacetic acid therapy was initiated three days later, the bone levels of the radioelement were reduced about one-half in each case. The liver burden of mice injected with the monomeric form of plutonium was nearly completely removed after a few days of treatment, but that of mice injected with the polymeric form was reduced slowly and by only about one-third. In the case of the monomeric form of plutonium all the fecal plutonium was derived from the liver in both control and treated mice, while the urine contained plutonium from the other soft tissues and also from the bone of the treated animals. (auth)

Studies on the mechanism of protection by aurintricarboxylic acid in beryllium poisoning. III. Correlation of molecular structure with reversal of biologic effects of beryllium.

Abstract More than seventy different substances have been tested to ascertain the relations between the number, kind, and position of functional groups, and the ability of an organic molecule to reverse two biologic effects of Be—the inhibition of plasma alkaline phosphatase and death in acutely poisoned mice. All compounds that failed to reverse the Be-induced inhibition of the enzyme also lacked antidotal activity. On the other hand, a compound that reversed the enzymatic inhibition did not necessarily protect mice from Be poisoning. The effectiveness of a molecule in reversing the biologic effects of Be is dependent upon a number of chemical and biologic factors, including the ability to form a stable five- or six-membered chelate ring with Be, molecular size, presence of hydrophilic groups, proton affinity of chelating groups, metabolism, and toxicity.

Organic peroxides and the antibacterial action of irradiated sucrose as affected by catalase.

Sucrose solutions irradiated in the presence or absence of oxygen inhibit the growth of Salmonella typhimurium. The addition of catalase prior to or shortly after inoculation of the organisms into ...

Induced accumulation of citrate in therapy of experimental lead poisoning.

Summary The concept of interference in a metabolic cycle as a means of modifying metal toxicity has been tested. The accumulation of citric acid in certain soft tissues of the rat has been induced by administration of small, non-lethal doses of sodium fluoroacetate. This has been found to give partial protection to rats acutely poisoned with lead nitrate. Of rats given the LD90 of lead nitrate, 53% survived when treated with sodium fluoroacetate. The LD50 of lead nitrate was increased from 58.2 mg/kg (as Pb) in saline controls to 67.7 mg/kg in fluoroacetate-treated rats.

Studies on the mechanism of protection by aurintricarboxylic acid in beryllium poisoning. IV. Comparative effects of related compounds on survival of Be-poisoned animals and on distribution of Be

Abstract The ability of an injection of either sulfosalicylic acid or gentisic acid, given 1 hr. before or after beryllium, to prevent death of mice injected with the LD 95 of BeSO 4 is lost when these compounds are injected 4 hr. after or 2 hr. before the Be. Salicylic acid loses its effectiveness when given about 8 hr. before or after Be. Aurintricarboxylic acid (ATA) loses effectiveness when given between 10 and 16 hr. after Be and gradually loses protective ability when given more than 1 day before Be. When small, partially effective doses were compared on a molar basis, ATA was much more effective in protecting Be-poisoned mice than either salicylic acid or sulfosalicylic acid. ATA was equally effective injected 5 min. or 1 hr. after the Be, while small doses of salicylic acid and especially of sulfosalicylic acid were less effective given at 1 hr. In comparison to ATA, which has been shown to have no effect on the distribution of Be that might explain its therapeutic effect in Be-poisoned mice, salicylic and sulfosalicylic acids injected 1 hr. after radioberyllium caused a marked increase in Be 7 excretion and a reduction in the over-all retention of Be 7 . Since sulfosalicylic acid given 4 hr. after the Be still causes this increase in excretion but does not prevent the death of the mice, the increase in Be excretion is not thought to be responsible for protecting the animals treated at 1 hr. Inactivation of Be by chelation in situ in critical tissues appears to be the important factor in preventing death of mice acutely poisoned with Be.

Comparison of 3 Chelating Agents in Treatment of Experimental Manganese Poisoning

Summary Three chelating agents of the polyamino polycarboxylic acid type, ethylene-diaminetetraacetic acid, diethylenetriamine-pentaacetic acid, and ethylene bis(α-imino-o-hydroxyphenylacetic acid) have been compared in treatment of acute experimental manganese poisoning. EBAA had no therapeutic value, whereas both EDTA and DTPA provided significant protection to rats given lethal amounts of manganese gluconate. It is shown that DTPA is somewhat more effective than EDTA.

Studies on the Mechanism of Protection by Aurintricarboxylic Acid in Beryllium Poisoning. V. Long-Term Distribution Studies with C14. Labeled ATA.

Abstract 1. 1. The distribution of a single injection of C 14 -methyl-labeled aurintricarboxylic acid (ATA) in tissues was determined over a period of 8 months in rats, and after 24 hr. in dogs. 2. 2. The levels of ATA retained in all rat tissues studied 24 hr. after administration were retained for as long as 1–3 months. The highest concentrations were found in kidney, spleen, and liver. There were measurable amounts in all tissues for as long as 8 months. 3. 3. ATA appeared to be uniformly distributed in soft tissues, presumably as a protein-ATA complex, and was not detected in inorganic bone.

Comparison of antipyretic activity of salicylic and aurintricarboxylic acids.

Summary The antipyretic effects of salicylic acid and of a structurally related compound, the dye aurintricarboxylic acid (ATA), were compared in rats with fevers induced by subcutaneous injection of yeast. The two compounds had comparable effects on fever and, when injected together, their effects were additive. ATA had a more transient effect, reduced the temperature of rats without fevers, and reduced fevers by a specific amount rather than to a specific temperature as did salicylate. These differences led to the postu-lation of a direct peripheral action of ATA.

Effect of adrenocorticotrophic hormone on tissue distribution and acute toxicity of beryllium

Summary Adrenocorticotrophic hormone (ACTH) had no appreciable effect on the distribution or retention of radioberyllium, injected into mice with and without carrier beryllium sulfate. The survival of mice acutely poisoned with beryllium sulfate was not influenced by ACTH.