Cure of mice infected with Trypanosoma rhodesiense by cis-diamminedichloroplatinum (II) and disulfiram rescue.

Mice infected with Trypanosoma rhodesiense were treatment concurrently with cis-diamminedichloroplatinum (II) (DDP), disulfiram, and hydration. Most of the mice (92.5 percent) were cured; inoculation of blood or suspensions of brain or heart from these animals did not produce disease in recipient mice. The dose of DDP needed to eliminate the trypanosomes, 3 milligrams per kilogram of body weight per day for 7 days, was lethally toxic unless the animals received disulfiram orally and subcutaneous injections of physiologic saline, which reduced the acute renal necrosis caused by DDP alone. Some mild to moderate reversible renal damage was noted upon pathologic examination of the treated mice.

The autoradiographic utilization and distribution of [1-3H]-galactose by the dental tissues of ageing mice.

The uptake, turnover and distribution of [1-3H]-galactose by periodontal tissues associated with maxillary first molars of mice 5, 26 and 78 weeks of age showed that galactose was utilized by all oral tissues studied throughout the life-span. Uptake and turnover of the tracer revealed pulsed events. Synchrony of the pulsed events was noted. With increasing age, diminished utilization of galactose was evident, as well as a change in peak-time of the curves characteristic of ageing. The complex plots represent several metabolic events occurring simultaneously. The uptake of galactose by fibrogenic, osteogenic and cementogenic cells was low. Matrical output, on the other hand, remained high. Cementogenic cell output was the highest of all the tissues over the 30-day period. Despite decreased physiological activity with age and superimposed age changes, galactose utilization remained high throughout the study.

Orally-administered silver sulfadiazine: chemotherapy and toxicology in CF-1 mice; Plasmodium berghei (Malaria) and Pseudomonas aeruginosa.

Silver sulfadiazine when administered orally and subcutaneously to CF-1 mice in doses not exceeding 1,050 mg/kg proved to have minimal toxicity. No pathology or abnormal reactions were seen in CF-1 mice after receiving 1,050 mg/kg orally and subcutaneously once a day for 30 days. Silver sulfadiazine in doses of 1,050 mg/kg, once a day for 5 days cured mice of Plasmodium berghei even after splenectomy. Parasitemia was reduced to zero in 1-3 days and antimalarial activity was not inhibited significantly with doses of 313 mg/kg/day of PABA, thereby indicating that silver sulfadiazine's antimalarial mode of action is different from that of the sulfonamides. Doses of 1,050 mg/kg/day had significant activity against systemic infections of Pseudomonas aeruginosa.

Model of the antimicrobial silver uracil.

A model is proposed for the antimicrobial agent, silver uracil, whereby silver interacts with uracil forming a silver uracil combination with the silver in the +1 state intercalating between stacked uracils in a manner similar to a 'sandwich' model. The uracils maintain stability by hydrogen bonding with the water solvent, and 'flip-flop' through an antiparallism mode at 220 degrees. The silver bonds to the uracil by a charge transfer mechanism, increasing the nuclear shielding field of the pyrimidine. The presence of the water (solvent) is necessary for the structure.

Antimalarials: screening of (orally administered) silver solfonamides against Plasmodium berghei.

Orally administered silver sulfadiazine is effective against Plasmodium berghei. Attempts to synthesize an active analogue with antimalarial activity failed. Although several of the analogues were chemically stable (like silver sulfadiazine) in sodium chloride, none of the analogues were biologically active. This suggests that the antimalarial activity of silver sulfadiazine is stereo-specific.