Abstract
Fractional dose therapy of rat trypanosomiasis has shown the trypanocidal action of mapharsen in vivo to be of relatively short duration. 1 The brief trypanocidal activity of rabbit serum after administration of the related trivalent arsenical, reduced tryparsamide, is also indicative of this fact. 2 On the contrary, arsenic has been found in the blood and tissues of rats for relatively long periods after mapharsen injection. 3 This study was concerned with an investigation of the apparent lack of parallelism between these two factors.
The procedure consisted in determining the minimum trypanocidal concentration (M.T.C.) of the blood arsenic of rats at various intervals after intravenous injection of the maximum tolerated dose (12.5 mg/kg) of mapharsen and comparing this with the M.T.C. of the unijected drug. The blood samples were taken at 1/4, 1/2, 1, 4, 8, 12, 18, 24, 36, 48 or 240 hr after injection, heparin being used as an anticoagulant. The arsenic content was determined by the A.O.A.C. Gutzeit method, 4 and was expressed as μ (γ) of mapharsen per cc of blood. The M.T.C. was determined by a modification of the method of Murgatroyd et al., 2 and Hawking et al., 3 sterile technic being used throughout. A series of dilutions of the blood was made, on the basis of arsenic content, with a medium consisting of 1 part of heparinized rat blood and 2 parts of Locke's solution (0.2% glucose). The tubes were then inoculated with a dilute suspension of Trypanosoma equiperdum from infected rats and incubated for 18 hr at 37°C. After incubation, cultures which showed no motile organisms in microscopic cover-glass preparations were injected intra-peritoneally into young rats, which were observed for septicemia and death for 30 days.
Get full access to this article
View all access options for this article.