Since the work of Pfeiffer(1) on Hemo-progressively elucidated Studies on the in-PhiZus influenzae, and of Novy and MacNeal fluenza organism by Granick and Gilder (3) (2) on Trypanosoma brucei, the nature of and on non-pathogenic members of the Tryfactors occurring in blood necessary for panosomatidae by Lwoff (4,s) have revealed growth of certain microorganisms has been certain differences between porphyrin re-
SYNOPSIS.
Certain polyoxyethylene ethers, derived from p‐tert.‐octylphenol and representatives of series which have activity against murine tuberculosis and leprosy were tested in several protozoal infections. Triton WR‐1339 represented the series in which the phenolic groups are arranged linearly while HOC‐12½ and LOC‐60 represented series in which the phenolic groups were condensed into a cyclic structure. WR‐1339 was found to be active against infections with Trypanosoma gambiense, T. rhodesiense, T. brucei, T. congolense, and T. equipevdum in mice, and against Leishmania donovani in the golden hamster. The “macrocyclic” HOC‐12:4 also had activity, but of a much lower order, against the first three trypanosome infections listed, and in leishmaniasis it had activity equivalent to that of WR‐1339. Neither of these compounds was active against Trypanosoma cruzi, Plasmodium berghei nor Toxoplasma gondii in mice, nor against Leptospira icterohemorrhagiae in guinea pigs. The other macrocyclic compound, LOC‐60, was inactive in the infections in which it was tested (T. congolense and T. rhodesiense).
Although the action of the polyoxyethylene hers in murine tuberculosis and leprosy had been reported to be an indirect one, affecting the host rather than the mycobacteria (which are said to be resistant to these materials in vitro) it was found that the differential effects in trypanosomiasis, observed with WR‐1339 (which had good activity in vivo) and HOC‐12½ (which had poor activity in v i v o), were well correlated with their effects in vitro. In the light of the strength of the dilutions which killed T. congolense in the t a t tube and the blood levels of WR‐1339 obtaining after medication the control of the infection could be attributed to the direct action of the compound on the parasite although some indirect effect on the host, perhaps of the nature of reticulo‐endothelial stimulation, could not be excluded.
Summary
The administration of rabbit antimouse spleen serum to mice on either the day before or the day after infection with Plasmodium berghei did not result in any alterations in the course of the infection as measured by parasitemia, reticulocyte counts or mortality in comparison with controls. The administration of rabbit antimouse spleen serum to mice infected with Trypanosoma congolense may result in an acceleration of the infection, if large quantities are used, or in a delay in the course of the disease, if smaller quantities are used.
The administration of rabbit antispleen sera prepared with heterologous antigens of bovine and human origin results in delays in the course of T. congolense infections, the median survival time of the treated mice sometimes being extended as much as 24 days beyond the median survival time of the untreated controls. Less pronounced extensions of survival time were observed when antilymph node and antithymus sera were used, and antisera prepared against bovine blood and bone marrow were ineffective.
Heterologous antispleen sera which were active in T. congolense infections had only barely detectable influence on infections with T. gambiense, which are more acute. The results obtained are compatible with Bogomolets' explanation of the mode of action of antireticular cytotoxic sera which depress the reticuloendothelial system when administered in large quantities and stimulate the same system when given in smaller amounts. The studies herein reported suggest that interesting observations might be made using other types of antisera in infections which are of a subacute or chronic nature which would allow time for the therapy and show its effect.
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