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Histological and ultrastructural aspects of acute and chronic pre-erythrocytic schizonts of P. yoelii yoelii were studied with: a) acute schizonts in normal rodents; b) chronic schizonts induced in rodents receiving ethionine injections or on a low methionine diet; Experimentally induced chronic schizonts frequently have the same histological aspect as those observed in wild Thamnomys from Africa. The ultrastructural evolution of the vacuole system described by Seureau et al. in acute schizonts is discussed; new evidence is presented to support the hypothesis according to which the contents of the vacuoles are enzymatic in nature. Ultrastructural studies of chronic schizonts show alterations in the sites of synthesis (zones of rough endoplasmic reticulum small and not numerous, absent in the most delayed schizonts; vesicle system poorly developed and also disturbances of nuclear development (slow division, apparently inhibited in the most retarded forms.) A peripheral accumulation of vacuoles in many chronic schizonts without discharge of their contents to the parasitophorous space, might indicate an alteration of their membranes, leaving them unable to fuse with the schizont plasmalemma.

One hundred eleven male adult rats of a pathogen-free Sherman or Charles River strain were divided into 3 series. Each of them contained non-treated controls and rats treated with intraperitoneal (i.p.) injections of DL-ethionine (E) [75 mg/d p. 100 g] for 6 weeks (series 1) or for only 2 weeks (series 2 and 3). Series 1 and 2 included also rats injected simultaneously with E and DL-methionine (68.4 mg/d p. 100 g). In the series 2 there were also groups receiving at the same time E, ME and tryptophan (5 mg/d p. 100 g) or E, Me and ATP (1.65 mg/d), and in the series 3, groups were injected with E + adenosine (31.2 mg/d p. 100 g) and (or) uridine (284 mg/d p. 100 g). All animals were immunized i.p. 1 week before killing with sheep red blood cells (SRBC): either 2.4 X 10(9) SRBC p. 100 g without adjuvant (series 1 and 2) or 1 X 10(9) SRBC with Freund's adjuvant added (series 3). Rosette-and plaque-forming cells (RFC and PFC) were counted in the spleen, and titers of serum hemagglutinins and hemolysins were determined with separation of 2-mercaptoethanol-resistant IgG from non-resistant immunoglobulins. E provoked within 2 weeks a drastic inhibition of the immune responses: drop in the RFC and PFC levels p. 10(6) (approximately 2900 leads to approximately 320 and approximately 415 leads to 40 respectively, in the study 3), and significant decrease in the serum antibody titer, especially IgG. Addition of Me still amplified the immunosuppression. Supplementation with tryptophan, ATP, adenosine and (or) uridine was also ineffective. Though not displaying any immunoprotective potency, Me partly neutralized the non-immunological effects of E: arrest of the body growth and involution of lymphoid organs and male genital organs, particularly apparent after 6 weeks of treatment. In conclusion, the ethionine-induced immunosuppression does not result from a metabolic exclusion of labile methyl groups or from an acute ATP deficiency due to an excess trapping of adenine as S-adenosyl-ethionine. Lack of pyrimidines or tryptophan must also be discarded. On the other hand, the possibility of maintaining the immunosuppressive activity of E, while reducing the toxicity of this compound, by addition of Me deserves to be emphasized.

Injections of DL-ethionine during the preerythrocytic period of Plasmodium yoeli in Thammomys were followed by: 1. A delayed prepatent period; 2. A relapsing parasitaemia with alternatively positive and negative blood at subinoculation of clean mice; 3. A peculiar morphology of the exoerythrocytic schizonts which remain small with a scanty cytoplasm and very few large nuclei. Although the authors consider the origin of the relapses to be the rupture of delayed hepatic schizonts under the influence of ethionine, none were found after the 5th day.