Antischistosomal activity of acridanone-hydrazones in Cebus monkeys experimentally infected with the SJ strain of Schistosoma mansoni.

In this study, four compounds were utilized at the dose of 12.5 mg/kg body weight, p.o., to treat Cebus monkeys experimentally infected with about 200 cercariae of Schistosoma mansoni (SJ strain), via transcutaneous route. The oograms performed with rectal snips, as well as stool examinations carried out periodically, showed no viable eggs of the parasite, from day 29 to 226 post-treatment. The perfusion undertaken after killing the animals showed absence of worms in the treated monkeys, whereas 83 worms were recovered from the control, thus corroborating the results obtained by means of oograms and coproscopy. These results confirm the efficacy of 9-acridanone-hydrazones previously tested against the LE strain of S. mansoni. The low curative dose and apparent absence of toxicity render these drugs an important therapeutic reserve, taking into consideration the reports on the resistance of S. mansoni to the modern drugs oxamniquine and praziquantel.

Activity of 9-acridanone-hydrazone drugs detected at the pre-postural phase, in the experimental schistosomiasis mansoni.

The compound Ro-15.5458/000, derivative in the class of 9-acridanone-hydrazones, was found to be effective against Schistosoma mansoni in mice, killing almost all the skin schistosomules (24 hr after infection), when administered at the dose of 100 mg/kg. In experiments carried out with Cebus monkeys, the drug was shown to be fully effective at 25 mg/kg, 7 days after infection. These data, associated with the good results obtained earlier at the post-postural phase of schistosomiasis, allow the inference that this promising compound may be important in the set of antischistosomal drugs, depending on further toxicological and clinical tests.

Schistosoma mansoni in mice: modulation of granulomatous response after reinfection and chemotherapeutic treatment.

Mice previously infected with Schistosoma mansoni, and cured by specific treatment (400mg/kg oxamniquine, p.o.) in the chronic phase of the disease, were reinfected 20 days after treatment to assess their capacity for modulation of the granulomatous response. Histopathologic examination of the animals' liver, at 60 days after reinfection, evidenced the presence of typical granulomas of the chronic phase in most animals. This infer that the capacity for modulation of the granulomatous response had been maintained, thus preventing a new acute phase of the disease. Conversely, a group of previously infected mice, untreated and submitted to reinfection, showed reactivation of the granulomatous response in 50% of the animals. The possible implications of these findings in human schistosomiasis mansoni are discussed.

Schistosoma mansoni: evaluation of the activity of oxamniquine on schistosomules, at 24 hours after infection.

Mice transcutaneously infected with about 400 cercariae were submitted to treatment with oxamniquine (400 mg/kg), 24 hours after infection. The recovery of schistosomules, at 4, 24, 48 and 72 hours and 35 days after treatment, showed the activity of the drug on the parasites, thus practically preventing their migration from the skin to the lungs. Worm recovery performed in the lungs (96 hours after treatment) showed recovery means of 0.6 worms/mouse in the treated group and 53.8 in the control group (untreated). The perfusion of the portal system carried out at 35 days after treatment clearly showed the elimination of all the parasites in the treated group, whereas a recovery mean of 144.7 worms/mouse was detected in the control group (untreated). These findings confirm the efficacy of oxamniquine at the skin phase of infection, and also show similarity with the immunization method that uses irradiated cercariae. The practical application of these findings in the medical clinic is discussed too.

[Size of hepatic granuloma produced by eggs of 2 geographic strains of Schistosoma mansoni, in mice]. / Dimensões do granuloma hepático produzido por ovos de duas linhagens geográficas do Schistosoma mansoni, no camundongo.

The authors have determined the mean diameter of granulomas in the liver of mice infected with cercariae from two different and well definite geographic strains of Schistosoma mansoni (LE, Belo Horizonte, MG, and SJ, São José dos Campos, SP). A total of 1,170 granulomas has been measured. Granulomas measured on the 60th day after infection showed larger size than the other ones measured on the 90th day. Modulation of the immunopathologic response was significantly more efficient for the LE strain, whereas the granulomas (with 60 and 90 days) related to SJ strain were significantly larger. Data suggested a higher pathogenicity for the SJ strain. It is speculated whether these findings could explain, in part, the occurrence of regional variations of the anatomo-clinical forms of schistosomiasis.

Schistosoma mansoni: acquired resistance in mice by implantation of young irradiated worms into the portal system.

In two distinct experiments, immature S. mansoni worms (LE strain, Belo Horizonte, Brazil), aged 20 days, obtained from the portal system of white outbred mice, were irradiated with 14 and 4 Krad, respectively. Afterwards, the worms were directly inoculated into the portal vein of normal mice. Inoculation was performed with 20 irradiated worms per animal. Fifty days after inoculation, the mice that received 4 and 14 Krad-irradiated worms and their respective controls were infected with S. mansoni cercariae (LE strain), by transcutaneous route. Twenty days after this challenge infection, the animals were sacrificed and perfused for mature irradiated (90-day-old) and immature (20-day-old) worm counts. Analysis of the results showed that statistically significant protection against cercariae occurred in both groups with irradiated worms.

[Use of natural sources in the preparation of biologically active compounds. II: Anti-inflammatory agents]. / Utilização de sintons naturais na preparação de compostos biologicamente ativos. II: Anti-inflamatórios.

In order to improve the knowledge on the natural sources of Brazilian florae, a research program is in course for the preparation of different groups of compounds which could have biological activity using abundant Natural Products as starting materials. This paper deals with work and results in the synthesis of anti-inflammatory analogs.