Rômulo Teixeira de Mello

Schistosomiasis mansoni: blockage of cercarial skin penetration by chemical agents: I. naphthoquinones and derivatives

Skin penetration by Schistosoma mansoni cercariae may be blocked by 1,4-and 1,2-naphthoquinones applied topically. Of 23 naphthoquinone derivatives synthesized, 15 afforded almost complete protection when applied in solution to the tails of mice 24 hours before exposure to cercariae. On the basis of present evidence the 5-carbon atom side chain present in naturally occurring lapachol seems to be important for activity, and this is in accord with the previous observation that effective protective agents are liposoluble. Topically applied cercarial penetration inhibitors are presently the only prophylactic agents available for use in the field.

Synergistic action of praziquantel and host specific immune response against Schistosoma mansoni at different phases of infection

The interaction between specific immune response to Schistosoma mansoni and praziquantel (PZQ) was studied in mice. In mice harboring concomitant immunity, 6-day-old parasites treated with PZQ were more effectively removed than 24 h treated parasites despite both had a significant worm burden reduction when compared with respective treated controls. These results show that PZQ can be effective at the skin and lung stages of parasites development mainly acting with a established specific immune response, and particularly at the lung phase.

Antischistosomal activity of aminoalkanethiols, aminoalkanethiosulfuric acids and the corresponding disulfides.

This paper discusses the development of a series of sulfur-containing compounds that show an interesting in vivo activity against infection by Schistosoma mansoni. These substances include the aminoalkanethiols, aminoalkanethiosulfuric acids and aminoalkyl disulfides, among others. Although the aminoethanethiols and their disulfide derivatives have presented a relatively high toxicity for the host animal, the aminoalkanethiosulfuric acids have a low toxicity and a high specificity for the adult female S. mansoni worms. In vitro studies with schistosomula, lung-phase schistosomula and adult worms have demonstrated effects on the tegument and the metabolism on these different stages of S. mansoni worms. The encapsulation of these drugs in a nanoemulsion has resulted in an increase in the in vitro activity.

Activity of oxamniquine at skin, pulmonary and sexual maturation phases, on a Schistosoma mansoni strain (R1) previously reported as resistant at the adult phase

Departamento de Analises Clinicas e Toxicologicas,Faculdade de Farmacia *Departamento deParasitologia, Instituto de Ciencias Biologicas,Universidade Federal de Minas Gerais, Caixa Postal486, 30l6l-970 Belo Horizonte, MG, Brasil **SantaCasa de Misericordia, Belo Horizonte, MG, BrasilKey words: Schistosoma mansoni - drug resistance -evolutive stage - oxamniquine - experimentalchemotherapy

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.

Detection of a Giardia lamblia coproantigen by using a commercially available immunoenzymatic assay, in Belo Horizonte, Brazil

It is known that fecal examination to detect Giardia lamblia cysts or trophozoites produces a high percentage of false-negative results. A commercially available immunoenzymatic assay (ProSpecT Giardia Microplate Assay, Alexon, Inc., BIOBRAS) to detect G. lamblia specific coproantigen was evaluated for the first time in Brazil. A total of 90 specimens were tested. Each specimen was first tested as unpreserved stool, and then it was preserved in 10% Formalin to be tested 2 months later. The assay was able to identify all the 30 positive patients (sensitivity = 100.0%) by visual or spectrophotometric examination in the unpreserved specimens and was negative in 57 of the 60 patients without G. lamblia (specificity = 95.0%). The assay identified 27 of the 30 positive patients (sensitivity = 90.0%) and was negative in 59 of the 60 negatives (specificity = 98.3%) in the preserved stools according to both readings. A marked difference was observed in the optical densities in both groups, preserved and unpreserved stools, when the G. lamblia-positive specimens were compared to the negative or positive for other intestinal parasites than G. lamblia. The assay seems a good alternative for giardiasis diagnosis, especially when the fecal examination was repeatedly negative and the patient presents giardiasislike symptoms.

Schistosoma mansoni: Infected snails as a tool to screen antischistosomal drugs

Abstract Coelho P. M. Z. , Katz N. , Rocha M. O. , Souza C. P. and Mello R. T. 1988. Schistosoma mansoni : infected snails as a tool to screen antischistosomal drugs. International Journal for Parasitology 18 : 167–170. An attempt has been made to standardize a technique for the screening of schistosomicide drugs, using infected snails. The technique is easy to execute and of low cost. Most of the well-known curative and prophylactic drugs showed activity against the intra-molluscan stage of S. mansoni . However, some active drugs were found to be inactive against sporocysts. On the other hand, inactive drugs against adult worms showed activity on the intra-molluscan stage of the parasite.

Schistosoma mansoni : Permanence of modulation of the granulomatous inflammatory response in mice cured in the chronic phase

Persistence of down regulation of granuloma size was studied in mice chronically infected with Schistosoma mansoni and cured by chemotherapy. The animals were reinfected at 20-, 50-, 110-, and 140-day intervals after treatment, and sacrificed 60 days post-infection. Reinfected animals were able to modulate the granulomatous inflammatory response, thus preventing a new acute phase. These findings may contribute to the explanation for the decrease of morbidity from human schistosomiasis seen in endemic areas following mass treatment.

Schistosoma mansoni: reinfections and concomitant immunity in mice: importance of perfusion time after challenge infection for evaluation of immunoprotection

The concomitant immunity in the presence of repeated infections (with 15 cercariae) was studied in mice sacrificed on the 20th day after each infection. The comparison of the averages of immature worms, recovered from mice submitted to reinfection, with those of their respective controls (previously uninfected) showed a significantly lower worm recovery rate in the animals with previous infections (concomitant immunity). However, statistically significant differences could not be detected among the various groups of animals, when the mice that accumulated worms in this mature stage were perfused. The theoretical projection based on the accumulation of young worms which developed to adult ones indicates a lower recovery rate of adult worms in the animals with concomitant immunity, but this projection was not corroborated by the experimental data. The visceral hemodynamic alterations that occurred in reinfections due to the pathogeny, favouring recirculation of the recent arriving worms to the portal system, could explain the lower recovery rate of immature worms, which could remain in other organs on the occasion of perfusion of the portal system. These results suggest that special care should be taken when one wants to investigate concomitant immunity in mice based on the distinction of the immature worms from challenge infection and the mature ones from primary infection.

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.