Experimental chemotherapy ofSchistosoma mansoni with praziquantel and oxamniquine: differential effect of single or combined formulations of drugs on various strains and on both sexes of the parasite

Delgado, Víctor; Suarez, Diego; Cesari, Italo M.; Incani, Renzo Nino

doi:10.1007/bf00931515

Cited by 42 publications

(41 citation statements)

References 18 publications

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“…This strain also showed tolerance to the lethal activity of praziquantel or oxamniquine used at 6 weeks of infection (Delgado et al 1992), suggesting that the time of maturation may be an important factor in the evaluation of dierent parasite strains for susceptibility to chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

“…The BH strain has been maintained under laboratory conditions for about 35 years, which may account for the selection of the above-mentioned characteristics. It does not show polymorphism as evaluated by isoenzyme electrophoresis of individual worms (Navarro et al 1992), and it has remained highly susceptible to all chemotherapeutic agents tested in the laboratory for several years (DõÂ as et al 1988;Delgado et al 1992).…”

Section: Discussionmentioning

confidence: 99%

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Parasite and vertebrate host genetic heterogeneity determine the outcome of infection by Schistosoma mansoni

Incani¹,

Morales

Cesari

2001

Parasitol Res

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Intraspecific variation in Schistosoma mansoni infection and modulation of its expression by vertebrate host genetics was studied by evaluation of some biological parameters of the infection in BALB/c and C57BL/6 mice infected with one Brazilian (BH) and two Venezuelan (YT and SM) laboratory strains of the parasite. Mice infected with 60 cercariae of each parasite strain were euthanized at 5, 6, 8, and 12 weeks. Parameters recorded included the number of adult worms recovered by portal perfusion (infectivity); the number of eggs in the feces, the intestine, and the liver; and the ability of the eggs to cross the intestine, expressed as a quotient of the number of eggs in the intestine versus the feces. Results showed that the parasite appeared to determine the infectivity, the sex ratio, the onset and timing of oviposition, the number of eggs produced, initial egg laying toward the liver, and the ability to cross the intestinal wall. In this sense the BH strain appeared to be the most efficient and the SM strain, the most delayed; the YT strain was intermediate, although closer to the SM strain. On the other hand, the host appeared to influence the susceptibility to infection, the fecundity, and the percentage of eggs distributed in the liver and in the intestine during the chronic stage. In this sense, although they have been shown to be less susceptible to infection than BALB/c mice, C57BL/6 mice permit more eggs to be produced and exhibit similar numbers of eggs in the intestine and the liver at certain time points. It appears from these results that parasite genetics is essential for the outcome of infection with S. mansoni, but some characteristics may be quantitatively modulated by host genetics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Parasite and vertebrate host genetic heterogeneity determine the outcome of infection by Schistosoma mansoni

Incani¹,

Morales

Cesari

2001

Parasitol Res

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“…Studying the oogram pattern permits a direct assessment of the production and development of S. mansoni eggs, and their passage from mesenteric vessels into the intestinal lumen in mice (Mati & Melo, 2013). A drug that shows a chemotherapeutic effect causes a progressive change in the percentages of different developmental stages with a decrease in immature stages and an increase in the percentages of mature and/or dead eggs (Delgado et al, 1992). These changes are due to the interruption of oviposition in the intestinal wall and the maturation of viable eggs already there (Delgado et al, 1992;Pellegrino et al, 1962).…”

Section: Mice Groupsmentioning

confidence: 99%

“…A drug that shows a chemotherapeutic effect causes a progressive change in the percentages of different developmental stages with a decrease in immature stages and an increase in the percentages of mature and/or dead eggs (Delgado et al, 1992). These changes are due to the interruption of oviposition in the intestinal wall and the maturation of viable eggs already there (Delgado et al, 1992;Pellegrino et al, 1962). Results of the present work indicate that without mice treatment the differences between the two mice groups as regards percentages of immature or mature S. mansoni eggs were insignificant (Table 3).…”

Section: Mice Groupsmentioning

confidence: 99%

Evaluation of a method for induction of praziquantel resistance inSchistosoma mansoni

Lotfy

Hishmat

Nashar

et al. 2015

Pharmaceutical Biology

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Context: Praziquantel (PZQ) is a highly efficacious anthelmintic against many flatworms including schistosomes. PZQ has been in use for more than 25 years, and concern is increasing that resistance has emerged in human schistosomes in Egypt and other endemic countries. Objective: The current study was designed to evaluate a recently described method for induction of PZQ resistance in Schistosoma mansoni. Materials and methods: Successive subcurative drug treatments of Biomphalaria alexandrina snails infected with an Egyptian strain of S. mansoni were undertaken. Cercariae shed from snails exposed and unexposed to PZQ were used to infect mice. Forty-five days after infection, mice were treated with a single oral dose of PZQ in 2% aqueous solution of Cremophor-EL Õ . The concentration of PZQ was 0, 200, 400, or 800 mg/kg. Thirty-three days after treatment, all groups of mice were dissected to collect the S. mansoni worms by the perfusion technique. In addition, the oogram pattern was examined to study the production, maturity, and death of S. mansoni eggs in the different groups of mice. Results: The present study has shown that the sublethal dose for induction of PZQ resistance in the intra-molluscan S. mansoni stages was 500 mg/kg. The worm count and the percentage of immature eggs in different groups of mice were significantly affected by the intra-molluscan exposure to PZQ and the drug concentration used to treat infected mice. Discussion and conclusion: The results obtained herein confirm the possibility of using successive drug treatments of infected B. alexandrina to induce PZO resistance in S. mansoni.

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“…Drugs: Praziquantel PZQ, purchased from BAYER, dipeptide 1 and dioxopiperazine 2 were suspended in 0.2 ml of a solution of cremophor EL 1% (Sigma, St Louis M.O., USA) in glycerol 25% (Delgado et al, 1992). The latter solution without any drug was used as placebo.…”

Section: Anthelmintic Activitymentioning

confidence: 99%

Anthelmintic activity of 3,6-dibenzyl-2,5-dioxopiperazine, cyclo(L-Phe-L-Phe)

Walchshofer

Sarciron²,

Garnier

et al. 1997

Amino Acids

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Summary.After oral administration, dipeptide Phe-Phe-OMe 1 exhibits anthelmintic activity against Echinococcus multilocularis larvae, cestoda, in mongolian gerbils (intraperitoneal localization), but not against Hymenolepis nana, cestoda, in fasted mice (gastro-intestinal localization). This compound rapidly provides its cyclization product dioxopiperazine 2 in pH 7.4 buffer at 37°C, but was stable at pH 2.4 during 16h at 30°C. It was postulated that dipeptide 1 could act as a prodrug of 2. Initial pharmacokinetics studies were carried out in mice and dogs. After oral administration, biotransformation of 1 into 2 occurred to some extent in mice but not in fasted dogs. Results of these studies did not allow to ascertain that 1 is a prodrug of 2. Compound 2 has been tested in mice against H. nana and Schistosoma rnansoni, a gastrointestinal trematoda. Albeit less active than the reference compound praziquantel, 2 has shown a good activity against both worms. 2,5-dioxopiperazines represent therefore a new class of anthelmintics.

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Experimental chemotherapy ofSchistosoma mansoni with praziquantel and oxamniquine: differential effect of single or combined formulations of drugs on various strains and on both sexes of the parasite

Cited by 42 publications

References 18 publications

Parasite and vertebrate host genetic heterogeneity determine the outcome of infection by Schistosoma mansoni

Parasite and vertebrate host genetic heterogeneity determine the outcome of infection by Schistosoma mansoni

Evaluation of a method for induction of praziquantel resistance inSchistosoma mansoni

Anthelmintic activity of 3,6-dibenzyl-2,5-dioxopiperazine, cyclo(L-Phe-L-Phe)

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