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Biomedical subjects

D Cioli

Publications and source records attributed to D Cioli.

At least 55 records · Page 3Linked to original sources
PubMed1985

Studies on the mode of action of oxamniquine and related schistosomicidal drugs.

Adult Schistosoma mansoni were incubated for 1 hour in vitro with various drugs and then returned into the mesenteric veins of permissive animal hosts. Survival of schistosomes was assessed 3-4 weeks later by portal perfusion. Under these conditions, oxamniquine and hycanthone proved effective in killing S. mansoni, whereas UK-3883, lucanthone and lucanthone-4-desmethyl had no lethal activity. The same drugs which were schistosomicidal in vitro also persistently inhibited DNA, RNA, and protein synthesis in S. mansoni, whereas they were only transiently inhibitory against Schistosoma japonicum, against hycanthone-resistant S. mansoni and against immature worms. When drugs were administered in vivo to infected mice and the synthesis of macromolecules was assayed in vitro on worms obtained 1 or 3 days after treatment, not only oxamniquine and hycanthone, but also UK-3883 and lucanthone, proved effective in inhibiting the synthesis of macromolecules in sensitive--but not in resistant--S. mansoni. It is suggested that oxamniquine, like hycanthone, may exert its schistosomicidal activity by inhibiting nucleic acid synthesis in the parasite.

Animals↗
PubMed1984

Genetic analysis of hycanthone resistance in Schistosoma mansoni.

Interbreeding between hycanthone-resistant and hycanthone-sensitive schistosomes was achieved using a worm transfer technique which considerably reduced the length and the complexity of the operations generally involved in performing schistosome genetic crosses. A mouse was considered to harbor resistant schistosomes if, three weeks or more after a single intrasmuscular injection of 80 mg/kg hycanthone schistosome eggs were still excreted in the feces, at least one normal worm pair was obtained by perfusion, or miracidia could be seen hatching from the liver. The F1 hybrid progeny from crosses between sensitive and resistant schistosomes proved to be sensitive to hycanthone, irrespective of whether the resistant parent was the male or the female. The resistant phenotype reappeared in back-crosses and in the F2 progeny. These results could be confirmed using the traditional technique of single sex infections. It can thus be concluded that hycanthone resistance behaves like an autosomal recessive trait. These results suggest that hycanthone-resistant schistosomes are deficient in some factor, possibly an enzymatic activity which transforms hycanthone into a biologically active molecule, as suggested in a recent hypothesis on the mode of action of hycanthone.

Animals↗
PubMed1983

Effect of hycanthone administered in vivo upon the incorporation of radioactive precursors into macromolecules of Schistosoma mansoni.

Mice infected with Schistosoma mansoni were treated with hycanthone or with 8-chloro-2[2-(diethylamino)ethyl]-2H-[1]benzothiopirano-[4,3, 2-cd]-indazole-5-methanesulphonate (IA-4). Schistosomes were obtained by perfusion at various times after drug administration and tested for their ability to incorporate radioactive precursors of DNA, RNA and protein. In adult worms, male or female, the incorporation of radioactive thymidine was severely and irreversibly inhibited after treatment with either drug. Uridine and leucine incorporations were also inhibited, though to a lesser extent. On the contrary, the synthetic activities of immature worms were unaffected by hycanthone and only partially or temporarily depressed by IA-4. Hycanthone-resistant schistosomes, when tested between 1 and 7 days after treatment, showed a pattern of precursor incorporation which was virtually identical to that of untreated worms. These results are consistent with the hypothesis that hycanthone and IA-4 may kill schistosomes by interfering with their nucleic acid synthesis.

Animals↗
PubMed1981

Effect of hycanthone on Schistosoma mansoni macromolecular synthesis in vitro.

Adult, immature and hycanthone-resistant schistosomes were allowed to incorporate tritiated precursors of macromolecule synthesis in vitro, either in the presence of various concentrations of hycanthone, or at various times after removal of the drug. The effect on worms was compared to that on HeLa cells. The results show that hycanthone markedly inhibited the incorporation of uridine in all the systems studied, while the incorporation of thymidine and leucine was only secondarily affected. The inhibition of uridine incorporation reflected in part a decreased uptake of the radioactive precursor. The hycanthone-induced inhibition of uridine incorporation was essentially irreversible upon removal of the drug in adult schistosomes, while it was completely reversible in hycanthone-resistant worms, in immature worms and in HeLa cells. The effects of a hycanthone analog, IA-4, were largely comparable to the effects of the parent compound. These results suggest that the inhibition of RNA synthesis can be a possible explanation for the mechanism of the schistosomicidal action of hycanthone.

Dactinomycin↗
PubMed1981

Schistosoma mansoni: age-dependent susceptibility to immune elimination of schistosomula artificially introduced into preinfected mice.

Mice chronically infected with Schistosoma mansoni exhibited a significant resistance to a second infection with the same parasite, as demonstrated by their challenge worm burdens measured by portal perfusion. A decreased worm recovery was also exhibited by chronically infected mice when the challenge was administered intravenously using 3-h schistosomula obtained by the isolated skin technique or using 5-, 6-, 7- and 9-day-old schistosomula obtained from the lungs of infected donor mice. Variable results were obtained with 10- and 11-day-old forms, while schistosomula which were 12 days old or older, did not undergo significant rejection when introduced into the mesenteric veins of preinfected mice. Attempts to analyse these phenomena using the 'lung assay' were made complicated by the observation that the day of maximum recovery from the lungs was dependent upon the age of injected worms.

Age Factors↗
PubMed1981

Resistance induced by normal and irradiated Schistosoma mansoni: ability of various worm stages to serve as inducers and targets in mice.

Lung stage schistosomula exposed to 50 kilorads of gamma irradiation induced significant resistance to challenge infection with Schistosoma mansoni following intravenous (tail or mesenteric vein), intramuscular, or intraperitoneal injection into mice. Similar or higher levels were induced with irradiated cercariae, while irradiated 3- or 4-week-old worms induced little resistance. Non-irradiated day 6 and day 12 lung schistosomula injected into mice immunized with irradiated cercariae were susceptible to elimination, though to a lesser extent than a challenge infection administered at the cercarial stage. Day 20 liver worms injected into a mesenteric vein were not susceptible to irradiated cercaria-induced resistance. In contrast, cercariae, day 6 lung schistosomula, day 12 lung schistosomula and day 20 liver worms were all susceptible to the resistance induced by a chronic (non-irradiated) infection.

Animals↗
PubMed1980

Resistance to cercarial challenge upon transfer of Schistosoma mansoni into mice.

Various numbers of 25- to 28-day-old schistosomes of both sexes were surgically transferred into the mesenteric veins of mice. Recipient animals (plus sham-operated controls) were percutaneously challenged with cercariae at various times after transfer, and the number of surviving worms was subsequently determined by portal perfusion. Significantly fewer challenge parasites were recovered from mice which had received a worm transfer than from sham controls; the reduction was comparable to that observed in mouse recipients of a percutaneous primary infection with cercariae. Resistance of mice to cercarial challenge was dependent upon the number of schistosome pairs transferred, and upon the time interval between transfer and challenge.

Animals↗
PubMed1980

A study of the mode of action of hycanthone against Schistosoma mansoni in vivo and in vitro.

Schistosomes obtained by perfusion from host animals as early as 2 hours after in vivo treatment with hycanthone and transferred into untreated recipient hamsters died in the recipient host. In contrast, unexposed schistosomes transferred into recipient hamsters treated from 7 days to 36 hours previously showed a normal survival. In vitro treatment of schistosomes with hycanthone concentrations comparable to those used in in vivo studies, followed by transfer of the parasites into normal hamsters, resulted in death of the worms. The time of lethal hycanthone exposure in vitro could be as short as 15 minutes. Hycanthone-resistant schistosomes or immature worms were not affected under similar in vitro conditions. Our data suggest that the schistosomicidal effect of hycanthone is not caused by a host-derived metabolite.

Animals↗
PubMed1978

Behavior of Biozzi high and low responder mice upon infection with Schistosoma mansoni.

Mice genetically selected for high (Ab/H) or low (Ab/L) humoral antibody responses were infected with Schistosoma mansoni in order to assess the role of antibodies in innate and acquired immunity to this parasite. AbH mice produced higher levels of humoral antibodies to schistosome antigens, but were more susceptible to infection than Ab/L mice. This was shown by the higher number of parasites recovered from Ab/H mice, by the larger size of the parasites themselves, by the number of schistosome eggs and their rate of deposition in the host liver. In addition, Ab/L mice could develop an acquired resistance to schistosome re-infection which was as good as, or possibly even better than the resistance developed by Ab/H mice. These findings suggest that humoral antibodies per se may not play a critical role in schistosome immunity, and at the same time call attention to the possible importance of macrophages in determining the results observed.

Animals↗
PubMed1976

Immune complex nephritis in Schistosoma mansoni-infected mice.

Swiss outbred mice infected with 80-100 cercariae of Schistosoma mansoni developed in 60% of the cases a wide range of glomerular lesions involving mainly the mesangium. The lesions were associated with the presence of granular deposits of murine immunoglobulins and C3, suggesting an immune complex mechanism. In addition, nephritic glomeruli in about 20% of the cases could be stained by a specific rabbit antischistosoma serum after removal of excess host immunoglobulins. The presence of circulating immune complexes in the serum of infected animals was suggested by the increased molecular weight of circulating C3. The onset of the immunopathologic lesions appeared to be related to duration, intensity and type of infection. Single-sex parasite infection, in fact, led to significant reduction of glomerular lesions.

Animals↗