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Echinococcus granulosus: the effects of praziquantel, in vivo and in vitro, on the ultrastructure of equine strain murine cysts

Published online by Cambridge University Press:  06 April 2009

K. Sylvia Richards
Affiliation:
Parasitology Research Laboratory, Department of Biological Sciences, University of Keele, Keele, Staffs. ST5 5BG
D. L. Morris
Affiliation:
Department of Surgery, University Hospital, Nottingham NG7 2UH
D. Daniels
Affiliation:
Parasitology Research Laboratory, Department of Biological Sciences, University of Keele, Keele, Staffs. ST5 5BG
E. M. Riley
Affiliation:
Parasitology Research Laboratory, Department of Biological Sciences, University of Keele, Keele, Staffs. ST5 5BG

Summary

Praziquantel (500 mg/kg) administered orally to BALB/c mice with secondary equine E. granulosus daily for 21, 30 or 30 + 30 days without the drug resulted in the majority of cysts, using bench criteria of turgidity and eosin exclusion, being assessed as ‘alive’. Ultrastructural examination of 54 of these ‘alive’ cysts did not support this conclusion. They all showed increased vesiculation of the germinal layer leading, in many, to the loss of its integrity. Increased mitochondrial numbers occurred frequently. The longer drug treatments appeared to have greater effects on the germinal layer of ‘alive’ cysts and there was no detectable re-establishment of structural organization within 30 days after drug withdrawal. Subjectively, there was no substantial difference between cysts from 4-month and 9-month infections or between affected peritoneal and hepatic cysts. Tissue from collapsed cysts was necrotic. Peak serum levels of praziquantel (6430–6136 μg/l) occurred 5–10 min after drug administration (500 mg/kg) and dropped rapidly to less than 10 μg/l at 3 h. In an in vitro study at praziquantel concentrations of 1000 and 5000 μg/l over a 10-day period, most cysts were judged ‘alive’ by bench criteria but showed ultrastructurally a time- and concentration-dependent loss of integrity identical to that seen in vivo. Turgidity and eosin exclusion therefore underestimate the effect of praziquantel and the results indicate that in vitro experiments can fulfil a legitimate preliminary role in a hydatid chemotherapy programme.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1988

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