Document Detail


Drug activity against Onchocerca gutturosa males in vitro: a model for chemotherapeutic research on onchocerciasis.
MedLine Citation:
PMID:  3437107     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An in vitro system for chemotherapeutic research using adult male Onchocerca gutturosa has been developed as a model for O. volvulus. Using a culture system consisting of medium MEM + 10% heat inactivated foetal calf serum (IFCS) + LLCMK2 (monkey kidney) feeder cells in an atmosphere of 5% CO2 in air, we examined the effects of a range of antiparasitic drugs on worm motility. Ivermectin, levamisole, furapyrimidone, Mel W, chloroquine, metrifonate, flubendazole, amoscanate and the Ciba-Geigy compounds CGP 6140, CGP 20'376 and CGI 17658 either immobilized or significantly reduced motility levels at a concentration of 5 X 10(-5) M or less within a 7-day period. Worms were affected at very low concentrations by ivermectin (effective conc. to reduce motility levels to 50% of controls, 3.14 X 10(-8) M), levamisole (7.95 X 10(-8) M), CGP 6140 (8.87 X 10(-9) M) and CGP 20'376 (2.78 X 10(-8) M). Difficulties were experienced in accurately repeating the immotile endpoint for levamisole due to an inconsistent partial recovery of motility. Over a 7-day period diethylcarbamazine had little effect on motility levels, while suramin caused a slight increase in activity compared to controls at some timepoints. Subsequent experiments demonstrated some differences in drug efficacy depending on the presence or absence of serum and feeder cells in the culture system probably because of drug avidly binding to serum proteins. However, serum and cells were found to be essential ingredients of the culture system to maintain worms in good condition, indicating that new drugs should be evaluated both in the presence and absence of serum and cells. Comparisons were made between the responses of O. gutturosa and Brugia pahangi to certain drugs and these species were found to significantly differ in their sensitivities to ivermectin and a novel compound (Wellcome), indicating that Onchocerca parasites should be used wherever possible for compound identification and development intended for the treatment of onchocerciasis. The in vitro system described here, using male O. gutturosa, provides a basis for further research and a practical alternative to O. volvulus.
Authors:
S Townson; C Connelly; A Dobinson; R Muller
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of helminthology     Volume:  61     ISSN:  0022-149X     ISO Abbreviation:  J. Helminthol.     Publication Date:  1987 Dec 
Date Detail:
Created Date:  1988-04-05     Completed Date:  1988-04-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985115R     Medline TA:  J Helminthol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  271-81     Citation Subset:  IM    
Affiliation:
CAB International Institute of Parasitology, St Albans, Herts, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anthelmintics / pharmacology*
Brugia / drug effects
Filaricides / pharmacology
Ivermectin / pharmacology
Levamisole / pharmacology
Male
Movement / drug effects
Onchocerca / drug effects*,  physiology
Onchocerciasis / drug therapy*
Piperazines / pharmacology
Thiazoles / pharmacology
Chemical
Reg. No./Substance:
0/Anthelmintics; 0/Filaricides; 0/Piperazines; 0/Thiazoles; 14769-73-4/Levamisole; 70288-86-7/Ivermectin; 81059-04-3/CGP 20376; 99402-78-5/amocarzine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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