Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of four new antifilarial compounds, (CGP 6140, 20376, 20309 and 21833, Ciba Geigy Ltd. Basle) on the viability of third and fourth stage larvae of Onchocerca volvulus was tested in vitro and in vivo. The motility of the larval stages and the moulting process from the third to the fourth stage were used as parameters for the drug activity in vitro. All four compounds showed good effects in vitro on the moulting rates compared to the controls after incubation at different concentrations in culture medium with serum. After an exposure for three hours to different concentrations of the compounds in medium without serum, only CGP 20376 had a clear inhibitory effect on the developing larvae. The moulting rate was reduced by this compound to 20% of the control values with 1 microgram/ml, a concentration that is comparable to plasma levels reported from chimpanzees. In both experimental situations, with serum and without serum, the motility of the developing larvae was only affected at very high concentrations of the compounds. The results obtained with fourth stage larvae were comparable. CGP 6140 and CGP 20376 were tested in vivo, using a diffusion chamber technique for the implantation of infective larvae into the peritoneum of Mastomys natalensis and assessing the survival of the implanted parasites. High doses of CGP 6140 had only unsatisfactory effects on the larvae in this model system whereas CGP 20376 had inhibited moulting and killed most larvae with a daily dose of 25 mg/kg for five consecutive days.
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PMID:Studies on the activity of the Ciba Geigy compounds CGP 6140, 20376, 20309 and 21833 against third and fourth stage larvae of Onchocerca volvulus. 274 Jul 28

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.
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PMID:Drug activity against Onchocerca gutturosa males in vitro: a model for chemotherapeutic research on onchocerciasis. 343 7