caa a22 4500 386400296 CHVBK 20180307112156.0 cr unu---uuuuu 161130e198912 xx s 000 0 eng 10.1017/S003118200005914X doi S003118200005914X pii (NATIONALLICENCE)cambridge-10.1017/S003118200005914X A preliminary assessment of the feasibility of evaluating promising antifilarials in vitro against adult Onchocerca volvulus [Elektronische Daten] The suitability of motility indices and tetrazolium-based colorimetric assays for the determination of the viability of adult Onchocerca volvulus after in vitro exposure to potential macrofilaricides has been examined. Experimentation showed that both techniques could be applied to adult O. volvulus, although the variability between individual worms necessitated the use of large experimental groups. The potential of using cut anterior tips of female O. volvulus for screening was also investigated. These were shown to give reasonably consistent motility indices, and drug effects were discernible even after 72 h in vitro culture. Application of these viability criteria to studies on the short-term in vitro survival of intact male and female O. volvulus incubated in Eagles MEM plus serum, under 5% CO2 in air, showed this medium to be suboptimal with a greater than 50 % loss of worm viability within 144 h of nodulectomy. Males isolated by the collagenase technique were shown to be significantly less viable than dissected males, by both motility indices and tetrazolium reduction. The results highlight the need to use either dissected males, or in the case of females, the need to minimize exposure to collagenase solution. A possible mechanism for selecting a more uniformly viable female worm population is discussed. Examination of the in vitro effects of CGP 20376 using these viability criteria/assay systems showed some delayed suppression of worm motility, but after 120 h in vitro CGP 20376 was not macrofilaricidal against male or female O. volvulus. Male worms were also implanted subcutaneously into gerbils. Treatment of these animals with CGP 20376, with autopsy 2 weeks later, resulted in a small macrofilaricidal effect (28% worm death). Some reduction in the motility of living worms recovered from CGP 20376-treated gerbils was also evident. Good survival of control worms recovered 2 weeks post-implantation suggests that male O. volvulus might survive longer subcutaneously. The prospects for undertaking meaningful drug evaluations against O. volvulus in vitro (and in vivo in rodents) is therefore promising, but because of parasite availability will probably be limited to those compounds which have shown potential in other filarial test systems. Copyright © Cambridge University Press 1989 Onchocerca volvulus nationallicence viability nationallicence motility nationallicence tetrazolium reduction nationallicence collagenase isolation nationallicence drug evaluation nationallicence Comley J. C. W. Molecular Sciences Department, The Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS, UK Szopa T. M. Biochemistry Department, The London Hospital Medical College, Turner Street, London El 2AD, UK Strote G. Helminthology Department, Bernard Nocht Institute, Bernard Nocht Street 74, D-2000 Hamburg 36, FRG Buttner M. Helminthology Department, Bernard Nocht Institute, Bernard Nocht Street 74, D-2000 Hamburg 36, FRG Darge K. Helminthology Department, Bernard Nocht Institute, Bernard Nocht Street 74, D-2000 Hamburg 36, FRG Buttner W. Helminthology Department, Bernard Nocht Institute, Bernard Nocht Street 74, D-2000 Hamburg 36, FRG Parasitology Cambridge University Press 99/3(1989-12), 417-425 0031-1820 99:3<417 1989 99 PAR https://doi.org/10.1017/S003118200005914X text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1017/S003118200005914X text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Comley J. C. W. Molecular Sciences Department, The Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS, UK NATIONALLICENCE 700 1- Szopa T. M. Biochemistry Department, The London Hospital Medical College, Turner Street, London El 2AD, UK NATIONALLICENCE 700 1- Strote G. Helminthology Department, Bernard Nocht Institute, Bernard Nocht Street 74, D-2000 Hamburg 36, FRG NATIONALLICENCE 700 1- Buttner M. Helminthology Department, Bernard Nocht Institute, Bernard Nocht Street 74, D-2000 Hamburg 36, FRG NATIONALLICENCE 700 1- Darge K. Helminthology Department, Bernard Nocht Institute, Bernard Nocht Street 74, D-2000 Hamburg 36, FRG NATIONALLICENCE 700 1- Buttner W. Helminthology Department, Bernard Nocht Institute, Bernard Nocht Street 74, D-2000 Hamburg 36, FRG NATIONALLICENCE 773 0- Parasitology Cambridge University Press 99/3(1989-12), 417-425 0031-1820 99:3<417 1989 99 PAR CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-cambridge