The alkaloid cryptolepine (1) and eight synthetic analogues (2-8) were assessed for in vitro activities against Trypanosoma brucei. Four of the analogues were found to be highly potent with IC 50 values of less than 3 nM and three of these were assessed against T. brucei brucei infection in rats. The most effective compound was 2, 7-dibromocryptolepine (7); a single oral dose of 20 mg/kg suppressed parasitaemia and increased the mean survival time to 13.6 days compared with 8.4 days for untreated controls. In addition, four huperzine derivatives (9-12) were shown to have in vitro antitrypanosomal activities with IC 50 values ranging from 303-377 nM.
SummaryWe tested a rapid visually read monoclonal antibody (MoAb) based dipstick assay for specific diagnosis of urinary schistosomiasis against microscopy and the use of haematuria and proteinuria in a schistosomiasis haematobia endemic area in the Central Region of Ghana. The study group consisted of 141 school children (83 males, 58 females) aged 8-19 years. A total of 129 of 141 (91.5%) submitted stool samples, and 7.8% had Schistosoma mansoni, 55% had hookworms and 6.2% had tapeworms. The presence of S. mansoni and intestinal parasites did not appear to influence the results of the MoAb-dipstick assay. The urinary schistosomiasis prevalence by MoAb-dipstick (78%) was higher (P < 0.05) than the estimate by microscopy (60.3%), microhaematuria (27%) and proteinuria (30.5%). The MoAb-dipstick correctly identified 98.8% of microscopically confirmed cases and missed one (1.3%). The dipstick was also positive for 26 of 56 (46.4%) egg-negative individuals, thereby giving a sensitivity of 98.8% and a specificity of 53.6%. On the other hand, microhaematuria and proteinuria were 38.8% and 30.6% sensitive, and 91.1% and 69.6% specific, respectively. Microhaematuria and proteinuria were less sensitive (P < 0.05) than both microscopy and MoAb-dipstick.keywords urinary schistosomiasis, monoclonal antibody, diagnosis, dipstick
Sonicated suspensions of epimastigote, metacyclic, or bloodstream forms of Trypanosoma cruzi were emulsified in Freund's complete adjuvant. Rabbits immunized with epimastigotes or metacyclics received five intramuscular (i.m.) injections of 1 x 10(9) sonicated trypanosomes at weekly intervals. Immunization with bloodstream forms included three i.m. injections of 5 x 10(7) and six injections of 2 x 10(8) sonicated trypanosomes. Selected antisera from these rabbits were employed in crossed immunoelectrophoretic studies against the homologous or heterologous extracts of sonicated trypanosomes. Extracts of epimastigote, metacyclic, and trypomastigotes produced 31, 29, and 11 precipitin peaks respectively against the homologous rabbit antisera. Tandem, crossed-immunoelectrophoresis of these extracts against antiepimastigote or antimetacyclic sera revealed that epimastigotes or metacyclics may each have at least four antigens that did not appear to be shared by the other, whereas each of these forms may have at least eight or nine antigens that were not detected with extracts from trypomastigotes. Cross-absorptions of antiepimastigote or antimetacyclic sera with live trypanosomes caused marked reductions in the numbers of precipitin peaks formed against the homologous extracts, but cross-absorptions with sonicated suspensions of epimastigotes or metacyclics showed that epimastigotes or metacyclics each have at least two antigens that were not detected in extracts of the other. Differentiation appeared to be accompanied by antigenic change. More antigens appear to be shared by epimastigotes and metacyclic forms than by trypomastigotes and epimastigotes or metacyclics.
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