Worm burden reductions of <i>S</i>.<i>mansoni-</i>infected mice treated with <i>in vitro-</i>hit FDA Pharmakon compounds.

<p>*Indicates that the 4^th mouse of this group died prematurely.</p><p>** WBR for clofazimine (200 mg/kg) was calculated based on worm burden of Control Batch 2.</p><p>Worm burden reductions of <i>S</i>.<i>mansoni-</i>infected mice treated with <i>in vitro-</i>hit FDA Pharmakon compounds.</p

IC₅₀ values of compounds selected for <i>in vivo</i> testing.

<p>IC₅₀ values of compounds selected for <i>in vivo</i> testing.</p

121 Hit compounds at NTS screening stage.

<p>Compounds were tested at a concentration of 10 μM and hits were defined as compounds for which the NTS scored ≤ 0.5 on our viability scale at 72 hours post-exposure.</p><p>*Indicates compound excluded due to toxicity concerns.</p><p>**Indicates compound that has already been well-characterized on <i>Schistosoma spp</i>. and hence was excluded.</p><p>121 Hit compounds at NTS screening stage.</p

Venn diagrams representing overlaps between: (A) our NTS screen and that of Abdulla et al., (B) our NTS screen and <i>in silico</i> hits from Neves et al. and (C) NTS hits from Abdulla et al. and hits from Neves et al.

<p>The small dark circles within each large circle represent the number of compounds that were not present in the comparator’s library.</p

Structures and pharmacokinetic data of <i>in vivo-</i>active clofazimine (A) and doramectin (B).

<p>Clofazimine data is based on a single oral dose of 200 mg give to healthy male volunteers [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003962#pntd.0003962.ref045" target="_blank">45</a>]. Doramectin data is based on a single oral dose of 200 μg/kg administered to horses [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003962#pntd.0003962.ref046" target="_blank">46</a>].</p

Compounds active on adult <i>S</i>. <i>mansoni</i> at a concentration of 33.33 μM at 24 hours.

<p>Activity was defined as scoring an average of ≤ 0.5 on the viability scale. The reason for exclusion is also listed and the data is based on compound material safety data sheets, FDA documents and previous publications.</p><p>Compounds active on adult <i>S</i>. <i>mansoni</i> at a concentration of 33.33 μM at 24 hours.</p

Additional file 5: Figure S3. of Fluorescence/luminescence-based markers for the assessment of Schistosoma mansoni schistosomula drug assays

Fluorescence generated from culture medium as measured by (A) Omnicathepsin, (B) DAPI and (C) Hoechst 33258. Since our standard culture medium could also contribute to high fluorescence, RPMI medium was also tested. Graphs presented here correspond to optimal marker concentrations and incubation times are indicated in the main text. (PPTX 79 kb

Boletín de Segovia: Número 131 - 1838 noviembre 8

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 200

Characterizing the Biochemical Response to <i>Schistosoma mansoni</i> Infection and Treatment with Praziquantel in Preschool and School Aged Children

Schistosomiasis is a widespread chronic neglected tropical disease prevalent mostly in children in under-resourced rural areas. Its pathological effects have been clinically characterized, yet the molecular-level effects are understudied. In this study, the biochemical effects of <i>Schistosoma mansoni</i> infection and praziquantel treatment were studied in 130 preschool aged and 159 school aged infected children and 11 noninfected children in Azaguié, Côte d’Ivoire. Urine samples were collected prior to receiving 20, 40, or 60 mg/kg of praziquantel or a placebo, as well as 24 h post-treatment, and at the 3-week follow up. Urinary metabolic phenotypes were measured using ¹H NMR spectroscopy, and metabolic variation associated with <i>S. mansoni</i> infection and praziquantel administration was identified using multivariate statistical techniques. Discriminatory metabolic signatures were detected between heavily infected and noninfected children at baseline as well as according to the dose of praziquantel administered 24 h post treatment. These signatures were primarily associated with the metabolic activity of the gut microbiota, gut health and growth biomarkers and energy and liver metabolism. These analyses provide insights into the metabolic phenotype of schistosomiasis and treatment with praziquantel in two important demographics

Additional file 2: of Investigations on the interplays between Schistosoma mansoni, praziquantel and the gut microbiome

Table S2. Barcodes and DNA concentrations. Summary table showing the pooling barcodes and pre-sequencing DNA concentrations. (XLSX 10 kb