A racemic mixture ofRandSenantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though theSenantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth side-by-side studies are lacking. The aim of this study was to investigate thein vitroactivities of PZQ and its main metabolites, namely,R- andS-cis- andR- andS-trans-4′-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored thein vivoactivity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations ofR-PZQ,S-PZQ, andR-trans- andR-cis-4′-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 μg/ml, respectively, for adultS. mansoniwere determinedin vitro. S-trans- andS-cis-4′-hydroxypraziquantel were not active at 100 μg/ml. These results are consistent with microcalorimetry data and studies with NTS.In vivo, single 400-mg/kg oral doses ofR-PZQ andS-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treatedin vivowithS-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm thatR-PZQ is the main effector molecule, whileS-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ.

Isothermal microcalorimetry is a label‐free assay that allows monitoring of enzymatic and metabolic activities. The technique has strengths, but most instruments have a low throughput, which has limited their use for bioassays. Here, an isothermal microcalorimeter, equipped with a vessel holder similar to a 48‐well plate, was used. The increased throughput of this microcalorimeter makes it valuable for biomedical and pharmaceutical applications. Our results show that the sensitivity of the instrument allows the detection of 3 × 10⁴ bacteria per vial. Growth of P. mirabilis in Luria Broth medium was detected between 2 and 9 h with decreasing inoculum. The culture released 2.1J with a maximum thermal power of 76 μW. The growth rate calculated using calorimetric and spectrophotometric data were 0.60 and 0.57 h^–1, respectively. Additional insight on protease activities of P. mirabilis matching the last peak in heat production could be gathered as well. Growth of tumor microtissues releasing a maximum thermal power of 2.1 μW was also monitored and corresponds to a diameter increase of the microtissues from ca. 100 to 428 μm. This opens new research avenues in cancer research, diagnostics, and development of new antitumor drugs. For parasitic worms, the technique allows assessment of parasite survival using motor and metabolic activities even with a single worm.

Accurate metabolite identification remains one of the primary challenges in a metabolomics study. A reliable chemical spectral library increases the confidence in annotation, and the availability of raw and annotated data in public databases facilitates the transfer of Liquid chromatography coupled to mass spectrometry (LC–MS) methods across laboratories. Here, we illustrate how the combination of MS2 spectra, accurate mass, and retention time can improve the confidence of annotation and provide techniques to create a reliable library for all ion fragmentation (AIF) data with a focus on the characterization of the retention time. The resulting spectral library incorporates information on adducts and in-source fragmentation in AIF data, while noise peaks are effectively minimized through multiple deconvolution processes. We also report the development of the Mass Spectral LIbrary MAnager (MS-LIMA) tool to accelerate library sharing and transfer across laboratories. This library construction strategy improves the confidence in annotation for AIF data in LC–MS-based metabolomics and will facilitate the sharing of retention time and mass spectral data in the metabolomics community.

The liver fluke Opisthorchis viverrini, highly prevalent in Southeast Asia, is an important public health burden, including a risk factor for developing an aggressive bile duct cancer, cholangiocarcinoma, in chronically infected patients. Praziquantel, administered at a single 40 mg/kg dose in preventive chemotherapy programs and 3 × 25 mg/kg for individual treatment, is the drug of choice, yet information on the nature of the dose-response relationship is lacking. We performed a randomized, parallel, single-blind dose-ranging phase 2 trial in the Lao People’s Democratic Republic in O. viverrini–infected adults. Patients were randomly assigned to 30 mg/kg, 40 mg/kg, 50 mg/kg, or 3 × 25 mg/kg praziquantel or placebo. Adverse events were recorded at baseline, 3 hours, and 24 hours posttreatment. Cure rates (CRs) and egg reduction rates (ERRs) were estimated 3 weeks after drug administration using available case analysis. Dose-response curves were predicted using E_max models. Two-hundred seventeen O. viverrini–infected patients were assigned to the 5 treatment arms. The majority (94.3%) of patients harbored light infections. The E_max model predicted a high efficacy among the observed dose range. We observed CRs ranging from 92.7% to 95.5% and ERRs >99.5% for all praziquantel treatment groups. Adverse events were mild but higher in the standard treatment group (3 × 25 mg/kg) than in the single-dose treatment arms. Single-dose praziquantel appears to be as efficacious as the standard 3 × 25 mg/kg regimen for the treatment of O. viverrini infections, while presenting fewer adverse events. Further studies are necessary in moderate and heavy O. viverrini infections. Randomized Controlled Trials (ISRCTN77186750).