Activity of Praziquantel Enantiomers and Main Metabolites against Schistosoma mansoni

A racemic mixture of R and S enantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though the S enantiomer 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 the in vitro activities of PZQ and its main metabolites, namely, R- and S-cis- and R- and S-trans-4′-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored the in vivo activity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations of R-PZQ, S-PZQ, and R-trans- and R-cis-4′-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 μg/ml, respectively, for adult S. mansoni were determined in vitro. S-trans- and S-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 of R-PZQ and S-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treated in vivo with S-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm that R-PZQ is the main effector molecule, while S-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ.     

Schistosoma mansoni tetraspanning orphan receptor (SmTOR): a new vaccine candidate against schistosomiasis

One approach to fight against schistosomiasis is to develop an efficient vaccine. Schistosoma mansoni tetraspanning orphan receptor (SmTOR) might be a vaccine candidate, as it is a tegument membrane protein expressed most highly in cercariae. In this study we characterized the recombinant first extracellular domain of SmTOR (rSmTORed1) as having the expected property to bind C2 of complement similarly to a smaller peptide of the same domain, and to produce specific and high-titre antibodies in BALB/c mice immunized using complete Freund''s adjuvant/incomplete Freund''s adjuvant (CFA/IFA). Immunization was protective against parasite infection, as demonstrated by a significant decrease in worm burden in immunized BALB/c mice versus the control groups over two independent trials [64 and 45% reduction for mean adult worm burden in immunized versus phosphate-bufferd saline (PBS) injected mice]. Interestingly, infection by itself did not lead to the generation of anti-rSmTORed1 antibodies, corresponding to the low frequency of specific anti-rSmTORed1 antibodies detected in the sera of patients infected with S. mansoni (2/20; 10%). These data suggest that, as opposed to the natural infection during which SmTOR induces antibodies only rarely, immunization with its smaller first extracellular domain might be more efficient.     

Effects of neurodevelopmental stimulation on premature infants in neonatal intensive care: Randomized controlled trial

The purpose of the current study was to identify effects of neurodevelopmental stimulation as administered by board certified music therapists to premature infants admitted to the neonatal intensive care unit. Premature infants (N = 108) admitted and meeting inclusion criteria were included. Experimental subjects received the developmental multimodal stimulation protocol paired with live singing (n = 25) or live singing with guitar accompaniment (n = 29). The no contact control group received standard neonatal intensive care unit care (n = 54). An ANCOVA analyses with birth weight as a covariate resulted in significant main effects found for infant length of stay (p < .05). When comparing the means, differences were found between gender and types of music paired with the developmental multimodal stimulation. The results of this study suggest an increase in neurodevelopment for infants receiving developmental multimodal stimulation as hypothesized.     

The role of race/ethnicity in cerclage efficacy

Objective: To measure the impact of race/ethnicity on cerclage efficacy, as measured by the prevalence of spontaneous preterm birth (PTB), in a cohort of patients with history-indicated, ultrasound-indicated and physical-exam indicated cerclages.

Methods: We conducted a retrospective cohort study of patients undergoing history-indicated, ultrasound-indicated and physical-exam indicated cerclage placement from January 2003 to July 2013 at a tertiary care hospital. Patients’ race/ethnicity was self-declared. Our primary outcome was spontaneous preterm birth (SPTB) Results: One hundred and eighty-one subjects met inclusion criteria. Forty-seven percent self-identified as non-Hispanic black (NHB), 12% as Hispanic and 41% as non-Hispanic white (NHW). There was no significant difference in the prevalence of SPTB p?=?0.22), nor for SPTB less than 34 or 28 weeks. Finally, there was no difference in SPTB prevalence by race after controlling for smoking, history of CKC/LEEP, and 17-OHPC with logistic regression.

Conclusion: Race/ethnicity does not appear to be associated with cerclage efficacy, as measured by the risk of SPTB, in a cohort of patients with history-indicated, ultrasound-indicated and physical-exam indicated cerclages.