Tegumental hexose transporters have been kinetically characterized in mated and separated male and female Schistosoma mansoni 8-12 wk postinfection. Significant gender-specific differences in Km and Vmax were observed. In mated males, the estimated constants (mean +/- SE) were: Km = 0.63 +/- 0.31 mM, Vmax = 0.93 +/- 0.44 nmol/mg worm water/min, and the Kd = 0.25 +/- 0.09 microliter/mg worm water/min. In mated females the kinetics were: Km = 0.99 +/- 0.40 mM, Vmax = 1.22 +/- 0.42 nmol/mg worm water/min, and Kd = 0.60 +/- 0.14 microliter/mg worm water/min. The influx of 2-deoxy-D-glucose and 3-O-methylglucose has been similarly characterized; these analogs share the same glucose transporter in male and female schistosomes. 2-Deoxy-D-glucose has a higher affinity, and 3-O-methylglucose a lower affinity, than does glucose. Because mated male schistosomes supply glucose to female partners, similarities between the free glucose concentration of the male and the affinity of the transporter determined for mated female schistosomes suggest that male-to-female transfer may be a potentially rate-limiting step in glucose utilization by the female. Permeability x surface are (PS) products and Vmax/Km ratios were significantly elevated in mated schistosomes, suggesting that the transporter is primarily localized to the dorsal surface of the male. Gender- and mating-specific analyses of PS products indicate that tegumental permeability to glucose is significantly increased in mated schistosomes, and compares very favorably to that of the host liver.
Competing interest statement: Cleveland Clinic has applied for patents on HSD3B1.
BackgroundMany unlicensed medicinal products routinely used to treat the paediatric population do not undergo the same rigorous assessment that adult preparations do prior to coming to market. This means that many preparations are not authorised for paediatric use and consequently there is widespread use of unlicensed medicines and ‘off-label’ use of licensed medicines. Evaluation of excipients in unlicensed medicines is an integral part of assessing their suitability for use in paediatric patients.1 Excipients of concern include (but are not limited to) propylene glycol, ethanol, hydroxybenzoates, artificial sweeteners. Medicines are carefully selected for use based on agreed criteria. The assessment tool used in this centre is the ‘New Products Assessment Form’ and helps the assessor identify potential issues with excipients.AimThis review aimed to reassess excipients in one manufacturer’s portfolio of unlicensed liquid preparations, stocked and regularly used at this centre. An informed decision could then be made to switch to a more suitable alternative if necessary.MethodA list of the manufacturer’s unlicensed liquid preparations was compiled, 14 in total. The company was contacted and requested to provide a comprehensive list of excipients. A New Products Assessment Form was completed for each product, which identified potential issues with excipients, in line with European Medicines Agency (EMA) guidelines. A list of all preparations where excipients exceeded acceptable daily intake (ADI) was made. Based on dosing regimens and weight/age the ADI of each excipient was calculated and documented. Where a preparation exceeded ADI for a particular excipient the manufacturing company was informed and a request for reformulation made. Alternative preparations were sought from other specialist manufacturing companies where necessary. Each product was assessed in the same manner. Pharmacy colleagues were consulted throughout the process and provided feedback on alternative preparations available. Concerns around labelling and similarities with other products, cost and reimbursement status, whether tablets could be crushed and dispersed in water as an alternative were highlighted and discussed. Relevant prescribing consultants were also informed. An informed decision was made to switch to an alternative product where indicated.ResultsIn total, a review of fourteen preparations stocked was conducted. Five out of 14 (36%) were changed to an alternative more appropriate preparation in terms of excipients. Four of the fourteen (29%) were suitable for use in patients across all age groups. Four of the fourteen (29%) exceeded the ADI for a particular excipient for preparations for use in neonates (suitable for all other age groups). Of the four, two were not routinely prescribed in neonates. One preparation was removed from the market. The remaining two products were considered suitable for use for their respective indications and dosing regimens.ConclusionUnlicensed medicines and medicines that are used in neonate and paediatric patients must be carefully assessed for excipients before use.1–3 A risk benefit assessment4 should be conducted to establish if an unlicensed medicine should be used and prescribers notified of any excipients of concern.ReferencesAnnex to the European Commission guideline on ‘Excipients in the labelling and package leaflet of medicinal products for human use’ (SANTE-2017-11668). Available at: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003412.pdfEuropean Medicines Agency. Committee for Medicinal Products for Human Use (CHMP): Information for the package leaflet regarding ethanol used as an excipient in medicinal products for human use (EMA/CHMP/43486/2018); September 2018. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/information-package-leaflet-regarding-ethanol-used-excipient-medicinal-products-human-use_en.pdfNPPG Neonatal and Paediatric Pharmacists Group Newsletter No 61 Autumn 2016. Excipients in medicines for Children. Available at: www.nppg.scot.nhs.uk/wp-content/uploads/2017/04/NPPG-61.pdfNeonatal and Paediatric Pharmacists Group and Royal College of Paediatrics and Child Health, UK. Using Standardised Concentrations of Unlicensed Liquid Medicines in Children. April 2020. Available at: https://nppg.org.uk/wp-content/uploads/2020/04/NPPG-Position-Statement-18-01-V5-April-2020.pdf
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.