Analysis of human chorionic gonadotropin (hCG): Application of routine immunological methods for initial testing and confirmation analysis in doping control

Human chorionic gonadotropin (hCG) is dimeric glycoprotein produced by placenta in pregnancy and also in low levels by pituitary gland. The main clinical use for exogenous hCG‐administration is typically linked to infertility. The desired effect of hCG misuse in sport is due to the enhancement of testicular production of testosterone. Therefore, hCG is listed by the World Anti‐Doping Agency (WADA) as a prohibited substance in male athletes and according to the recently published WADA guideline urinary concentrations of hCG > 5 IU/L may be an indicator of doping. In this study two independent immunoassays were used to implement the new WADA guideline. The assay for initial testing (Siemens Immulite 2000 XPi hCG assay) recognizes various hCG variants (e.g. hCG and β‐core fragment of hCG) whereas the confirmatory assay (PerkinElmer DELFIA Xpress hCG) is sensitive to intact and nicked hCG only. Both assays showed adequate sensitivity and were proven fit‐for‐purpose in routine doping control. Population‐based distribution of the assays was in good agreement with results of earlier studies and supported well the current threshold of 5 IU/L. Copyright © 2013 John Wiley & Sons, Ltd.     

A comparison of immunogenicity of norovirus GII-4 virus-like particles and P-particles

Norovirus (NoV) -derived virus-like particles (VLPs) resemble empty shells of the virus and NoV P-particles contain only protruding domains of the NoV capsid. Both NoV-derived subviral particles show similar functionality and antigenicity in vitro and are considered to be potential vaccine candidates against NoV gastroenteritis. BALB/c mice were immunized with baculovirus-produced GII-4 VLPs or the corresponding Escherichia coli-produced P-particles by the intramuscular or intradermal route and the NoV-specific antibody and T-cell immune responses were compared. Elevated antibody levels were induced with a single VLP immunization, whereas P-particle immunization required a boost. High avidity antibodies were raised only by VLP immunization. VLP immunization resulted in a balanced T helper type 1/type 2 immune response whereas P-particles induced a T helper type 2-biased response. Only VLP immunization primed T cells for interferon-γ production. Most importantly, cross-reactive B and T cells were induced solely by VLP immunization. In addition, VLP antiserum blocked the binding of heterotypic VLPs to human histo-blood group antigen receptor and saliva. The findings in this study are relevant for the development of NoV vaccines.     

The Traditional Medicine Spilanthes acmella,and the Alkylamides Spilanthol and Undeca‐2E‐ene‐8,10‐diynoic Acid Isobutylamide,Demonstrate In Vitro and In Vivo Antimalarial Activity

Spilanthes spp. are used as traditional herbal medicines in Africa and India to treat malaria. Yet, to date, there are no data on the active constituents or the most effective extraction methods for this indication. The isolated alkylamides, spilanthol and undeca‐2E‐ene‐8,10‐diynoic acid isobutylamide, found in S. acmella Murr., were shown to have IC₅₀s of 16.5 μg/mL and 41.4 μg/mL on Plasmodium falciparum strain PFB and IC₅₀s of 5.8 μg/mL and 16.3 μg/mL for the chloroquine resistant P. falciparum K1 strain, respectively. Further investigations revealed that at relatively low concentrations, spilanthol and the water extract of S. acmella reduced the parasitemia 59% and 53% in mice infected with P. yoelii yoelii 17XNL at 5 mg/kg and 50 mg/kg, respectively. Unexpectedly, the 95% ethanol extract of S. acmella was less effective (36% reduction in parasitemia) at 50 mg/kg. These results provide the first evidence supporting S. acmella against malaria and demonstrating active constituents in S. acmella against P. falciparum. Copyright © 2011 John Wiley & Sons, Ltd.     

Annual banned-substance review: analytical approaches in human sports drug testing

The timely update of the list of prohibited substances and methods of doping (as issued by the World Anti-Doping Agency) is an essential aspect of international anti-doping efforts and represents consensual agreement by expert panels regarding substances and the methods of performance manipulation in sports. The annual banned-substance review for human doping controls critically summarizes recent innovations in analytical approaches; its purpose is to improve the quality of doping controls by reporting emerging and advancing methods that focus on detecting known and recently outlawed substances. This review surveys new and/or enhanced procedures and techniques of doping analysis together with information relevant to doping control that has been published in the literature between October 2009 and September 2010.     

Mobile phone effects on children's event-related oscillatory EEG during an auditory memory task

PURPOSE: To assess the effects of electromagnetic fields (EMF) emitted by mobile phones (MP) on the 1 - 20 Hz event-related brain oscillatory EEG (electroencephalogram) responses in children performing an auditory memory task (encoding and recognition). MATERIALS AND METHODS: EEG data were gathered while 15 subjects (age 10 - 14 years) performed an auditory memory task both with and without exposure to a digital 902 MHz MP in counterbalanced order. RESULTS: During memory encoding, the active MP modulated the event-related desynchronization/synchronization (ERD/ERS) responses in the approximately 4 - 8 Hz EEG frequencies. During recognition, the active MP transformed these brain oscillatory responses in the approximately 4 - 8 Hz and approximately 15 Hz frequencies. CONCLUSIONS: The current findings suggest that EMF emitted by mobile phones has effects on brain oscillatory responses during cognitive processing in children.     

Synthesis and antimalarial activity of new amino analogues of amodiaquine

Amodiaquine remains one of the most prescribed antimalarial 4-aminoquinoline. To assess the importance of the 4'-hydroxyl group and subsequent hydrogen bond in the antimalarial activity of amodiaquine (AQ), a series of new analogues in which this functionality was replaced by various amino groups was synthesized. The incorporation of a 3'-pyrrolidinamino group instead of the 3'-diethylamino function of AQ allowed the development of a parallel series of amopyroquine derivatives. The compounds were screened against both chloroquine (CQ)-sensitive and -resistant strains of Plasmodium falciparum and their cytotoxicity evaluated upon the MRC5 cell line. Antimalarial activity in a low nanomolar range was recorded showing that the 4'-hydroxy function can be successfully replaced by various amino substituents in terms of activity without any influence of the level of CQ-resistance of the strains. Furthermore the ability of the compounds to inhibit beta-hematin formation was measured in order to discuss the mechanism of action of these new compounds. Compounds 7d and 8d exhibit a high selectivity index and may be considered as promising leads for further development.