Annual banned‐substance review: Analytical approaches in human sports drug testing

A number of high profile revelations concerning anti‐doping rule violations over the past 12 months have outlined the importance of tackling prevailing challenges and reducing the limitations of the current anti‐doping system. At this time, the necessity to enhance, expand, and improve analytical test methods in response to the substances outlined in the World Anti‐Doping Agency (WADA) Prohibited List represents an increasingly crucial task for modern sports drug testing programs. The ability to improve analytical testing methods often relies on the expedient application of novel information regarding superior target analytes for sports drug testing assays, drug elimination profiles, and alternative sample matrices, together with recent advances in instrumental developments. This annual banned‐substance review evaluates literature published between October 2017 and September 2018 offering an in‐depth evaluation of developments in these arenas and their potential application to substances reported in WADA's 2018 Prohibited List.     

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

The aim of improving anti‐doping efforts is predicated on several different pillars, including, amongst others, optimized analytical methods. These commonly result from exploiting most recent developments in analytical instrumentation as well as research data on elite athletes' physiology in general, and pharmacology, metabolism, elimination, and downstream effects of prohibited substances and methods of doping, in particular. The need for frequent and adequate adaptations of sports drug testing procedures has been incessant, largely due to the uninterrupted emergence of new chemical entities but also due to the apparent use of established or even obsolete drugs for reasons other than therapeutic means, such as assumed beneficial effects on endurance, strength, and regeneration capacities. Continuing the series of annual banned‐substance reviews, literature concerning human sports drug testing published between October 2014 and September 2015 is summarized and reviewed in reference to the content of the 2015 Prohibited List as issued by the World Anti‐Doping Agency (WADA), with particular emphasis on analytical approaches and their contribution to enhanced doping controls.     

Do dried blood spots (DBS) have the potential to support result management processes in routine sports drug testing?

Dried blood spots (DBS) have been considered as complementary matrix in sports drug testing for many years. Especially concerning substances prohibited in‐competition only, the added value of DBS collected concomitantly with routine doping control urine samples has been debated, and an increasing potential of DBS has been discussed in the scientific literature. To which extent and under which prerequisites DBS can contribute to enhanced anti‐doping efforts is currently evaluated. As a proof‐of‐principle, two analytical applications, one targeting cocaine/benzoyl ecgonine and the other prednisone/prednisolone, are presented in this perspective to indicate potential added value but also presently existing limitations of the DBS approach.     

Drug metabolism in the horse: a review

A detailed understanding of equine drug metabolism is important for detection of drug abuse in horseracing and also in veterinary drug development and practice. To date, however, no comprehensive review of equine drug metabolism has been published. The majority of literature regarding equine drug metabolite profiles is derived from sports drug detection research and is generally targeted at detecting marker metabolites of drug abuse. However, the bulk of the literature on equine drug metabolism enzymology is derived from veterinary studies aimed at determining the molecular basis of metabolism. In this article, the phase 1 and 2 metabolisms of seven of the most important classes of drugs monitored in horseracing are reviewed, including: anabolic-androgenic steroids (AAS), β? -agonists, stimulants, sedatives/tranquilizers, local anesthetics, non-steroidal anti-inflammatory analgesics (NSAIDS)/cyclooxygenase-2 (COX-2) inhibitors, and opioid analgesics. A summary of the literature relating to the enzymology of drug metabolism in this species is also be presented. The future of equine drug metabolism in the area of doping research will be influenced by several factors, including: a possible move towards the increased use of blood and other alternative testing matrices; the development of assays based on intact drug conjugates; the increasing threat of 'designer' and herbal- based products; advances in the use of in vitro technologies; the increased use of liquid-chromatography/high-resolution mass spectrometry; and the possibility of screening using 'omics' approaches. Also, the recent cloning of a range of equine cytochrome P450 (CYP) enzymes opens up the potential for carrying out more detailed mechanistic pharmacological and toxicological veterinary studies.     

The final outcome of primary infrainguinal percutaneous transluminal angioplasty in 100 consecutive patients with chronic critical limb ischemia

PURPOSE: This study was performed to determine final outcomes in patients treated with infrainguinal percutaneous transluminal angioplasty (PTA) for chronic critical limb ischemia (CLI). MATERIALS AND METHODS: The study population consisted of 100 consecutive patients (mean age, 72 y; range, 38-90 y; 40 men and 60 women) with 116 treated limbs. CLI was defined as rest pain or ischemic tissue defect combined with an ankle systolic pressure < or = 50 mm Hg. Indication for treatment was rest pain in 23 limbs (20%), ischemic ulcer in 50 (43%), and gangrene in 43 (37%). All patients were followed until they had met the study endpoints: major amputation or death. The mean follow-up period was 38 months (1-119 mo). Limb salvage, survival, and life with limb rates were determined along with their determinants. RESULTS: On average, 1.9 invasive procedures were required during the lifespan of a critically ischemic limb, including primary PTA and 32 repeat PTA procedures, 11 surgical revascularizations, and 51 amputations. The major amputation rate was 32% (n = 37). Limb salvage for endovascular treatments at 3, 5, and 8 years was 65%, 60%, and 60%, respectively (SE of estimate [SEE] 相似文献   

Purification of norovirus-like particles (VLPs) by ion exchange chromatography

Recombinant expression of the norovirus capsid protein VP1 leads to self-assembly of non-infectious virus-like particles (VLPs), which are recognized as promising vaccine candidates against norovirus infections. To overcome the scalability issues connected to the ultracentrifugation-based purification strategies used in previous studies, an anion exchange-based purification method for norovirus VLPs was developed in this study. The method consists of precipitation by polyethylene glycol (PEG) and a single anion exchange chromatography step for purifying baculovirus-expressed GII.4 norovirus VLPs, which can be performed within one day. High product purity was obtained using chromatography. The purified material also contained fully assembled monodispersed VLPs, which were recognized by human sera containing polyclonal antibodies against norovirus GII.4.