Comparison of Microcapillary Blood Sampling Devices for Use in Anti-Doping.

Blood collection is an important facet of anti-doping testing, forming the basis of the hematological module of the athlete biological passport (ABP). Presently, whole blood is collected via venepucture under standardized conditions, in accordance with the World Anti-doping Agency's International Standard for Testing and Investigations (ISTI). Advances in capillary whole blood collection technology now afford the ability to collect microvolumetric capillary whole blood from the upper arm (or other suitable vascular location such as the abdomen) that is "needle-free" and virtually painless.

Long-Term Excretion of Roxadustat in Urine.

Roxadustat (FG-4592), an orally active hypoxia-inducible factor prolyl hydroxylase stabilizer, has been shown to enhance erythropoiesis by increasing endogenous erythropoietin. It is indicated for the treatment of anemia and chronic kidney disease and is approved for clinical use in several countries, including the European Union, Japan and others. Due to its reasonably anticipated performance-enhancing effect in athletes, roxadustat is prohibited for use in sports at all times.

Doping Prevalence among U.S. Elite Athletes Subject to Drug Testing under the World Anti-Doping Code.

Background: Determining the prevalence of doping within an elite athlete population is challenging due to the extreme sensitivity of the topic; however, understanding true doping prevalence is important when designing anti-doping programs and measuring their effectiveness. The objective of this study was to estimate the prevalence of doping among Olympic, Paralympic, World, and National-level competitive athletes in the United States subject to the World Anti-Doping Code. All athletes who were subject to the U.

Application of micro capillary blood sampling in an anti-doping setting.

Blood collection is an important facet of anti-doping testing, forming the basis of the Athlete Biological Passport (ABP). Traditional blood collection via venipuncture can be uncomfortable for athletes, especially those who are tested frequently or close to competition. Athletes may also have negative perceptions of venipuncture due to past experiences or the risks of adverse health events such as bruising, hematomas, syncope, and general discomfort that has the potential to affect performance.

Detection of capromorelin in urine following oral and dermal routes of administration.

Capromorelin is a growth hormone secretagogue. Despite promising results to alleviate muscle-wasting in the elderly, it has not advanced further in human development. Subsequent studies demonstrated capromorelin's ability to increase food intake in animals, leading to approval in the United States and Europe as an appetite stimulant for cats (Elura) and dogs (Entyce).

δ C values of urinary 19-norandrosterone in antidoping samples and potential for adverse findings from boar offal consumption.

19-Norandrosterone (19NA) is the preferred urinary target compound to identify doping with nandrolone or related 19-norsteroids. At concentrations between 2.5 and 15 ng/mL, isotope ratio mass spectrometry (IRMS) is required to establish exogenous origin of urinary 19NA.

Feasibility of microvolumetric capillary whole blood collections for usage in Athlete Biological Passport analysis.

The hematological module of the Athlete Biological Passport (ABP) represents an important tool in the pursuit to detect blood doping in athletes. Currently, collecting blood samples for ABP analysis can be cumbersome, invasive, and expensive, involving a venous blood draw performed by a trained phlebotomist followed by cold-chain monitored shipping to the analysis laboratory. Developing innovative methods to collect and transport ABP blood samples while adhering to strict preanalytical and analytical requirements has the potential to greatly increase testing frequency and, consequently, the effectiveness of the ABP program globally.

Generic Pharmaceuticals as a Source of Diuretic Contamination in Athletes Subject to Sport Drug Testing.

This paper describes nine instances of positive anti-doping tests that could be accounted for by the use of permitted generic prescription drugs contaminated with diuretics, which are prohibited in sport at all times under the WADA Prohibited List. The contamination levels found in the medications are reported and were below FDA limits for manufacturers that are based primarily on safety considerations. These cases demonstrate that great care must be taken to identify the source of low-level anti-doping positives for diuretics reported by WADA-accredited laboratories, and possibly other prohibited substances as well, in order to avoid sanctioning innocent athletes.

Sports drug testing and the athletes' exposome.

Similar to the general population, elite athletes are exposed to a complex set of environmental factors including chemicals and radiation and also biological and physical stressors, which constitute an exposome that is, unlike for the general population, subjected to specific scrutiny for athletes due to applicable antidoping regulations and associated (frequent) routine doping controls. Hence, investigations into the athlete's exposome and how to distinguish between deliberate drug use and different contamination scenarios has become a central topic of antidoping research, as a delicate balance is to be managed between the vital and continually evolving developments of sensitive analytical techniques on the one hand, and the risk of the athletes' exposome potentially causing adverse analytical findings on the other.

Chromatographic-mass spectrometric analysis of the urinary metabolite profile of chlorphenesin observed after dermal application of chlorphenesin-containing sunscreen.

Rationale: Chlorphenesin is an approved biocide frequently used in cosmetics, and its carbamate ester is an approved skeletal muscle relaxant in certain countries for the treatment of discomfort related to skeletal muscle trauma and inflammation. A major urinary metabolite is 4-chlorophenoxy acetic acid (4-CPA), also known as para-chlorophenoxyacetate, which is also employed as a target analyte in sports drug testing to detect the use of the prohibited nootropic stimulant meclofenoxate. To distinguish between 4-CPA resulting from chlorphenesin, chlorphenesin carbamate, and meclofenoxate, urinary metabolite profiles of chlorphenesin after legitimate use were investigated.

Investigating oral fluid and exhaled breath as alternative matrices for anti-doping testing: Analysis of 521 matched samples.

Current anti-doping testing is primarily conducted in urine and blood. Recently, due to confounding factors with urine and blood collections such as invasiveness, cost, and stringent shipping conditions, there has been a push for the use of alternative sample matrices to ameliorate these issues. Gaining support within the anti-doping field is the use of oral fluid, and more recently exhaled breath, as viable alternative or complementary matrices to traditional urine and blood for drug testing.

Essential Features of Third-Party Certification Programs for Dietary Supplements: A Consensus Statement.

The presence of performance-enhancing drugs in dietary supplements poses serious anti-doping and health risks to athletes and military service members. A positive drug test, suboptimal health, or adverse event can ruin a career in either setting. These populations need to be certain in advance that a product is of high quality and free from performance-enhancing drugs and other banned substances.

Trading Health Risks for Glory: A Reformulation of the Goldman Dilemma.

Background: The Goldman dilemma presented athletes with a Faustian bargain that guaranteed winning an Olympic gold medal in their sport but resulted in certain death 5 years later. Athletes' responses to Goldman's bargain were reported from 1982 to 1995. Several studies subsequently evaluated people's willingness to accept the bargain proposed in the Goldman question.

Treating the elite athlete: anti-doping information for the health professional.

Physicians and health professionals are a vital component in preserving the integrity of competition and the core principles of true sport. When treating an athlete, health professionals need to be cognizant of the anti-doping rules of the relevant sport organization. This review aims to provide an overview of the World Anti-Doping Agency Prohibited List, Therapeutic Use Exemptions, roles and responsibilities of the health professional, as well as provide resources that will guide their work with athletes.

Human genetic variation: new challenges and opportunities for doping control.

Sport celebrates differences in competitors that lead to the often razor-thin margins between victory and defeat. The source of this variation is the interaction between the environment in which the athletes develop and compete and their genetic make-up. However, a darker side of sports may also be genetically influenced: some anti-doping tests are affected by the athlete's genotype.

The effects of exercise in hypoxic and normoxic conditions on endothelin-1 and arterial compliance.

The purpose of this study was to determine the effects of short-term normoxic and hypoxic exercise on plasma endothelin-1 and nitric oxide levels, and the relationship of arterial compliance and pulmonary artery pressure to endothelin-1. Seven endurance-trained males completed two incremental and two steady-state exercise tests performed at ventilatory threshold in normoxia and hypoxia (fraction of inspired oxygen = 0.14).

Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents?

In the decade since the angiotensin-converting enzyme (ACE) gene was first proposed to be a 'human gene for physical performance', there have been numerous studies examining the effects of ACE genotype on physical performance phenotypes such as aerobic capacity, muscle function, trainability, and athletic status. While the results are variable and sometimes inconsistent, and corroborating phenotypic data limited, carriers of the ACE 'insertion' allele (the presence of an alu repeat element in intron 16 of the gene) have been reported to have higher maximum oxygen uptake (VO2max), greater response to training, and increased muscle efficiency when compared with individuals carrying the 'deletion' allele (absence of the alu repeat). Furthermore, the insertion allele has been reported to be over-represented in elite athletes from a variety of populations representing a number of endurance sports.

RNAi-mediated gene silencing in non-human primates.

The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates.

pH modulation using CsCl enhances therapeutic effects of vitamin D in LNCaP tumor bearing mice.

Background: The downstream effects of pH modulation significantly impact the biological fate of chemotherapeutic agents and tumor responsiveness to therapy. We have studied the effects of cesium chloride (CsCl) on pH modulation and subsequent vitamin D treatment in vitamin D receptor (VDR) positive LNCaP tumors and VDR null MDA/LCC6 tumors in vivo.

Methods: Mice bearing LNCaP or MDA/LCC6 tumors were dosed orally with CsCl (150 mg/kg) or vitamin D (1 microg/kg) alone and in combination.

YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activity.

Background: Currently, the main obstacle to curing advanced prostate cancer is development of androgen independence (AI), where malignant cells acquire the ability to survive in the absence of androgens. Our initial experimental approach used cDNA microarrays to characterize changes in gene expression in the LNCaP human prostate tumor model during progression to AI. The transcription factor Y-box binding protein (YB-1) was shown to be one of the genes upregulated.

P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells.

Background: P-glycoprotein (P-gp) is commonly associated with multi-drug resistance (MDR) in cancer cells and the efflux of a broad spectrum of chemicals from the cell, including many chemotherapeutics and certain steroid hormones. The impact of P-gp and mechanisms involved in androgen transport and cellular accumulation within normal and malignant prostate cells remains unclear.

Methods: Following incubation of LNCaP, PC-3, HeLa, and HeLa FLAG-androgen receptor (AR) cells with (3)H-dihydrotestosterone (DHT) alone and in combination with P-gp inhibitors, PSC-833 and verapamil, we examined the cellular accumulation and efflux of androgens, as well as gene transcriptional response.