Mass Spectrometry Method to Measure Membrane Proteins in Dried Blood Spots for the Detection of Blood Doping Practices in Sport

22 Aug 2017

Mass Spectrometry Method to Measure Membrane Proteins in Dried Blood Spots for the Detection of Blood Doping Practices in Sport / Holly D. Cox, Daniel Eichner. - (Analytical chemistry 89 (2017) 18 (September) ; p. 10029-10036)

  • PMID: 28829585
  • DOI: 10.1021/acs.analchem.7b02492

Abstract:

The dried blood spot (DBS) matrix has significant utility for applications in the field where venous blood collection and timely shipment of labile blood samples is difficult. Unfortunately, protein measurement in DBS is hindered by high abundance proteins and matrix interference that increases with hematocrit. We developed a DBS method to enrich for membrane proteins and remove soluble proteins and matrix interference. Following a wash in a series of buffers, the membrane proteins are digested with trypsin and quantitated by parallel reaction monitoring mass spectrometry methods. The DBS method was applied to the quantification of four cell-specific cluster of differentiation (CD) proteins used to count cells by flow cytometry, band 3 (CD233), CD71, CD45, and CD41. We demonstrate that the DBS method counts low abundance cell types such as immature reticulocytes as well as high abundance cell types such as red blood cells, white blood cells, and platelets. When tested in 82 individuals, counts obtained by the DBS method demonstrated good agreement with flow cytometry and automated hematology analyzers. Importantly, the method allows longitudinal monitoring of CD protein concentration and calculation of interindividual variation which is difficult by other methods. Interindividual variation of band 3 and CD45 was low, 6 and 8%, respectively, while variation of CD41 and CD71 was higher, 18 and 78%, respectively. Longitudinal measurement of CD71 concentration in DBS over an 8-week period demonstrated intraindividual variation 17.1-38.7%. Thus, the method may allow stable longitudinal measurement of blood parameters currently monitored to detect blood doping practices.

Mass spectrometry of selective androgen receptor modulators

2 Jun 2008

Mass spectrometry of selective androgen receptor modulators / Mario Thevis, Wilhelm Schänzer. - (Journal of Mass Spectrometry 43 (2008) 7 (July); p. 865-876)

  • PMID: 18521833
  • DOI: 10.1002/jms.1438


Abstract

Nonsteroidal selective androgen receptor modulators (SARMs) are an emerging class of drugs for treatment of various diseases including osteoporosis and muscle wasting as well as the correction of age-related functional decline such as muscle strength and power. Several SARMs, which have advanced to preclinical and clinical trials, are composed of diverse chemical structures including arylpropionamide-, bicyclic hydantoin-, quinoline-, and tetrahydroquinoline-derived nuclei. Since January 2008, SARMs have been categorized as anabolic agents and prohibited by the World Anti-Doping Agency (WADA). Suitable detection methods for these low-molecular weight drugs were based on mass spectrometric approaches, which necessitated the elucidation of dissociation pathways in order to characterize and identify the target analytes in doping control samples as well as potential metabolic products and synthetic analogs. Fragmentation patterns of representatives of each category of SARMs after electrospray ionization (ESI) and collision-induced dissociation (CID) as well as electron ionization (EI) are summarized. The complexity and structural heterogeneity of these drugs is a daunting challenge for detection methods.

Mass spectrometry-based characterization of new drugs and methods of performance manipulation in doping control analysis

1 Feb 2010

Mass spectrometry-based characterization of new drugs and methods of performance manipulation in doping control analysis / Mario Thevis, Andreas Thomas, Maxie Kohler, Simon Beuck, Ines Möller, Mathias Schäfer, Grigory Rodchenkov, Sheng Yin, Joseph A. Loo, Hans Geyer, Wilhelm Schänzer. - (
European Journal of Mass Spectrometry 16 (2010) 3 (1 February); p. 301-312)

  • PMID: 20530837
  • DOI: 10.1255/ejms.1047


Abstract

Efficient and comprehensive sports drug testing necessitates frequent updating and proactive, preventive anti-doping research, and the early implementation of new, emerging drugs into routine doping controls is an essential aspect. Several new drugs and drug candidates with potential for abuse, including so-called Rycals (ryanodine receptor calstabin complex stabilizers, for example, S-107), hypoxia-inducible factor (HIF) stabilizers, and peroxisome-proliferator-activated receptor (PPAR) delta agonists (for example, GW1516), were studied using different mass spectrometry- and ion mobility-based approaches, and their gas phase dissociation behaviors were elucidated. The detailed knowledge of fragmentation routes allows a more rapid identification of metabolites and structurally related, presumably "tailor-made", analogs potentially designed for doping purposes. The utility of product ion characterization is demonstrated in particular with GW1516, for which oxidation products were readily identified in urine samples by means of diagnostic fragment ions as measured using high resolution/high accuracy mass spectrometry and higher energy collision-induced dissociation (HCD).

May the blessed man win: a critique of the categorical preference for natural talent over doping as proper origins of athletic ability

5 Jul 2014

May the blessed man win: a critique of the categorical preference for natural talent over doping as proper origins of athletic ability / Pieter Bonte, Sigrid Sterckx, Guido Pennings. - (Journal of Medicine and Philosphy 39 (2014) 4 (August); p. 368-386)

  • PMID: 24997251
  • DOI: 10.1093/jmp/jhu024


Abstract

Doping scandals can reveal unresolved tensions between the meritocratic values of equal opportunity + reward for effort and the "talentocratic" love of hereditary privilege. Whence this special reverence for talent? We analyze the following arguments: (1) talent is a unique indicator of greater potential, whereas doping enables only temporary boosts (the fluke critique); (2) developing a talent is an authentic endeavor of "becoming who you are," whereas reforming the fundamentals of your birth suit via artifice is an act of alienation (the phony critique); (3) your (lack of) talent informs you of your proper place and purpose in life, whereas doping frustrates such an amor fati self-understanding (the fateless critique). We conclude that these arguments fail to justify a categorical preference for natural talent over integrated artifice. Instead, they illustrate the extent to which unsavory beliefs about "nature's aristocracy" may still be at play in the moral theatre of sports.

McLaren Independent Weightlifting Investigation

4 Jun 2020

McLaren Independent Weightlifting Investigation : Independent Investigator Report to the Oversight and Integrity Commission of International Weightlifiting Federation / Richard H. McLaren; McLaren Independent Investigation Team (MIIT). - Toronto : McLaren Global Sport Solutions, 2020


On 5 January 2020 the German television network, ARD aired the program “Der Herr de Heber” (The Lord of the Lifters), a documentary film by Hajo Seppelt, Nick Butler and Gritt Hartmann (the ARD Documentary). The documentary claimed the leadership of the International Weightlifting Federation (IWF), including President Tamás Aján (Dr. Aján) participated in or had knowledge of numerous irregularities occurring within the IWF. The allegations related to corruption, financial irregularities, property investment, doping control testing and sample manipulation combined with doping fine payment irregularities. There were also suggestions of favouritism and the deliberate undermining of certain Member Federations accomplished through cronyism and nepotism.

This Report contains the outcomes, background and detailed findings of the investigation conducted by the McLaren Independent Investigation Team (MIIT) under the direction of and by the Independent Investigator Richard H. McLaren appointed by the IWF’s Executive Board and the Acting President, through the Oversight and Integrity Commission (O&I Commission).

Key Findings of the Report:

1.) Dr. Aján’s autocratic authoritarian leadership of the International Weightlifting Federation resulted in a dysfunctional, ineffective oversight of the organisation by the Executive Board, which had an ill-informed understanding of the organisation. This was achieved through various control mechanisms. As a consequence, Dr. Aján disabled anyone other than himself from understanding the overall affairs of the IWF.

2.) The foundational control mechanism used by Dr. Aján was the tyranny of cash. Cash collected, cash withdrawn, and cash unaccounted for, which Dr. Aján was the sole collector. The primary sources of this cash were doping fines paid personally to the President and cash withdrawals of large amounts from the IWF’s accounts, usually withdrawn before major competitions or IWF congresses. It is absolutely impossible to determine how much of the cash collected or withdrawn was used for legitimate expenses. The McLaren Independent Investigation Team has determined that $10.4 million USD is unaccounted for.

3.) Weightlifting has a history of use of performance enhancing drugs. Over 600 lifters in the past decade have tested positive. While Dr. Aján has impermissibly interfered with the IWF Anti-Doping Commission, the real problem is the culture of doping that exists in the sport. The investigation uncovered 40 positive Adverse Analytical Findings hidden in the IWF records. This includes gold and silver medalists who have not had their samples dealt with. This information has been passed on to WADA for further investigation.

4.) HUNADO is not the cause of doping sample manipulation or hidden results. It has operated in compliance with WADA standards. The investigation found that the procedures followed by Doping Control Officer Barbara Kallo were correct and in accordance with the WADA Code. The source of antidoping issues that have plagued the IWF and sport of weightlifting lie elsewhere. HUNADO and its DCOs are not the cause of the positive testing results or the alleged influence on weightlifters to be tested.

5.) The financial records are a jumble of incomplete and inaccurate figures distorted by a failure to accurately record cash expenditures and revenues and disclose hidden bank accounts by Dr. Aján.

6.) The two most recent Electoral Congresses were rampant with vote buying for the President and senior level positions of the Executive Board, despite monitoring. Such actions are a fundamental violation of the sport’s By-Laws on Disciplinary and Ethics Procedures.


Contents:

Chapter 1: Executive Summary of this Report

A. IMMEDIATE ACTION
B. OVERALL RECOMMENDATIONS
- i. Constitutional Reform
- ii. Electoral Reform
- iii. Financial Reform
- iv. Governance Reform
- v. Anti-doping Control Reform

Chapter 2: The Dr. Aján Presidency

2.1 Constitutional Structure & Hierarchy of IWF
2.2 A Half-Century of Unfettered Autonomous Control
2.3 Presidential Coercion
- i. Cash Control
- ii. Redundant Treasurer
- iii. Exclusive Financial Control
- iv. EB Approval Without Questions
- v. Cash for votes: Rigging Electoral Congresses
- vi. The Presidentially Anointed Executive Board
- vii. The IWF’s Secretariat
- viii. Cash from Doping Fines
2.4 Infiltration of the Anti-Doping Control Program
2.5 Conclusion

Chapter 3: The Hijacking of Financial Control

Chapter 4: Electoral Corruption - Cash for Votes
4.1 Introduction
4.2 Preparations for the Electoral Congress
4.3 How a Presidency is Bought
4.4 Conclusion

Chapter 5: Anti-Doping Over the Decades
5.1 Introduction
5.2 The 1980s & 1990s
5.3 Weightlifting Scandals Morphed into the Twenty-first Century
5.4 A Dirty Decade in the Twenty-first Century
5.5 Legal Structure and Operation of the Anti-Doping Commission
5.6 Presidential Meddling in Antidoping
5.6.1 Test Distribution Plans
5.6.2 Interference in Results Management
- i. Delay of Results Management: A Case Study of Azeri Lifters.
- ii. Missing Positives Results
5.7 Doping Fines
5.8 Role of HUNADO
- i. HUNADO at Houston World Championships 2015
- ii. Suspicious Out-of-Competition Test Results prior to Houston
5.7 Conclusion

Me, myself, and my muscles: associations between narcissism and muscle dysmorphia

17 Aug 2021

Me, myself, and my muscles: associations between narcissism and muscle dysmorphia / Matt W. Boulter, Sebastian S. Sandgren. - (Eating Disorders (2021) 17 August; p. 1-7)

  • PMID: 34402405
  • DOI: 10.1080/10640266.2021.1930348


Abstact

The conceptualisation and measurement of the associations between narcissism and muscle dysmorphia (MD) are poorly understood in the literature. It is recognised that narcissism features two broad dimensions: vulnerable and grandiose. Studying both narcissism dimensions is important given their differences in etiology and health-related outcomes. Therefore, the aim of this study was to investigate the associations between MD, vulnerable and grandiose narcissism. A total of 336 participants (48% male; Mage = 26.4 years) completed measures of MD and narcissism. Hierarchical regression analysis revealed that vulnerable narcissism was significantly, positively associated with MD, whilst grandiose narcissism was not. Practitioners should be aware that vulnerable narcissism may be a potential risk factor of MD.

Measurement of urinary cobalt as its complex with 2-(5-chloro-2-pyridylazo)-5-diethylaminophenol by liquid chromatography-tandem mass spectrometry for the purpose of anti-doping control

22 Jan 2021

Measurement of urinary cobalt as its complex with 2-(5-chloro-2-pyridylazo)-5-diethylaminophenol by liquid chromatography-tandem mass spectrometry for the purpose of anti-doping control / Tim Sobolevsky, Brian Ahrens. - (Drug Testing and Analysis (2021) 22 January)

  • PMID: 33484083
  • DOI: 10.1002/dta.3004


Abstract

Cobalt is well known for its ability to stimulate erythropoiesis via stabilization of hypoxia-inducible factors. In sports, this can provide a competitive benefit to athletes, so the World Anti-Doping Agency prohibits the use of cobalt in any form except its cobalamin vitamers. As of now, cobalt in biological fluids is detected by inductively coupled plasma mass spectrometry (ICP-MS), a technique which has very limited availability in anti-doping laboratories. Therefore, a quantitative method based on liquid chromatography-tandem mass spectrometry capable of measuring urinary cobalt in the form of its complex with 2-(5-chloro-2-pyridylazo)-5-diethylaminophenol (5-Cl-PADAP) has been developed and validated. A cobalt complex with deuterium-labeled 5-Cl-PADAP was used as internal standard. The method was found linear over the concentration range of 5-500 ng/ml with a combined standard uncertainty less than 10% at 15, 200, and 450 ng/ml. Stability of cobalt ions in urine was investigated over the course of 2 months; the concentration of free Co2+ was observed to decline by approximately 50% but restored upon hydrolysis with hydrochloric acid. Unlike ICP-MS, this method is practically unaffected by the presence of cyanocobalamin as the latter is resistant to acid hydrolysis. Notwithstanding the lack of formalized threshold concentration of cobalt in urine, it is highly desirable that more anti-doping laboratories engage in testing for cobalt levels to better understand the prevalence of cobalt misuse in athletes. Given that cobalt salts are inexpensive and easily obtainable, the risk of such abuse should not be underestimated.

Meat products as potential doping traps?

1 Oct 2008

Meat products as potential doping traps? / Hans Braun, Hans Geyer, Karsten Koehler. - (International Journal of Sport Nutrition and Exercise Metabolism 18 (2009) 5 (October); p. 539-542).
- PMID: 19051433.
- DOI: https://doi.org/10.1123/ijsnem.18.5.539


Abstract:

Recently published news regarding food safety in China caused some worldwide disturbance and uncertainty among top athletes and their supporting staff. According to an article in The New York Times, a member of the U.S. Olympic team discovered oversized chicken breast when visiting a supermarket in Beijing, China. More interesting, the chicken contained considerable amounts of anabolic steroids, which were reported to be large enough to cause a failed doping test after ingesting the meat (Shpigel, 2008). Based on this case report it appears necessary to assess the danger posed to our (Olympic) athletes by foods and especially meat products on a more general basis. More important, our athletes are involved in worldwide travel during the competitive season. Therefore we must consider not only our athletes’ local food choices but also the wide variety of foods and regional delicacies our athletes might be confronted with in foreign countries.

Mediating mechanisms in a program to reduce intentions to use anabolic steroids and improve exercise self-efficacy and dietary behavior

1 Mar 2001

Mediating mechanisms in a program to reduce intentions to use anabolic steroids and improve exercise self-efficacy and dietary behavior / D.P. MacKinnon, L. Goldberg, G.N. Clarke, D.L. Elliot, J. Cheong, A. Lapin, E.L. Moe, J.L. Krull.- (Prevention Science 2 (2001) 1 (March); p. 15-28.)

  • PMID: 11519372
  • DOI: 10.1023/a:1010082828000


Abstract

This study investigated the mediating mechanisms responsible for the effects of a program designed to reduce intentions to use anabolic steroids, improve nutrition, and increase strength training self-efficacy. Fifteen of 31 high school football teams (N = 1,506 players at baseline) in Oregon and Washington were assigned to receive the intervention. The multicomponent program addressed the social influences promoting ergogenic drug use and engaging students in healthy nutrition and strength training alternative behaviors. Although the results differed across the three dependent variables, the program appeared to work by changing team norms. Unlike prevention of other drugs, changes in knowledge and perceived severity were mediators of program effects in this study.

Mediating Mechanisms in a Program to Reduce Intentions to Use Anabolic Steroids and Improve Exercise Self-Efficacy and Dietary Behavior

1 Mar 2001

Mediating mechanisms in a program to reduce intentions to use anabolic steroids and improve exercise self-efficacy and dietary behavior / David P. MacKinnon, L. Goldberg, G.N. Clarke, D.L. Elliot, J. Cheong, A. Lapin, E.L. Moe, J.L. Krull. - (Prevention Science 2 (2001) 1 (March); p. 15-28)

  • PMID: 11519372
  • DOI: 10.1023/a:1010082828000


Abstract

This study investigated the mediating mechanisms responsible for the effects of a program designed to reduce intentions to use anabolic steroids, improve nutrition, and increase strength training self-efficacy. Fifteen of 31 high school football teams (N = 1,506 players at baseline) in Oregon and Washington were assigned to receive the intervention. The multicomponent program addressed the social influences promoting ergogenic drug use and engaging students in healthy nutrition and strength training alternative behaviors. Although the results differed across the three dependent variables, the program appeared to work by changing team norms. Unlike prevention of other drugs, changes in knowledge and perceived severity were mediators of program effects in this study.

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