The detection of trans gene fragments of hEPO in gene doping model mice by Taqman qPCR assay / Kai Aoki, Takehito Sugasawa, Kouki Yanazawa, Koichi Watanabe, Tohru Takemasa, Yoshinori Takeuchi, Yuichi Aita, Naoya Yahagi, Yasuko Yoshida, Tomoaki Kuji, Nanami Sekine, Kaoru Takeuchi, Haruna Ueda, Yasushi Kawakami, Kazuhiro Takekoshi. - (PeerJ 8 (2020) e8595 (25 February); p. 1-14).
- doi: 10.7717/peerj.8595.
- PMCID: PMC7047860.
- PMID: 32140302

Abstract

Background
With the rapid progress of genetic engineering and gene therapy methods, the World Anti-Doping Agency has raised concerns regarding gene doping, which is prohibited in sports. However, there is no standard method available for detecting transgenes delivered by injection of naked plasmids. Here, we developed a detection method for detecting transgenes delivered by injection of naked plasmids in a mouse model that mimics gene doping.

Methods
Whole blood from the tail tip and one piece of stool were used as pre-samples of injection. Next, a plasmid vector containing the human erythropoietin (hEPO) gene was injected into mice through intravenous (IV), intraperitoneal (IP), or local muscular (IM) injection. At 1, 2, 3, 6, 12, 24, and 48 h after injection, approximately 50 µL whole blood was collected from the tail tip. One piece of stool was collected at 6, 12, 24, and 48 h. From each sample, total DNA was extracted and transgene fragments were analyzed by Taqman quantitative PCR (qPCR) and SYBR green qPCR.

Results
In whole blood DNA samples evaluated by Taqman qPCR, the transgene fragments were detected at all time points in the IP sample and at 1, 2, 3, 6, and 12 h in the IV and IM samples. In the stool-DNA samples, the transgene fragments were detected at 6, 12, 24, and 48 h in the IV and IM samples by Taqman qPCR. In the analysis by SYBR green qPCR, the transgene fragments were detected at some time point in both specimens; however, many non-specific amplicons were detected.

Conclusions
These results indicate that transgene fragments evaluated after each injection method of naked plasmids were detected in whole-blood and stool DNA samples. These findings may facilitate the development of methods for detecting gene doping.

The Development and Validation of a Doping Attitudes and Behaviour Scale / S. Guerin, K. Kirby, A.Moran

Athletes’ use of prohibited ergogenic substances for performance enhancement is a form of cheating behaviour which can jeopardise both their health and their careers. Given such importance, it is not surprising that the problem of drug-use in competitive sport has been widely studied. Unfortunately, research in this field has at least three obvious limitations. First, few studies have attempted to explain why athletes are willing to use these substances, given the risks involved (Anshel, 2005). Second, little effort has been made to understand the theoretical mechanisms underlying cheating/doping behaviour in athletes. Finally, there is a paucity of research on elite athletes’ attitudes to, and beliefs about, doping in sport. These oversights are unfortunate because antidoping measures cannot be fully effective unless they are based on solid evidence about why athletes (especially elite performers) engage in drug-taking in the first place. To address these gaps in the literature, the first phase of the present study examines the psychological variables underlying attitudes to drug use in sport.
To date, 375 high performance (HP) athletes have been surveyed on their attitudes to doping, and a number of relevant psychological variables have also been measured. Interesting findings have emerged on the perceived and reported incidence of doping in sport, athletes’ knowledge of doping substances and differences in attitudes between various demographic groups. Statistical results also show some significant relationships emerging between doping attitudes and psychological characteristics, including perfectionist tendencies and motivational variables. This is the first time an empirical investigation has examined such a multitude of relationships, and the results have guided the next stage of the research; a qualitative focus on the views of athletes
who have direct experience of doping.

Phase 2 of the study involved exhaustive searches of media reports, seeking athletes who publicly admitted to engaging in doping practices. Over a 30-month period, this list extended to almost 80 elite athletes who were identified as potential interview candidates for this qualitative phase of the research. Following the compilation of the list, efforts were made to contact these athletes through their national governing bodies, national anti-doping agencies, and journalists with whom they had spoken in the past.
However, this proved much more difficult than originally anticipated for two reasons:
(a) because it was not possible to obtain contact details for high profile athletes and
(b) because those who were contacted were not willing to partake in the research, despite assurances of anonymity and confidentiality. The sample size totals 4 athletes who have
admitted doping offences, but in light of the very limited number of potential participants and the sensitive nature of the research topic, this was a reasonable number from which to extract a thematic analysis. Interesting explorations of both the internal and external sources of influence on athletes’ doping practices emerged, along with more in-depth analysis of the psychological variables which may guide doping decisions.

The final stage of the research, the development and validation of a doping attitudes and behaviour scale (DABS) will be informed by findings from both the aforementioned quantitative and qualitative research studies.

The development of multiple drug use among anabolic-androgenic steroid users : six subjective case reports / Kurt Skårberg, Fred Nyberg, Ingemar Engström. - (Substance Abuse Treatment, Prevention, and Policy 3 (2008) 24 (28 November); p. 1-10).

• PMID: 19040748.
• PMCID: PMC2612649.
• DOI: 10.1186/1747-597X-3-24

 
Abstract

Background: The inappropriate use of anabolic androgenic steroids (AAS) was originally a problem among athletes but AAS are now often used in nonsport situations and by patients attending regular addiction clinics. The aim of this study was to improve understanding of the development of multiple drug use in patients seeking treatment at an addiction clinic for AAS-related problems.

Methods: We interviewed six patients (four men and two women) with experience of AAS use who were attending an addiction clinic for what they believed were AAS-related problems. The patients were interviewed in-depth about their life stories, with special emphasis on social background, substance use, the development of total drug use and subjective experienced psychological and physical side effects.

Results: There was significant variation in the development of drug use in relation to social background, onset of drug use, relationship to AAS use and experience of AAS effects. All patients had initially experienced positive effects from AAS but, over time, the negative experiences had outweighed the positive effects. All patients were dedicated to excess training and took AAS in combination with gym training, indicating that the use of these drugs is closely related to this form of training. Use of multiple drugs was common either in parallel with AAS use or serially.

Conclusion: The study shows the importance of understanding how AAS use can develop either with or without the concomitant use of other drugs of abuse. The use of AAS can, however, progress to the use of other drugs. The study also indicates the importance of obtaining accurate, comprehensive information about the development of AAS use in designing treatment programmes and prevention strategies in this area.

The diagnostic dilemma of pathological appearance and performance enhancing drug use / Tom Hildebrandt, Justine K. Lai, James W. Langenbucher, Melanie Schneider, Rachel Yehuda, Donald W. Pfaff. - (Drug and Alcohol Dependence 114 (2011) 1 (1 March); p. 1-11)

• PMID: 21115306
• PMCID: PMC3039045
• DOI: 10.1016/j.drugalcdep.2010.09.018

Abstract

Appearance and performance enhancing drug (APED) use includes the use of a range of pharmacologically distinct substances and concurrent investment in outward appearance or achievement, dietary control, and frequent exercise. A number of existing reviews and conceptual papers have defined pathological forms of APED use within the APED class of anabolic-androgenic steroids (AASs) and using the framework of AAS dependence. We review published data on APED use including human studies of AAS users and identified three defining phenomenological features associated with increased health risk and pathology. These features included (1) polypharmacy or the concurrent use of several pharmacologically distinct substances used to change outward appearance or increase likelihood of personal achievement; (2) significant body image disturbance; (3) rigid practices and preoccupations with diet and exercise. Investigations into the latent structure of APED use suggest these features cluster together in a homogenous group of APED users who have the highest health risk and most psychopathology. These features are discussed in the context of AAS dependence and problems with defining classic tolerance-withdrawal symptoms among APED users. Suggestions for a resolution and outline for future research needed to determine the best system for identifying and diagnosing pathological APED use are discussed.

The Disordered-Eating, Obsessive-Compulsive, and Body Dysmorphic Characteristics of Muscle Dysmorphia : A Bimodal Perspective / Beau James Diehl, Timothy Baghurst. - (New Male Studies 5 (2016) 1; p. 68-94)

Abstract:

Muscle dysmorphia (MD) is a proposed subtype of body dysmorphic disorder whereby individuals have a pathological preoccupation with their muscular build and leanness. MD remains an underrecognized and misunderstood disorder, and is currently disputed in the extant literature. This paper proposes that MD be reanalyzed through a bimodal lens that accounts for the diverse, spectrumbased characteristics of the disorder while concomitantly considering for the temporal, continuumbased characteristics of the disorder as a means to better contextualize the operationalization of MD symptoms. It is suggested that MD behaviors exist in cyclical formats of both severity and practice whereby the goals of the individual influence the nature and activities illustrative of MD. Therefore, it is theoretically plausible to consider MD behaviors in a bimodal perspective where frequency as well as severity are salient factors. Future research should address the temporal, continuum-based component of MD through increased longitudinal and qualitative studies.

The doping cases and the need for the International Court of Arbitration for Sport (CAS) / Tricia Kavanagh
In: UNSW Law Journal, no. 3 (Vol. 22) p. 721-745

There is a long recorded history of the use by athletes of substances for performance enhancement. The use of substances in the form of drugs was officially recognised after the 1928 Winter Olympics when the International Federation of Sports Mediation (FIMS) was established as a forum to discuss doping in sport. Slowly an awareness grew in the international community that athletes were competing assisted by drugs to enhance performance. This awareness became sharper after the Second World War when amateur sporting events became much more competitive. France enacted anti-doping legislation in 1963, Belgium in 1965. Other countries followed suit. There were attempts to detect drug use at the 1964 Tokyo Olympics but such attempts were not successful. When prominent athlete Tommy Simpson died in the Tour de France and his death was exposed as drug induced, it led to the International Olympic Committee (IOC) establishing a Medical Commission (the IOCMC). Historically this became one of the most significant developments, as through the Medical Commission was published the International Charter Against Doping in Sport (now known as the IOC Medical Code) was published. The Charter included a ‘list’ of banned substances, which was used as the foundation for all drug testing programs in sport around the world. It is now annually reviewed by the IOCMC. Its contents are often challenged. The Charter provides:

• guidelines as to functions and penalties;
• a model national anti-doping program;
• the list of doping classes and methods of doping; the requirements for accreditation of laboratories and laboratory practice; the standard operating procedures for doping control; the rights, responsibilities and status of athletes and their entourages;
• and, principles and guidelines for in and out of competition testing.

Up until the International Charter Against Doping in Sport, anti-doping efforts had been somewhat ad hoc. However, when the preeminent sports organisation, the IOC, set a standard and imposed it upon its sporting federations an imprimatur was given to policies committed to drug free sport. Over the last ten years, international co-operation and initiatives improved as drug testing programs were put in place by National Olympic Committees (NOCs) (for example the Australian Olympic Committee (AOC)), international and national federations (ISFs and NSOs) through their rules and by-laws, and by governments through legislative reform or administrative process (for example the Australian Sports Drug Agency (ASDA)).
However, three impediments to successful anti-doping programs were quickly exposed. There was a lack of harmonisation and consistency of procedures and accountability for the integrity of the urine testing. Secondly, there was a lack of agreement between sports federations internally between national and international organisations and externally between the various sports as to the appropriate sanctions for breaches. Thirdly, when doping disputes went to the sporting tribunals and from the tribunals to domestic courts on appeal, there developed an awareness and appreciation of the need for sound jurisprudential and equitable principles in the hearing of doping disputes. In response to these impediments, the sports organisations have attempted to harmonize sanctions and testing procedures. However, the sports tribunals have met some difficulties as they have traveled through the legal labyrinth revealed by sports appeals, particularly appeals from positive findings of drug use.

In examining the legal complexities and legal principles revealed in the doping cases, this paper traces the steps taken by parties involved in sports law to bring consistency and integrity to international sports law through the establishment by revised rules and procedures of an International Court of Arbitration for Sport (CAS). The role of the CAS was praised by Ms Watt’s Counsel, David Grace QC, as a “terrific way” of settling disputes. He stated: This is a perfect system for settling these disputes in an atmosphere that's much more relaxed, where the procedures are easy to comply with and the dispute can be heardquickly, efficiently and inexpensively.
The Court is an independent forum which allows each side to put its case anyway it likes. The procedures are often moulded to suit the subject matter of the hearing and the ordinary rules of evidence don not necessarily apply.
The fundamental question now is the extent to which national courts will follow the Swiss lead in recognizing and enforcing CAS awards in the face of due process or public order claims. The result will be what Nafziger calls “a blending of national and international institutions into a single process of justice that avoids judicial complexity”. This is the voice of the hopeful, who have been perplexed by the anomalies that have developed in the jurisprudential principles so far enunciated in doping disputes.

Normative trends confirm the growing commitment of national legal systems to the process of international sports law. Adjudication is a last resort. If there should be adjudication it is hoped the CAS provides the final orders.
Nevertheless, as jurisprudential principles flow from the CAS, effective monitoring must be built into the process to protect the interests of all parties. It is imperative that the court promptly publish reasons for any decisions it makes. Gradually through arbitrary decisions a distinctive lex specialis should emerge.
The motivation behind the establishment and recognition of the CAS has been to protect the interests of international sporting competition while giving due recognition to the legal rights of the athletes. The process of refining its procedural rules must be a continuous one. There is no room for complacency.

De Nederlandse topsporter en het antidopingbeleid / Irene Eijs, Aarno Havenga, Olivier de Hon. - Dopingautoriteit; NL Sporter; Vereniging van Contractspelers (VVCS); AtletenCommissie NOC*NSF. - Capelle aan den IJssel : Dopingautoriteit, 2010

Background and research methods
Doping use is a real threat to sports. It undermines the spirit of fair play and poses health risks to the athletes. Athletes have no choice but to follow existing doping procedures. The Anti-Doping Authority the Netherlands (‘Dopingautoriteit’) periodically assesses the opinions of Dutch (elite) athletes on several aspects of doping policies in order to evaluate these policies, and possibly to adjust them. In 2009/2010 this study was performed in cooperation with NL Sporter (the Dutch independent interest group for elite athletes), the ‘Vereniging van Contractspelers’ (VVCS, the Dutch representative organisation for professional football/soccer players), and the Athlete Committee of the National Olympic Committee NOC*NSF. The study was financed by the Ministry of Health, Welfare, and Sports. In cooperation with certified research company Intomart GfK a digital questionnaire was sent to 888 elite athletes with an official ‘elite status’, as determined by NOC*NSF. In addition, 453 professional football/soccer players (all members of the VVCS) were approached via email. A representative group of 38% of all ‘status athletes’ responded. The response amongst football players was 21% and can be considered to be indicative of this particular group of athletes. The study was performed in the first few months of 2010.

Whereabouts , dopingcontrols en Therapeutic Use Exemptions (TUEs)
One of the most recent changes in the doping regulations, the introduction of a whereabouts administration, is the most controversial antidoping rule. Less than 20% of all status athletes think this rule is necessary for their own sport, with 61% having experience in fulfilling this requirement. A group of 38% of these athletes regularly experiences problems in filing whereabouts information. This percentage is somewhat lower in younger athletes and in females. The two most important antidoping organisations that collect whereabouts information from Dutch athletes receive similar complaints, but WADA’s ‘ADAMS system’ experiences technical and software related problems more often than Dopingautoriteit’s ‘Sportergegevens’. Athletes perceive whereabouts regulations as a major impact on their personal lives. The software used to collect whereabouts information is considered unnecessary laborious and filing whereabouts information, and keeping them updated, costs a lot of time. The combination of not knowing where one will be at a certain point of time in the future, and the knowledge that administrative mistakes may lead to ‘missed tests’ and possible sanctions leads to a high level of uncertainty. This uncertainty is increased by the fear that a doping control officer might not be able to find an athlete, even when the athlete is present at the specified location. This leads to the situation that of all athletes that have to fulfil whereabouts requirements, 47% feels that the influence of doping regulations on their personal lives is too big. Amongst those athletes who do not have this requirement, this percentage is much lower: 19%. There are strong clues that irritation about the whereabouts requirements seriously lowers the support of antidoping regulations in general.

Submitting to the practice of doping controls receives far more support. Problems are encountered less frequently and more than half of the ‘status athletes’ find it important that out of competition controls are performed to discourage doping use. 79% Of these athletes have been tested themselves in the previous year; in the last survey (in 2003) this was 57%. Football/ soccer players are tested less frequently (32% has been tested in the previous year). One in every twenty athletes (of those who have been tested) has one or more registered ‘missed tests’ in its name. These were most often caused by filing the wrong whereabouts information, or sudden changes in schedule due to traffic jams, changed weather, or other unforeseen circumstances. It is of more concern that two cases of registered ‘missed tests’ have been caused by the inability to find the particular athlete, who actually was present at the filed location.

Athletes are well-informed on the possibility to ask for a therapeutic exemption to use prohibited substances or methods (TUE procedure). Knowledge about, and experiences with, this procedure is somewhat scarcer amongst football/soccer players. Approximately 20% of all athletes with TUE-experience has encountered a problem of some sort, like the return of an (incomplete) request or a lack of clarity related to the duration and/or region of validity of the acquired exemption.

Attitudes ,policy, and knowledge
The attitude of Dutch athletes towards doping in general is very dismissive. No less than 91% would feel guilty if doping would be used and 95% states that they only want to win if this can be achieved on their own strength. Athletes prefer that antidoping efforts are predominantly focussed on internationally harmonised policies, increased education in general, and especially targeted at coaches and support personnel. Relatively speaking, older athletes expect more often that tougher sanctions and the availability of alternative methods to improve performance (better training facilities, better nutrition, innovations) will be efficient deterrents of doping use. When compared to other athletes, football/soccer players favour more out of competition controls. Knowledge on the Prohibited List is reasonable; on the procedures surrounding doping controls it is even better. In the past seven years, knowledge on doping related issues has improved.

Education
Of all educational materials that are offered by ‘Dopingautoriteit’, the fan booklet and the website are best known, and are used most often. Status athletes seek doping related information at the Dopingautoriteit, or consult a specialised sports physician. Football/ soccer players seek this sort of information in their direct (club) environment; they have not yet found the way to Dopingautoriteit. Over the last decade, the general practitioners are increasingly less often consulted on doping matters. Consultation of specialised physicians, internet, and NOC*NSF is on the rise.
Existing educational materials receive great satisfaction. One noticeable result is that satisfaction about educational meetings has dropped somewhat over the last seven years (from 95% to 84%). These meetings could be personalised and targeted at specific questions and requests of the athletes that are present. An email service ranked highest for athletes when asked in what way they would like to receive future updates on doping related issues.

The ‘100% Dope Free’ campaign’, started in 2007 at the initiative of the Athlete Committee of NOC*NSF and Dopingautoriteit, is not yet known amongst all elite athletes. About two thirds of all status athletes are familiar with the campaign; for football/soccer players this percentage is just 8%. The different aspects of the campaign are judged in a positive manner by 50-66% of all athletes.

Based on the results, a number of actionable recommendations have been made. These are listed in the last paragraph of this report (page 23).

De Nederlandse topsporter en het anti-dopingbeleid 2014-2015 / Erik Duiven en Olivier de Hon. - Capelle aan de IJssel, 2015

Athletes must comply with the doping regulations adopted by the sports organisations. There is also some resistance among some athletes to the implementation of the anti-doping policy. The Anti-Doping Authority Netherlands (ADAN) periodically surveys Dutch elite athletes to determine their views of this policy.

The goals of this study were:
1. to establish a picture of the efficacy, and the perception, of the current anti-doping policy and procedures within the total field of Dutch elite sports;
2. to evaluate the anti-doping policy of ADAN;
3. to establish concrete recommendations with the aim of making doping detection methods more effective and developing educational resources that will prevent unnecessary pressure on the athletes.

In line with previous years, the ‘elite-status athletes’ were the main target group. These are athletes who have been granted the official elite status by the Netherlands Olympic Committee*Netherlands Sports Confederation (NOC*NSF) and as such they have shown to be able to place in the top-8 in world championships in their respective disciplines, or can be expected to reach this level in the near future.
For the first time, the group surveyed also included elite Track & Field (T&F) athletes, elite cyclists and a group of other elite athletes, all competing at the highest national level in their respective disciplines.

The doping prevalence questions were established using the ‘Randomised Response’ method. This method uses randomisation to produce more honest answers to questions that are socially sensitive. This was the first time this method had been used in a study of doping in elite sports in the Netherlands.

Dutch elite sport is not doping-free. The best available estimate is that 4.2% of elite-status athletes use doping. The estimate of the number of doping users in Dutch elite sports is higher than the estimates from previous studies of Dutch elite athletes. This is most probably due to the use of the ‘Randomised Response’ method.

De Nederlandse topsporter en het anti-dopingbeleid 2014-2015 / Erik Duiven en Olivier de Hon. - Capelle aan de IJssel : Dopingautoriteit, 2015

Abstract:

Athletes must comply with the doping regulations adopted by the sports organisations. There is also some resistance among some athletes to the implementation of the anti-doping policy. The Anti-Doping Authority Netherlands (ADAN) periodically surveys Dutch elite athletes to determine their views of this policy.

The goals of this study were:

1. to establish a picture of the efficacy, and the perception, of the current anti-doping policy and procedures within the total field of Dutch elite sports;
2. to evaluate the anti-doping policy of ADAN;
3. to establish concrete recommendations with the aim of making doping detection methods more effective and developing educational resources that will prevent unnecessary pressure on the athletes.

In line with previous years, the ‘elite-status athletes’ were the main target group. These are athletes who have been granted the official elite status by the Netherlands Olympic Committee*Netherlands Sports Confederation (NOC*NSF) and as such they have shown to be able to place in the top-8 in world championships in their respective disciplines, or can be expected to reach this level in the near future.
For the first time, the group surveyed also included elite Track & Field (T&F) athletes, elite cyclists and a group of other elite athletes, all competing at the highest national level in their respective disciplines.

The doping prevalence questions were established using the ‘Randomised Response’ method. This method uses randomisation to produce more honest answers to questions that are socially sensitive. This was the first time this method had been used in a study of doping in elite sports in the Netherlands.

Dutch elite sport is not doping-free. The best available estimate is that 4.2% of elite-status athletes use doping. The estimate of the number of doping users in Dutch elite sports is higher than the estimates from previous studies of Dutch elite athletes. This is most probably due to the use of the ‘Randomised Response’ method.

The eating disorder that paved the way for anabolic steroid use. - (Tidsskrifter den Norske Legeforening (2017, 28 November); p. 1-2. - doi: 10.4045/tidsskr.17.0168

This is a story of how the pursuit of self-control ended in eating disorders and misuse of anabolic steroids. I encountered a health service that knew very little about steroids. My hope is that telling my story will enable others like me to be treated with greater understanding.