Prevalence of therapeutic use exemptions at the Olympic Games and Paralympic Games: an analysis of data from 2016 to 2022.

OBJECTIVES: The objectives of this study are to describe the prevalence of therapeutic use exemptions (TUEs) among athletes competing in four Olympic and four Paralympic games. The secondary objective was to present the prohibited substance and methods classes associated with TUEs. METHODS: Data from the Anti-Doping Administration and Management System were extracted for this cross-sectional observation study. Eight cohorts were created to include athletes with TUEs who competed in the Rio 2016, Pyeongchang 2018, Tokyo 2020 and Beijing 2022 Olympic and Paralympic games. Prevalence of TUEs and proportion of prohibited substance and methods classes were defined as percentages among all athletes competing at each games. RESULTS: 28 583 athletes competed in four editions of the Olympic games. Total prevalence of athletes with TUEs was 0.90% among all competitors. At the four Paralympic games, a total of 9852 athletes competed and the total TUE prevalence was 2.76%. The most frequently observed substances associated with TUEs at the Summer Olympics were glucocorticoids (0.50% in Rio) and stimulants (0.39% in Tokyo). At the Summer Paralympics, diuretics (0.79% in Rio) and stimulants (0.75% in Tokyo) were the most common. Winter games had somewhat similar trends, although TUE numbers were very low. CONCLUSIONS: The number of athletes competing with valid TUEs at the Olympic and Paralympic games was <1% and <3%, respectively. Variations in substances and methods associated with TUEs for different medical conditions were identified. Nevertheless, numbers were low, further reaffirming that TUEs are not widespread in elite sport.

Psychosocial predictors of doping intentions and use in sport and exercise: a systematic review and meta-analysis.

OBJECTIVE: To conduct a meta-analytic review of psychosocial predictors of doping intention, doping use and inadvertent doping in sport and exercise settings. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Scopus, Medline, Embase, PsychINFO, CINAHL Plus, ProQuest Dissertations/Theses and Open Grey. ELIGIBILITY CRITERIA: Studies (of any design) that measured the outcome variables of doping intention, doping use and/or inadvertent doping and at least one psychosocial determinant of those three variables. RESULTS: We included studies from 25 experiments (N=13 586) and 186 observational samples (N=3 09 130). Experimental groups reported lower doping intentions (g=-0.21, 95% CI (-0.31 to -0.12)) and doping use (g=-0.08, 95% CI (-0.14 to -0.03), but not inadvertent doping (g=-0.70, 95% CI (-1.95 to 0.55)), relative to comparators. For observational studies, protective factors were inversely associated with doping intentions (z=-0.28, 95% CI -0.31 to -0.24), doping use (z=-0.09, 95% CI -0.13 to to -0.05) and inadvertent doping (z=-0.19, 95% CI -0.32 to -0.06). Risk factors were positively associated with doping intentions (z=0.29, 95% CI 0.26 to 0.32) and use (z=0.17, 95% CI 0.15 to 0.19), but not inadvertent doping (z=0.08, 95% CI -0.06 to 0.22). Risk factors for both doping intentions and use included prodoping norms and attitudes, supplement use, body dissatisfaction and ill-being. Protective factors for both doping intentions and use included self-efficacy and positive morality. CONCLUSION: This study identified several protective and risk factors for doping intention and use that may be viable intervention targets for antidoping programmes. Protective factors were negatively associated with inadvertent doping; however, the empirical volume is limited to draw firm conclusions.

DOPING CONTROL IN MALE SOCCER PLAYERS IN BRAZIL: 10 YEARS OF FOLLOW-UP.

Objective: To understand the Adverse Analytical Finding (AAF) that have occurred in Brazilian soccer in a recent 10-year period, comparing them to international data, to know the Brazilian profile. Methods: A review of the AAR in the Doping Control Commission database of the Brazilian Football Association from 2008 to 2017. The AAR in professional male soccer players between 2008 and 2017 were considered. Results: The sample selected in this research was composed of 40,092 doping tests, with 113 AAR, identified in 18 different competitions (0.28%) in the professional category, in Brazilian national and state competitions between 2008 and 2017, flagged in doping control exams through urine samples. Stimulants were detected most frequently (31.0%), followed by glucocorticoids (21.2%), diuretics, and masking agents (19.5%). The Brazilian Championship series did not show a relationship with any of the World Anti-Doping Agency (WADA) groups of substances. Series A showed 0.07% of AAR, Series B 0.21%, Series C 0.75% and Series D 1.49. Conclusion: The rate of AAR in Brazilian soccer was 0.28%, lower than the average for all soccer worldwide, and shows similar percentages among field positions. Stimulants were the most prevalent drugs. The national elite soccer competitions showed significantly fewer cases than the lower divisions. Level of Evidence II; Retrospective Study.

Objetivo: Compreender os Resultados Analíticos Adversos (RAA) ocorridos no futebol brasileiro nos últimos 10 anos, comparando-os aos dados internacionais, para conhecer o perfil do futebol brasileiro. Métodos: Revisão dos RAA no banco de dados da Comissão de Controle de Doping da Confederação Brasileira de Futebol de 2008 a 2017. Foram consideradas os RAA entre 2008 e 2017. Resultados: A amostra selecionada nesta pesquisa foi composta por 40.092 exames antidoping com 113 RAA, os quais foram identificados em 18 competições diferentes (0,28%) em atletas da categoria professional, entre 2008 e 2017, sinalizadas em exames de controle de doping através de amostras de urina. Estimulantes foram detectados com maior frequencia (31%), seguidos de glicocorticoides (21,2%), diuréticos e agentes mascarantes (19,5%). A série do Campeonato Brasileiro não apresentou relação com nenhum dos grupos de substâncias da World Anti-Doping Agency (WADA). A série A apresentou 0,07% da AAR, Série B 0,21%, Série C 0,75% e Série D 1,49%. Conclusão: A taxa de RAA no futebol brasileiro foi de 0,28%, inferior à media do futebol mundial e apresenta percentuais semelhantes entre as posições do campo. Os estimulantes foram as drogas mais prevalentes. As competições nacionais de futebol das Séries superiores apresentaram significativamente menos casos do que as inferiores. Nível de Evidência II; Estudo Retrospectivo.

The effects of anti-doping measures on sports performance in weightlifting.

BACKGROUND: Evaluating anti-doping measures is essential to optimise their effectiveness. Comparing sporting results that have a higher doping prevalence, such as weightlifting, before and after the implementation of anti-doping measures may serve as an effectiveness indicator. METHODS: The results of the most successful weightlifters of both sexes in two time periods, 2009-2015 and 2016-2022 were analysed. The Sinclair Total (ST) to compare the relative strength of weightlifters from different weight categories was calculated. RESULTS: A significant decrease in the ST during 2016-2022 (p < 0.001) in athletes of all ages and both sexes overall was reported. When analysed by age, there was a decrease in ST in juniors and seniors of both sexes (p = 0.010 and p < 0.001, respectively), but not in youth. There was a decrease in the ST in senior men (p < 0.001), junior women (p < 0.001) and senior women (p < 0.001). CONCLUSION: In elite weightlifting, adult athletic results declined during 2016-2022, which may partly be explained by the implementation of new methods to detect long-term anabolic androgenic steroid metabolites as well as other policies. This may highlight the effectiveness of these methods both in the prevention and detection of anti-doping rule violations.

Identification of erythropoietin mimetic peptide 1 linear form in a sealed vial and its administration study in horses for doping control purpose.

The erythropoietin mimetic peptide 1 linear form (EMP1-linear), GGTYSCHFGPLTWVCKPQGG-NH2 , was identified in an unknown preparation consisting of white crystalline powder contained in sealed glass vials using ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). The white crystalline powder, allegedly used for doping racehorses, was found to contain around 2% (w/w) of EMP1-linear. EMP1-linear can be cyclised in equine plasma at physiological temperature of 37°C by forming an intramolecular disulfide bond to give EMP1, which is a well-known erythropoiesis stimulating agent that can bind to and activate the receptor for cytokine erythropoietin (EPO). Thus, EMP1-linear is a prodrug of EMP1, which is a performance-enhancing doping agent that can be misused in equine sports. In order to identify potential target(s) for detecting the misuse of EMP1-linear in horses, an in vitro metabolic study using horse liver S9 fraction was performed. After incubation, EMP1-linear mainly existed in its cyclic form as EMP1, and four N-terminus truncated in vitro metabolites TYSCHFGPLTWVCKPQGG-NH2 (M1), SCHFGPLTWVCKPQGG-NH2 (M2), WVCKPQGG-NH2 (M3) and VCKPQGG-NH2 (M4) were identified. An intravenous administration study with the preparation of white crystalline powder containing EMP1-linear was also conducted using three retired thoroughbred geldings. EMP1 was detectable only in the postadministration plasma samples, whereas the four identified in vitro metabolites were detected in both postadministration plasma and urine samples. For controlling the misuse of EMP1-linear in horse, its metabolite M3 gave the longest detection time in both plasma and urine and could be detected for up to 4 and 27 h postadministration, respectively.

Doping control in male soccer players in brazil: 10 years of follow-up / Controle de doping no futebol masculino no brasil: 10 anos de acompanhamento

ABSTRACT Objective: To understand the Adverse Analytical Finding (AAF) that have occurred in Brazilian soccer in a recent 10-year period, comparing them to international data, to know the Brazilian profile. Methods: A review of the AAR in the Doping Control Commission database of the Brazilian Football Association from 2008 to 2017. The AAR in professional male soccer players between 2008 and 2017 were considered. Results: The sample selected in this research was composed of 40,092 doping tests, with 113 AAR, identified in 18 different competitions (0.28%) in the professional category, in Brazilian national and state competitions between 2008 and 2017, flagged in doping control exams through urine samples. Stimulants were detected most frequently (31.0%), followed by glucocorticoids (21.2%), diuretics, and masking agents (19.5%). The Brazilian Championship series did not show a relationship with any of the World Anti-Doping Agency (WADA) groups of substances. Series A showed 0.07% of AAR, Series B 0.21%, Series C 0.75% and Series D 1.49. Conclusion: The rate of AAR in Brazilian soccer was 0.28%, lower than the average for all soccer worldwide, and shows similar percentages among field positions. Stimulants were the most prevalent drugs. The national elite soccer competitions showed significantly fewer cases than the lower divisions. Level of Evidence II; Retrospective Study.

RESUMO Objetivo: Compreender os Resultados Analíticos Adversos (RAA) ocorridos no futebol brasileiro nos últimos 10 anos, comparando-os aos dados internacionais, para conhecer o perfil do futebol brasileiro. Métodos: Revisão dos RAA no banco de dados da Comissão de Controle de Doping da Confederação Brasileira de Futebol de 2008 a 2017. Foram consideradas os RAA entre 2008 e 2017. Resultados: A amostra selecionada nesta pesquisa foi composta por 40.092 exames antidoping com 113 RAA, os quais foram identificados em 18 competições diferentes (0,28%) em atletas da categoria professional, entre 2008 e 2017, sinalizadas em exames de controle de doping através de amostras de urina. Estimulantes foram detectados com maior frequencia (31%), seguidos de glicocorticoides (21,2%), diuréticos e agentes mascarantes (19,5%). A série do Campeonato Brasileiro não apresentou relação com nenhum dos grupos de substâncias da World Anti-Doping Agency (WADA). A série A apresentou 0,07% da AAR, Série B 0,21%, Série C 0,75% e Série D 1,49%. Conclusão: A taxa de RAA no futebol brasileiro foi de 0,28%, inferior à media do futebol mundial e apresenta percentuais semelhantes entre as posições do campo. Os estimulantes foram as drogas mais prevalentes. As competições nacionais de futebol das Séries superiores apresentaram significativamente menos casos do que as inferiores. Nível de Evidência II; Estudo Retrospectivo.

An enhanced label-free proteomics approach for deep-diving into equine plasma proteome, including the discovery of protein biomarkers for strenuous exercise.

Plasma proteins have been a valuable source of biomarkers for clinical uses and for monitoring of the illicit use of prohibited substances or practices in equine sports. We have previously reported the first use of label-free proteomics in profiling equine plasma proteome. This study aimed to refine the method by systematically evaluating various plasma fractionation methods and the use of narrower precursor mass ranges in data-independent acquisition (DIA) mass spectrometry (MS). Tandem fractionations of equine plasma with octanoic acid precipitation followed by solid-phase extraction (SPE) with C4 cartridges provided the largest increase in the number of new proteins identified. The use of two narrow precursor mass ranges of m/z 400-600 and 600-800 in DIA not only identified most proteins detectable by using a single mass range of m/z 350-1500 but also identified ~27% more proteins. The improved method was applied to analyse the plasma proteome of 'postrace' samples which, unlike other samples, had been collected from racehorses soon after racing. Multivariate data analysis has identified upregulation of 14 proteins and downregulation of six proteins in postrace plasma compared with the non-postrace plasma samples. Literature review of these proteins has provided evidence of exercise-induced haemolysis and changes in antioxidant enzyme activities, kinin system, insulin signalling and energy metabolism after strenuous exercise. The improved method has enabled a deeper profiling of the equine plasma proteome and identified the proteins associated with normal physiological changes after racing which are potential confounding factors in the development of a biomarker approach for doping control.

Effects of new anti-doping measures on sports performance in elite female athletes.

Studies examining the effects of new anti-doping measures on sports performance in elite athletes are scarce. During the last decade, a number of new anti-doping methods for the detection of anabolic androgenic steroids were developed. We hypothesized that the implementation of these methods may cause a decrease of performance in athletic disciplines where given substances are widely used. For this purpose, the performance results for 10 athletic disciplines from country (Country A), which was widely accused of systematic doping use, were gathered and pooled into the 2012-2015 and 2016-2019 periods. These periods were seen as before and following the implementation periods, where the effects of new anti-doping methods could be manifested. Also, the performance results of their rival athletes from Country B were analyzed for comparison. The incidence of anti-doping rule violations for both countries was followed. The analysis revealed a decrease in performance results of Country A athletes in eight of 10 disciplines. The performance results of Country B's athletes in seven of 10 disciplines did not and in three disciplines did demonstrate statistically significant change. The decrease in performance of Country A athletes followed a high incidence of steroid detection cases by means of new anti-doping methods. It is highly likely that the consequent performance decrease is due to the implementation of new anti-doping methods. The results of the study bring new facts on the effects of new anti-doping methods implementation and demonstrate following decrease in performance results in population of athletes from the country widely accused of doping use.

Use of Anabolic-Androgenic Steroids and Male Fertility: A Systematic Review and Meta-analysis.

Background: Anabolic-androgenic steroids (AASs) are often used by men for bodybuilding and to improve sports performance. The use is not limited to professional competitive athletes, but many amateur men. Objective: The objective of this study was to assess and systematically review the effects of AAS on male fertility parameters, spermiogram, testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) and to review reversibility and other morbidity impacting fertility. Methods: Eligibility criteria - We included studies mentioning data about adult males using supraphysiologic doses of AAS for sports performance or appearance enhancement, with comparison data from general population or matched controls if available reporting fertility parameters and sexual performance. Information sources - A systematic literature search was performed using PubMed, MEDLINE, EMBASE, Google Scholar and World of Science. Controlled clinical trials randomised or nonrandomised (if available), case series with or without matched controls, case reports, cross-sectional surveys, reports on follow-up of subjects caught in doping test and their fertility parameters when reported. Risk of bias/quality assessment - The quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. Results: Included studies - Thirty-two studies were included. There were 12 cohort studies, 5 case-control studies, 9 cross-sectional surveys and 6 case reports. The study population comprised 9371 individuals, of which 2671 were AAS users. Synthesis of results - AAS users had reduced levels of FSH and LH than the naïve population. These levels remained low for 3-6 months after stopping AAS. One year after stopping AAS, the users and naïve population had insignificant differences in FSH and LH values. The total testosterone (TT) levels were comparable in users and naïve populations at baseline, 3 months and 6 months after stopping, but at 1 year, TT values were lower in AAS users. Sperm concentration in AAS users and naïve population was similar, but sperm motility was lower in AAS users. The testicular size was lower in AAS users. The erectile function improved with AAS use, but on withdrawal, there was decreased libido and erectile dysfunction. Most AAS users need additional medications to mitigate detrimental effects on fertility. Description of the effect - AAS use negatively impacted the gonadotrophin levels and had lower sperm motility and testicular size. Strength - Comprehensive review of 32 publications, study population of 9371 individuals, of which 2671 were AAS users, meta-analysis of reproductive hormones, semen parameters and testis size. Limitations: The limitations are small sample size of most of the studies, polypharmacy, lack of information on dosing and high heterogeneity. Interpretation: AAS use is detrimental for sperm motility and has a partially reversible negative impact on male fertility. Users must be cautioned about its negative impact on libido and erectile function.Registration: PROSPERO Registration No. CRD42023411294.

Electrochemical sensor for anti-doping in athletes / Sensor eletroquímico para anti-doping em atletas / Sensor electroquímico para antidoping en deportistas

ABSTRACT Introduction: Several athletes use steroids such as nandrolone aiming at muscle hypertrophy and performance gain. The current research focused on developing a GO-TiO2 nanostructure as an electrochemical sensor for detecting Nandrolone (ND) like doping agents. Objective: Develop a graphene oxide and carbon paste-modified TiO2 nanocomposite electrode (TiO2-GO/CPE) as an electrochemical biosensor for the detection of anabolic steroids in the urine of athletes. Methods: The hydrothermal approach was employed to make GO-TiO2 nanocomposites, while the modified Hummers approach was used to make GO nanofilaments. Results: The interaction of TiO2 nanostructures with GOES resulted in the anchoring of TiO2 nanoparticles on the surface of GO nanowires, as demonstrated by structural investigations of the generated nanocomposite using SEM. The DPV approach was used to investigate the electrochemical properties of an anabolic steroid sensor, which revealed a stable and selective response to anabolic steroids and superior performance to previously reported anabolic steroid sensors. Conclusion: RSD values ranged from 3.20% to 4.45%, indicating that the developed electrochemical anabolic steroid sensor can be used as a viable detection technique to identify anabolic steroids in human biological fluids. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Vários atletas fazem uso de esteróides como nandrolone visando a hipertrofia muscular e ganho de performance. A pesquisa atual se concentrou no desenvolvimento de uma nanoestrutura GO-TiO2 como um sensor eletroquímico para detecção de Nandrolone (ND) como agente dopante. Objetivo: Desenvolver um eletrodo de nanocomposto de óxido de grafite e pasta de carbono modificado (TiO2-GO/CPE) como um biossensor eletroquímico para a detecção de esteróides anabólicos na urina de atletas. Métodos: A abordagem hidrotérmica foi empregada para fazer nanocompósitos de GO-TiO2, enquanto a abordagem Hummers modificada foi usada para fazer nanofilamentos de GO. Resultados: A interação das nanoestruturas de TiO2 com GOES resultou na ancoragem de nanopartículas de TiO2 na superfície dos nanofilamentos de GO, como demonstrado pelas investigações estruturais do nanocomposto gerado usando SEM. A abordagem DPV foi utilizada para investigar as propriedades eletroquímicas de um sensor de esteróides anabólicos, que revelou uma resposta estável e seletiva aos esteróides anabólicos, bem como um desempenho superior ao dos sensores de esteróides anabólicos anteriormente relatados. Conclusão: Os valores de RSD variaram de 3,20% a 4,45%, indicando que o sensor de esteróides anabolizantes eletroquímicos desenvolvido pode ser usado como uma técnica de detecção viável para identificar esteróides anabolizantes em fluidos biológicos humanos. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Varios atletas hacen uso de esteroides como la nandrolona con el objetivo de hipertrofia muscular y aumento de rendimiento. La presente investigación se centró en el desarrollo de una nanoestructura de GO-TiO2 como sensor electroquímico para la detección de nandrolona (ND) como agente dopante. Objetivo: Desarrollar un electrodo de nanocompuesto de óxido de grafito y pasta de carbono modificado (TiO2-GO/CPE) como biosensor electroquímico para la detección de esteroides anabólicos en la orina de atletas. Métodos: Se empleó el enfoque hidrotérmico para hacer nanocompuestos de GO-TiO2, mientras que el enfoque de Hummers modificado se utilizó para hacer nanofilamentos de GO. Resultados: La interacción de las nanoestructuras de TiO2 con el GOES dio lugar al anclaje de las nanopartículas de TiO2 en la superficie de los nanofilamentos de GO, tal y como demostraron las investigaciones estructurales del nanocompuesto generado mediante SEM. El enfoque de DPV se utilizó para investigar las propiedades electroquímicas de un sensor de esteroides anabólicos, que reveló una respuesta estable y selectiva a los esteroides anabólicos, así como un rendimiento superior a los sensores de esteroides anabólicos reportados anteriormente. Conclusión: Los valores de RSD oscilaron entre el 3,20% y el 4,45%, lo que indica que el sensor electroquímico de esteroides anabólicos desarrollado puede utilizarse como una técnica de detección viable para identificar esteroides anabólicos en fluidos biológicos humanos. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Sensor for prednisolone detection in sports doping / Sensor para detecção de prednisolona no doping esportivo / Sensor para la detección de prednisolona en el dopaje deportivo

ABSTRACT Introduction: Prednisolone causes pro-inflammatory impulses to be inhibited and anti-inflammatory signals to be promoted. As a result, it alters how the body's immune system reacts to certain diseases. The World Anti-Doping Agency, however, has banned SNP and other glucocorticosteroids. An electrochemical sensor can be developed using a gold nanocomposite, polypyrrole nanoparticles and synthesized carbon nanotubes (Au-PPy NPs@CNTs). Objective: Develop an electrochemical sensor to detect prednisolone. Method: Au-PPy NPs@CNTs nanocomposite was chemically synthesized with a modified glassy carbon electrode (GCE) surface. Results: According to SEM data, the nanocomposite was composed of amorphous Au NPs, and PPy NPs deposited in tubes strongly entangled in a CNTs network. The wide linear range and low detection limit of the Au-PPy NPs@CNTs/GCE as prednisolone sensors were attributed to the combined catalytic performance of the Au and PPy NPs@CNTs nanostructures. Conclusion: The results of prednisolone detection in each specimen using the amperometric method indicated good accuracy. The accuracy and precision of Au-PPy NPs@CNTs/GCE for prednisolone detection were explored in blood samples from 5 young athletes aged 20-24 years who used prednisolone tablets (RSD less than 4.25%). In addition to monitoring prednisolone concentrations in athletes' serum, Au-PPy NPs@CNTs/GCE can be used as a reliable prednisolone sensor. Level of evidence II; Therapeutic studies - investigating treatment outcomes.

RESUMO Introdução: A prednisolona faz com que os impulsos pró-inflamatórios sejam inibidos e os sinais anti-inflamatórios sejam promovidos. Como resultado, ela altera a forma como o sistema imunológico do corpo reage a certas doenças. A Agência Mundial Antidoping, no entanto, proibiu o SNP e outros glucocorticoesteroides. Usando um nanocomposto de ouro, nanopartículas de polipirrol e nanotubos de carbono sintetizados (Au-PPy NPs@CNTs), um sensor eletroquímico pode ser desenvolvido. Objetivo: Desenvolver um sensor eletroquímico para detectar a prednisolona. Método: O nanocompósito Au-PPy NPs@CNTs foi sintetizado quimicamente com uma superfície de eletrodo de carbono vítreo modificado (GCE). Resultados: De acordo com dados da SEM, o nanocomposto foi descoberto como sendo composto de Au NPs e NPs de PPy amorfo, depositados em tubos fortemente emaranhados em uma rede de CNTs. O amplo alcance linear e o baixo limite de detecção do Au-PPy NPs@CNTs/GCE como sensores de prednisolona foram atribuídos ao desempenho catalítico combinado das nanoestruturas de Au e PPy NPs@CNTs. Conclusão: Os resultados da detecção de prednisolona em cada espécime usando o método de amperometria indicaram boa precisão. A precisão e a acurácia de Au-PPy NPs@CNTs/GCE para a detecção de prednisolona foram exploradas em amostras de sangue preparadas de 5 atletas jovens de 20 a 24 anos que usaram comprimidos de prednisolona (RSD inferior a 4,25%). Além de monitorar as concentrações de prednisolona no soro dos atletas, Au-PPy NPs@CNTs/GCE pode ser usado como um sensor confiável de prednisolona. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La prednisolona hace que se inhiban los impulsos proinflamatorios y se promuevan las señales antiinflamatorias. Como resultado, altera la forma en que el sistema inmunológico del cuerpo reacciona a ciertas enfermedades. Sin embargo, la Agencia Mundial Antidopaje ha prohibido el SNP y otros glucocorticosteroides. Utilizando un nanocompuesto de oro, nanopartículas de polipirrol y nanotubos de carbono sintetizados (Au-PPy NPs@CNTs), se puede desarrollar un sensor electroquímico. Objetivo: Desarrollar un sensor electroquímico para detectar la prednisolona. Método: Se sintetizó químicamente el nanocompuesto Au-PPy NPs@CNTs con una superficie de electrodo de carbono vítreo (GCE) modificada. Resultados: Según los datos del SEM, se comprobó que el nanocompuesto estaba compuesto de Au NPs y NPs de PP amorfo y depositados en tubos fuertemente enredados en una red de CNTs. El amplio rango lineal y el bajo límite de detección de Au-PPy NPs@CNTs/GCE como sensores de prednisolona se atribuyeron al rendimiento catalítico combinado de las nanoestructuras de Au y PPy NPs@CNTs. Conclusión: Los resultados de la detección de prednisolona en cada muestra mediante el método amperométrico indicaron una buena precisión. Se exploró la exactitud y precisión de las Au-PPy NPs@CNTs/GCE para la detección de prednisolona en muestras de sangre preparadas a partir de 5 jóvenes atletas de entre 20 y 24 años de edad que utilizaban tabletas de prednisolona (RSD inferior al 4,25%). Además de controlar las concentraciones de prednisolona en el suero de los deportistas, Au-PPy NPs@CNTs/GCE puede utilizarse como un sensor fiable de prednisolona. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Biosensor development in sports doping with dexamethasone / Desenvolvimento de biossensor no doping esportivo com dexametasona / Desarrollo de un biosensor en el doping deportivo con dexametasona

ABSTRACT Introduction: Dexamethasone is a type of drug that is considered a steroid. It belongs to a class of drugs known as corticosteroids. Objective: Develop an electrochemical sensor of dexamethasone in a pharmaceutical sample using electrodes modified with nanostructures of MnO2 and reduced graphene oxide (MnO2/rGO). The glassy carbon electrodes (GCE) used to make the GO nanostructures were first modified using a modified Hummers technique before electrochemically reduced. Methods: MnO2 nanomaterials were electrochemically deposited on rGO/GCE. SEM structural investigation indicated vertical tetragonal crystal development of -MnO2 nanostructures in sprayed rGO nanostructures. Results: Because of the high composite surface area, multiple exposed active sites, and the synergistic effect of MnO2 and rGO, the electrocatalytic reaction to dexamethasone of MnO2/rGO/CPE was shown to be broad, selective, stable, and sensitive in electrochemical tests using amperometry. It was established that the linear range, sensitivities, and detection limit of the sensor are 0 to 260 µM, 4.6153µA/µM and 0.005 µM, respectively. The MnO2/rGO/CPE was tested for accuracy and applicability in determining dexamethasone in pharmacological and human urine samples. Conclusion: The results revealed that the sensor could prepare acceptable recovery (96.34%) and RSD (3.58%), suggesting that it could be used as a reliable dexamethasone sensor in clinical samples. Level of evidence II; Therapeutic studies - Investigation of treatment outcomes.

RESUMO Introdução: A dexametasona é um tipo de medicamento considerado um esteróide. Pertence a uma classe de medicamentos conhecida como corticosteróides. Objetivo: Este estudo teve como objetivo desenvolver um sensor eletroquímico de dexametasona em uma amostra farmacêutica utilizando eletrodos modificados com nanoestruturas de MnO2 e óxido grafeno reduzido (MnO2/rGO). Os eletrodos de carbono vítreo (GCE), que foram utilizados para fazer as nanoestruturas GO, foram primeiramente alterados através de uma técnica Hummers modificada antes de serem reduzidos eletroquimicamente. Métodos: Os nanomateriais de MnO2 foram depositados eletroquimicamente no rGO/GCE. A investigação estrutural do SEM indicou o desenvolvimento vertical do cristal tetragonal de -MnO2 nanoestruturas em nanoestruturas de rGO pulverizadas. Resultados: Em virtude da alta área de superfície composta, dos múltiplos locais ativos expostos e do efeito sinérgico de MnO2 e rGO, a reação eletrocatalítica à dexametasona de MnO2/rGO/CPE mostrou ser ampla, seletiva, estável e sensível nos testes eletroquímicos utilizando a amperometria. Foi estabelecido que o alcance linear, sensibilidades e limite de detecção do sensor são de 0 a 260 µM, 4,6153µA/µM e 0,005 µM, respectivamente. O MnO2/rGO/CPE foi testado para precisão e aplicabilidade na determinação de dexametasona em amostras farmacológicas e de urina humana. Conclusão: Os resultados revelaram que o sensor é capaz de preparar uma recuperação aceitável (96,34%) e RSD (3,58%), sugerindo que ele poderia ser usado como um sensor de dexametasona confiável em amostras clínicas. Nível de evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Introducción: La dexametasona es un tipo de fármaco considerado como un esteroide. Pertenece a una clase de medicamentos conocidos como corticosteroides. Objetivo: Este estudio tiene como objetivo desarrollar un sensor electroquímico de dexametasona en una muestra farmacéutica utilizando electrodos modificados con nanoestructuras de MnO2 y óxido de grafeno reducido (MnO2/rGO). Los electrodos de carbono vítreo (GCE), que se utilizaron para fabricar las nanoestructuras de GO, se modificaron primero mediante una técnica de Hummers modificada antes de ser reducidos electroquímicamente. Métodos: Los nanomateriales de MnO2 se depositaron electroquímicamente sobre rGO/GCE. La investigación estructural por SEM indicó el desarrollo vertical del cristal tetragonal de las nanoestructuras de -MnO2 en las nanoestructuras de rGO pulverizadas. Resultados: En virtud de la elevada área superficial del compuesto, los múltiples sitios activos expuestos y el efecto sinérgico del MnO2 y el rGO, la reacción electrocatalítica a la dexametasona del MnO2/rGO/CPE demostró ser amplia, selectiva, estable y sensible en pruebas electroquímicas mediante amperometría. Se estableció que el rango lineal, las sensibilidades y el límite de detección del sensor son de 0 a 260 µM, 4,6153µA/µM y 0,005 µM, respectivamente. Se probó la precisión y aplicabilidad del MnO2/rGO/CPE en la determinación de dexametasona en muestras farmacológicas y de orina humana. Conclusión: Los resultados revelaron que el sensor es capaz de preparar una recuperación aceptable (96,34%) y una RSD (3,58%), lo que sugiere que podría utilizarse como un sensor fiable de dexametasona en muestras clínicas. Nivel de evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Testosterone biosensor in sports doping / Biossensor de testosterona no doping esportivo / Biosensor de testosterona en el dopaje deportivo

ABSTRACT Introduction: Testosterone is a steroid that can help with blood disorders, sexual dysfunctions, connective tissue diseases, some malignancies, intractable pain, and other serious diseases. However, it must be prescribed under medical supervision because of the risk of major adverse effects such as liver disease, heart disease, stroke, blood clots, and cancer. There is an urgent need for research on developing an electrochemical sensor to detect testosterone as a doping substance in sports. Objective: Develop an electrochemical sensor of poly(ionic liquid)-graphene oxide molecularly printed polymers (PIL/MIs/GO) to detect testosterone as a doping substance in sports. Methods: Morphological characterization of modified electrodes was performed by field emission scanning electron microscopy (FESEM), allowing the GO to be surface-mounted with fragments and apertures. Due to the holes generated by the agglomeration of PIL and MIs molecules on the wavy edges of the GO nanosheets, the surface morphology of PIL/MIs/GO/GCE also revealed a high porosity structure. Results: Compared to other synergistic influences of GO nanosheets with PIL and MIs molecules, electrochemical investigations using a differential pulse voltammetry approach indicated high selectivity, good stability, appropriate linear range, lower detection limit, and higher selectivity. Conclusion: In pharmaceutical samples and human biological fluids, the validity and accuracy of PIL/MIs/GO/GCE for the determination of testosterone demonstrated practical application. PIL/MIs/GO/GCE can thus be used as an accurate and reliable sensor for detecting testosterone as a doping agent in sports. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A testosterona é um esteróide que pode ajudar com distúrbios sanguíneos, disfunções sexuais, doenças do tecido conjuntivo, algumas malignidades, dores intratáveis e outras doenças graves. No entanto, devido ao risco de grandes efeitos adversos como doenças hepáticas, doenças cardíacas, derrames, coágulos sanguíneos e câncer, ela deve ser prescrita sob supervisão médica. Há uma necessidade urgente da pesquisa sobre o desenvolvimento de um sensor eletroquímico para detectar a testosterona como substância dopante nos esportes. Objetivo: Desenvolver um sensor eletroquímico de poli-(líquido iônico)-polímeros impressos molecularmente em óxido de grafeno (PIL/MIs/GO) para detectar a testosterona como substância dopante nos esportes. Métodos: Efetuou-se a caracterização morfológica de eletrodos modificados por microscopia eletrônica de varredura de emissão de campo (FESEM) permitindo que o GO fosse em superfície com fragmentos e aberturas. Devido aos orifícios gerados pela aglomeração das moléculas de PIL e MIs nas bordas onduladas das nano folhas de GO, a morfologia da superfície de PIL/MIs/GO/GCE também revelou uma estrutura de alta porosidade. Resultados: Em comparação com outras influências sinergéticas das nanoquetas GO com as moléculas PIL e MIs, os resultados das investigações eletroquímicas utilizando a abordagem de voltametria de pulso diferencial indicaram alta seletividade, boa estabilidade, faixa linear apropriada, limite de detecção mais baixo e seletividade mais alta. Conclusão: Em amostras farmacêuticas e fluidos biológicos humanos, a validade e a precisão do PIL/MIs/GO/GCE para a determinação de testosterona demonstraram aplicação prática. O PIL/MIs/GO/GCE pode assim ser utilizado como um sensor preciso e confiável para a detecção de testosterona como agente dopante no esporte. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La testosterona es un esteroide que puede ayudar en los trastornos sanguíneos, la disfunción sexual, las enfermedades del tejido conectivo, algunos tumores malignos, el dolor intratable y otras enfermedades graves. Sin embargo, debido al riesgo de que se produzcan efectos adversos importantes, como enfermedades hepáticas, cardíacas, accidentes cerebrovasculares, coágulos sanguíneos y cáncer, debe prescribirse bajo supervisión médica. Es urgente investigar el desarrollo de un sensor electroquímico para detectar la testosterona como sustancia dopante en el deporte. Objetivo: Desarrollar un sensor electroquímico de polímeros impresos molecularmente de poli(líquido iónico)-óxido de grafeno (PIL/MIs/GO) para detectar la testosterona como sustancia dopante en el deporte. Métodos: La caracterización morfológica de los electrodos modificados se llevó a cabo mediante microscopía electrónica de barrido de emisión de campo (FESEM) permitiendo que el GO estuviera en la superficie con fragmentos y aberturas. Debido a los agujeros generados por la aglomeración de moléculas de PIL y MIs en los bordes ondulados de las nanohojas de GO, la morfología superficial de PIL/MIs/GO/GCE también reveló una estructura de alta porosidad. Resultados: En comparación con otras influencias sinérgicas de las nanohojas de GO con las moléculas PIL y MIs, los resultados de las investigaciones electroquímicas utilizando el enfoque de la voltamperometría diferencial de impulsos indicaron una alta selectividad, una buena estabilidad, un rango lineal apropiado, un límite de detección más bajo y una mayor selectividad. Conclusión: En muestras farmacéuticas y fluidos biológicos humanos, la validez y precisión de PIL/MIs/GO/GCE para la determinación de testosterona demostró su aplicación práctica. Así pues, PIL/MIs/GO/GCE puede utilizarse como un sensor preciso y fiable para la detección de la testosterona como agente dopante en el deporte. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Blood insulin level biosensor for athletes / Biossensor para nível de insulina sanguíneo em atletas / Biosensor para el nivel de insulina en sangre de deportistas

ABSTRACT Introduction: The pancreas releases insulin to assist the human body in utilizing blood glucose. It regulates metabolism by promoting the absorption of glucose into the blood. Objective: This work aimed to create an electrochemical biosensor based on magnetic graphene nanomaterial to measure insulin levels in athletes' blood. Method: A magnetic graphene nanocomposite created by graphene oxide (GO) and Fe-Ni bimetallic oxides on a glassy carbon electrode was synthesized using the electrochemical deposition method (GCE). Results: The immediate electrical deposition of Fe-Ni bimetallic oxide nanoparticles with the spherical shape on the GO nanosheet without aggregations was validated by structural characterizations of Fe-Ni/GO/GCE using XRD and SEM. The electrochemical results for insulin determination showed good sensitivity and anti-interference capability. The applicability and accuracy of the proposed electrochemical sensor to detect insulin were explored by blood serum samples from sportsmen. Conclusion: The results assigned acceptable RSD values (3.31% to 4.30%) and confirmed the feasibility of the proposed sensor for detecting athletes' blood insulin. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A insulina é liberada pelo pâncreas para auxiliar o corpo humano na utilização da glicose sanguínea. Ela regula o metabolismo, promovendo a absorção da glicose pelo sangue. Objetivo: O objetivo deste trabalho foi criar um biossensor eletroquímico baseado em nanomaterial de grafeno magnético para medir os níveis de insulina no sangue dos atletas. Método: Em um eletrodo de carbono vítreo, um nanocomposto magnético de grafeno criado por óxido de grafeno (GO) e óxidos bimetálicos de Fe-Ni foi sintetizado usando o método de deposição eletroquímica (GCE). Resultados: A deposição elétrica imediata de nanopartículas de óxido bimetal Fe-Ni com a forma esférica na nano folha GO sem agregações foi validada por caracterizações estruturais de Fe-Ni/GO/GCE utilizando XRD e SEM. Os resultados eletroquímicos para determinação da insulina demonstraram boa sensibilidade e capacidade anti-interferência. A aplicabilidade e precisão do sensor eletroquímico proposto para detectar insulina foram exploradas por amostras de soro sanguíneo dos esportistas. Conclusão: Os resultados designados para os valores aceitáveis de RSD (3,31% a 4,30%) confirmaram a viabilidade do sensor proposto para detecção de insulina sanguínea de atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El páncreas libera insulina para ayudar al cuerpo humano a utilizar la glucosa en sangre. Regula el metabolismo, favoreciendo la absorción de la glucosa por la sangre. Objetivo: El objetivo de este trabajo fue crear un biosensor electroquímico basado en un nanomaterial de grafeno magnético para medir los niveles de insulina en la sangre de los deportistas. Método: Sobre un electrodo de carbono vítreo, se sintetizó un nanocompuesto de grafeno magnético creado por óxido de grafeno (GO) y óxidos bimetálicos de Fe-Ni mediante el método de deposición electroquímica (GCE). Resultados: La deposición eléctrica inmediata de las nanopartículas de óxido bimetálico Fe-Ni con forma esférica sobre la nano plancha de GO sin agregaciones fue validada por las caracterizaciones estructurales de Fe-Ni/GO/GCE mediante XRD y SEM. Los resultados electroquímicos para la determinación de la insulina mostraron una buena sensibilidad y capacidad anti-interferencia. La aplicabilidad y la precisión del sensor electroquímico propuesto para detectar la insulina se exploraron con muestras de suero sanguíneo de deportistas. Conclusión: Los resultados asignados a valores aceptables de RSD (3,31% a 4,30%) confirmaron la viabilidad del sensor propuesto para detectar la insulina en sangre de los atletas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Electrochemical sensor for doping corticosteroids in sports / Sensor eletroquímico para corticosteróides dopantes nos esportes / Sensor electroquímico para el dopaje de corticoesteroides en los deportes

ABSTRACT Introduction: Identifying and measuring the concentration of Triamcinolone (TA) in biological fluids is essential, especially for patients receiving intensive antibiotic medication. Objective: Make a sensor for electrochemical detection of Triamcinolone (TA) as an anabolic steroid in sports using copper oxide nanomaterials-reduced graphene oxide nanoparticles (CuNPs/rGO). Method: After preparing rGO nanoparticles on a glassy carbon electrode (GCE) using the modified Hummers technique, Cu NPs were deposited on rGO/GCE. The applicability of Cu NPs/rGO/GCE was investigated to determine the TA concentration in a real sample that had been prepared. Results: The deposited irregular Cu NPs evidenced a diameter of about 80 nm, in agreement with SEM morphological investigations. Amperometric studies revealed that the linear range, detection limits, and sensitivity of CuNPs/rGO/GCE as a TA sensor were 10 to 80 µM, 10nM, and 0.06584 µA/µM, respectively. Conclusion: The results revealed that the RSD and recovery values were valid, providing adequate quality and reliability for practical analysis of real samples using Cu NPS/rGO/GCE. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: É essencial identificar e medir a concentração de triamcinolona (TA) em fluidos biológicos, especialmente para pacientes que recebem medicação antibiótica intensiva. Objetivo: Confeccionar um sensor para detecção eletroquímica da triamcinolona como esteróides anabolizantes em esportes utilizando nanomateriais de óxido de cobre-nanopartículas de óxido de grafite reduzido (CuNPs/rGO). Métodos: Após a elaboração das nanopartículas rGO em eletrodo de carbono vítreo (GCE) utilizando a técnica Hummers modificada, os NPs Cu foram depositados no rGO/GCE. A fim de determinar a concentração de TA em uma amostra real que tinha sido preparada, foi investigada a aplicabilidade de Cu NPs/rGO/GCE. Resultados: Os Cu NPs irregulares depositados evidenciaram um diâmetro de cerca de 80 nm, de acordo com as investigações morfológicas do SEM. Estudos de amperometria revelaram que a faixa linear, limites de detecção e sensibilidade do CuNPs/rGO/GCE como sensor TA foram de 10 a 80 µM, 10nM e 0,06584 µA/µM, respectivamente. Conclusão: Os resultados revelaram que os valores de RSD e recuperação eram válidas, fornecendo qualidade e confiabilidade adequadas para análises práticas de amostras reais usando Cu NPs/rGO/GCE. Nível de evidência II; Estudos terapêuticos - investigação dos resultados de tratamento.

RESUMEN Introducción: Es esencial identificar y medir la concentración de triamcinolona (TA) en los fluidos biológicos, especialmente en los pacientes que reciben medicación antibiótica intensiva. Objetivo: Fabricar un sensor para la detección electroquímica de triamcinolona como esteroides anabólicos en el deporte utilizando nanomateriales de óxido de cobre-nanopartículas de óxido de grafeno reducido (CuNPs/rGO). Método: Tras la preparación de las nanopartículas de rGO sobre el electrodo de carbono vítreo (GCE) utilizando la técnica de Hummers modificada, se depositaron los NPs de Cu sobre el rGO/GCE. Para determinar la concentración de TA en una muestra real que había sido preparada, se investigó la aplicabilidad de los NPs de Cu/rGO/GCE. Resultados: Los NPs de Cu irregulares depositados presentaban un diámetro de unos 80 nm, de acuerdo con las investigaciones morfológicas del SEM. Los estudios amperométricos revelaron que el rango lineal, los límites de detección y la sensibilidad de Cu NPs/rGO/GCE como sensor de TA era de 10 a 80 µM, 10nM y 0,06584 µA/µM, respectivamente. Conclusión: Los resultados revelaron que los valores de RSD y recuperación eran válidos, proporcionando una calidad y fiabilidad adecuadas para el análisis práctico de muestras reales utilizando Cu NPs/rGO/GCE. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Rapid Selective Detection and Quantification of ß-Blockers Used in Doping Based on Molecularly Imprinted Nanoparticles (NanoMIPs).

Human performance enhancing drugs (PEDs), frequently used in sport competitions, are strictly prohibited by the World Anti-Doping Agency (WADA). Biological samples collected from athletes and regular patients are continuously tested regarding the identification and/or quantification of the banned substances. Current work is focused on the application of a new analytical method, molecularly imprinted nanoparticles (nanoMIPs), to detect and determine concentrations of certain prohibited drugs, such as ß-blockers, in water and human urine samples. These medications are used in the treatment of cardiovascular conditions, negative effects of adrenaline (helping to relief stress), and hypertension (slowing down the pulse and softening the arteries). They can also significantly increase muscle relaxation and improve heart efficiency. The new method of the detection and quantification of ß-blockers is based on synthesis, characterization, and implementation of nanoMIPs (so-called plastic antibodies). It offers numerous advantages over the traditional methods, including high binding capacity, affinity, and selectivity for target molecules. Additionally, the whole process is less complicated, cheaper, and better controlled. The size and shape of the nanoMIPs is evaluated by dynamic light scattering (DLS) and transmission electron microscope (TEM). The affinity and selectivity of the nanoparticles are investigated by competitive pseudo enzyme-linked immunosorbent assay (pseudo-ELISA) similar to common immunoassays employing natural antibodies. To provide reliable results towards either doping detection or therapeutic monitoring using the minimal invasive method, the qualitative and quantitative analysis of these drugs is performed in water and human urine samples. It is demonstrated that the assay can detect ß-blockers in water within the linear range 1 nmol·L-1-1 mmol·L-1 for atenolol with the detection limit 50.6 ng mL-1, and the linear range 1 mmol·L-1-10 mmol·L-1 for labetalol with the detection limit of 90.5 ng·mL-1. In human urine samples, the linear range is recorded in the concentration range 0.1 mmol·L-1-10 nmol·L-1 for atenolol and 1 mmol·L-1-10 nmol·L-1 for labetalol with a detection limit of 61.0 ng·mL-1 for atenolol and 99.4 ng·mL-1 for labetalol.

Practical Efficacy of Prior Checks on Athletes' Medication Use for the Prevention of Unintentional Doping.

Background: Athletes are subjected to disciplinary action for even unintentional doping. This study aimed to clarify the effectiveness of prior checks on athletes' drug regimens by medical personnel with knowledge of anti-doping to prevent unintentional doping. Methods: This is a retrospective evaluation of the inquiries to the Anti-Doping Committee by the Japan Table Tennis Association national team athletes and athlete support personnel between 2011 and 2019 regarding whether the drug in question was permitted and whether it contained any prohibited substance. Discrete evaluations were performed for ethical and over-the-counter drugs, in addition to the evaluation of all drugs. Additionally, we evaluated the drugs according to therapeutic category and World Anti-Doping Agency's classification. Results: Overall, 85/1238 (6.9%) ethical drugs, 49/259 (18.9%) over-the-counter drugs and 134/1497 (9.0%) total drugs were considered as not allowed for use. The proportion of over-the-counter drugs judged as not allowed for use was higher than that of ethical drugs (p < 0.001). When tabulating the drugs not allowed for use in the therapeutic category, numerous prohibited substances were identified in adrenal hormone preparations, Kampo products, synthetic narcotics, antitussives, antihemorrhoidals, and bronchodilators among ethical drugs and in cold remedies, gastrointestinal drugs, and antitussives and expectorants among over-the-counter drugs. Conclusions: Of the ethical and over-the-counter drugs that elite athletes wanted to use, approximately 10% were not allowed because of the risk of unintentional doping. These results suggest that conducting prior checks of the athletes' drug regimens by medical personnel with anti-doping knowledge are effective measures to prevent unintentional doping.