Francesco BotrèUniversity of Lausanne | UNIL · Institute of Sports Science
Francesco Botrè
Chemistry; Pharmacy; Experimental Pharmacology
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336
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Introduction
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December 2012 - present
Publications
Publications (336)
BACKGROUND
Atherosclerotic plaques form unevenly due to disturbed blood flow, causing localized endothelial cell (EC) dysfunction. Obesity exacerbates this process, but the underlying molecular mechanisms are unclear. The transcription factor EPAS1 (HIF2A) has regulatory roles in endothelium, but its involvement in atherosclerosis remains unexplore...
This paper aims to study the metabolism of thyroid hormones (TH) in urine by liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The method was applied to samples collected before and after the administration of sodium triiodothyronine (T3) and sodium levothyroxine (T4) to a euthyroid volunteer and to samples of athletes declaring and not de...
This work aims to characterize the serum profile of athletes after the administration of ecdysteroids, natural steroid hormones recently reported to enhance athletic performance. The combination of mass spectrometry and chemometric tools may allow to differentiate physiological effects from post‐training and intake‐driven effects. Serum samples wer...
Recently, the trend of thyroid hormones (TH) consumption in the sports community has been published. It is known the capacity of the exogenously administered TH to enhance metabolism, being an attractive feature for athletes, who search for weight control and increased caloric expenditure. This paper aimed the validation of a method to measure TH a...
Current guidelines for prolonged altitude exposure suggest altitude levels ranging from 2000 to 2500 m to optimize an increase in total hemoglobin mass (Hbmass). However, natural low altitude locations (<2000 m) remain popular, highlighting the interest to investigate any possible benefit of low altitude camps for endurance athletes. Ten elite race...
The phytosteroid ecdysterone is classified as an anabolic agent and has been included on the monitoring list of the World Anti‐Doping Agency since 2020. Therefore, the consumption of food rich in ecdysterone, such as quinoa and spinach, is the focus of a lively debate. Thus, the urinary excretion of ecdysterone and its metabolites in humans was inv...
Supercritical fluid chromatography-mass spectrometry (SFC-MS) has proved to be a beneficial tool for sample analysis for a wide variety of compounds and, as such, has recently gained the attention of the anti-doping community. We have tested the applicability of SFC-MS for routine doping control analysing approximately 3 × 1000 identical anti-dopin...
We performed genotyping analysis of human biallelic polymorphisms (single nucleotide polymorphisms) for the detection of homologous blood transfusion in sports doping. DNA was extracted from dried blood spots and quantified real‐time fast PCR. The method was proven to allow the detection of transfusions up to a donor percentage of 1%, with a signif...
Confounding factors including exercise and environments challenge the interpretation of individual Athlete Biological Passports (ABPs). This study aimed to investigate the natural variability of hematological ABP parameters over 1 year in elite athletes compared with healthy control subjects and the validity of a multiparametric model estimating pl...
Rationale
High‐resolution mass spectrometry (HRMS) has been demonstrated to be an alternative platform for quantitative analyses, identifying unknown compounds and gathering information for the elucidation of chemical structures. This work describes a method to detect 13 esters of testosterone (T) and 5 biomarkers in 0.1 mL of human serum using gas...
We considered in this study the possibility of developing an indirect procedure for detecting myostatin inhibition/suppression, a practice that is prohibited as doping in sport. We have specifically considered the potential diagnostic utility of human serum myokines as indirect markers of myostatin inhibition. Myostatin, its main antagonist follist...
Background
Autologous blood transfusion is one of the illicit strategies, banned by the World Anti-Doping Agency, to increase the levels of hemoglobin, with a consequent improvement in the delivery of oxygen to tissues. At present, this practice is detectable exclusively by the individual, longitudinal monitoring of hematological biomarkers, as in...
Hemoglobin concentration ([Hb]) is used for the clinical diagnosis of anemia, and in sports as a marker of blood doping. [Hb] is however subject to significant variations mainly due to shifts in plasma volume (PV). This study proposes a newly developed model able to accurately predict total hemoglobin mass (Hbmass) and PV from a single complete blo...
The phytosteroid ecdysterone is included on the monitoring list of the World Anti-Doping Agency. Therefore, the consumption of food rich in ecdysterone is the focus of a lively debate. Thus, urinary excretion of ecdysterone and its metabolites in humans was investigated following quinoa consumption alone and in combination with spinach.
After intak...
Awareness of human rights and related principles, such as equality and non-discrimination, is growing in sports. While debates on doping regulation typically target the contours of the prohibition and the sanctioning regime, much less attention has been given to how anti-doping detection impacts the level playing field, i.e . whether equality is re...
Insulin-like growth factor 1 analogues are prohibited in sport for their ability to enhance athletic performance in several sport disciplines. Their detection presents several analytical challenges, mainly due to the minimum required performance limits fixed by the World Anti-Doping Agency. Here, we are presenting analytical workflows to detect IGF...
Background: In doping control, the presence of the exon5 c.577del variant in the human erythropoietin gene may be a confounding factor in the interpretation of the results from the analytical method currently in force for the detection of human recombinant erythropoietin, based on immunoelectrophoresis on SDS-PAGE and/or SAR-PAGE. This variant, det...
This work focused on the possible alterations of the markers of the steroidal module of the athlete biological passport, considering samples of athletes declaring and not-declaring the supplementation of thyroid hormones (TH) in the Doping Control Form (DCF). Concentrations of 5α-androstane-3α,17β-diol (5α-Adiol), 5β-androstane-3α,17β-diol (5β-Adio...
This study investigated the impact of low-volume blood withdrawal on the hematological biomarkers currently considered for anti-doping purposes. After baseline measurement (D - 7), a 140 mL blood withdrawal was completed (D + 0) on 12 healthy volunteers, followed by weekly monitoring for 21 days (D + 7 - 21). Each visit consisted of a full blood co...
Background and objective: Autologous blood transfusion is a form of “blood doping” banned by the World Anti-Doping Agency. At present, this practice is detectable exclusively by the individual, longitudinal monitoring of hematological biomarkers, as in the hematological module of the Athlete Biological Passport; but this indirect approach may suffe...
Scope:
The phytosteroid ecdysterone is present in spinach. In this study, the urinary elimination of ecdysterone and its metabolites in humans was investigated following spinach consumption of two different culinary preparations.
Methods and results:
Eight participants (4 male, 4 female) ingested 950 (27.1) g sautéed spinach (average (±SD)) and...
The detection of blood doping represents a current major issue in sports and an ongoing challenge for anti-doping research. Initially focusing on direct detection methods to identify a banned substance or its metabolites, the anti-doping effort has been progressively complemented by indirect approaches. The longitudinal and individual monitoring of...
Rationale:
The proposed metabolomic workflow, based on coupling high-resolution mass spectrometry with computational tools, can be an alternative strategy for metabolite detection and identification. This approach allows the extension of the investigation field to chemically different compounds, maximizing the information obtainable from the data...
Background:
Most current state-of-the-art strategies to generate individual adaptive reference ranges are designed to monitor one clinical parameter at a time. An innovative methodology is proposed for the simultaneous longitudinal monitoring of multiple biomarkers. The estimation of individual thresholds is performed by applying a Bayesian modeli...
Background
Nicotine is a psychostimulant drug with purported use in sports environments, though the use of nicotine among athletes has not been studied extensively.
Objective
The aim of this study was to assess the nicotine positivity rate in 60,802 anti-doping urine samples from 2012 to 2020.
Methods
Urine samples obtained in-competition at diff...
It was the aim of this study to compare the ratio of salbutamol and its major metabolite salbutamol-4’-O-sulfate as well as the quantity excreted renally after oral and inhalative administration. Additionally, the excretion pattern after application of racemic salbutamol opposed to the pure enantiomer levosalbutamol was evaluated. For quantitation...
Anemia is a widespread disease commonly diagnosed through hemoglobin concentration ([Hb]) thresholds set by the World Health Organization (WHO). However, [Hb] is subject to significant variations mainly due to shifts in plasma volume (PV) which impair the diagnosis of anemia and other medical conditions. The aim of this study was to develop a model...
Introduction
The hematological module of the Athlete Biological Passport (ABP) consists of individual and longitudinal monitoring of hematological parameters biomarkers responsive to erythropoiesis alteration. Based on an adaptive Bayesian model, the ABP seeks to identify non-physiological variations that may correspond to different types of blood...
Supercritical fluid chromatography is proving to be a good separation and sample preparation tool for various analytical applications and, as such, has gained the attention of the anti-doping community. Here, the applicability of supercritical fluid chromatography hyphenated to MS/MS for routine doping control analysis was tested. A multi-analyte m...
We present a novel procedure to monitor the fluctuations of the levels of IGF-1 in capillary blood in the framework of doping control analysis. Being an endogenous hormone, direct methods are not applicable, so the most effective way to detect the intake of the exogenous hormone would be based on the longitudinal monitoring of the athlete. We have...
Purpose: To assess the prevalence of tramadol use among athletes from 2012 to 2020. Methods: All urine samples were collected
from national and international in-competition doping-control tests that took place in Italy between 2012 and 2020. The analysis of the
samples was performed by gas chromatography coupled with mass spectrometry with electron...
The Athlete Biological Passport (ABP) was introduced to complement the direct anti-doping approach by indirectly outlining the possible use of prohibited substances or methods in sports. The ABP proved its effectiveness, at least through a deterrent effect, even though the matrices used for longitudinal monitoring (urine and blood) are subject to m...
The steroidal module of the athlete biological passport (ABP) targets the use of pseudo‐endogenous androgenous anabolic steroids in elite sport by monitoring urinary steroid profiles.
Urine and blood samples were collected weekly during two consecutive oral contraceptive pill (OCP) cycles in 15 physically active women to investigate the low urinary...
Introduction: The immunomodulatory effect of physical activity can impact insulin signaling differentially in adipose tissues and skeletal muscle cells, depending on sport intensity. In this study, the effect of serum from elite athletes with varying endurance levels and playing different power sports on cytokine secretion and insulin signaling in...
The steroidal module of the Athlete Biological Passport (ABP) targets the use of exogenous androgenous anabolic steroids (EAAS) in elite sport by monitoring urinary steroid profiles. Urine and blood samples were collected weekly during two consecutive OCP cycles (8 weeks) in 15 physically active women to investigate the low urinary steroid concentr...
We present a quick and simple multi-targeted analytical workflow based on ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry for the screening in dried blood spots and dried plasma spots of a wide variety of drugs with different chemical properties. Seven different microsampling devices were evaluated in view...
The rectal administration of glucocorticoids, as well as any injectable, and oral ones, is currently prohibited by the World Anti‐Doping Agency when occurs “in competition”. A reporting level of 100 ng/mL for prednisolone and 300 ng/mL for prednisone was established to discriminate the allowed and the prohibited administration. Here, the urinary ex...
3-(1-Naphthalenylmethyl)-1-pentyl-1H-indole (JWH-175) is a synthetic cannabinoid illegally marketed for its psychoactive cannabis-like effects. This study aimed to investigate and compare in vitro and in vivo pharmacodynamic activity of JWH-175 with that of 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018), as well as evaluate the in vitr...
The detection of testosterone and its precursors' abuse in Antidoping sports analysis, is based on the longitudinal evaluation of markers of the urinary endogenous steroid profile. A Bayesian statistical approach is applied, allowing the establishment of credible intervals of the selected parameters for every athlete. Samples showing values outside...
The hematological module of the Athlete's Biological Passport (ABP) identifies doping methods and/or substances used to increase the blood's capacity to transport or deliver oxygen to the tissues. Recombinant human erythropoietin (rhEPOs) are doping substances known to boost the production of red blood cells and might have an effect on the blood bi...
Background
Humanin and the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are mitochondrial encoded peptides involved in energy metabolism, cytoprotection, longevity, insulin sensitivity and their expression decrease with age. Levels of these molecules have been shown to respond to acute exercise, however little is known about their mo...
Hematopoietic stem cells (HSC) are multipotent progenitor cells, resident primarily in human bone marrow. Their main function is the continuous renewal of all hematopoietic cells. A small fraction of HSC is also circulating in peripheral blood (cHSC) where they can be possibly detected thanks to the application of the new very sensitive flow cytome...
Growth factors (GFs) are a wide class of polypeptides that can regulate cellular proliferation, migration and differentiation. Due to their ability to extensively impact on tissue regeneration, the use of GFs in sports is currently prohibited in and out of competition and included in the 2022 List of Prohibited Substances of the World Anti‐Doping A...
In the last decade, the market for new psychoactive substances has been enriched by numerous psychedelic phenethylamines, which mimic the psychoactive effect of lysergic acid diethylamide (LSD). In particular, the -NBOMe series, which are more potent than their 2C compounds analogs, are considered worthy substitutes for LSD by users. The purpose of...
Genomics, transcriptomics and metabolomics are increasingly generating key insights for the development of precision approaches in heath and disease. Omics technologies have unlocked the high-throughput discovery of diagnostic biomarker and the systems-level evaluation of the efficacy and toxicity of novel therapies. In the subfield of sport medici...
Objectives:
This paper aimed to consider those features that may suggest a link between thyroid hormones pharmacology and athletes' health based on current consumption trends in a population of athletes.
Methods:
Methods used were observation, description, and synthesis, mainly. Among the documents reviewed were: books, scientific articles, and...
Thyroid hormones and their derivatives are structurally related to the non-essential amino acid tyrosine (4-hydroxyphenylalanine). However, there are physicochemical differences that make it difficult to apply an analytical method for their simultaneous detection. This work focused on the optimization of a method using liquid chromatography-electro...
This article presents the results of a study aimed to give new suggestions and strategies for improving the implementation of the flow cytofluorimetry-based method for the detection of homologous blood transfusions in doping control. The method is based on the recognition of the phenotypic mismatch between minority blood group antigens possessed by...
Endurance training is associated with physiological changes in elite athletes, but little is known about female-specific effects of endurance training. Despite the significant rise in female sports participation, findings from studies performed on male athletes are largely extrapolated to females without taking into consideration sex-specific diffe...
We present a liquid chromatography tandem mass spectrometry method for the simultaneous analysis of 16 endogenous steroids (androgens, estrogens, glucocorticoids, and progestogens) in human serum. Samples (250 μL of matrix) were extracted with t‐butylmethyl ether prior to LC‐MS/MS analysis. The chromatographic separation was achieved on a reversed‐...
Doping is considered as cheating in sports and contradicts the ethics of sports. Anti-doping laboratories accredited by the World Anti-Doping Agency target the administration of prohibited compounds or application of prohibited methods by means of instrumental analysis. The majority of methods is based on mass spectrometry with prior chromatographi...
Introduction: Biological aging is associated with changes in the metabolic pathways. Leukocyte telomere length (LTL) is a predictive marker of biological aging; however, the underlying metabolic pathways remain largely unknown. The aim of this study was to investigate the metabolic alterations and identify the metabolic predictors of LTL in elite m...
Rationale:
This work demonstrated the high potential of combining high-resolution mass spectrometry with chemometric tools, using metabolomics as a guided tool for anti-doping analysis. The administration of 7-keto-DHEA was studied as a proof-of-concept of the effectiveness of the combination of knowledge-based and machine-learning approaches to d...
Γ-Valero-lactone (GVL) is a freely marketed organic solvent and food additive. GVL is also an underrated legal substitute for γ-hydroxybutyric acid (GHB), and it is sold under the trade name "Tranquili-G". GVL is usually not included in forensic drug testing, even though it has been reported in drug-facilitated sexual assaults (DFSA).
To date, few...
We have investigated the metabolic profile of N-ethyl heptedrone, a new designer synthetic stimulant drug, by using data independent acquisition mass spectrometry. Phase I and phase II metabolism was studied by in vitro models, followed by liquid-chromatography coupled to mass spectrometry, to characterize and pre-select the most diagnostic markers...
Mexedrone is a synthetic cathinone structurally related to mephedrone, which belongs to the class of N‐alkyl cathinone derivatives, whose metabolic profile has not been fully clarified yet. This study considers the in vitro phase I metabolism of mexedrone, to pre‐select the most appropriate marker(s) of intake. Mexedrone was incubated in the presen...
Rationale:
Systematic electron ionization fragmentation studies of steroids have been performed to elucidate and trace their characteristic fragmentation pattern. However, the electron ionization source setting at 70 eV electron energy is much higher than the ionization potential (7-15 eV) of most organic compounds, leading to extensive fragmentat...
Introduction: Aerobic exercise activates the complement system in the peripheral blood. However, the effect of age and high intensity endurance training on the levels of circulating complements and sassociated inflammatory cytokines, oxidative stress markers and cellular aging remains unknown.
Methods: In this study, serum samples from 79 elite ath...
4,4’-Dimethylaminorex (4,4’-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1–60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their...
Dehydrochloromethyltestosterone (DHCMT) is an anabolic-androgenic steroid that was developed by Jenapharm in the 1960s and was marketed as Oral Turinabol ® . It is prohibited in sports at all times; nevertheless, there are several findings by anti-doping laboratories every year. New long-term metabolites have been proposed in 2011/12, which resulte...
In this work we have investigated the influence of the intake of two synthetic isoflavones, methoxyisoflavone and ipriflavone, on the urinary concentration of endogenous steroids, and on their relative ratios, of doping relevance. Specifically, the concentrations of testosterone (T), epitestosterone (E), androsterone (A), etiocholanolone (Etio), 5α...
Dehydrochloromethyltestosterone (DHCMT) is an anabolic-androgenic steroid that was developed by Jenapharm in the 1960s and was marketed as Oral Turinabol®. It is prohibited in sports at all times; nevertheless, there are several findings by anti-doping laboratories every year. New long-term metabolites have been proposed in 2011/12, which resulted...
This article reports the results obtained from the investigation of the influence of miconazole administration on the physiological fluctuation of the markers of the steroid profile included in the "steroidal module" of the Athlete Biological Passport. Urines collected from male Caucasian subjects before, during, and after either systemic (i.e., or...
5α‐reductase inhibitors (5‐ARIs) are considered by the World Anti‐doping Agency as potential confounding factors in evaluating the athlete steroid profile, since they may interfere with the urinary excretion of several diagnostic compounds. We herein investigated 5α‐reductase inhibitors from a different perspective, by verifying their influence on...
Background:
Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes.
Methods:
In this study, 80 blood samples from consenting elite athletes were collected for anti-...
Ecdysterone is a phytosteroid widely discussed for its various pharmacological, growth-promoting, and anabolic effects, mediated by the activation of estrogen receptor beta (ERbeta). Performance-enhancement in sports was demonstrated recently, and ecdysterone was consequently included in the Monitoring Program, to detect potential patterns of misus...
Cytochrome P450s (CYPs) are an essential family of enzymes in the human body. They play a crucial role in metabolism, especially in human steroid biosynthesis. Reactions catalyzed by these enzymes are highly stereo- and regio-specific. Lack or severe malfunctions of CYPs can cause severe diseases and even shorten life. Hence, investigations on meta...
Ecdysterone is a phytosteroid widely discussed for its various pharmacological, growth-promoting and anabolic effects mediated by activation of estrogen receptor beta (ERbeta). Performance-enhancement in sports was demonstrated recently, and ecdysterone was consequently included in the Monitoring Program to detect potential patterns of misuse in sp...
Homologous blood transfusions (hBT) are prohibited by the World Anti-Doping Agency (WADA) as they represent one of the methods that athletes can attempt to improve the oxygen supply to the tissues and consequently the sports performance. The current method of detection of hBT in sport doping is based on the phenotypic mismatch analysis of red blood...