The role of toxic substances in sudden cardiac death

13 Feb 2018

The role of toxic substances in sudden cardiac death / Benito Morentina, Luis F. Callado, Soledad García-Hernández, Andrés Bodegase, Joaquín Lucena. (Spanish Journal of Legal Medicin 44 (2018) 1 (January-March); p. 13-21)

  • DOI: 10.1016/j.reml.2017.05.005

Abstract

The use of toxic substances is a main risk factor for sudden cardiac death. The most relevant toxic substances are the illegal drugs (especially cocaine), ethanol, tobacco, and doping substances. Additionally, several therapeutic drugs are able to increase the risk for sudden cardiac death. The aim of the present paper is to review the mechanism of action and the main pathological problems induced by toxic substances. Moreover, we provide epidemiological information, underlie the importance of a standardised forensic investigation, and discuss the role of forensic pathology in the prevention of this phenomenon. The possibility of consumption of any drug of abuse should be considered in any case of sudden cardiac death in adolescents, young, or middle-age patients, especially in men. In athletes the use of doping substances should be ruled-out. In patients under psychopharmacological treatment, the putative influence of these drugs should be borne in mind.

Forensic Post-Mortem Investigation in AAS Abusers: Investigative Diagnostic Protocol. A Systematic Review

21 Jul 2021

Forensic Post-Mortem Investigation in AAS Abusers : Investigative Diagnostic Protocol. A Systematic Review / Massimiliano Esposito, Gabriele Licciardello, Federico Privitera, Salvatore Iannuzzi, Aldo Liberto, Francesco Sessa, Monica Salerno. - (Diagnostics 11 (2021) 8 (21 July); 1307)

  • PMID: 34441242
  • PMCID: PMC8393338
  • DOI: 10.3390/diagnostics11081307


Abstract

Anabolic-androgenic steroids (AASs) are a group of synthetic molecules derived from testosterone and its precursors. AASs are widely used illicitly by adolescents and athletes, especially by bodybuilders; AASs are among the most used drugs for improving physical performance, as well as for aesthetic purposes. The use of AASs by professional and recreational athletes is increasing worldwide. This review focused on deaths related to AAS abuse and to investigation of the autopsy results and histopathological findings using a rigorous methodology protocol covering: a complete autopsy, histological analysis, and a broad toxicological investigation. Moreover, we aimed to define an investigative diagnostic protocol supporting forensic pathologists during the post-mortem investigation of AAS abusers. This review was conducted using PubMed Central and Google Scholar databases to find articles published between 1 January 1968 and 30 June 2021, using the following key terms: "(anabolic-androgenic steroids) AND (autopsy); (anabolic-androgenic steroids) AND (forensic)". A total of 939 articles were screened and 926 did not meet the inclusion criteria. In conclusion, 14 articles were included in this systematic review, reporting 137 fatal cases of AAS abuse in total. The histopathologic studies showed myocardial damage characterized by myocyte hypertrophy, focal myocyte damage with myofibrillar loss, interstitial fibrosis, mostly subepicardial, and small vessel disease. Indeed, in AAS-related cases, autopsy plays a pivotal role in the study of AAS adverse effects and organ damage related to their use or abuse. This systematic review aimed to define a specific workflow in death cases related to AASs, suggesting important future insights to better clarify sudden deaths related to AASs, such as the use of miRNAs. The forensic community needs a unified approach in cases of suspected death related to the use of AASs. There are several occasions to apply this workflow, for example in cases of death of bodybuilders and of young people who die in gymnasiums or during sports activities.

Urinary Excretion of Ecgonine Methyl Ester, a Major Metabolite of Cocaine in Humans

4 Jan 1984

Urinary Excretion of Ecgonine Methyl Ester, a Major Metabolite of Cocaine in Humans / John Ambre, Marian Fischman, Tsuen-ih Ruo. - (Journal of Analytical Toxicology 8 (1984) 1 (January/February); p. 23-25)

  • DOI: 10.1093/jat/8.1.23


Abstract

In this study, cocaine, benzoylecgonine, and ecgonine methyl ester excretion in urine was measured after intravenous and intranasal administration of cocaine at 16, 32, 48, and 96 mg doses to healthy cocaine users. Ecgonine methyl ester and cocaine were analyzed by gas chromatography/mass spectrometry. Benzoylecgonine was measured by immunoassay (EMIT) and liquid chromatography. Urinary ecgonine methyl ester accounted for 26 to 60% of the cocaine dose. Ecgonine methyl ester had an elimination halflife of 4.2 hr, compared with 5.1 hr for benzoylecgonine. These results indicate that ecgonine methyl ester accounts for most of the previously unidentified urinary metabolic products of cocaine. The time course of ecgonine methyl ester excretion is such that its detection can substitute for benzoylecgonine detection as a marker of cocaine use.

A Netnography and a Survey on Doping Use among Competitive Doping-untested Strength-sport Athletes

27 Jan 2021

A Netnography and a Survey on Doping Use among Competitive Doping-untested Strength-sport Athletes / Iiro Jokipalo, Anna Khudayarov. - (International Journal of Sports Medicine 42 (2021) 7 (January) ; p. 645-650)

  • PMID: 33506442
  • DOI: 10.1055/a-1342-7312

Abstract

Doping-untested strength-sport athletes (powerlifters, strongmen, armlifters, etc.,) are infamous for their doping use, but their exact doping regimens are not known. The purpose of this study was to provide a reasonable portrait of doping history in this specific athlete group for medical practitioners. Seventy-five athletes were selected by netnography of the social media community around the Finnish doping-untested strength-sport federations on the basis of their activity in doping-related discussions, and the athletes were invited to answer a detailed doping-related anonymous survey. Fifty respondents completed the survey. 100% of the respondents reported use of anabolic androgenic steroids, 66% reported use of stimulants, and 80% use of non-steroidal anabolic substances. The doses of both testosterone products and human growth hormone were notably larger than reported in previous studies of gym users (mostly non-competitive athletes). The subjects reported simultaneous use of an average 5.66 illegal substances, and lifetime use of 16.78 illegal substances. The doses of illicit drugs, as well as polypharmacy, among competitive doping-untested strength-sport athletes are higher than previously reported among recreational gym users, and side effects are likely in this specific population.

Procollagen type III amino-terminal propeptide and insulin-like growth factor I as biomarkers of growth hormone administration

21 Aug 2021

Procollagen type III amino-terminal propeptide and insulin-like growth factor I as biomarkers of growth hormone administration / David A. Cowan, Danielle A. Moncrieffe. - (Drug Testing and Analysis (2021) 21 August)

  • PMID: 34418311
  • DOI: 10.1002/dta.3155


Abstract

The acceptance in 2012 by the World Anti-Doping Agency (WADA) of the biomarker test for human growth hormone (hGH) based on procollagen type III amino-terminal propeptide (P-III-NP) and insulin-like growth factor I (IGF-I) was perhaps the first time that such a method has been used for forensic purposes. Developing a biomarker test to anti-doping standards, where the strict liability principle applies, is discussed. An alternative WADA-accepted approach is based on the measurement of different hGH isoforms, a method that suffers from the very short half-life of hGH limiting the detection period. Modification or withdrawal of the immunoassays, on which the biomarker measurements largely depend, has necessitated revalidation of the assays, remeasurement of samples and adjustment of the decision limits above which an athlete will be assumed to have administered hGH. When a liquid chromatography coupled mass spectrometry (LC-MS) method became a reality for the measurement of IGF-I, more consistency of results was assured. Measurement of P-III-NP is still dependent on immunoassays although work is underway to develop an LC-MS method. The promised long-term detection time for the biomarker assay does not appear to have been realised in practice, and this is perhaps partly the result of decision limits being set too high. Nevertheless, more robust assays are needed before a further adjustment of the decision limit is warranted. In the meantime, WADA is considering using P-III-NP and IGF-I as components of a biomarker passport system recording data from an individual athlete, rather than the population. Using this approach, smaller perturbations in the growth hormone (GH) score would mandate an investigation and possible action for hGH administration.

Determination of ghrelin and desacyl ghrelin in human plasma and urine by means of LC-MS/MS for doping controls

11 Oct 2021

Determination of ghrelin and desacyl ghrelin in human plasma and urine by means of LC-MS/MS for doping controls / Andreas Thomas, Sophia Krombholz, Carina Wolf, Mario Thevis. - (Drug Testing and Analysis (2021) 11 October)

  • PMID: 34633773
  • DOI: 10.1002/dta.3176


Abstract

The hunger hormone ghrelin (G) is classified as prohibited substance in professional sport by the World Anti-Doping Agency (WADA), due to its known growth hormone releasing properties. The endogenous bioactive peptide consists of 28 amino acids with a caprylic acid attached to serine at position 3. Within this study it was aimed to develop methods to determine G and desacyl ghrelin (DAG) in plasma and urine by means of LC-MS/MS. Two strategies were applied with a bottom-up approach for plasma and top-down analyses for urine. Both sample preparation procedures were based on solid-phase extraction for enrichment and sample clean-up. Method validation showed good results for plasma and urine with limits of detection (LODs) for G and DAG between 30 and 50 pg/mL, recoveries between 45-50 %, and imprecisions (intra- and inter-day) between 3 - 24 %. Plasma analysis was also valid for quantification with accuracies determined with ~100 % for G and ~106 % for DAG. The minimum required performance level for doping control laboratories is set to 2 ng/mL in urine, and the herein established method yielded acceptable results even at 5 % of this level. As proof-of-concept, plasma levels (G and DAG) of healthy volunteers were determined and ranged between 30 and 100 pg/mL for G and 100 - 1200 pg/mL for DAG. In contrast to earlier reported studies using ligand binding assays for urinary G and DAG, in this mass spectrometry-based study no endogenous urinary G and DAG were found, although the LODs should enable this.

Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review

19 Jan 2021

Adverse Effects of Anabolic-Androgenic Steroids : A Literature Review / Giuseppe Davide Albano, Francesco Amico, Giuseppe Cocimano, Aldo Liberto, Francesca Maglietta, Massimiliano Esposito, Giuseppe Li Rosi, Nunzio Di Nunno, Monica Salerno, Angelo Montana. - (Healthcare 9 (2021) 1 (January 19) 97; p. 1-19)

  • PMID: 33477800
  • PMCID: PMC7832337
  • DOI: 10.3390/healthcare9010097


Abstract

Anabolic-androgenic steroids (AASs) are a large group of molecules including endogenously produced androgens, such as testosterone, as well as synthetically manufactured derivatives. AAS use is widespread due to their ability to improve muscle growth for aesthetic purposes and athletes' performance, minimizing androgenic effects. AAS use is very popular and 1-3% of US inhabitants have been estimated to be AAS users. However, AASs have side effects, involving all organs, tissues and body functions, especially long-term toxicity involving the cardiovascular system and the reproductive system, thereby, their abuse is considered a public health issue. The aim of the proposed review is to highlight the most recent evidence regarding the mechanisms of action of AASs and their unwanted effects on organs and lifestyle, as well as suggesting that AAS misuse and abuse lead to adverse effects in all body tissues and organs. Oxidative stress, apoptosis, and protein synthesis alteration are common mechanisms involved in AAS-related damage in the whole body. The cardiovascular system and the reproductive system are the most frequently involved apparatuses. Epidemiology as well as the molecular and pathological mechanisms involved in the neuropsychiatric side-effects of AAS abuse are still unclear, further research is needed in this field. In addition, diagnostically reliable tests for AAS abuse should be standardized. In this regard, to prevent the use of AASs, public health measures in all settings are crucial. These measures consist of improved knowledge among healthcare workers, proper doping screening tests, educational interventions, and updated legislation.

Identification of Factors Associated with Potential Doping Behavior in Sports: A Cross-Sectional Analysis in High-Level Competitive Swimmers

10 Aug 2018

Identification of Factors Associated with Potential Doping Behavior in Sports : A Cross-Sectional Analysis in High-Level Competitive Swimmers / Sime Devcic, Jakob Bednarik, Dora Maric, Sime Versic, Damir Sekulic, Zvonimir Kutlesa, Antonino Bianco, Jelena Rodek, Silvester Liposek. - (International Journal of Environmental Research and Public Health 15 (2018) 8 (10 August); 1720)

  • PMID: 30103461
  • PMCID: PMC6121562
  • DOI: 10.3390/ijerph15081720


Abstract

Background: Doping behavior, including the misuse of performance-enhancing drugs, is currently a serious problem in sports, and the efficacy of preventive efforts directly depends on information regarding the associations among different precipitating factors (PF) and doping behavior. This study aimed to establish the PF of potential doping behavior (PDB) in competitive swimmers. Methods: The study included 301 swimmers from Slovenia (153 females, 16.4 ± 2.4 years), tested during the 2017 National Championship. Variables were collected by previously validated questionnaires, which included questions on sociodemographics, sports-related factors, consumption of dietary supplements, knowledge of doping, factors of hesitation, and doping-related factors (i.e., number of doping tests, opinion about the presence of doping in sport). The PDB (positive, neutral, or negative intention toward doping) was observed as a criterion, while other variables were included as predictors in multinomial regression analyses (with "negative" as reference value), which additionally controlled for gender and age category (cadet-, junior-, and senior-level) as confounders. Results: The results confirmed higher susceptibility to doping in males (positive: odds ratio (OR): 2.77, 95% confidence interval (CI): 1.27⁻6.04), those swimmers who reported higher alcohol consumption (neutral: OR: 2.18, 95%CI: 1.06⁻4.16, positive: OR: 2.14, 95%CI: 1.05⁻4.37), and those regularly used dietary supplements (positive: OR: 3.62, 95%CI: 1.25⁻10.52). Competitive achievement in Olympic- (neutral: OR: 0.57, 95%CI: 0.41⁻0.81, positive: OR: 0.59, 95%CI: 0.39⁻0.88), and non-Olympic disciplines (positive: OR: 0.54, 95%CI: 0.35⁻0.83) was protective against PDB. Swimmers who were more concerned about the negative social consequences of doping behavior (i.e., condemnation by family and friends) were less likely to declare a positive intention toward the PDB (family condemnation: OR: 0.69, 95%CI: 0.56⁻0.86, friends' condemnation: OR: 0.65, 95%CI: 0.52⁻0.80). Conclusions: The results of the study provide more precise insight into the specific factors associated with PDB in swimming. The established precipitating factors should be incorporated into targeted anti-doping campaigns in this sport.

Dietary supplementation and doping-related factors in high-level sailing

7 Dec 2012

Dietary supplementation and doping-related factors in high-level sailing / Jelena Rodek, Damir Sekulic, Miran Kondric. - (Journal of the International Society of Sports Nutrition 9 (2012) 1; 51)

  • PMID: 23217197
  • PMCID: PMC3536606
  • DOI: 10.1186/1550-2783-9-51


Abstract

Background: Although dietary supplements (DSs) in sports are considered a natural need resulting from athletes' increased physical demands, and although they are often consumed by athletes, data on DS usage in Olympic sailing are scarce. The aim of this study was to study the use of and attitudes towards DSs and doping problems in high-level competitive sailing.

Methods: The sample consisted of 44 high-level sailing athletes (5 of whom were female; total mean age 24.13 ± 6.67 years) and 34 coaches (1 of whom was female; total mean age 37.01 ± 11.70). An extensive, self-administered questionnaire of substance use was used, and the subjects were asked about sociodemographic data, sport-related factors, DS-related factors (i.e., usage of and knowledge about DSs, sources of information), and doping-related factors. The Kruskal-Wallis ANOVA was used to determine the differences in group characteristics, and Spearman's rank order correlation and a logistic regression analysis were used to define the relationships between the studied variables.

Results: DS usage is relatively high. More than 77% of athletes consume DSs, and 38% do so on a regular basis (daily). The athletes place a high degree of trust in their coaches and/or physicians regarding DSs and doping. The most important reason for not consuming DSs is the opinion that DSs are useless and a lack of knowledge about DSs. The likelihood of doping is low, and one-third of the subjects believe that doping occurs in sailing (no significant differences between athletes and coaches). The logistic regression found crew number (i.e., single vs. double crew) to be the single significant predictor of DS usage, with a higher probability of DS consumption among single crews.

Conclusion: Because of the high consumption of DSs future investigations should focus on real nutritional needs in sailing sport. Also, since athletes reported that their coaches are the primary source of information about nutrition and DSs, further studies are necessary to determine the knowledge about nutrition, DSs and doping problems among athletes and their support teams (i.e., coaches, physicians, and strength and conditioning specialists).

Sport nutrition and doping in tennis: an analysis of athletes' attitudes and knowledge

1 Jun 2013

Sport nutrition and doping in tennis: an analysis of athletes' attitudes and knowledge / Miran Kondric, Damir Sekulic, Ognjen Uljevic, Goran Gabrilo, Milan Zvan. - (Journal of Sports Science and Medicine 12 (2013) 2 (1 June); p. 290-297)

  • PMID: 24149808
  • PMCID: PMC3761838

 

Abstract

Nutrition and doping issues are rarely studied in the sport of tennis. The aims of this investigation were to determine knowledge on doping (KD) and knowledge on sport nutrition (KSN), and corresponding socio-demographic-, sport-, and sport-nutrition- and doping-factors among an international sample of high-level tennis players of both sexes (43 females; 22 years old on average). In the first phase of the investigation, the KSN and KD questionnaires were studied for their reliability and validity. The consumption of NS is found to be very high, with almost of all the females and 80% of the males using NS at least occasionally. The athletes showed a low tendency regarding future doping usage, although most of them are convinced that doping does exist in tennis. Since athletes declared that their coaches are their main source of information about NS and doping, future studies should investigate what coaches actually know about such problems. KSN has been found to be protective against potential doping behavior in the future. Males are found to be more prone to doping than females. Therefore, in order to prevent doping behavior in tennis we strongly suggest intensive educational programs on sports nutrition and doping-related problems. Key PointsThe incidence of nutritional supplementation use among the tennis players is found to be very high, especially among the females.Although most of the subjects are of the opinion that the doping behavior is present in tennis circuit, we have found a low tendency regarding future doping usage, and high levels of athletes' trust in their coaches with regard to nutritional supplementation and doping.There are indices that the knowledge about nutrition is protective factor against potential doping behavior. It clearly reinforces the need to include a wide educational program on sports nutrition in tennis, but also in other sports.

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