Biomedical subjects
Publications and source records attributed to P Mangin.
The conclusions reached while considering various aspects of the implemented strategy in the identification procedures in the wake of the tsunami disaster of December 26, 2004 are outlined. The lessons to be learned are discussed.
Two retrospective epidemiologic studies have shown that cannabis is the main psychoactive substance detected in the blood of drivers suspected of driving under the influence of psychotropic drugs. An oral administration double-blind crossover study was carried out with eight healthy male subjects, aged 22 to 30 years, all occasional cannabis smokers. Three treatments and one placebo were administered to all participants at a two week interval: 20 mg dronabinol, 16.5 mg D9-tétrahydrocannabinol (THC) and 45.7 mg THC as a cannabis milk decoction. Participants were asked to report the subjective drug effects and their willingness to drive under various circumstances on a visual analog scale. Clinical observations, a psychomotor test and a tracking test on a driving simulator were also carried out. Compared to cannabis smoking, THC, 11-OH-THC and THC-COOH blood concentrations remained low through the whole study (<13.1 ng THC/mL,<24.7 ng 11-OH-THC/mL and<99.9 ng THC-COOH/mL). Two subjects experienced deep anxiety symptoms suggesting that this unwanted side-effect may occur when driving under the influence of cannabis or when driving and smoking a joint. No clear association could be found between these adverse reactions and a susceptibility gene to propensity to anxiety and psychotic symptoms (genetic polymorphism of the catechol-O-methyltransferase). The questionnaires have shown that the willingness to drive was lower when the drivers were assigned an insignificant task and was higher when the mission was of crucial importance. The subjects were aware of the effects of cannabis and their performances on the road sign and tracking test were greatly impaired, especially after ingestion of the strongest dose. The Cannabis Influence Factor (CIF) which relies on the molar ratio of active and inactive cannabinoids in blood provided a good estimate of the fitness to drive.
The purpose of this study was to analyze the composition of 103 dietary supplements bought on the internet. The supplements were dispatched in four different categories according to their announced contents [creatine, prohormones, "mental enhancers" and branched chain amino acids (BCAA)]. All the supplements were screened for the presence of stimulants and main anabolic steroids parent compounds. At the same time, the research was focused on the precursors and metabolites of testosterone and nandrolone. The study pointed out three products containing an anabolic steroid, metandienone, in a very high amount. The ingestion of such products induced a high quantity of metandienone metabolites in urines that would be considered as a positive antidoping test. The results have also shown that one creatine product and three "mental enhancers" contained traces of hormones or prohormones not claimed on the labels and 14 prohormone products contained substances other than those indicated by the manufacturer. The oral intake of the creatine product revealed the presence of the two main nandrolone metabolites (19-norandrosterone and 19-noretiocholanolone) in urine.
BACKGROUND AND OBJECTIVES: Anabolic steroids are synthetic derivatives of testosterone, modified to enhance its anabolic actions (promotion of protein synthesis and muscle growth). They have numerous side effects, and are on the International Olympic Committee's list of banned substances. Gas chromatography-mass spectrometry allows identification and characterisation of steroids and their metabolites in the urine but may not distinguish between pharmaceutical and natural testosterone. Indirect methods to detect doping include determination of the testosterone/epitestosterone glucuronide ratio with suitable cut-off values. Direct evidence may be obtained with a method based on the determination of the carbon isotope ratio of the urinary steroids. This paper aims to give an overview of the use of anabolic-androgenic steroids in sport and methods used in anti-doping laboratories for their detection in urine, with special emphasis on doping with testosterone. METHODS: Review of the recent literature of anabolic steroid testing, athletic use, and adverse effects of anabolic-androgenic steroids. RESULTS: Procedures used for detection of doping with endogenous steroids are outlined. The World Anti-Doping Agency provided a guide in August 2004 to ensure that laboratories can report, in a uniform way, the presence of abnormal profiles of urinary steroids resulting from the administration of testosterone or its precursors, androstenediol, androstenedione, dehydroepiandrosterone or a testosterone metabolite, dihydrotestosterone, or a masking agent, epitestosterone. CONCLUSIONS: Technology developed for detection of testosterone in urine samples appears suitable when the substance has been administered intramuscularly. Oral administration leads to rapid pharmacokinetics, so urine samples need to be collected in the initial hours after intake. Thus there is a need to find specific biomarkers in urine or plasma to enable detection of long term oral administration of testosterone.
OBJECTIVE AND METHOD: To outline the direct and indirect approaches in the fight against blood doping in sports, the different strategies that have been used and are currently being used to fight efficiently against blood doping are presented and discussed. RESULTS AND CONCLUSIONS: The paper outlines the different approaches and diagnostic tools that some federations have to identify and target sports people demonstrating abnormal blood profiles. Originally blood tests were introduced for medical reasons and for limiting misuse of recombinant human erythropoietin (rHuEPO). In this way it became possible to prevent athletes with haematocrit levels well above normal, and potentially dangerous for their health, competing in sport. Today, with nearly a decade of blood testing experience, sports authorities should be familiar with some of the limitations and specially the ability of blood tests performed prior to competitions to fight efficiently against the misuse of rHuEPO, blood transfusion, and artificial haemoglobin.
BACKGROUND AND OBJECTIVES: Central nervous system (CNS) stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport. METHODS: Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine. RESULTS: CNS stimulants have psychotropic effects that may be perceived to be ergogenic. Some are prescription drugs, such as Ephedra alkaloids, and there are issues regarding their appropriate therapeutic use. Recently attention has been given to their widespread use by athletes, despite the lack of evidence regarding any ergogenic or real performance benefit, and their potentially serious side effects. Recreational drugs, some of which are illegal (cocaine, amfetamines), are commonly used by athletes and cause potential ergolytic effects. Overall, these drugs are important for their frequent use and mention in anti-doping laboratories statistics and the media, and their potentially serious adverse effects. CONCLUSIONS: Doping with CNS stimulants is a real public health problem and all sports authorities should participate in its prevention. Dissemination of information is essential to prevent doping in sport and to provide alternatives. Adequate training and education in this domain should be introduced.
BACKGROUND AND OBJECTIVES: Recombinant human growth hormone (rhGH) has been on the list of forbidden substances since availability of its recombinant form improved in the early 1990s. Although its effectiveness in enhancing physical performance is still unproved, the compound is likely used for its potential anabolic effect on the muscle growth, and also in combination with other products (androgens, erythropoietin, etc.). The degree of similarity between the endogenous and the recombinant forms, the pulsatile secretion and marked interindividual variability makes detection of doping difficult. Two approaches proposed to overcome this problem are: the indirect method, which measures a combination of several factors in the biological cascade affected by administration of GH; and the direct method, which measures the difference between the circulating and the recombinant (represented by the unique 22 kD molecule) forms of GH. This article gives an overview of what is presently known about hGH in relation to sport. The available methods of detection are also evaluated. METHODS: Review of the literature on GH in relation to exercise, and its adverse effects and methods of detection when used for doping. RESULTS AND CONCLUSION: The main effects of exercise on hGH production and the use and effects of rhGH in athletes are discussed. Difficulties encountered by laboratories to prove misuse of this substance by both indirect and direct analyses are emphasised. The direct method currently seems to have the best reliability, even though the time window of detection is too short. hGH doping is a major challenge in the fight against doping. The effect of exercise on hGH and its short half-life are still presenting difficulties during doping analysis. To date the most promising method appears to be the direct approach utilising immunoassays.
BACKGROUND AND OBJECTIVES: Cannabis is on the list of prohibited substances in the practice of sport, although its performance enhancing effect has not yet been proved. Its popularity among the younger generations as a social drug puts cannabis at the top of the list of compounds detected by the anti-doping laboratories accredited by the World Anti-Doping Agency worldwide. The management of the results of urine analysis is quite difficult for the medical and disciplinary committees not only because of the social use of the substance, but also because of the interpretation of the analytical data from urine samples. This paper gives an overview of what is presently known about cannabis in relation with the practice of sport. METHODS: Review of literature on the cannabis and exercise, its effect in the body, and the problems with interpretation of results when it is detected in urine. RESULTS: The paper outlines the major effects of cannabis in the context of its social use and its use for sport activities. The difficulties in the interpretation of urine sample analysis results because of the protracted excretion time of the main metabolite, long after the intake, are described. CONCLUSIONS: There is an urgent need for sport authorities to take measures necessary to avoid players misusing cannabis.
The potential to recover genetic profiles from evidence samples has substantially increased since robust and sensitive amplification kits are commercially available. Nevertheless, even the best amplification kits cannot succeed when the extracted DNA is of poor quality. In this study we compared the efficiency of silica (QIAamp DNA Mini Kit), Chelex and Phenol-Chloroform (PC) based protocols to recover DNA from different categories of samples (blood and saliva on cotton swabs, muscles, cigarette butts, saliva on foods and epidermal cells on clothes). The efficiency of the QIAamp system was improved when samples were treated with QIAshredder homogenizing columns. Overall, conventional Chelex or PC protocols allowed to recover conclusive SGM Plus profiles for 61% of the samples considered in this study. Contrastingly, 82% of them were successfully genotyped after being treated with a combination of QIAshredder and QIAamp systems. Our results further suggested that the QIAshredder/QIAamp protocol was particularly helpful to analyze evidence samples with few DNA and/or that were collected on substrates containing PCR inhibitors.
Urine samples from 20 male volunteers of European Caucasian origin were stored at 4 degrees C over a 4-month period in order to compare the identification potential of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) markers. The amount of nDNA recovered from urines dramatically declined over time. Consequently, nDNA likelihood ratios (LRs) greater than 1,000 were obtained for 100, 70 and 55% of the urines analysed after 6, 60 and 120 days, respectively. For the mtDNA, HVI and HVII sequences were obtained for all samples tested, whatever the period considered. Nevertheless, the highest mtDNA LR of 435 was relatively low compared to its nDNA equivalent. Indeed, LRs obtained with only three nDNA loci could easily exceed this value and are quite easier to obtain. Overall, the joint use of nDNA and mtDNA markers enabled the 20 urine samples to be identified, even after the 4-month period.
Since the introduction of blood analysis performed before major cycling events in 1997, there have been discussions concerning the quality of the results. The aim of our study therefore was to measure blood samples and compare the results obtained on the field with those obtained in the laboratory. For this it was necessary to have blood samples analysed with different instruments to determine the exactness of the results and evaluate the performances of these instruments in order to validate the haematological testing used to reveal athletes abusing recombinant erythropoietin. We report on the haematological analysis of 177 professional cyclists who took part in the Tour de France 2001. All the blood samples were withdrawn in the morning between 7 and 9 am in Dunkerque (France) and were analysed immediately with a transportable analyser. Then the samples were flown to Lausanne (Switzerland) and were reanalysed in two independent ISO 17 025 accredited laboratories with three different analysers. The results confirmed that the most effective haematological follow-up should be performed under standardized pre-analytical conditions and with identical analysers of the same manufacturer to avoid too many variations notably on the haematocrit level and the reticulocyte count. Furthermore, this study suggests that analyses performed on the site are good and could enable the federations to perform a urinary test to detect rhEPO abuse right after the blood analysis. This time saving is essential to fight efficiently recombinant erythropoietin doping, because the half life of the hormone is very short.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The discovery and the use of serum prostate specific antigen (PSA) has considerably improved the diagnosis of prostate cancer during the past 20 years. Before PSA era, early diagnosis was only based on the digital rectal examination (DRE) of which the Limitations have been evidenced; over half of the tumours diagnosed by such means had already spread out of the prostate and were incurable. Assessment of serum PSA has allowed the diagnosis to be made at an earlier stage of the disease, curable by current treatments. Whichever the diagnostic tools, transrectal ultrasound (TRUS) prostatic biopsies remain necessary for diagnosis ascertainment, taking into account the low specificity of PSA assessment. The feasibility of a diagnosis at an early and curable stage of the disease has logically resulted in screening procedures aimed at reducing the high mortality related to prostate cancer. The numerous publications on prostate cancer screening provide precise information on the accuracy of available diagnostic means (PSA, DRE, TRUS, combined PSA and DRE), on the characteristics of screened tumours (stage and differentiation), and also on the population of men likely to benefit from the screening (age at beginning and end of the screening, frequency of PSA testing, identification of the men with ethnic and/or genetic predisposition). In those early diagnosed prostate cancers, the assessment of loco-regional cancer extension (extracapsular and/or, microscopic nodal involvement), remains unsatisfactory because no imaging technique (ultrasonography, CT scan, MRI,...) allows visualising the tumour itself or microscopic metastases. Nevertheless, the combination of multiple parameters such as DRE data, PSA level, biopsy data and tumour differentiation helps approaching with an increasing precision (nomograms) the true pathologic stage of the disease. Such advances allow distinguishing, among the very heterogeneous group of prostate cancers, tumours that differ from one to another in terms of disease stage, progression and prognosis, which is helpful for the determination of an adapted therapeutic strategy.
The discovery and the utilisation of the prostate specific antigen (PSA) that allows early diagnosis of prostate cancer, have considerably improved the management of this disease. Before the PSA era, prostate cancer was just a disease of the old man, generally detected at an advanced stage and incurable, with a fatal outcome delayed by the androgenic deprivation. Since early 1990's, prostate cancer has become primarily a disease of the man of 60 years, detectable earlier, and curable provided no extraprostatic dissemination has occurred. Early treatment of prostate cancer has benefited from important advances in surgical and radio-therapeutic techniques (conformational irradiation, brachytherapy), with, as principal goal, the combination of a better survival and the reduction of the potential adverse effects that alter quality of life. A better definition of the characteristics of the tumours in terms of progression regarding various parameters (clinical stage, PSA, tumoral differentiation) have resulted, despite the heterogeneity of the disease, in the determination of subgroups of tumours with different prognosis, which leads to an improved therapeutic strategy. The assessment of men's life expectancy (< or > 10 years) is the second primary parameter on which is based the indication for curative or non curative therapy in case of localized tumour. Roughly, before the age of 75, a curative therapy is indicated whereas after this age a surveillance is reasonable as first-line treatment, followed by hormone therapy in case of onset of symptoms indicating some progression of the disease (urinary symptoms, bone lesion). At a Later stage, in case of a metastatic or locally advanced cancer, hormone therapy by androgenic deprivation is highly indicated. The hormone sensitivity characterizes prostate cancer; it has been discovered more than 50 years ago by Charles Huggins (Nobel prize-winner). This hormone therapy is a palliative treatment since its efficacy is transient (ineluctable occurrence of hormone resistance in a variable time delay), but it constitutes an essential therapeutic means with a well-established efficacy. Hormone therapy has progressively improved, with the renunciation of oestrogen therapy and surgical castration which has been replaced by luteinizing hormone-releasing hormone (LH-RH) analogues, and/ or anti-androgens. Numerous works have resulted in a better rationalization of the prescription (date of treatment initiation, interest of combined androgenic deprivation, ...) but uncertainties remain, such as the therapeutic interest of intermittent treatment, or of earlier hormone therapy combined with the treatment of the primitive tumour (adjuvant hormone therapy). Finally, at the time of the hormonal escape of which the molecular mechanisms remain unclear, no therapy has proven any efficacy in survival lengthening, and the treatment remains palliative and symptomatic. Although improved knowledge of prostate cancer aetiology is expected for a real disease prevention, early diagnosis at a curable stage of the disease (by PSA assessment) remains the only means for mortality reduction.
Prostate cancer (prostate adenocarcinoma) has become an important concern in terms of public health these past fifteen years; recent French epidemiological data revealed 10,104 deaths due to this disease in 2000. The two main factors involved are the serum prostatic specific antigen (PSA), routinely used since late 1980's and which allows early diagnosis (before symptom onset), and the lengthened duration of life. Such cancer is rare before the age of 50, but its frequency increases with age, making it the most frequent type of cancer in French men. Although the aetiology of this disease is unknown, the ethnic origin, and a familial history of prostate or breast cancer are known risk factors. Predisposing genes to such hereditary types remain to be identified. Other genetic factors (polymorphisms), combined with environmental factors such as nutrition, have been incriminated, which is likely to explain the geographical variations of this affection. At the molecular level, the mechanisms involved in the tumoral initiation and progression remain unclear. Various genetic alterations have been identified among the genome of cancerous cells, at various stages of the affection: intraepithelial neoplasia, localized, locally advanced, metastatic or hormone refractory stage -, hormonal escape). However, the precise sequence and nature of the complex molecular events remain to be determined prior to their routine utilisation in the determination of subjects at risk, or as prognostic factors, and even as therapeutic targets. The anatomopathology is a key for the diagnosis. Intraepithelial neoplasia is the pre-cancerous lesion observed in most adenocarcinomas; these are localized in the peripheral part of the prostate gland in 70% of the cases. Gleason's classification is the current gold standard for the determination of tumoral aggressiveness and categorisation of the adenocarcinomas which are basically heterogeneous (coexistence of tumors cells with different degrees of differenciation in the same tumor). This anatomopathological classification allows distinguishing the tumours in terms of potential progressiveness and prognosis, and hence, to orientate the therapeutic strategy in case of localised or locally advanced prostate cancer.
ADP and TxA2 are secondary agonists which play an important role as cofactors when platelets are activated by agonists such as collagen or thrombin. The aim of the present study was to characterize the role of the ADP receptor P2Y(1) in collagen-induced activation of washed platelets. Inhibition of P2Y(1) alone with the selective antagonist MRS2179 prolonged the lag phase preceding aggregation in response to low or high concentrations of fibrillar collagen, without affecting the maximum amplitude of aggregation or secretion. A combination of MRS2179 and aspirin resulted in complete inhibition of platelet shape change at low and high collagen concentrations, together with a profound decrease in aggregation and secretion. Scanning electron microscopy showed that these platelets had conserved the discoid morphology typical of the resting state. A lack of shape change was also observed in aspirin-treated P2Y(1)- and G(alphaq)-deficient mouse platelets and in delta-storage pool-deficient platelets from Fawn Hooded rats. In contrast, when the second ADP receptor P2Y(12) was inhibited with AR-C69931MX, aspirin-treated platelets were still able to change shape and displayed only a moderate decrease in aggregation and secretion. In conclusion, this study provides evidence that collagen requires not only the TxA2 receptor Tpalpha, but also P2Y(1), to induce platelet shape change.
BACKGROUND: An international, longitudinal medical follow up examination of male professional road cyclists revealed excessively elevated serum ferritin levels. OBJECTIVE: To evaluate the importance of elevated ferritin values among professional cyclists, their relationship with age and nationality, and their evolution over 3 years. METHODS: Over 1000 serum ferritin values were collected. Other parameters were included in order to exclude conditions which might have increased ferritin levels without changing body iron stores. RESULTS: In 1999, over 45% of riders displayed ferritin values above 300 ng/ml and one fourth levels over 500 ng/ml. These percentages had decreased to 27% and 9%, respectively, 3 years later, while the overall average, which was above the normal limits in 1999, had decreased by 33% in 3 years. Older cyclists had higher ferritin values than younger cyclists. There was also a relationship between ferritin levels and the nationality of the cyclists. Analysis of 714 riders in 2000 and 2002 showed only a slight and insignificant decrease in the mean ferritin value although those with initially elevated iron stores had a much greater decrease. CONCLUSION: Professional road cyclists used excessive iron supplementation leading to high serum ferritin levels correlating with increased body iron stores. Although the situation progressively improved over 3 years, it remains worrying as increased body iron stores are related to health complications. Therefore, prevention in addition to the fight against doping should be a main goal of the UCI. Aggressive therapy for athletes with excessive ferritin values should be carried out at or before the end of their careers.