Experimental evaluation of rigor mortis IX. The influence of the breaking (mechanical solution) on the development of rigor mortis.

Objective measurements were carried out to study the possible re-establishment of rigor mortis on rats after "breaking" (mechanical solution). Our experiments showed that: *Cadaveric rigidity can re-establish after breaking. *A significant rigidity can reappear if the breaking occurs before the process is complete.

Combination of polymorphisms from genes related to estrogen metabolism and risk of prostate cancers: the hidden face of estrogens.

Purpose: The association between common functional polymorphisms from the CYP17, CYP19, CYP1B1, and COMT genes involved in the estrogen metabolism and the risk of prostate carcinoma was evaluated.

Patients And Methods: The study investigated 1,983 white French men (1,101 patients with prostate cancer and 882 healthy controls) aged between 40 and 98 years. The different alleles and genotypes were analyzed according to case-control status, aggressiveness pattern of the tumors, age at onset, and family history of cancers.

Possible origins of undetectable EPO in urine samples.

Background: In order to determine the possible origins of undetectable EPO profiles in athletes' urine, we analyzed the data obtained from a large number of official anti-doping urine tests aimed at detecting recombinant erythropoietin. The following variables were considered as potential causes for lack of EPO detection: athlete's gender, competition effect, urine specific gravity as well as possible usage of proteasic adulterants to evade doping detection.

Results: Statistical analyses indicated that undetectable EPO profiles were clearly related to urine properties such as low EPO concentrations or extreme specific gravities.

Identification of a unique co-operative phosphoinositide 3-kinase signaling mechanism regulating integrin alpha IIb beta 3 adhesive function in platelets.

Phosphoinositide (PI) 3-kinases play an important role in regulating the adhesive function of a variety of cell types through affinity modulation of integrins. Two type I PI 3-kinase isoforms (p110 beta and p110 gamma) have been implicated in G(i)-dependent integrin alpha(IIb)beta(3) regulation in platelets, however, the mechanisms by which they coordinate their signaling function remains unknown. By employing isoform-selective PI 3-kinase inhibitors and knock-out mouse models we have identified a unique mechanism of PI 3-kinase signaling co-operativity in platelets.

Bayesian detection of abnormal hematological values to introduce a no-start rule for heterogeneous populations of athletes.

Sports authorities exclude athletes with abnormal levels of blood parameters. Here, the consideration of longitudinal blood profiles together with heterogeneous factors such as ethnicity and age produces a model with enhanced sensitivity to detect blood doping. Sports disciplines with heterogeneous populations now have a general method to introduce the no-start rule.

[Impact of obesity on PSA in prostate cancer screening].

Objective: Obesity is associated with changes of serum levels of androgens and oestrogens which could modulate prostate metabolism. The objective of this study was to investigate a possible correlation between the PSA level and the degree of obesity in a candidate population for prostate cancer screening in order to determine whether the PSA level needs to be adapted before performing biopsy.

Material: During a screening campaign in a French district, serum PSA results and body mass index (BMI) were available for 541 men.

Determination and distribution of clotiapine (Entumine) in human plasma, post-mortem blood and tissue samples from clotiapine-treated patients and from autopsy cases.

The antipsychotic drug clotiapine (Entumine) has been marketed for more than 35 years, however there is little published data on the therapeutic and toxic concentrations of this drug. To fill this gap, two rapid and sensitive methods were developed for the determination of clotiapine (2-chloro-11-(4-methyl-1-piperazinyl)dibenzo-[b,f][1,4]-thiazepine), in human plasma and post-mortem blood and tissue samples. After simple liquid-liquid extraction at pH 9.

BRCA2 mutation screening is clinically relevant in breast and early prostate cancer families.

It is known that in some families an association exists between breast and prostate cancer. Several reports have suggested that BRCA2 mutations may be associated with an increased risk of these cancers. Herein, we report three cases of early onset of prostate cancer in families with female and male breast cancers.

From population- to subject-based limits of T/E ratio to detect testosterone abuse in elite sports.

In elite sports, indirect testing of testosterone abuse is mainly based on the testosterone over epitestosterone (T/E) ratio. Since this marker is characterized by a small ratio of intra- to inter-individual variation, it is surprising that current anti-doping strategy uses a screening test based on a population-based limit. From a database of more than 15,000 steroid profiles obtained from routine controls, the collection of steroids profiles of 11 elite athletes followed during 2 years, and a longitudinal study involving 17 amateur athletes, 8 of which were orally administrated testosterone undecanoate pills, we selected 12 case studies to represent the possible scenarios to which the anti-doping laboratories are confronted.

Low-activity V89L variant in SRD5A2 is associated with aggressive prostate cancer risk: an explanation for the adverse effects observed in chemoprevention trials using 5-alpha-reductase inhibitors.

Objective: The 5-alpha-reductase type 2 (5A2) enzyme catalyses the irreversible conversion of testosterone to dihydrotestosterone, the most active androgen in the prostate. This key enzyme in prostate gland physiopathology has recently been targeted by using inhibitors for chemoprevention of prostate cancer. However, some controversies have arisen by the observation of greater than expected high-grade tumours in men diagnosed with prostate cancer in the finasteride chemoprevention trial.

Concentrations of nandrolone metabolites in urine after the therapeutic administration of an ophthalmic solution.

Nandrolone, an anabolic steroid, is used for the treatment of several diseases and is available in various pharmaceutical formulations. The most widely used pharmaceutical formulation is Deca-Durabolin, but other products, such as Keratyl eye drops solution, are also currently administered. Nandrolone is one of the most abused anabolic steroid in sports.

Direct detection and quantification of 19-norandrosterone sulfate in human urine by liquid chromatography-linear ion trap mass spectrometry.

19-Norandrosterone sulfate (19-NAS) is the sulfoconjugated form of 19-norandrosterone (19-NA), the major metabolite of the steroid nandrolone. A sensitive and accurate liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay was developed for the direct measurement of 19-NAS in human urine samples. The method involved a quaternary amine SPE protocol and subsequently injection of the extract onto an analytical column (Uptisphere ODB, 150 mm x 3.

Detection window of Darbepoetin-alpha following one single subcutaneous injection.

Background: The current official direct recombinant erythropoietin (rHuEPO) detection anti-doping test based on 1D isoelectric focusing (IEF) of urinary proteins was performed to determine the detection window of Darbepoietin-alpha when applying the positivity criteria established by the World Anti-Doping Agency (WADA).

Results: Following WADA's positivity criteria, the IEF based urinary EPO test enabled to determine that the detection window after a single subcutaneous injection of Darbepoietin-alpha (40 microg of ARANESP injected) is close to 7 days, that is to say approximately two times more than for rHuEPO-beta (4000 IU of Recormon injected). The detection window can be different from one subject to another, because the actual positivity criteria take into consideration in someway the endogenous EPO production rate which differs enormously from one subject to another.

Relevance of the prostate-specific antigen (PSA) nanotest compared to the classical PSA test in the organized mass screening of prostate cancer.

Objective: To assess the reliability of a new measurement of prostate-specific antigen (PSA) using a blotting-paper assay (nanotest) compared to the standard PSA immunoassay.

Subjects And Methods: The PSA level was measured in 205 men volunteers (median age 70 years, range 41-75) using a nanotest and a standard PSA immunoassay, collected at the same time; 30 microL of capillary blood placed on to a blotting paper were collected for the nanotest and sent by mail to the same laboratory for the two assays. The results were compared statistically using the Spearman test, the intraclass correlation coefficient and the Bland-Altman test.

A mechanistic model for paradoxical platelet activation by ligand-mimetic alphaIIb beta3 (GPIIb/IIIa) antagonists.

Objective: Integrins are attractive therapeutic targets. Inhibition of integrin alphaIIb beta3 effectively blocks platelet aggregation. However, limitations with intravenous alphaIIb beta3 antagonists and failure of oral alphaIIb beta3 antagonists prompted doubts on the current concept of ligand-mimetic integrin blockade.

The impact of blood rheology on the molecular and cellular events underlying arterial thrombosis.

There is an increasing appreciation of the importance of disturbed blood flow, especially turbulent flow, in the pathogenesis of vascular disease. However, the precise mechanism(s) by which rheological changes accelerate the atherothrombotic process remains incompletely understood. Atherosclerotic lesions typically develop in vascular regions exhibiting bifurcated or curved architectures.

Effect of multiple oral doses of androgenic anabolic steroids on endurance performance and serum indices of physical stress in healthy male subjects.

Anabolic androgenic steroids (AAS) are doping agents that are mostly used for improvement of strength and muscle hypertrophy. In some sports, athletes reported that the intake of AAS is associated with a better recovery, a higher training load capacity and therefore an increase in physical and mental performances. The purpose of this study was to evaluate, the effect of multiple doses of AAS on different physiological parameters that could indirectly relate the physical state of athletes during a hard endurance training program.

Short-term stability of testosterone and epitestosterone conjugates in urine samples: quantification by liquid chromatography-linear ion trap mass spectrometry.

A simple method using liquid chromatography-linear ion trap mass spectrometry for simultaneous determination of testosterone glucuronide (TG), testosterone sulfate (TS), epitestosterone glucuronide (EG) and epitestosterone sulfate (ES) in urine samples was developed. For validation purposes, a urine containing no detectable amount of TG, TS and EG was selected and fortified with steroid conjugate standards. Quantification was performed using deuterated testosterone conjugates to correct for ion suppression/enhancement during ESI.

Performance characteristics of two immunoassays for the measurement of urinary luteinizing hormone.

Urine luteinizing hormone (LH) concentration is routinely measured in all anti-doping laboratories to exclude recombinant LH abuse and to test any potential alteration of the hypophyseal-gonadal axis. Before establishing proper reference values among professional top level athletes, an extended validation of two commercial immunoassays for LH measurements was performed. Elecsys 1010 and Access are two automated immunoanalyzers for central laboratories.

Human growth hormone doping in sport.

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.).

Erythropoietin and blood doping.

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).

Testosterone and doping control.

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.