Metabolites of ephedrines in human urine after administration of a single therapeutic dose / Ying Lung Tseng, Min-Hua Shieh, Fan-Hsin Kuo. - (Forensic Science International 157 (2006) 2-3 (10 March); p. 149-155)

• PMID: 15885945
• DOI: 10.1016/j.forsciint.2005.04.008

Abstract

Ephedrine (EPH), pseudoephedrine (PEPH), phenylpropanolamine (PPA), methylephedrine (MEPH) and cathine are sympathomimetic amines. These drugs are commonly found in over-the-counter (OTC) cold medicines and some dietary supplements. In Taiwan, the misuse of these drugs has resulted in an increase in athletic violations. Excretion studies of the ephedrine-related drugs have been performed to better understand the metabolic yields of ephedrines in urine. After consuming a single clinical dose of each of these drugs, urine samples from volunteers (n=3 for each drug) were subjected to tert-butyl-methyl-ether (TBME) extraction and trifluoroacetic acid (TFAA) derivatization before gas chromatography-mass spectrometry (GC-MS) analysis. Most ephedrines were excreted unchanged in urine, including EPH (40.9%), PEPH (72.2%), and PPA (59.3%). However, only a relatively small amount of MEPH (15.5%) was excreted unchanged in urine. In addition, a trace amount of PPA (1.6%) and cathine (0.7%) was found to be the metabolites of EPH and PEPH, respectively. Urinary EPH, PEPH, and PPA reached peaks at 2-6h and disappeared in urine at approximately 24-48 h post-administration. For MEPH, the peaks of excretion extended from 4 to 12h post-administration and were undetectable at approximately 48 h. A single clinical dose of EPH (25 mg) may exceed threshold level (10 microg/mL) in sport drug testing if the urine samples are tested within approximately 8h post-administration. However, a single dose of MEPH (20 mg) never reached the threshold value (10 microg/mL).

Facts
The French Basketball Federation (Fédération Française de Basket-Ball, FFBB) charges respondent M22 for a violation of the Anti-Doping Rules. During a match on September 18, 2004, a sample was taken for doping tests purposes. The analysis of the sample showed the presence of a metabolite of cannabis. Cannabis is a prohibited substance according the World Anti-Doping Agency (WADA) prohibited list.

History
The respondent admits the use of cannabis.

Decision
1. The sanction is a period of ineligibility of 2 months, for which one month conditionally, in which respondent can't take part in competition or manifestations organized or authorized by the FFBB.
2. The decision starts after October 1, 2005.
5. The decision will be published and sent to the parties involved.

In November 2004 the Canadian Centre for Ethics in Sport (CCES) has reported an anti-doping rule violation against the Athlete after his sample tested positive for the prohibited substance cannabis at a concentration of 130 ng/mL. The Athlete had used cannabis after the competition and before he provided a sample for drug testing, which explains the reason why his results were so high. Also the Athlete walked away to smoke cannabis with some fans after he was notified by the DCO and Chaperone and finally showed up within the allotted time to provide a sample.

The Athlete filed a statement in his defence and was heard for the SDRCC Doping Tribunal. The Athlete admitted that he had used cannabis and stated that he already had expressed his apologies to the DCO and Chaperone for his behavior after he had returned to provide a sample.
The arbitrator finds that the Athlete had no intention to enhance sport performance and normally only a warning and reprimand would be imposed as first anti-doping violation. However the arbitrator considers the Athlete’s disappearance after notification by the DCO an aggravating factor.

Therefore on 6 May 2005 the SDRCC Doping Tribunal decides to impose a 1 year period of ineligibility on the Athlete, starting on the date of the decision. Any period of provisional suspenstion shall be credited against the total period of ineligibility to be served.

The New Zealand Sports Drug Agency (NZSD) and the New Zealand Rugby League (NZRL) have reported an anti-doping rule violation against the Athlete after he failed to provide a sample for testing by NZSD. After notification by the NZRL a provisional suspension was ordered and the Athlete was heard for the Tribunal.

After initially failing to provide a sample (by discarding a sample down a toilet during the sampling process), the Athlete left the drug control room but returned a few minutes later. He provided a second sample which proved negative on analysis.

The Tribunal holds that a failure to provide a sample would be sanctioned severely when this sample returned with a positive result. The Tribunal finds that, although the initial refusal to provide a sample was a clear breach of the anti-doping code, there were truly exceptional circumstances which justifies the imposition of reduced sanction.

The Sports Disputes Tribunal of New Zealand decides on 6 May 2005 to impose a 1 year period of ineligibility on the Athlete starting on 18 November 2004.

Facts
The Canadian Center for Ethics in Sport (CCES) charges Yvan Darsigny (the athlete) for a violation of the Anti-Doping Rules. The athlete Yvan Darsigny committed a violation by refusing or avoiding the sample collection on January 23, 2005.

History
Due to family matters the applicant didn't treat the Doping Control Officer in a kind way and refused to comply when they came for an unannounced doping test. According to his testimony, the technique of no advance notice testing was unknown to the athlete. The DCO indentified herself correctly and the athlete understood the reason for her visit.

Decision
The period of Ineligibility imposed for this anti-doping rule violation shall be: Two (2) years Ineligibility

Androgen regulation of satellite cell function / Yue Chen, Jeffrey D. Zajac, Helen E. MacLean. - (Journal of Endocrinology 186 (2005) 1 (July); p. 21–31)

• PMID: 16002532
• DOI: 10.1677/joe.1.05976

Abstract

Androgen treatment can enhance the size and strength of muscle. However, the mechanisms of androgen action in skeletal muscle are poorly understood. This review discusses potential mechanisms by which androgens regulate satellite cell activation and function. Studies have demonstrated that androgen administration increases satellite cell numbers in animals and humans in a dose-dependent manner. Moreover, androgens increase androgen receptor levels in satellite cells. In vitro, the results are contradictory as to whether androgens regulate satellite cell proliferation or differentiation. IGF-I is one major target of androgen action in satellite cells. In addition, the possibility of non-genomic actions of androgens on satellite cells is discussed. In summary, this review focuses on exploring potential mechanisms through which androgens regulate satellite cells, by analyzing developments from research in this area.

2004 Adverse Analytical Findings Reported by Accredited Laboratories / WADA (World Anti-Doping Agency). - Montreal : WADA, 2005

Jamie Burdekin (player) was reported for an Anti-Doping Rules violation. On 20 July 2004 at the wheelchair British Open in Nottingham he provided samples for testing. The player’s A and B samples both tested positive for cocaine and metabolites of cocaine, a prohibited substance. The player did not dispute (though he did not formally admit) the presence of the drug in his urine sample, but contended that he was innocent of any intention to use a prohibited substance, that he did not knowingly take cocaine and that the drug must have entered his body by means of illicit administration (“spiking”) by a person or persons who were present with him in a bar in Liverpool during the evening of 17 July 2004.

Consideration of the player
Documents were provided very late, by reason of unjustified delay the mandatory two year disqualification should be dismissed.
The laboratory test result documents where written in French, which is not the player’s mother tongue.
It's highly probable that an acquaintance spiked his drinks for this reason no fault or negligence or no significant fault or negligence should apply.

Tribunal conclusions
There are considerations about informing the player too late about his positive drug test and not informing about analyzing the B-sample. But the delays are not regarded to be abnormal. However he should have been notified that the B-sample would be analyzed. For this the starting point of the ineligibility can be adjusted.
Also a claim to ban the two years of disqualification for reason of proportionality are not met in this case.
The problem for the report being in French is not a problem because when requested a translation would have been available.
Fact is that the player has to establish how the prohibited substance entered his body. No fault or negligence was not significant in relation to the offense.
What remains is the starting date of the ineligibility and the forfeiture of results.

Decision
The tribunal:
(1) confirms the commission of the doping offence specified in the notice of charge set out in the ITF’s letter to the player dated December 6 2004: namely that a prohibited substance, cocaine and metabolites of cocaine, has been found to be present in the urine sample that the player provided at the British Open in Nottingham on July 20, 2004;
(2) orders that the player’s individual result in both the singles and doubles competition must be disqualified, and in consequence rules that the ranking points and prize money obtained by the player through his participation in the singles and doubles competitions in that event, must be forfeited;
(3) orders, further, that the player’s individual results in competitions in which he participated shall be disqualified and in consequence rules that the ranking points and prize money obtained by the player through his participation in those events, must be forfeited;
(4) declares that the player is ineligible for a period of two years from 23 August 2004 to 22 August 2006 to participate in any capacity in any event or activity (other than authorized anti-doping education or rehabilitation programs) authorized by the ITF or any national or regional entity which is a member of or is recognized by the ITF as the entity governing the sport of tennis in that nation or region.

The effect of nandrolone decanoate on bone mineral density, muscle mass, and hemoglobin levels in elderly women with osteoporosis : a double-blind, randomized, placebo-controlled clinical trial /  Alberto Frisoli Jr, Paulo H.M. Chaves, Marcelo Medeiros Pinheiro, Vera Lucia Szejnfeld. - (Journal of Gerontlolgy 60 (2005) 5 (May); p. 648-653)

• PMID: 15972619
• DOI: 10.1093/gerona/60.5.648

Abstract

Methods: In a randomized, double-blind, placebo-controlled clinical trial, we evaluated the effect of a 2-year treatment with nandrolone decanoate (ND) on bone mineral density (BMD) of lumbar spine, femoral neck, and trochanter and on vertebral fracture rate, muscle mass, and hemoglobin levels. Sixty-five osteoporotic women older than 70 years were studied. Thirty-two patients received injections of 50 mg ND, and 33 received placebos every 3 weeks. All patients received 500 mg calcium tablets daily.

Results: Compared to baseline, ND increased the BMD of the lumbar spine (3.4% +/- 6.0 and 3.7% +/- 7.4; p < .05) and femoral neck (4.1% +/- 7.3 and 4.7% +/- 8.0; p < .05) after 1 and 2 years, respectively. The BMD of trochanter increased significantly only after the first year (4.8% +/- 9.3, p < .05). Compared to the placebo group, the ND group presented with significantly increased BMD of the trochanter and neck. ND significantly reduced incidence of new vertebral fractures (21% vs 43% in the placebo group; p < .05). ND showed a significant statistical increase in lean body mass after the first (6.2% +/- 5.8; p < .01) and second years (11.9% +/- 29.2; p < .01). In addition, a 2-year treatment with ND significantly increased hemoglobin levels compared to baseline (14.3%; p < .01) and placebo (p < .01).

Conclusions: ND increased BMD, hemoglobin levels, and muscle mass, and reduced the vertebral fracture rate of elderly osteoporotic women.

Discontinuation of estrogen replacement therapy in GH-treated hypopituitary women alters androgen status and IGF-I / Jens Juel Christiansen, Sanne Fisker, Claus Højbjerg Gravholt, Paul Bennett, Birgit Svenstrup, Marianne Andersen, Ulla Feldt-Rasmussen, Jens Sandahl Christiansen, Jens Otto Lunde Jørgensen. - (European Journal of Endocrinology 152 (2005) 5 (May); p. 719-726)

• PMID: 15879357
• DOI: 10.1530/eje.1.01898

Abstract

Objective and design: Compared with their male counterparts, healthy females secrete more growth hormone (GH) and those with GH-deficiency have lower insulin-like growth factor I (IGF-I) levels and are less responsive to GH substitution. To test whether this gender difference is related to sex hormones we measured androgen status and IGF-I related parameters in 38 hypopituitary women (mean (range) age 41.5 (20–58) years) during continued GH substitution as compared with a control group of 38 healthy women matched for age and menopausal status. Twenty six patients were studied twice: with estrogen replacement and after 28 days of estrogen discontinuation in a randomised design.

Results: The patients were androgen deficient compared with controls (median, range), dehydroepiandrosterone sulphate (DHEAS): 185 (99–7800) nmol/l vs 4400 (820–13 000) nmol/l, P = < 0.001; androstenedione: 0.5 (0.1–7.1) nmol/l vs 4.3 (1.6–8.8) nmol/l, P = < 0.001; dihydrotestosterone (DHT): 0.13 (0.09–0.54) nmol/l vs 0.55 (0.09–0.89) nmol/l, P = < 0.001; testosterone: 0.28 (0.09–1.56) nmol/l vs 1.1 (0.71–2.24) nmol/l, (P = < 0.001); free testosterone: 0.004 (0.001–0.030) nmol/l vs 0.016 (0.001–0.030) nmol/l, P = < 0.001. The circulating levels of IGF-I, IGF-II, IGF-binding protein 1 (IGFBP-1), and IGFBP-3 did not differ between patients and controls. The subgroup of patients receiving hydrocortisone (HC) replacement (n = 24) had significantly lower levels of androgens (suppressed by 80–100%) as well as IGF-I and IGFBP-3 as compared with the patients not receiving HC. IGF-I was correlated to free testosterone in patients (r = 0.57, P = 0.0005) as well as controls (r = 0.43, P = 0.008), and free testosterone was a significant positive predictor of IGF-I. Estrogen discontinuation induced an increase in IGF-I (167 ± 15 vs 206 ± 14 μg/l, P = 0.005 and IGFBP-3 (3887 ± 139 vs 4309 ± 138 μg/l, P = 0.0005). Estrogen discontinuation was associated with a significant increase in median (range) free testosterone (0.004 (0–0.02) vs 0.0065 (0–0.03) nmol/l, P = 0.001) and a significant decrease in median (range) sex-hormone binding globulin (SHBG; 93 (11–278) vs 55.5 (20–142) nmol/l, P = 0.001). ΔIGF-I correlated with ΔSHBG (r = −0.45 P = 0.033) and ΔIGFBP-3 (r = 0.67 P = < 0.001). In a regression model ΔE2, Δtestosterone, ΔSHBG and ΔIGFBP-3 explained 93% of the variation in ΔIGF-I.

Conclusions: Androgen levels are low in hypopituitary women and free testosterone correlates with IGF-I. Discontinuation of estrogen replacement in these patients induces elevations in IGF-I as well as free testosterone, and ΔIGF-I correlated positively with Δfree testosterone. These effects may contribute to the gender differences observed in the GH–IGF axis in healthy adults as well as in the responsiveness of hypopituitary patients to GH substitution.