Urinary excretion profile of higenamine in females after oral administration of supplements - Doping scenario.

In 2017, higenamine was added to the World Antidoping Agency's (WADA) Prohibited list under group S3: beta-2 agonists and it is banned for athletes both in - and out of competition. Aim of this study was to characterize the urinary excretion profile of higenamine and its metabolite coclaurine after oral administration of multiple doses of higenamine capsules. For this purpose, an administration study including female basketball players was performed. For the detection of higenamine and cocalurine in the collected urine samples, a new, fast, and highly sensitive quantitative on-line SPE LC HRMS method was developed and validated. The method was applied for the quantification of higenamine and cocalurine in urine and their excretion pattern was defined. Results obtained show substantial inter-individual differences in the excretion profile of higenamine and coclaurine. For higenamine, half-lives were estimated to be between 4 and 27 h, and for coclaurine between 5 and 25 h. Furthermore, the data indicate that the elimination of coclaurine is rate-limited by its formation. Higenamine could be detected at a urine concentration above 10 ng/mL for at least 20 h after the last application for all study participants.

Long-term electromagnetic field treatment enhances brain mitochondrial function of both Alzheimer's transgenic mice and normal mice: a mechanism for electromagnetic field-induced cognitive benefit?

We have recently reported that long-term exposure to high frequency electromagnetic field (EMF) treatment not only prevents or reverses cognitive impairment in Alzheimer's transgenic (Tg) mice, but also improves memory in normal mice. To elucidate the possible mechanism(s) for these EMF-induced cognitive benefits, brain mitochondrial function was evaluated in aged Tg mice and non-transgenic (NT) littermates following 1 month of daily EMF exposure. In Tg mice, EMF treatment enhanced brain mitochondrial function by 50-150% across six established measures, being greatest in cognitively-important brain areas (e.g. cerebral cortex and hippocampus). EMF treatment also increased brain mitochondrial function in normal aged mice, although the enhancement was not as robust and less widespread compared to that of Tg mice. The EMF-induced enhancement of brain mitochondrial function in Tg mice was accompanied by 5-10 fold increases in soluble Aß1-40 within the same mitochondrial preparations. These increases in mitochondrial soluble amyloid-ß peptide (Aß) were apparently due to the ability of EMF treatment to disaggregate Aß oligomers, which are believed to be the form of Aß causative to mitochondrial dysfunction in Alzheimer's disease (AD). Finally, the EMF-induced mitochondrial enhancement in both Tg and normal mice occurred through non-thermal effects because brain temperatures were either stable or decreased during/after EMF treatment. These results collectively suggest that brain mitochondrial enhancement may be a primary mechanism through which EMF treatment provides cognitive benefit to both Tg and NT mice. Especially in the context that mitochondrial dysfunction is an early and prominent characteristic of Alzheimer's pathogenesis, EMF treatment could have profound value in the disease's prevention and treatment through intervention at the mitochondrial level.