Rapid determination of anti-estrogens by gas chromatography/mass spectrometry in urine: Method validation and application to real samples

AbstractA fast screening protocol was developed for the simultaneous determination of nine anti-estrogenic agents (aminoglutethimide, anastrozole, clomiphene, drostanolone, formestane, letrozole, mesterolone, tamoxifen, testolactone) plus five of their metabolites in human urine. After an enzymatic hydrolysis, these compounds can be extracted simultaneously from urine with a simple liquid–liquid extraction at alkaline conditions. The analytes were subsequently analyzed by fast-gas chromatography/mass spectrometry (fast-GC/MS) after derivatization. The use of a short column, high-flow carrier gas velocity and fast temperature ramping produced an efficient separation of all analytes in about 4min, allowing a processing rate of 10samples/h. The present analytical method was validated according to UNI EN ISO/IEC 17025 guidelines for qualitative methods. The range of investigated parameters included the limit of detection, selectivity, linearity, repeatability, robustness and extraction efficiency. High MS-sampling rate, using a benchtop quadrupole mass analyzer, resulted in accurate peak shape definition under both scan and selected ion monitoring modes, and high sensitivity in the latter mode. Therefore, the performances of the method are comparable to the ones obtainable from traditional GC/MS analysis. The method was successfully tested on real samples arising from clinical treatments of hospitalized patients and could profitably be used for clinical studies on anti-estrogenic drug administration

Mitochondrial Abnormality Associates with Type-Specific Neuronal Loss and Cell Morphology Changes in the Pedunculopontine Nucleus in Parkinson Disease

Cholinergic neuronal loss in the pedunculopontine nucleus (PPN) associates with abnormal functions, including certain motor and nonmotor symptoms. This realization has led to low-frequency stimulation of the PPN for treating patients with Parkinson disease (PD) who are refractory to other treatment modalities. However, the molecular mechanisms underlying PPN neuronal loss and the therapeutic substrate for the clinical benefits following PPN stimulation remain poorly characterized, hampering progress toward designing more efficient therapies aimed at restoring the PPN's normal functions during progressive parkinsonism. Here, we investigated postmortem pathological changes in the PPN of PD cases. Our study detected a loss of neurons producing gamma-aminobutyric acid (GABA) as their output and glycinergic neurons, along with the pronounced loss of cholinergic neurons. These losses were accompanied by altered somatic cell size that affected the remaining neurons of all neuronal subtypes studied here. Because studies showed that mitochondrial dysfunction exists in sporadic PD and in PD animal models, we investigated whether altered mitochondrial composition exists in the PPN. A significant up-regulation of several mitochondrial proteins was seen in GABAergic and glycinergic neurons; however, cholinergic neurons indicated down-regulation of the same proteins. Our findings suggest an imbalance in the activity of key neuronal subgroups of the PPN in PD, potentially because of abnormal inhibitory activity and altered cholinergic outflow

Adherence to the traditional Mediterranean diet in a population of South of Italy: factors involved and proposal of an educational field-based survey tool

We developed and validated a tool assessing the adherence to the Mediterranean diet based on current nutritional recommendations for health promotion (MEDI-Quest). Four-hundred-and-eleven clinically healthy subjects completed both the MEDI-Quest-score and the validated MedDietScore (MDS). A good accordance between MEDI-Quest and MDS was observed (R = 0.638), as well as for the percentage of individuals having similar scores with both methods for each food group. Regarding socio-cultural-factors, higher adherence was observed in people with older-age (OR = 1.030, p < .0001), more qualifier-employment (OR = 1.136, p < .005), higher-income (OR = 1.925, p < .0001), interest in reading-food-labels (OR = 2.057, p < .0001), and having frequent physical activity (OR = 1.608, p < .05). In conclusion, our findings show that (1) the MEDI-Quest score well correlate with MDS, and (2) the adherence to the Mediterranean diet is not particularly high due to less cultural roots. It could be necessary to improve people's knowledge about food and nutrition, taking into consideration believes embedded in their family, tradition and religion

Solar sail capture trajectories at Mercury

Mercury is an ideal environment for future planetary exploration by solar sail since it has proved difficult to reach with conventional propulsion and hence remains largely unexplored. In addition, its proximity to the Sun provides a solar sail acceleration of order ten times the sail characteristic acceleration at 1 AU. Conventional capture techniques are shown to be unsuitable for solar sails and a new method is presented. It is shown that capture is bound by upper and lower limits on the orbital elements of the approach orbit and that failure to be within limits results in a catastrophic collision with the planet. These limits are presented for a range of capture inclinations and sail characteristic accelerations. It is found that sail hyperbolic excess velocity is a critical parameter during capture at Mercury, with only a narrow allowed band in order to avoid collision with the planet. The new capture methodis demonstrated for a Mercury sample return mission