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Trifonova S.T.,La Lumiere | Trifonova S.T.,University of Trier | Gantenbein M.,Clinical and Epidemiological Investigation Center | Turner J.D.,La Lumiere | And 3 more authors.
Psychoneuroendocrinology | Year: 2013

Cortisol is the key effector molecule of the HPA axis and is secreted in a pulsatile manner in all species studied. In order to understand cortisol signalling in health and disease, detailed analysis of hormone pulsatility is necessary. To dissect cortisol pulsatility in plasma deconvolution techniques have been applied. Blood sampling is a labour-intensive, expensive and invasive technique that causes stress and alters HPA axis activity. Therefore saliva has been extensively investigated as an alternative sample to measure cortisol. Here we use state of the art deconvolution algorithms to investigate cortisol pulsatility in saliva. Blood and saliva samples were obtained at 15-min intervals over an 8. h period in 18 healthy men to analyse their diurnal cortisol levels. A multiparameter deconvolution technique was used to generate statistically significant models of cortisol secretion and elimination in plasma and saliva. The models consisted of estimates of the number, amplitude, duration and frequency of secretory bursts as well as the elimination half-life (. t1/2) in a subject specific manner. No significant differences were noted between plasma and saliva with regard to the observed secretory bursts (7.8. ±. 1.5 vs. 7.0. ±. 1.4) and the interpeak interval (59.6. ±. 10.5. min vs. 61.0. ±. 11.5. min). Moreover a strong positive correlation between the numbers of peaks in both fluids was observed (. r=. 0.83, P<. 0.0001). Monte Carlo simulations revealed an 84% temporal concordance between plasma and saliva peaks in all donors (. P<. 0.05) with a mean of 1.3. ±. 0.8 plasma peaks unmatched in saliva. The percentage concordance increased to 90% when concording only the morning cortisol peaks in plasma and saliva up to 11:00. h. The deconvolution of the most distinct component of cortisol diurnal rhythm-cortisol awakening response (CAR), revealed an average 2.5. ±. 1.1 peaks based on the individual time for cortisol to return to baseline levels. In conclusion, deconvolution analysis of plasma and salivary cortisol concentration time series showed a close correlation and similar pulsatile characteristics between saliva and plasma cortisol. Similarly, Monte Carlo simulations revealed a high concordance between the peaks in these coupled time series suggesting that saliva is a suitable medium for subsequent deconvolution analysis yielding accurate and reliable models of cortisol secretion in particular during the morning hours. © 2012. Source

Droste D.W.,Center Hospitalier Of Luxembourg | Iliescu C.,Clinical and Epidemiological Investigation Center | Vaillant M.,Methodology and Statistical Competence Center | Gantenbein M.,Clinical and Epidemiological Investigation Center | And 6 more authors.
Cerebrovascular Diseases | Year: 2014

Background: A Mediterranean diet, with and without small daily amounts of red wine, and physical activity reduce the risk of cerebrovascular disease and improve cognition. An increase in cerebral blood flow may be the underlying mechanism. Under normal conditions, cerebral blood flow velocity changes in the internal carotid arteries and in large basal cerebral arteries correlate closely with cerebral blood flow changes, as the diameter of these vessels hardly changes and only the smaller vessels downstream change their diameter. Methods: A prospective randomized controlled trial was performed in 108 patients with carotid atherosclerosis (mean age 64 years, 67% men, 66% on statin therapy). Half of them were advised to follow a polyphenol-rich modified Mediterranean diet including 1-2 tomatoes, 3-5 walnuts and a bar of dark chocolate (25 g) a day and to perform moderate physical exercise for 30 min/day (lifestyle changes). Within these two groups, half of the patients were randomized either to avoid any alcohol or to drink 100 ml of red wine (women) or 200 ml of red wine (men) daily. Bilateral middle cerebral and internal carotid blood flow velocity (peak systolic, peak end-diastolic and mean) was measured at baseline and after 4 and 20 weeks using colour-coded duplex ultrasound. Insonation depth and insonation angle were used to identically place the sample volume during follow-up investigations. A general linear model with Tukey-Kramer adjustment for multiple comparisons was used to assess the primary end points. For the analysis we used the mean values of the right and left artery. Results: Neither lifestyle changes nor red wine had an effect on peak systolic, peak end-diastolic or mean cerebral blood flow velocity. Conclusions: Advice on lifestyle changes, including a modified polyphenol-rich Mediterranean diet, a glass of red wine daily and physical exercise, did not affect middle cerebral and internal carotid blood flow velocity in our patient group with carotid atherosclerosis. An increase in cerebral blood flow is thus unlikely to be the cause of the reduced risk of cerebrovascular disease and improved cognitive functioning described in the literature. One possible explanation for the fact that blood flow velocity was not affected by red wine, diet and physical activity advice is that two thirds of our patients were already on statin therapy. Statins increase cerebral blood flow and vasomotor reactivity via nitric oxide. © 2014 S. Karger AG, Basel. Source

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