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Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples.

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Résolvez cette énigme ou ce paradoxe ! Tous les indices sont dans la vidéo.

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The steroid glycoside H.g.-12 from Hoodia gordonii activates the human bitter receptor TAS2R14 and induces CCK release from HuTu-80 cells
Boris Le Nevé  Am J Physiol Gastrointest Liver Physiol 299: G1368-G1375, 2010

Steroid glycosides extracted from the succulent plant Hoodia gordonii are suggested to have appetite-suppressant effects both in animals and humans. Yet, the mechanisms underlying the putative satiety action of Hoodia steroid glycosides are not fully understood. We found that H.g.-12, a steroid glycoside purified from H. gordonii extract, initiated cholecystokinin (CCK) secretion both ex vivo in rat intestine and in vitro in the human enteroendocrine (EC) cell line HuTu-80. CCK is known to exert central effects on appetite suppression via the vagus nerve which afferents terminate in the gut wall. Recent data show that G protein-coupled receptors signaling bitter taste (T2Rs) are expressed in both rodent and human gastrointestinal tract. It was further demonstrated that bitter sensing is functional in mouse STC-1 EC cells and leads to CCK secretion via increased intracellular Ca2+ concentrations. Based on the bitter taste of H. gordonii purified extracts, we assessed whether H.g.-12 could activate human bitter receptors. The steroid glycoside activated selectively TAS2R7 and TAS2R14, both heterologously expressed in HEK 293 cells. Removing an essential structural feature from the steroid glycoside inhibited H.g.-12-induced Ca2+ increase in TAS2R14-expressing HEK cells and abolished H.g.-12-induced CCK secretion from human EC cells. Similarly, a nonspecific bitter receptor antagonist abolished H.g.-12-induced CCK secretion in HuTu-80 cells. These results point to a potential route of action by which components of Hoodia might influence appetite control. Our data also provide additional evidence that bitter taste-sensing mechanisms are coupled to hormone release from EC cells in the intestine. Moreover, we identified a natural agonist of TAS2R7 and TAS2R14 for further studies on the role of bitter receptors in satiety control and food intake.

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Caffeinated chewing gum increases repeated sprint performance and augments increases in testosterone in competitive cyclists
Carl D. Paton, Timothy Lowe and Athena Irvine         European Journal of Applied Physiology Volume 110, Number 6, 1243-1250

This investigation reports the effects of caffeinated chewing gum on fatigue and hormone response during repeated sprint performance with competitive cyclists. Nine male cyclists (mean ± SD, age 24 ± 7 years, VO2max 62.5 ± 5.4 mL kg−1 min−1) completed four high-intensity experimental sessions, consisting of four sets of 30 s sprints (5 sprints each set). Caffeine (240 mg) or placebo was administered via chewing gum following the second set of each experimental session. Testosterone and cortisol concentrations were assayed in saliva samples collected at rest and after each set of sprints. Mean power output in the first 10 sprints relative to the last 10 sprints declined by 5.8 ± 4.0% in the placebo and 0.4 ± 7.7% in the caffeine trials, respectively. The reduced fatigue in the caffeine trials equated to a 5.4% (90% confidence limit ±3.6%, effect size 0.25; ±0.16) performance enhancement in favour of caffeine. Salivary testosterone increased rapidly from rest (~53%) and prior to treatments in all trials. Following caffeine treatment, testosterone increased by a further 12 ± 14% (ES 0.50; ± 0.56) relative to the placebo condition. In contrast, cortisol concentrations were not elevated until after the third exercise set; following the caffeine treatment cortisol was reduced by 21 ± 31% (ES −0.30; ± 0.34) relative to placebo. The acute ingestion of caffeine via chewing gum attenuated fatigue during repeated, high-intensity sprint exercise in competitive cyclists. Furthermore, the delayed fatigue was associated with substantially elevated testosterone concentrations and decreased cortisol in the caffeine trials.

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Influence d’une supplémentation en vitamines sur performance musculaire maximale au cours d’un programme d’entraînement en force chez des athlètes masters
Science & Sports Volume 25, Issue 5, November 2010, Pages 253-259 J. Louis

Objectifs :

Le but de ce travail était d’étudier l’effet d’une stratégie de supplémentation en vitamines selon des doses et une composition correspondantes aux apports nutritionnels conseillés (ANC) pendant l’entraînement sur la variation de force maximale volontaire d’athlètes masters engagés dans un programme d’entraînement en force.

Méthodes :

Vingt athlètes masters bien entraînés en endurance ont réalisé un programme d’entraînement en force des muscles extenseurs de la cuisse d’une durée de trois semaines. Avant et après la période d’entraînement, les marqueurs sanguins de l’inflammation musculaire ont été mesurés. Avant chaque séance d’entraînement, la force maximale volontaire isométrique était testée. Ces sujets étaient divisés selon une méthode en double insu en deux groupes expérimentaux avec (groupe supplémenté [Ao]) ou sans (groupe placebo [Pl]) apport nutritionnel en vitamines et micronutriments, Isoxan Force®.

Résultats :

À la suite de la période d’entraînement, la force maximale volontaire des muscles extenseurs de la cuisse a augmenté dans les deux groupes, (+9,7 % pour le groupe Ao versus +6,3 % pour le groupe Pl). Dans le groupe Ao l’amélioration est supérieure à celle du groupe Pl et la récupération entre les séances est améliorée. Enfin, en fin d’entraînement, une différence significative des marqueurs sanguins des dommages et de l’inflammation musculaires est relevée entre les deux groupes.

Conclusion :

Les résultats de cette étude confirment les bénéfices liés à une courte période d’entraînement en force sur la performance maximale musculaire chez des athlètes masters. Par ailleurs, l’apport micronutritionnel pendant l’entraînement s’accompagne de dommages musculaires moins importants suggérant un effet de potentialisation des bénéfices de l’entraînement en force avec une supplémentation en vitamines et minéraux.

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Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids
Christophe Morisseau The Journal of Lipid Research, December 2010 51, 3481-3490.

Beneficial physiological effects of long-chain n-3 polyunsaturated fatty acids are widely accepted but the mechanism(s) by which these fatty acids act remains unclear. Herein, we report the presence, distribution, and regulation of the levels of n-3 epoxy-fatty acids by soluble epoxide hydrolase (sEH) and a direct antinociceptive role of n-3 epoxy-fatty acids, specifically those originating from docosahexaenoic acid (DHA). The monoepoxides of the C18:1 to C22:6 fatty acids in both the n-6 and n-3 series were prepared and the individual regioisomers purified. The kinetic constants of the hydrolysis of the pure regioisomers by sEH were measured. Surprisingly, the best substrates are the mid-chain DHA epoxides. We also demonstrate that the DHA epoxides are present in considerable amounts in the rat central nervous system. Furthermore, using an animal model of pain associated with inflammation, we show that DHA epoxides, but neither the parent fatty acid nor the corresponding diols, selectively modulate nociceptive pathophysiology. Our findings support an important function of epoxy-fatty acids in the n-3 series in modulating nociceptive signaling. Consequently, the DHA and eicosapentaenoic acid epoxides may be responsible for some of the beneficial effects associated with dietary n-3 fatty acid intake.

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