Curcumin, a nontoxic, naturally occurring polyphenol, has been recently proposed for the management of neurodegenerative and neurological diseases. However, a discrepancy exists between the well-documented pharmacological activities that curcumin seems to possess in vivo and its poor aqueous solubility, bioavailability, and pharmacokinetic profiles that should limit any therapeutic effect. Thus, it is possible that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of curcumin are present after oral administration. Indeed, a new working hypothesis that could explain the neuroprotective role of curcumin despite its limited availability is that curcumin acts indirectly on the central nervous system by influencing the “microbiota–gut–brain axis”, a complex bidirectional system in which the microbiome and its composition represent a factor which preserves and determines brain “health”. Interestingly, curcumin and its metabolites might provide benefit by restoring dysbiosis of gut microbiome. Conversely, curcumin is subject to bacterial enzymatic modifications, forming pharmacologically more active metabolites than curcumin. These mutual interactions allow to keep proper individual physiologic functions and play a key role in neuroprotection.

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Abstract. Incalzi RA, Capparella O, Gemma A, Landi F, Bruno E, Di Meo F, Carbonin P (Instituto di Medicina Interna e Geriatria dell'Universita' Cattolica del Sacro Cuore, Rome, and the Teaching Nursing Home 'Cittadella della Carita', Taranto, Italy. The interaction between age and comorbidity contributes to predicting the mortality of geriatric patients in the acute-care hospital. J Intern Med 1997; 242: 291᎐8.Objective. To test the predictive power of comorbidity and of the interaction between age and comorbidity in geriatric patients with acute medical illness. Design. Prospective observational study. Setting. Medical and geriatric wards of an acute-care hospital. Subjects. Three hundred and seventy patients over 70 years of age consecutively admitted in an 18-month period. Main outcome measure. In-hospital mortality. Method. On admission a multidimensional assessment was performed, and a comorbidity index and an age᎐comorbidity index developed on a comparable training population were calculated. The comorbidity index is based upon a scoring system that quantifies the prognostic weight of individual diseases, while the age᎐comorbidity index corrects the former for the age-related increase of the risk of death. The predictive power of variables univariately correlated with the outcome was tested by logistic regression. Results. Death was independently predicted by clinical diagnosis of malnutrition (odds ratio ϭ 1.87, confidence limits CL ϭ 1.20᎐2.86), age᎐comorbidity index Ͼ 7 (odds ratio ϭ 1.77, CL ϭ 1.15᎐2.72), preadmission impairment in activities of daily living (odds ratio ϭ 1.74, CL ϭ 1.13᎐2.69), lymphocytopenia (odds ratio ϭ 1.74, CL ϭ 1.15᎐2.61). A weaker predictive model was obtained by substituting the comorbidity index for the index of age᎐comorbidity. Excluding comorbidity from the logistic regression greatly weakened the predictive model.

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P Pu ur rp po os se e: : Stress response to surgery is modulated by several factors, including magnitude of the injury, type of procedure (e.g., laparoscopy vs laparotomy) and type of anesthesia. Our purpose was to compare intra-and postoperative hormonal changes during isoflurane vs sevoflurane anesthesia, in a clinical model of well defined operative stress (laparoscopic pelvic surgery). M Me et th ho od d: :In this prospective randomized clinical study, 20 women requiring laparoscopic pelvic surgery for benign ovarian cysts received either a standard isoflurane plus fentanyl (Group A) or sevoflurane plus fentanyl anesthesia (Group B). Blood samples were collected preoperatively, 30 min after the beginning of surgery, at the end of surgery after extubation, and two and four hours after the end of surgery. Intra-and postoperative plasma levels of norepinephrine, epinephrine, adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH) and prolactin (PRL) were measured. R Re es su ul lt ts s: : Catecholamine levels and postoperative pain were similar in both groups. Nonetheless, in comparison to Group A, Group B showed a significant decrease of ACTH, cortisol and GH levels (A vs B at the end of surgery: ACTH 160 ± 45 vs 100 ± 40 pg·mL -1 ; cortisol 45 ± 8 vs 23 ± 7 µg·dL -1 ; GH 3 ± 2 vs 0.8 ± 0.4 ng·mL -1 ; P < 0.001 for all), but enhanced PRL levels (A vs B, at 30 min after the beginning of surgery: 139 ± 54 vs 185 ± 22 ng·mL -1 ; at the end of surgery: 100 ± 27 vs 141 ± 45 ng·mL -1 ; P < 0.001 for both).C Co on nc cl lu us si io on ns s: : In the clinical setting of low stress laparoscopic surgery, the type of volatile anesthetic significantly affected the stress response; the changes associated with sevoflurane suggested a more favourable metabolic and immune response compared to isoflurane. Objectif Méthode : L'étude clinique, prospective et randomisée, a été faite auprès de 20 femmes devant subir une intervention par laparoscopie pelvienne pour des kystes bénins de l'ovaire. Les patientes ont reçu, soit une anesthésie normale à l'isoflurane avec du fentanyl (groupe A), soit au sévoflurane avec du fentanyl (groupe B). Le sang a été prélevé avant l'opération, 30 min après le début, à la fin après l'extubation et, deux et quatre heures après l'opération. Les niveaux plasmatiques peropératoire et postopératoire de noradrénaline, d'adrénaline, d'hormone adrénocorticotrope (ACTH), de cortisol, d'hormone de croissance (GH) et de prolactine (PRL) ont été mesurés.Résultats : Les niveaux de catécholamine et la douleur postopéra-toire ont été similaires dans les deux groupes. Néanmoins, comparé au groupe A, le groupe B a affiché une baisse significative d' ACTH, GH 3 ± 2 vs 0,8 ± 0,

Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promote cognitive functions. Biotransformation of polyphenols is needed to obtain metabolites active in brain and it occurs through their processing by gut microbiota. Polyphenols metabolites could directly act as neurotransmitters crossing the blood-brain barrier or indirectly by modulating the cerebrovascular system. The microbiota-gut-brain axis is considered a neuroendocrine system that acts bidirectionally and plays an important role in stress responses. The metabolites produced by microbiota metabolism can modulate gut bacterial composition and brain biochemistry acting as neurotransmitters in the central nervous system. Gut microbiota composition can be influenced by dietary ingestion of natural bioactive molecules such as probiotics, prebiotics and polyphenol. Microbiota composition can be altered by dietary changes and gastrointestinal dysfunctions are observed in neurodegenerative diseases. In addition, several pieces of evidence support the idea that alterations in gut microbiota and enteric neuroimmune system could contribute to onset and progression of these age-related disorders. The impact of polyphenols on microbiota composition strengthens the idea that maintaining a healthy microbiome by modulating diet is essential for having a healthy brain across the lifespan. Moreover, it is emerging that they could be used as novel therapeutics to prevent brain from neurodegeneration.

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β-TM is associated with significant changes in heterogeneity of ventricular repolarization. QTc and JTc dispersion are useful markers of risk of SCD in patients with β-TM.