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Scopo Indagare i cambiamenti di connettività funzionale nei giocatori patologici (GP) rispetto ai controlli sani (CS) mediante risonanza magnetica funzionale in condizioni di resting state. Materiale e metodi 13 CS e 14 GP sono stati reclutati in questo studio (tutti maschi destrimani, non in terapia farmacologica, età media 35,96 ± 9,56). Tutti i soggetti sono stati sottoposti ad RM encefalo utilizzando uno scanner da 1,5T. I dati di attivazione delle regioni cerebrali tra loro funzionalmente collegate sono stati ottenuti utilizzando un'analisi concat-ICA. Le componenti risultanti sono state quindi confrontate tra i due gruppi. Tra queste mappe sono state prese in considerazione solo quelle che presentavano differenze statisticamente significative (p

The aim of this study is to investigate the neurobiology of stress/emotionality, creating a multidisciplinary assessment model, which can help to provide psychological and physiological responses depending on the genetic background related to sport performances, social closeness and performance anxiety management in team sports. We enrolled 20 female volleyball players aged 13 ± 1 years old played in two different teams during a regional championship final. Saliva collection was carried out before and after the match. In order to evaluate the neuroendocrine effectors involved in stress and performance, we analyzed cortisol and progesterone levels through Elisa standard kit as well as HSP70 and amylase activity as stress-induced markers. As concern the psychometric assesment, we administrated he CSAI-2 test, Closeness Generating Procedure and STAI test. Genomic DNA was isolated from saliva cells using a QIAamp saliva kit according to the manufacturer’s protocols. The SNP of the 5-HTTLPR, BDNF, DRD4 were analyzed. The results of the T-test performed on the total results showed a statistically significant relationship (p < 0.05) in cortisol levels pre and post match, as well between amylase and HP70 according to the genetic background. The analysis performed using just post match samples show a negative correlation between social closeness, cortisol and progesterone levels, with p < 0.010 for progesterone vs social closeness and p < 0.012 for cortisol vs social closeness. About the winner teams and the looser teams, there is a negative correlation between pre match cortisol levels and performance anxiety (p < 0.042).

The aim of this study is to investigate the neurobiology of stress/emotionality, creating a multidisciplinary assessment model, which can help to provide psychological and physiological responses depending on the genetic background related to sport performances, social closeness and performance anxiety management in team sports. We enrolled 20 female volleyball players aged 13 ± 1 years old played in two different teams during a regional championship final. Saliva collection was carried out before and after the match. In order to evaluate the neuroendocrine effectors involved in stress and performance, we analyzed cortisol and progesterone levels through Elisa standard kit as well as HSP70 and amylase activity as stress-induced markers. As concern the psychometric assesment, we administrated he CSAI-2 test, Closeness Generating Procedure and STAI test. Genomic DNA was isolated from saliva cells using a QIAamp saliva kit according to the manufacturer’s protocols. The SNP of the 5-HTTLPR, BDNF, DRD4 were analyzed. The results of the T-test performed on the total results showed a statistically significant relationship (p < 0.05) in cortisol levels pre and post match, as well between amylase and HP70 according to the genetic background. The analysis performed using just post match samples show a negative correlation between social closeness, cortisol and progesterone levels, with p < 0.010 for progesterone vs social closeness and p < 0.012 for cortisol vs social closeness. About the winner teams and the looser teams, there is a negative correlation between pre match cortisol levels and performance anxiety (p < 0.042).

Introduction: Saliva collection and analysis is quickly becoming a useful and non-invasive tool for the evaluation of sport biomarkers. The aim of this study is to create a multidisciplinary assessment model, which can help to provide psychological and physiological responses, related to sport performances, social closeness and performance anxiety management in team sports. Materials and methods: We enrolled in our research 26 female volleyball players aged 13 ± 1 years old of three different teams (T1: 12 players; T2: 9 players; T3: 5 players). Saliva collection was carried out before and after the match for every team. Then we analyzed cortisol and progesterone concentrations through Elisa standard kits. Results: The results of the T-test performed on the total results showed a statistically significant relationship (p < 0.05) in cortisol levels pre and post match: in fact, it has been shown a statistical significant decrease (p < 0.001). The analysis performed using just samples post match shows a negative correlation between social closeness, cortisol and progesterone levels, with p < 0.010 for progesterone vs social closeness and p < 0.012 for cortisol vs social closeness, which indicates that increasing of one of the two hormones reduces relationship. About the winner teams and the looser teams, there is a negative correlation between pre match cortisol levels and performance anxiety (p < 0.042).

The purpose of this study was to determine the probability of soccer players having the best genetic background that could increase performance, evaluating the polymorphism that are considered Performance Enhancing Polymorphism (PEPs) distributed on five genes: PPARα, PPARGC1A, NRF2, ACE e CKMM. Particularly, we investigated how each polymorphism works directly or through another polymorphism to distinguish elite athletes from non-athletic population. Materials And Methods. Sixty professional soccer players (age 22.5 ± 2.2) and sixty healthy volunteers (age 21.2± 2.3) were enrolled. Samples of venous blood was used to prepare genomic DNA. The polymorphic sites were scanned using PCR-RFLP protocols with different enzyme. We used a multivariate logistic regression analysis to demonstrate an association between the five PEPs and elite phenotype. Results. We found statistical significance in NRF2 (AG/GG genotype) polymorphism/soccer players association (p < 0.05) as well as a stronger association in ACE polymorphism (p =0.02). Particularly, we noticed that the ACE ID genotype and even more the II genotype are associated with soccer player phenotype. Although the other PEPs had no statistical significance, we proved that some of these may work indirectly, amplifying the effect of another polymorphism; for example, seems that PPARα could acts on NRF2 (GG) enhancing the effect of the latter, notwithstanding it had not shown a statistical significance. Conclusions. In conclusion, it is not enough to examinate the influence that each polymorphism could have on physical performance, but it is necessary to understand how they act and interact, directly and indirectly, on each other.

The benefits of regular exercise are known for a long time, but the mechanisms underlying the exercise mode recommendations for specific chronic cardiovascular diseases remains unclear. The aim of this study was to evaluate and compare the effects of different circuit training protocols in sedentary overweight adults.

This literature review is a compilation of the most used methods to monitoring athletes in training and competition. Blood is certainly the best known and proven methodology and a wide range of markers can be analyzed through it, but it can be difficult to obtain, especially among athletes or people who are afraid of needles. The use of saliva is an interesting alternative especially for the easy and less invasive method of collecting. The saliva infact contains a few of compounds diffused in the plasma, like water, electrolytes, proteins, metabolites and hormones. However, new methods yet poorly understood are slowly catching on; sweat for example, may carry far more information, may provide useful biomarkers that can give indications about the physical state of the body (electrolytes, lactate, creatinine, glucose, proteins, amino acids) and may be easier to stimulate, gather, and analyze than previously thought.

The effects of alcohol have been widely studied during the past century as alcohol abuse is a major health problem in Western society. In the last years, a growing body of evidence indicates that acetaldehyde, the first oxidation product of ethanol, is one of the mediators of peripheral and central effects of ethanol. Indeed, acetaldehyde has been recently taken into account as the mediator of the rewarding properties of alcohol. The role of acetaldehyde in ethanol-related properties has been proved by enzymatic manipulation studies in which the inactivation of acetaldehyde potentially synthesized in the brain produces the same results as blocking the formation of acetaldehyde by inhibiting brain catalase activity. Moreover, electrophysiological and pharmacological analyses showed that acetaldehyde is able to stimulate dopamine release in the nucleus accumbens through enhancement of firing rate, spikes/burst, and burst firing of ventral tegmental neurons. Thus, the aim of this review is to summarize latest results on the role of acetaldehyde as the mediator of ethanol-central effects.

Background: The oxidative stress results from a change in the physiological balance between oxidant and antioxidant species. The purpose of this study is twofold: first, to investigate the effects of long-term training in sports with high energy requirements on the redox balance which exists between the plasma vs. the erythrocytes; second, to study the activity of the PMRS (Plasma Membrane Redox System), which is a compensatory mechanism of cellular redox homeostasis, in the rowers’ erythrocytes in order to determine the rowers’ counteraction to oxidative stress. Methods: Venous blood samples was collected from rowers and control group; then FRAP (Ferric Reducing Activity Power) method has been used to determine the antioxidant capabilities both in the plasma and in the erythrocytes of 22 rowers vs. 26 sedentary subjects. For the same groups of subjects, the PMRS in erythrocytes has been also evaluated. Results: The plasmatic antioxidant activity was 21% lower in the group of rowers compared to the sedentary group (p = 0,02). In contrast, no significant differences were found in the reducing activity of the erythrocytes; however the erythrocytes of the rowers have shown values of the PMRS 35% higher than the untrained group (p < 0.0001). Conclusions: Rowing induces a significant oxidative stress in the plasma corresponding to the high intensity training, while this effect lacks in erythrocytes. At the same time an increased quantity of the PMRS has been observed in the erythrocytes. In conclusion, in well trained athletes this not lead to established an oxidative stress condition because long-term training adaptatively improves the efficiency of the antioxidant system

During inflammation, endothelial cells (EC) are the first elements to be exposed to mediators circulating in the bloodstream. EC react with finely tuned responses mediated by different pathways, including the Phosphoinositide (PI) signal transduction system. The PI pathway contributes to a variety of cell functions, including hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking, ion channel activity, cytoskeleton regulation, cell cycle control, apoptosis, embryonic development, organogenesis, and cell/tissue polarity. The Phosphoinositide-specific phospholipase C (PI-PLC) enzymes contribute to the regulation of the spatio-temporal balance of molecules belonging to the PI system. Thirteen mammalian PI-PLC enzymes have been identified, divided into six sub-families on the basis of amino acid sequence, domain structure and mechanism of recruitment. Isoforms within sub-families share sequence similarity, common domain organization, and general regulatory mechanism. The expression of PI-PLCs is strictly tissue specific, and evidences suggest that it varies under different conditions, such as tumor progression or cell activation. We obtained the complete panel of expression of PI-PLC isoforms in human umbilical vein endothelial cells (HUVEC), a widely used experimental model for EC. Then, we analyzed the mRNA concentration of PI-PLCs in LPS treated HUVEC by using the multiliquid bioanalyzer methodology after 3, 6, 24 48 and 72 hours from LPS administration. Marked differences in the expression of most PI-PLC codifying genes were evident., Italian Journal of Anatomy and Embryology, Vol 118, No 2 (Supplement) 2013

Much recent experimental evidence suggests that inflammatory reactions are involved in aneurysm formation and progression [1]. Vessel wall weakening has been attributed to the infiltration of a variety of cells, which leads to the upregulation of multiple cytokines [2]. A growing interest is currently focused in the definition of cytokines associated with the final stage of the disease that precedes the rupture. In the present study full aortic segments were collected from patients with thoracic aortic aneurysms, according to the declaration of Helsinki. Control aorta tissue from organ donors was included as reference. Microtome sections of paraffin embedded samples were analyzed for the presence of IL-17 and IL-23 positivity. Aortic sections were also stained with hematoxylin and eosin and Verhoeff-Van Gieson for elastin. Immunohistochemistry detected IL-17 and IL-23 positive cells at the level of adventitia and muscle cell layer. Our data reinforce previous results showing that IL-17 plays a central role in the promotion of vascular inflammation. The identification of main cytokines released during inflammatory processes underlying aneurysm formation and progression may lead to the set up of pharmaceutic strategies that may prove effective for the stabilization of aortic aneurysms., Italian Journal of Anatomy and Embryology, Vol 118, No 2 (Supplement) 2013

The rationale of our study was to test the potential of the autologous elements of peripheral white blood cells and platelets to promote neoangiogenesis, thereby overcoming hypoxemia, the major obstacle to the regeneration of the tissue. An highly innovative technique, based on an autologous leuco-platelet preparation, applied by direct infiltration to the ulcer was employed to treat 65 patients with ulcers of different etiologies. Hyaluronic acid was used as a scaffold, supplemented with autologous cells. Patients were followed up until complete healing of the lesions. Morphometric analysis was perfomed on histologic sections to determine the presence of neoangiogenesis. The wound healing was obtained in all cases after 2 until 22 months with this treatment (median time is 11.4 months). More than half of the patients recovered completely within the first 12 months. Morphometric analysis on histologic sections determined the presence of an abundant neovasculature in the close proximity of the infiltrations of leuco-platelet concentrate. Our data show that autologous leucoplatelet preparation layered onto ischemic ulcers may improve neoangiogenesis leading to wound healing. These findings suggest that this cell-based therapy may be a useful tool for the treatment for intractable skin ulcers resulting from diabetes, ischemia and collagen diseases., Italian Journal of Anatomy and Embryology, Vol 118, No 2 (Supplement) 2013

Neuropeptide Y (NPY) is a potent inhibitor of neurotransmitter release through the Y2 receptor subtype. Specific antagonists for the Y2 receptors have not yet been described, Based on the concept of template-assembled synthetic proteins we have used a cyclic template molecule containing two p-turn mimetics for covalent attachment of four COOH-terminal fragments RQRYNH(2) (NPY 33-36), termed T-4-[NPY(33-36)](4). This structurally defined template-assembled synthetic protein has been tested for binding using SK-N-MC and LN319 cell lines that express the Y1 and Y2 receptor, respectively. T-4-[NPY(33-36)](4) binds to the Y2 receptor with high affinity (IC50 = 67.2 nM) and has poor binding to the Y1 receptor. This peptidomimetic tested on LN319 cells at concentrations up to 10 mu M shows no inhibitory effect on forskolin-stimulated cAMP levels (IC50 for NPY = 2.5 nM). Furthermore, we used confocal microscopy to examine the NPY-induced increase in intracellular calcium in single LN319 cells, Preincubation of the cells with T-4-[NPY(33-36)](4) shifted to the right the dose-response curves for intracellular mobilization of calcium induced by NPY at concentrations ranging from 0.1 nM to 10 mu m. Finally, we assessed the competitive antagonistic properties of T-4-[NPY(33-36)](4) at presynaptic peptidergic Y2 receptors modulating noradrenaline release, the compound T-4 [NPY(33-36)](4) caused a marked shift to the right of the concentration-response curve of NPY 13-36, a Y2-selective fragment, yielding a pA2 value of 8.48. Thus, to our best knowledge, T-4-[NPY(33-36)](4) represents the first potent and selective Y2 antagonist.

Tinnitus is a frequent symptom in audiological clinical practice characterized by an abnormal noise perceived in one or both ears or in the head, in which a patient has a conscious hearing percept in absence of external sound. Tinnitus might be caused by a homeostatic response of central dorsal cochlear nucleus auditory neurons that makes them hyperactive in compensation to auditory input loss. One hypothesis suggests that tinnitus is a sensory form of epilepsy that involves the cochlear nucleus and the inferior colliculus, which display impairment in the electrical activity in the auditory system. This alteration determines a synaptic plasticity in the dorsal cochlear nucleus that becomes a target for pharmacological compounds able to treat tinnitus. There is no effective drug treatment for tinnitus, but different studies propose the use of cannabinoid receptors agonist for their anti-epileptic activity, although their practical effects are still unclear. In this review, we want to analyze the emerging pharmacological approaches of cannabinoid receptor agonists to the therapy of tinnitus.

Optimal control of fed-batch fermenters S. Valentinotti† C. Cannizzaro‡ M.Rhiel‡ U. Holmberg† U. von Stockar‡ D. Bonvin† †Institut d’Automatique, EPFL, 1015 Lausanne, Switzerland ‡Institut de Genie Chimique, EPFL, 1015 Lausanne, Switzerland Fermentors are often run in a fed-batch manner to avoid the formation of overflow metabolites. At a high growth rate, the most efficient metabolic pathway(s) of certain microorganisms become saturated resulting in overflow metabolite production. These byproducts are undesirable since their accumulation in the reactor may be inhibitory and the productivity of biomass and growth-associated products is reduced. The ideal way to run such fed-batch fermentation is to grow the cells in the reactor at the critical growth rate, i.e., the point at which overflow metabolite production begins. However, since this value changes from run to run, or even during a given fermentation, its identification is not trivial. A simple way to overcome this difficulty is to maintain a very small, but constant overflow metabolite concentration in the reactor, ensuring that most of the substrate is consumed efficiently. However due to exponential cell growth, standard controllers can maintain a constant concentration only for a limited time period. In this work an adaptive control strategy to maintain a constant overflow metabolite concentration in fed-batch fermentation is presented. The proposed approach requires the knowledge of only two system parameters: the yield coefficient, expressing the relation between overflow metabolite and substrate, and the instantaneous concentration of the overflow metabolite. Baker’s yeast fed-batch experiments were performed with the ob jective of maximizing biomass productivity and minimizing ethanol production. Mid-infrared spectroscopy was used to measure the ethanol concentration that was provided on-line to the controller. The results from numerous experiments have demonstrated the effectiveness of the proposed control strategy. The specific growth rate was maintained constant, at a value close to the critical point, until oxygen transfer limitation occurred. Then, the controller automatically reduced the feed rate to prevent excess ethanol production. The biomass increased from 0.5 to 65 grams per liter during the exponential growth phase. Simulation results based on this control strategy show its applicability to other overflow metabolite organisms, such as Escherichia coli.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with onset in the first 3 years of life, with an incidence in Italy of 6–10 new cases per 10,000 children per year. Affected children show impaired social interactions, repetitive or stereotypical behaviors and interests. Disruption/dysregulation of neuroimmune functioning, whether expressed in the patient or during the course of the individual’s brain development, are implicated in Idiopathic ASD (1). Quantitative and qualitative differences in immune function between children with ASD and typically developing controls have been demonstrated, including evidence for increased neuroinflammation and cytokine production in brain specimens obtained from individuals with ASD(2). Peripheral innate immune activation is starting to be recognized as a prominent feature of diseases affecting the central nervous system.(3) In a recent study we have shown that elevated levels of the pro-inflammatory cytokines including interleukin-1, interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-alpha and BDNF were present in sera of autistic patients (4).We have recently observed that the levels of IL-18 detected in the sera of autistic children were rather lower than those measured in the sera of matched healthy children. We decided to inquire if an alteration in the amount of IL-18 in different areas of the CNS and in the serum was also detectable in Reeler eterozygous mice, a mouse model of autism, compared to wild type mice. IL-18 was localized in different brain regions by immunohistochemistry and in whole brain homogenates by western blots. Quantitative analysis of the cytokine in serum was performed by ELISA., Italian Journal of Anatomy and Embryology, Vol 118, No 2 (Supplement) 2013

There are some suggestions that, in the pineal gland, serotonin acts not only as a precursor of melatonin but also plays a role in the modulation of the pineal biosynthetic activity. To corroborate this possible neuromodulatory role of 5-hydroxytryptamine (serotonin) (5-HT) on the pineal gland, the effects of two 5-HT(2) receptor agonists meta-chlorophenylpiperazine (m-CPP) and 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane were assessed in vivo on pineal N-acetyltransferase (NAT) activity and melatonin content in rats. m-CPP potentiated the enhancement of NAT activity and pineal melatonin content induced by isoproterenol administration during daytime, whereas it did not affect the diurnal basal biosynthetic activity of the gland. At night, m-CPP and 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane enhanced significantly the physiological increases in both pineal NAT activity and melatonin content. This enhancement was prevented by pretreatment with N-(1-methyl-5-indolyl)-N'-(3-pyridyl) urea hydrochloride, an antagonist with higher affinity for 5-HT(2B/C) than for 5-HT(2A) receptor, as well as by pretreatment with 8-[5-(2, 4-dimethoxy-5-(4-trifluoromethyl-phenylsulphonamido)-phenyl-5-o xopent hyl]-1,3,8-triazospiro[4,5]decane-2,4-dione, the most specific 5-HT(2C) receptor now available, but not by pretreatment with ketanserin, an antagonist with higher affinity for 5-HT(2A) than for 5-HT(2C) receptor. These results suggest that 5-HT(2C) receptors are likely involved in the mediation of the serotonergic modulation of pineal biosynthetic activity in rats.

Alterations in dopamine (DA) reuptake are involved in several psychiatric disorders whose symptoms can be investigated in knock out rats for the DA transporter (DAT-KO). Recent studies evidenced the role of epigenetic DAT modulation in depressive-like behavior. Accordingly, we used heterozygous (HET) rats born from both HET parents (termed MIX-HET), compared to HET rats born from WT-mother and KO-father (MAT-HET), implementing the role of maternal care on DAT modulation. We developed a "sudden fright" paradigm (based on dark-light test) to study reaction to fearful inputs in the DAT-KO, MAT-HET, MIX-HET, and WT groups. Rats could freely explore the whole 3-chambers apparatus; then, they were gently confined in one room where they experienced the fright; finally, they could freely move again. As expected, after the fearful stimulus only MAT-HET rats showed a different behavior consisting of avoidance towards the fear-associated chamber, compared to WT rats. Furthermore, ex-vivo immuno-fluorescence reveals higher prefrontal DAT levels in MAT-HET compared to MIX-HET and WT rats. Immuno-fluorescence shows also a different histone deacetylase (HDAC) enzymes concentration. Since HDAC concentration could modulate gene expression, within MAT-HET fore brain, the enhanced expression of DAT could well impair the corticostriatal-thalamic circuit, thus causing aberrant avoidance behavior (observed only in MAT-HET rats). DAT expression seems to be linked to a simply different breeding condition, which points to a reduced care by HET dams for epigenetic regulation. This could imply significant prefronto-cortical influences onto the emotional processes: hence an excessively frightful response, even to mild stressful agents, may draw developmental trajectories toward anxious and depressed-like behavior.