A thermodynamic model of the sympathetic and parasympathetic nervous system

In light of the nonequilibrium thermodynamics by I. Prigogine, the autonomic nervous system as a whole may be viewed as a dissipative structure progressively assembled in the course of evolution, plastically and rhythmically interfaced between forebrain, internal and external environments, to regulate energy, matter and information exchanges. In the present paper, this hypothesis is further pursued to verify whether the two main divisions of the autonomic nervous system, the sympathetic and parasympathetic systems, may support different types of exchange with the external environment. Previous data from hypothalamic stimulation experiments, studies of locus coeruleus function and available data on behavioral functional organization indicate that (1) tight engagement with the external environment, (2) high level of energy mobilization and utilization and (3) information mainly related to exteroceptive sensory stimulation characterize a behavioral prevalence of sympathoadrenal activation. On the other hand, (1) disengagement from the external environment, (2) low levels of internal energy and (3) dominance of proprioceptive information characterize a behavioral prevalence of vagal tone. Behavioral matter exchanges such as feeding, drinking, micturition and defecation are equally absent at the extreme of sympathoadrenal and vagally driven behaviors. The autonomic nervous system as a whole is genetically determined, but the sympathoadrenal system has been mainly designed to organize the visceral apparatus for an action to be performed by the biological system in the external environment and to deal with the novelty of task and of the environment, while the functional role of the parasympathetic is to prepare the visceral apparatus for an action to be performed by the biological system on itself, for recovery and self-protection (homeostasis), and is reinforced by repetition of phylo- and ontogenetically determined patterns. The available clinical data further support this interpretation indicating that an increased sympathetic and a decreased vagal tone may represent a consistent risk factor for cardiovascular diseases

Age-related changes in phase-space distributionof ABPM data in normotensive and hypertensive patients

The data collected by ambulatory blood pressure monitoring have been studied in the phase-space of R-R interval and blood pressure and their individual distribution quantified by the slope of the regression line through 24-h values. This slope has been termed "ambulatory autonomic reciprocity index" and abbreviated as AARIs and AARId, the "s" and "d" indicating the relation with systolic and diastolic blood pressure respectively. Ambulatory monitoring was performed in 200 normotensive (NT: 135 females) and 200 untreated hypertensive patients (HT: 59 females). The AARIs was: NT: -6.04 \ub1 2.7 and HT: -4.69 \ub1 2.4. ms/mm. Hg, respectively (p< 0.001); the AARId was: -7.04 \ub1 2.9 for NT and -5.79 \ub1 2.8 for HT subjects (p< 0.001). When distributed by decades of life the steepest AARIs occurred at the 20-29 decade, while the flattest at the 60-69 decade. At the 60-69 decade and above, the AARIs was similar in both groups (ANOVA o.w. NT: p< 0.001; HT: p< 0.01). AARIs and AARId were strongly correlated with 24-h variability of R-R interval, either 24-h standard deviation or coefficient of variation (p< 0.001), and poorly correlated with 24-h variability of blood pressure. These data suggest that the AARI, when seen in the context of the "Autonomic Space", may be viewed as a 24-h period index of centrally driven cardiovagal function. Being based on both blood pressure and heart rate measurements, the AARI may become clinically useful to address life style changes and pharmacological treatment of hypertensive patients towards optimal results

A comparative study of diagnostic and imaging techniques for osteoarthritis of the trapezium

Objectives. The aims of this study were to determine whether micro-CT is a reliable investigation method to evaluate the severity of OA in the trapezium and to develop a novel micro-CT scoring system based on a quantitative assessment of the subchondral bone thickness in order to better assess OA through an objective parameter.Methods. We compared different diagnostic and imaging techniques performed consecutively on each sample: X-ray, visual analysis, micro-CT and histology. OA and healthy trapezia were subjected to semi-quantitative and quantitative analyses to be classified in four degrees of severity in OA (control, OA-2, OA-3 and OA-4). Specifically, samples were analysed using Dell's score for X-ray, Brown's score for visual analysis and Mankin's score for histology. Micro-CT was scored using a novel quantitative scoring system based on subchondral bone thickness measurements. Results obtained with each technique were then compared and correlated.Results. X-ray analysis showed a higher frequency of OA-2 (27%) and OA-3 (32%) compared with OA-4 (5%), whereas visual analysis, micro-CT and histology showed a lower percentage for OA-2 (18%, 18% and 14%) and OA-3 (23%) and increased frequency for OA-4 (45%, 32% and 40%). Only the micro-CT score of subchondral bone thickness correlated significantly with all the other techniques (P &lt; 0.05).Conclusion. This is the first comparison of techniques proposing a novel scoring system based on objective and quantitative micro-CT data that can be applied as a useful diagnostic tool for OA, providing a deeper comprehension of the pathophysiology of OA in trapezium

Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as chemopreventive agents for many tumours; however, the mechanism responsible for their anti-neoplastic activity remains elusive and the side effects due to cyclooxygenase (COX) inhibition prevent this clinical application. Methods: Molecular biology, in silico, cellular and in vivo tools, including innovative in vivo imaging and classical biochemical assays, were applied to identify and characterise the COX-independent anti-cancer mechanism of NSAIDs. Results: Here, we show that tumour-protective functions of NSAIDs and exisulind (a sulindac metabolite lacking anti-inflammatory activity) occur through a COX-independent mechanism. We demonstrate these NSAIDs counteract carcinogen-induced proliferation by inhibiting the sirtuin 1 (SIRT1) deacetylase activity, augmenting acetylation and activity of the tumour suppressor p53 and increasing the expression of the antiproliferative gene p21. These properties are shared by all NSAIDs except for ketoprofen lacking anti-cancer properties. The clinical interest of the mechanism identified is underlined by our finding that p53 is activated in mastectomy patients undergoing intraoperative ketorolac, a treatment associated with decreased relapse risk and increased survival. Conclusion: Our study, for the first-time, links NSAID chemopreventive activity with direct SIRT1 inhibition and activation of the p53/p21 anti-oncogenic pathway, suggesting a novel strategy for the design of tumour-protective drugs

Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science

Schizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations.Male Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive animals without any manipulations. Adult animals were implanted with E-Mitter transponders intraabdominally to record body temperature and locomotor activity continuously. The circadian rhythm of these parameters and the acute effects of changes in light conditions were analyzed under undisturbed circumstances, and the effects of different interventions (handling, bed changing or intraperitoneal vehicle injection) were also determined.Decreased motor activity with fragmented pattern was observed in the new substrain. However, these animals had higher body temperature during the active phase, and they showed wider range of its alterations, too. The changes in light conditions and different interventions produced blunted hyperactivity and altered body temperature responses in the new substrain. Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups. Furthermore, the new substrain showed increased short- and long-term variabilities with lower degree of asymmetry suggesting autonomic dysregulation.In summary, the new substrain with schizophrenia-related phenomena showed disturbed motor activity and thermoregulation suggesting that these objectively determined parameters can be biomarkers in translational research

An examination of the influence of L-DOPA and inhibitors of its catabolism, on metabolic processes in the mammal

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Soluzioni ed unita' di misura

La conoscenza della composizione e della distribuzione dei liquidi dell\u2019organismo e\u2019 alla base della Nefrologia Clinica. Questo capitolo fornisce le nozioni fondamentali per la conoscenza delle unita\u2019 di misura, e delle soluzioni che vengono utilizzate sia in Medicina Interna sia in Medicina d\u2019Urgenza per correggere le alterazioni dei liquidi intra- ed extracellulari. Particolare attenzione viene data alle unita\u2019 di misura utilizzate, mole, massa e volume, ed alle formule che servono al passaggio da una quantita\u2019 espressa in mole ed equivalenti ad una espressa in grammi e viceversa