Exercise intolerance and fatigue in chronic heart failure: is there a role for group III/IV afferent feedback?

Exercise intolerance and early fatiguability are hallmark symptoms of chronic heart failure. While the malfunction of the heart is certainly the leading cause of chronic heart failure, the patho-physiological mechanisms of exercise intolerance in these patients are more complex, multifactorial and only partially understood. Some evidence points towards a potential role of an exaggerated afferent feedback from group III/IV muscle afferents in the genesis of these symptoms. Overactivity of feedback from these muscle afferents may cause exercise intolerance with a double action: by inducing cardiovascular dysregulation, by reducing motor output and by facilitating the development of central and peripheral fatigue during exercise. Importantly, physical inactivity appears to affect the progression of the syndrome negatively, while physical training can partially counteract this condition. In the present review, the role played by group III/IV afferent feedback in cardiovascular regulation during exercise and exercise-induced muscle fatigue of healthy people and their potential role in inducing exercise intolerance in chronic heart failure patients will be summarised

Improved Renormalization of Lattice Operators: A Critical Reappraisal

We systematically examine various proposals which aim at increasing the accuracy in the determination of the renormalization of two-fermion lattice operators. We concentrate on three finite quantities which are particularly suitable for our study: the renormalization constants of the vector and axial currents and the ratio of the renormalization constants of the scalar and pseudoscalar densities. We calculate these quantities in boosted perturbation theory, with several running boosted couplings, at the "optimal" scale q*. We find that the results of boosted perturbation theory are usually (but not always) in better agreement with non-perturbative determinations of the renormalization constants than those obtained with standard perturbation theory. The finite renormalization constants of two-fermion lattice operators are also obtained non-perturbatively, using Ward Identities, both with the Wilson and the tree-level Clover improved actions, at fixed cutoff ($\beta$=6.4 and 6.0 respectively). In order to amplify finite cutoff effects, the quark masses (in lattice units) are varied in a large interval 0<am<1. We find that discretization effects are always large with the Wilson action, despite our relatively small value of the lattice spacing ($a^{-1} \simeq 3.7$ GeV). With the Clover action discretization errors are significantly reduced at small quark mass, even though our lattice spacing is larger ($a^{-1} \simeq 2$ GeV). However, these errors remain substantial in the heavy quark region. We have implemented a proposal for reducing O(am) effects, which consists in matching the lattice quantities to their continuum counterparts in the free theory. We find that this approach still leaves appreciable, mass dependent, discretization effects.Comment: 54 pages, Latex, 5 figures. Minor changes in text between eqs.(86) and (88

Non-perturbative Renormalization of Lattice Operators

We briefly review and compare three methods (one perturbative, one based on Ward Identities and one non-perturbative) for the calculation of the renormalization constants of lattice operators. The following results are presented: (a) non perturbative renormalization of the operators with light quarks; (b) the renormalization constants with a heavy (charm) quark mass and its KLM improvement; (c) the non perturbative determination of the mixing of the $\Delta S = 2$ operator.Comment: 9 pages, uuencoded PS file, 8 figures included, 1 tabl

Natural Killer cells responsiveness to physical esercise: a brief review

Natural killer cells (NK) are a group of peripheral blood lymphocytes which display cytotoxic ac- tivity against a wide range of tumour cells. They are a consistent part of the inflammatory re- sponse that is activated when either internal or external injuries occur as they are able to syn- thesize perforins. An important role is played by NK cells in the host defence against tumours without expressing any antigen-binding recap- tor in their membrane which, however, distin- guish T and B lymphocytes. NK activity appears early in the immune response, thus providing immediate protection during the time required for the activation and proliferation of cytotoxic T lymphocytes and for their differentiation into functional cells. Even though much research regarding the effects of aerobic training exercise on NK cell numbers and function, there appears to be much controversy regarding its effect. NK cells are rapidly mobilized into circulation in response to acute exercise, most likely by in- creased shear stress and catecholamine-in- duced down-regulation of adhesion molecule expression. However, tissue injury and inflam- mation which often accompanies strenuous ex- ercise have been associated to post-exercise NK cell suppression. Scientific evidence indicates exercise-induced changes in NK cell redistribu- tion and function should be strongly influenced by stress hormones including catecholamines, cortisol and prolactin as well as by soluble me- diators such as cytokines and prostaglandins. The role of exercise therapy in cancer patients and survivors rehabilitation is becoming increasingly important as it is thought to modulate immunity and inflammation. However, more knowledge about the effects of exercise on im-mune function in these patients is needed

Ireland: The Recurring Economic Miracle?

Ireland is enjoying a tremendous economic success. Is this success based solely on favorable corporate taxation policies? What is the effect of Ireland\u27s success and its taxation policies on the other EU nations? Ireland presents a model for economic growth and prosperity to be followed not only by the recent accession nations, but by the older EU member nations in an attempt to reform their socioeconomic context

Design of mid-IR and THz quantum cascade laser cavities with complete TM photonic bandgap

We present the design of mid-infrared and THz quantum cascade laser cavities formed from planar photonic crystals with a complete in-plane photonic bandgap. The design is based on a honeycomb lattice, and achieves a full in-plane photonic gap for transverse-magnetic polarized light while preserving a connected pattern for efficient electrical injection. Candidate defects modes for lasing are identified. This lattice is then used as a model system to demonstrate a novel effect: under certain conditions - that are typically satisfied in the THz range - a complete photonic gap can be obtained by the sole patterning of the top metal contact. This possibility greatly reduces the required fabrication complexity and avoids potential damage of the semiconductor active region.Comment: 14 pages, 14 figure

Studio della variabilita del gene caprino CCR5: analisi propedeutica all'individuazione di polimorfismi coinvolti nella resistenza alle lentivirosi (CAEV)

Il virus Maedi Visna (MVV) e il virus dell’Artrite-Encefalite caprina (CAEV) determinano una malattia virale contagiosa tipica di ovini e caprini; appartengono alla famiglia Retroviridae, genere Lentivirus, a cui è ascrivibile anche il virus dell’immunodeficienza acquisita dell’uomo (HIV). A fronte della grave situazione determinata da un’elevata percentuale di capi positivi alla CAEV e all’inesistenza di un trattamento terapeutico efficace, l’unica strategia di lotta, attualmente, è stata l’attuazione di piani di eradicazione volontaria. Tale approccio però si è rivelato inefficace, pertanto una via alternativa verso la quale si stanno orientando i recenti studi, risulta essere costituita dalla ricerca di marcatori genetici di resistenza alla malattia. Ampie prospettive sono state aperte da studi condotti sia nell’uomo che negli ovini che hanno evidenziato la presenza di mutazioni coinvolte nella modulazione della suscettibilità alle lentivirosi. Nell’uomo, il gene CCR5 codificante per una proteina di membrana con funzione di recettore per le chemochine, è stato descritto come marcatore genetico coinvolto nella resistenza all’infezione da HIV-1. Un recente studio condotto sugli ovini ha messo in evidenza una delezione di 4 pb nella regione del promotore di CCR5 (5436-5439) che determina un’alterazione dei siti di legame per fattori trascrizionali riducendo, in ovini omozigoti deleti, fino a 3.9 volte l’espressione di tale recettore e dimezzando la carica provirale. Questo lavoro, partendo dal contesto suddetto, ha lo scopo di indagare per la prima volta la sequenza del gene CCR5 nella capra ed il ruolo dei polimorfismi ad esso associati nella modulazione della suscettibilità/resistenza all’infezione da CAEV, al fine di porre le basi per l’allestimento in futuro di piani di selezione assistita da marcatori. A tale scopo, sono stati analizzati 20 campioni di sangue appartenenti a caprini di razza Camosciata. Gli animali sono stati scelti di differente età, non imparentati tra di loro e con una ratio tra i sessi di 1:1. E’ stato estratto il DNA, il gene CCR5 è stato analizzato mediante quattro PCR comprendenti la regione del promotore, Esone 1, Introne, Esone 2 comprendente il CDS, regione 3’ UTR. Ciascun amplificato è stato sottoposto a sequenziamento e le sequenze ottenute sono state analizzate mediante il Software Seqman. Gli aplotipi più probabili sono stati definiti attraverso l’applicazione del software PHASE (v 2.1.1). È stata inoltre condotta un’analisi funzionale dei polimorfismi rilevati nelle differenti regioni geniche utilizzando a tale scopo differenti software: TFSEARCH per individuare eventuali punti di interazione con fattori di trascrizione; UTRScan per rilevare l’eventuale presenza di siti polimorfici all’interno di consensus motifs; Rescue-ESE Web Server per valutare se i polimorfismi rilevati appartenessero a motivi regolatori collocati a livello esonico. Sono stati individuati 17 alleli, risultati tutti in equilibrio di Hardy-Weinberg, associati a costituire 5 aplotipi. Sei alleli, uno dei quali caratterizzato dall’inserzione di 2 basi TC, si localizzano all’interno del promotore, 6 nell’introne tra esone 1 e 2,4 nella regione 3’ UTR ed è stata invece rilevata la mutazione puntiforme in posizione 8121 codificante per la sostituzione aminoacidica I198T. Successivamente è stata eseguita un’analisi funzionale dei polimorfismi mediante software dedicati, che ha permesso di definirne il ruolo svolto. La mutazione puntiforme in posizione 8121 T>C codifica per la sostituzione aminoacidica I198T, dando luogo ad una sostituzione neutrale. I risultati ottenuti hanno evidenziato che il CCR5 caprino è moderatamente polimorfo e per quanto concerne le mutazioni descritte nel promotore, potrebbero avere un ruolo rilevante quelle ubicate entro le 500 pb dal Transcriptional Start Site (TSS) in quanto dati bibliografici riportano che un terzo di esse interferisce per più del 50% sui livelli di trascrizione. Questo consentirà di effettuare un studio caso-controllo per scoprire eventuali associazioni tra gli aplotipi rilevati e la resistenza a CAEV nei caprini

Neural regulation of cardiovascular response to exercise: role of central command and peripheral afferents

During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discusse