1,721,089 research outputs found
Restrizione calorica: come e perché.
No full textLa restrizione dell’apporto calorico giornaliero è un metodo potentissimo per il miglioramento dello stato di salute, nonché l’unico accertato per determinare un miglioramento della durata della vita massima e media in diverse specie animali. Sebbene rimangano dubbi circa l’efficacia della restrizione calorica sul prolungamento della vita massima dell’uomo, è ampiamente accertato il suo effetto di prevenzione delle comuni malattie dell’invecchiamento attraverso l’attivazione di processi cellulari che vedono anche il coinvolgimento del metabolismo energetico mitocondriale
3,5-Di-t-butylcatechol as a ryanodine receptor agonist in rat intact skeletal muscle fibers
No full text3,5-Di-t-butylcatechol (DTCAT) stimulates the rat skeletal muscle sarcoplasmic reticulum ryanodine receptor (RyR). In the present study, its effects on the contractile response of diaphragm preparation were characterized using electrically stimulated phrenic nerve–diaphragm preparations and diaphragm strips. DTCAT reduced, concentration-dependently, twitch contraction of the phrenic nerve– diaphragm preparation evoked by both direct and indirect stimulation and increased spontaneous tone. Twitch amplitude reduction was irreversible, while the increase of spontaneous tone was only partially reversible upon DTCAT washout. In diaphragm strips, caffeine > 4-chloro-m-cresol >> 3,5-diisopropylcatechol = ryanodine > DTCAT enhanced spontaneous tone, whereas quercetin reduced it with all the compounds reducing twitch amplitude. DTCAT-induced contracture was partly dependent on extracellular Ca2+ influx and antagonized by a Cd2+/La3+ mixture. In intact skeletal muscle preparations, DTCAT behaved as a RyR agonist
Voci di libertà. I combattenti alleati di origine italiana nella Seconda guerra mondiale / Voices of Liberty Allied Servicemembers of Italian Descent in WWII (Catalogo della mostra storico-documentaria, Firenze, spazio espositivo “Carlo Azeglio Ciampi”, Palazzo del Pegaso, 5-22 aprile 2022)
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The flavonoid scaffold as a template for the design of modulators of the vascular Cav1.2 channels
No full textBACKGROUND AND PURPOSE: Previous studies have pointed to the plant flavonoids myricetin and quercetin as two structurally related stimulators of vascular Ca(v) 1.2 channel current (I(Ca1.2) ). Here we have tested the proposition that the flavonoid structure confers the ability to modulate Ca(v) 1.2 channels.
EXPERIMENTAL APPROACH: Twenty-four flavonoids were analysed for their effects on I(Ca1.2) in rat tail artery myocytes, using the whole-cell patch-clamp method.
KEY RESULTS: Most of the flavonoids stimulated or inhibited I(Ca1.2) in a concentration- and voltage-dependent manner with EC(50) values ranging between 4.4 μM (kaempferol) and 16.0 μM (myricetin) for the stimulators and IC(50) values between 13.4 μM (galangin) and 100 μM [(±)-naringenin] for the inhibitors. Key structural requirements for I(Ca1.2) stimulatory activity were the double bond between C2 and C3 and the hydroxylation pattern on the flavonoid scaffold, the latter also determining the molecular charge, as shown by molecular modelling techniques. Absence of OH groups in the B ring was key in I(Ca1.2) inhibition. The functional interaction between quercetin and either the stimulator myricetin or the antagonists resokaempferol, crysin, genistein, and 5,7,2'-trihydroxyflavone revealed that quercetin expressed the highest apparent affinity, in the low μM range, for Ca(v) 1.2 channels. Neither protein tyrosine kinase nor protein kinase Cα were involved in quercetin-induced stimulation of I(Ca1.2).
CONCLUSIONS AND IMPLICATIONS: Quercetin-like plant flavonoids were active on vascular Ca(v)1.2 channels. Thus, the flavonoid scaffold may be a template for the design of novel modulators of vascular smooth muscle Ca(v)1.2 channels, valuable for the treatment of hypertension and stroke
Freeze-dried red wine effects on cardiac function and ECG of the Langendorff-perfused rat heart
No full textThe effect of freeze-dried red wine (FDRW) on cardiac function and electrocardiogram (ECG) in Langendorff-isolated rat hearts was investigated. FDRW significantly decreased left ventricular pressure and coronary perfusion pressure, the latter being dependent on the activation of both phosphatidylinositol 3-kinase and eNOS. FDRW did not affect the QRS and QT interval in the ECG, although at 56 μg of gallic acid equivalents/mL, it prolonged PQ interval and induced a second-degree atrioventricular block in 3 out of 6 hearts. This is the first study demonstrating that at concentrations resembling a moderate consumption of red wine, FDRW exhibited negative inotropic and coronary vasodilating activity leaving unaltered ECG, whereas at very high concentrations, it induced arrhythmogenic effects
Fine tuning by protein kinases of CaV1.2 channel current in rat tail artery myocytes
No full textSeventeen compounds, rather selective, direct or indirect inhibitors and activators of PKA, PKG, and PKC, were analysed for effects on vascular CaV1.2 channel current (ICa1.2) by using the patch-clamp technique in single rat tail artery myocytes. The aim was to investigate how PKs regulate ICa1.2 and disclose any unexpected modulation of CaV1.2 channel function by these agents. The cAMP analogues 8-Br-cAMP and 6-Bnz-cAMP partially reduced ICa1.2 in dialysed cells, while weakly increasing it under the perforated configuration. The β-adrenoceptor agonist isoproterenol and the adenylate cyclase activator forskolin concentration-dependently increased ICa1.2; this effect was reversed by PKA inhibitors H-89 and KT5720, but not by PKI 6-22. The cGMP analogue 8-Br-cGMP, similarly to the NO-donor SNP, moderately reduced ICa1.2, this effect being reversed to a slight stimulation under the perforated configuration. Among PKG inhibitors, Rp-8-Br-PET-cGMPS decreased current amplitude in a concentration-dependent manner while Rp-8-Br-cGMPS was ineffective. The non-specific phosphodiesterase inhibitor IBMX increased ICa1.2, while H-89, KT5720, and PKI 6-22 antagonized this effect. The PKC activator PMA, but not the diacylglycerol analogue OAG, stimulated ICa1.2 in a concentration-dependent manner; conversely, the PKCα inhibitor Gö6976 markedly reduced basal ICa1.2 and, similarly to the PKCδ (rottlerin) and PKCε translocation inhibitors antagonised PMA-induced current stimulation. The ensemble of findings indicates that the stimulation of cAMP/PKA, in spite of the paradoxical effect of both 8-Br-cAMP and 6-Bnz-cAMP, or PKC pathways enhanced, while that of cGMP/PKG weakly inhibited ICa1.2 in rat tail artery myocytes. Since Rp-8-Br-PET-cGMPS and Gö6976 appeared to block directly CaV1.2 channel, their docking to the channel protein was investigated. Both compounds appeared to bind the α1C subunit in a region involved in CaV1.2 channel inactivation, forming an interaction network comparable to that of CaV1.2 channel blockers. Therefore, caution should accompany the use of these agents as pharmacological tools to elucidate the mechanism of action of drugs on vascular preparations
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