Caso Suavinex: Diseño de producto y packaging con criterio ecológico y sostenible

The current economic context, immersed in conditions of a BANI environment (fragile, anxious, non-linear and incomprehensible) generates a high influence on consumer behavior. El actual contexto económico, inmerso en condiciones de un entorno BANI (frágil, ansioso, no lineal e incomprensible) genera una alta influencia en la conducta del consumidor. O contexto econômico atual, imerso em condições de um ambiente BANI (frágil, ansioso, não linear e incompreensível) gera grande influência no comportamento do consumidor.&nbsp

Marketing de guerrilla. Lo no convencional triunfa

La saturación publicitaria, la aparición de nuevos públicos y el desarrollo de las tecnologías son tres factores que han contribuido a que el marketing deba evolucionar. En la empresa están cada vez más presentes las estrategias basadas en mecanismos no convencionales, donde se prima el ingenio por encima del presupuesto. Ante tal situación aparece el marketing de guerrilla, una herramienta que pretende llamar la atención del receptor y despertar su interés para, finalmente, convertirlo en consumidor de la marca. El siguiente trabajo analiza las características que presenta el marketing de guerrilla, analizando la importancia y eficacia que puede proporcionar para la estrategia empresarial de la organización

Estrategia, liderazgo y actitud positiva: Tres claves del éxito empresarial

Conforme a las diferentes transformaciones que se producen en el mundo, las empresas han cambiado lo que demandan. La creatividad, como una herramienta estratégica de negocio, liderazgo, como la clave para lograr los objetivos y resultados esperados, y la actitud de las personas, como la diferencia en un entorno donde los productos y los precios son cada vez más parecidos, se convierten en los elementos más valorados por las compañías

Regional Alteration of the Transient Outward Current in Human Left Ventricular Septum During Compensated Hypertrophy

International audienceBackground A large calcium-insensitive transient outward current ( I to ) has been recorded in atria, left ventricular (LV) free wall, and right ventricular septal subendocardium of the human heart. Recent studies suggested a major contribution of this current to the electrical heterogeneity of the heart. However, no data have been reported on the distribution of I to density within the LV septal wall from compensated human LV hypertrophy. Methods and Results Microelectrode and patch-clamp techniques were used to record action potentials and I to in myocytes isolated from superficial (<3 mm deep) and deep (3 to 6 mm deep) layers of LV septum from patients with aortic stenosis and compensated LV hypertrophy. Subendocardial specimens were also obtained from undiseased donor hearts. In none of the superficial subendocardial cells from diseased hearts was a macroscopic I to recorded (n=42), whereas in cells from the same location from donor hearts, a typical I to was clearly present, with a peak density of 5.88±0.78 pA/pF at +60 mV (n=4). However, in deep layers from patients with compensated LV hypertrophy, macroscopic I to was present, with a peak density of 10.50±2.58 pA/pF at +60 mV (n=4). The absence of I to in superficial septal cells from hypertrophied hearts was not due to a divalent cation–related shift of the current kinetics. Instead, extracellular Ca 2+ removal induced an I to -like current, possibly carried by K + ions, with a peak density of 30.7±2.6 pA/pF at +60 mV (n=29). However, its magnitude, kinetics, and pharmacological characteristics did not allow identification of this current as the usual I to . Conclusions Both topography and pathology can be major modulating factors of the regional distribution of I to density in human LV septum. Therefore, they may play a prominent role in determining electrical gradients within this region from which the early depolarization vectors start and the left-to-right activation sequence of the interventricular septum proceeds

Co-marketing como herramienta estratégica empresarial

La colaboración y el establecimiento de alianzas son acciones que permiten obtener mayor fuerza y conseguir mejores resultados y más satisfactorios El co-marketing es una estrategia que persigue el acuerdo de colaboración entre dos o más marcas, empresas o instituciones para desarrollar un producto o servicio que genere unos resultados beneficiosos para las diferentes partes que componen el acuerdo de colaboración

Extracellular K +

International audienceBackground —In human ventricular cells, the inwardly rectifying K + current ( I K1 ) is very similar to that of other mammalian species, but detailed knowledge about the K + -dependent distribution of open and blocked states during rectification and about the K + -dependent modulation of inactivation on hyperpolarization is currently lacking. Methods and Results —We used the whole-cell patch-clamp technique to record I K1 in myocytes isolated from subendocardial layers of left ventricular septum from patients with nonfailing hearts with aortic stenosis and cardiac hypertrophy who were undergoing open-heart surgery. Outward currents were very small at voltages positive to the reversal potential but increased at high external [K + ]. Chord conductance measurements and kinetic analyses allowed us to estimate the proportion of channels in the open state and of those showing either slow unblock or instantaneous unblock (the so-called slow or instantaneous “activation”) on hyperpolarization: the distribution in the individual states was dependent on external [K + ]. The proportion of channels unblocking slowly was greater than that of channels unblocking instantaneously on hyperpolarization from the plateau voltage range. Hence, because of the previously reported link between the presence of highly protonated blocking molecules and slow unblock kinetics, it is suggested that high cellular concentrations of spermine may account for the low outward current density recorded in these cells. The current decrease observed on extended hyperpolarization was significantly relieved by an increase in external [K + ]. Conclusions —The pattern of I K1 current alterations observed in the present model of human ventricular hypertrophy might favor enhanced excitability and underlie ventricular arrhythmias, possibly via increased intracellular polyamine levels

Modulation of electrical heterogeneity by compensated hypertrophy in rat left ventricle

International audienceModulation of the regional distribution of the action potential by left ventricular hypertrophy and the role of the L-type Ca2+ current (I(Ca)) and transient outward current (I(to)) in the action potential duration (APD) were investigated in normal and hypertrophied rat ventricular myocytes from the apex (A), septum (S) and left ventricular free wall (FW) by using whole cell current- and voltage-clamp techniques. Hypertrophy was induced by abdominal aortic constriction. In control cells, the APD measured at 20% repolarization (APD20) assumed the shortest values in the A and the longest in the S, whereas FW cells showed intermediate values. Hypertrophy significantly prolonged the APD20 and increased APD variability within the A and FW regions but did not modify the APD in S cells. Analysis of the APD, I(Ca), and I(to) at the instant of 20% repolarization in the same cell showed that in control cells the shortest APD20 was associated with a prominent I(to) in the A and FW, whereas the long APD20 was identified with a lower I(to) in S myocytes. Hypertrophy-induced prolongation ofAPD20 was associated with a reduction in the I(to) in the A and FW. Significant correlations could be established between the APD20 and the "net current," defined as the algebraic addition of I(to) and I(Ca) in the A and FW control groups but not in the control S or hypertrophied cells whatever their origin. Our results indicate that interregional APD heterogeneity is lost while intraregional APD variability is increased in the A and FW during the hypertrophic process. These effects are largely due to a change in the balance between the I(Ca) and I(to), which is a major contributing factor to the heterogeneity of the initial phase of repolarization in the normal rat ventricle

Slow inward current in single cells isolated from adult human ventricles

International audienceCharacteristics of the slow inward current (Isi) in human ventricular myocytes isolated from septal specimens obtained in patients undergoing corrective cardiac surgery were studied using the whole-cell clamp method. A first series of experiments was performed under normal standard superfusion. Clamping from -60 mV evoked an inward current with a threshold at about -35 mV, a maximum around +10 mV and an apparent reversal potential at about +55 mV. No overlapping transient or background outward currents were detected in the -60 to +30 mV potential range, but time-dependent and steady-state outward currents were elicited at potentials above +30 mV. An overlap of steady-state activation and inactivation curves was present between -30 and +10 mV and a slight relief from inactivation was observed for voltages positive to +10 mV. The time course of inactivation consisted of fast and slow phases with time constants differing by a factor of eight. Slow time constants of inactivation were shorter at potentials that elicited larger Isi, and longer at potentials inducing smaller Isi. Recovery from inactivation evolved slowly with 100% reactivation occurring in about 4000 ms. Switching the holding potential from -60 to -40 mV led to a reversible decline of Isi without any change of the decay time constants. Isi was significantly increased by 0.1 microM isoproterenol. Total or partial inhibition by inorganic (2 mM Mn2+, 3 mM Co2+, 1 mM Cd2+) and organic (1 microM methoxyverapamil, 5 microM diltiazem) calcium antagonists did not unmask any transient outward current. However, a consistent increase of Isi was reversibly observed with 3 mM 4-aminopyridine while using standard solutions. A second series of experiments carried out with K(+)- and Na(+)-free solutions did not demonstrate any significant change from data observed with standard solutions except a reduction of outward currents at steps above +30 mV and alteration of inactivation kinetics. In this experimental setting, 4-aminopyridine also increased Isi but to a lesser degree. We conclude that Isi, as compared to the outward currents, is dominant in the diseased human ventricular cells we have studied

γ-Aminobutyric acid type B receptors are expressed and functional in mammalian cardiomyocytes

γ-Hydroxybutyrate (GHB), an anesthetic adjuvant analog of γ-aminobutyrate (GABA), depresses cell excitability in hippocampal neurons by inducing hyperpolarization through the activation of a prominent inwardly rectifying K(+) (Kir3) conductance. These GABA type B (GABA(B))-like effects are clearly shown at high concentrations of GHB corresponding to blood levels usually reached during anesthesia and are mimicked by the GABA(B) agonist baclofen. Recent studies of native GABA(B) receptors (GABA(B)Rs) have favored the concept that GHB is also a selective agonist. Furthermore, cloning has demonstrated that GABA(B)Rs assemble heteromeric complexes from the GABA(B)R1 and GABA(B)R2 subtypes and that these assemblies are activated by GHB. The surprisingly high tissue content, together with anti-ischemic and protective effects of GHB in the heart, raises the question of a possible influence of GABA(B) agonists on excitable cardiac cells. In the present study, we provide electrophysiological evidence that GHB activates an inwardly rectifying K(+) current in rat ventricular myocytes. This effect is mimicked by baclofen, reversibly inhibited by GABA(B) antagonists, and prevented by pertussis toxin pretreatment. Both GABA(B)R1 and GABA(B)R2 are detected in cardiomyocytes by Western blotting and are shown to coimmunoprecipitate. Laser scanning confocal microscopy discloses an even distribution of the two receptors in the sarcolemma and along the transverse tubular system. Hence, we conclude that GABA(B)Rs are distributed not only in neuronal tissues but also in the heart, where they can be activated and induce electrophysiological alterations through G-protein-coupled inward rectifier potassium channels

Cellular and in vivo electrophysiological effects of dronedarone in normal and post myocardial infracted rats. J Pharmacol Exp Ther

ABSTRACT We studied the effects of dronedarone (SR 33589) on the action potentials, membrane ionic currents, and arrhythmic activity in control rats and in rats after myocardial infarction, a model known to develop anomalous electrical activity. Dronedarone increased action potential duration in normal hearts. It had little effect on the action potentials that were already prolonged in the postmyocardial infarcted (PMI) rats. Particularly, dronedarone reduced the late sustained K ϩ current, I K (or Isus) by 69%. Dronedarone induced only a tonic block of I K . Similar relative inhibitions of I K by dronedarone were obtained in young, sham, and PMI rats, even if I K was less in sham than in young and further reduced in PMI rats. The EC 50 values were 0.78 and 0.85 M in sham and PMI rats. Dronedarone induced a weak increase in the fast transient outward current, I to . Time-to-peak and inactivation time constant of I to were decreased by dronedarone that also induced a marked slowing of I to recovery from inactivation. Similar effects were observed on the reduced I to recorded in PMI rats. Holter monitoring study in control, unthetered animals showed that dronedarone had no proarrhythmic effect. On rats, which after myocardial infarction exhibited ventricular premature beats, dronedarone significantly decreased beat occurrence during the 7-day treatment; this effect was sustained for two more weeks. Thus, dronedarone exerts antiarrhythmic effects on PMI rat heart. Its effects are attributable for the most part to the inhibition of outward K ϩ currents and the increase in effective refractory period. Arrhythmias are one of the most important causes of mortality in patients with heart failure (HF), although the mechanisms of ventricular arrhythmias (VA) during the development of the disease remain unclear Dronedarone, previously labeled SR 33589, is a noniodinated benzofurane derivative structurally related to amiodarone with proven effectiveness on ischemia and reperfusion-induced arrhythmias in animal models, but presumably without its deleterious effects The present study combines in vitro and in vivo models. Our purpose was to investigate the cellular electrophysiological effects of dronedarone on both ionic currents and action potential characteristics, as well as its effects on arrhythmias, in control rats and in postmyocardial infarcted (PMI) rats, a well documented model of ventricular remodeling with significant electrophysiological alteration