The Experts below are selected from a list of 4494 Experts worldwide ranked by ideXlab platform

José Henrique Leal-cardoso - One of the best experts on this subject based on the ideXlab platform.

  • Investigation of Terpinen-4-Ol effects on vascular smooth muscle relaxation.
    Life Sciences, 2014
    Co-Authors: Rebeca Peres Moreno Maia-joca, Francisca Jéssica Penha Ribeiro, Kerly Shamyra Da Silva-alves, Andrelina Noronha Coelho-de-souza, Renata Vieira Do Nascimento, Humberto Cavalcante Joca, Jader S. Cruz, José Henrique Leal-cardoso
    Abstract:

    Abstract Aims This study investigated the mechanisms underlying the vascular effects of Terpinen-4-Ol in isOlated rat aortic ring preparations. Main methods The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Key findings Terpinen-4-Ol reversibly relaxed endothelium-containing preparations pre-contracted with high K+ and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca2 +-free and high K+ (80 mM) medium, the contractions produced by Ba2 + were reduced by Terpinen-4-Ol (100–1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca2 +-free conditions, Terpinen-4-Ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbOl 12,13-dibutyrate (1 μM). Terpinen-4-Ol (10–1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by Terpinen-4-Ol exposure. Significance The present results suggest that Terpinen-4-Ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through vOltage-operated calcium channels.

  • Investigation of Terpinen-4-Ol effects on vascular smooth muscle relaxation.
    Life sciences, 2014
    Co-Authors: Rebeca Peres Moreno Maia-joca, Francisca Jéssica Penha Ribeiro, Kerly Shamyra Da Silva-alves, Andrelina Noronha Coelho-de-souza, Renata Vieira Do Nascimento, Humberto Cavalcante Joca, Jader S. Cruz, José Henrique Leal-cardoso
    Abstract:

    This study investigated the mechanisms underlying the vascular effects of Terpinen-4-Ol in isOlated rat aortic ring preparations. The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Terpinen-4-Ol reversibly relaxed endothelium-containing preparations pre-contracted with high K(+) and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca(2+)-free and high K(+) (80 mM) medium, the contractions produced by Ba(2+) were reduced by Terpinen-4-Ol (100-1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca(2+)-free conditions, Terpinen-4-Ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbOl 12,13-dibutyrate (1 μM). Terpinen-4-Ol (10-1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by Terpinen-4-Ol exposure. The present results suggest that Terpinen-4-Ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through vOltage-operated calcium channels. Copyright © 2014 Elsevier Inc. All rights reserved.

  • Terpinen-4-Ol: mechanisms of relaxation on rabbit duodenum
    The Journal of pharmacy and pharmacology, 2005
    Co-Authors: Nilberto R.f. Nascimento, José Henrique Leal-cardoso, Lucília M. A. Lessa, Jarbas S. Roriz-filho, Karina M. A. Cunha, Manassés C. Fonteles
    Abstract:

    The effect of Terpinen-4-Ol was studied on rabbit duodenum in-vitro. Terpinen-4-Ol induced relaxation of the basal tonus (IC50 170.2 (95% confidence interval, 175-204) microM) with a maximal relaxant response of 180.4+/-3.9% (n=6) of the contraction induced by 60 mM [K(+)]. The maximal relaxation induced in contrOl conditions was not affected (P>0.05) by pretreatment of the tissues with phentOlamine (50 microM) or propranOlOl (10 microM), N(G) nitro-L-arginine methyl ester (L-NAME; 1 mM), 1H-(1,2,4)oxadiazOlo[4,3-a]quinoxalin-1-one (ODQ; 100 microM), hexamethonium (1 mM), tetrodotoxin (1 microM), the mixture charybdotoxin-apamin (1 microM), glibenclamide (10 microM), 4-aminopyridine (10 microM) or tetraethyl-ammonium (100 microM). In addition, Terpinen-4-Ol completely relaxed tissues precontracted with 60 mM [K(+)] sOlutions (IC50 325.9 (245.1-433.1) microM) and also blocked (IC50 154.7 (117.7-191.7) microM) the phasic component of this contraction. At a concentration of 195 and 650 muM it reduced by 41.3+/-3.4% and 75.4+/-3.1%, respectively the maximal contractile response to Ca(2+) in depOlarized duodenum. Terpinen-4-Ol completely blocked the component of carbachOl-induced contraction, which was resistant to nifedipine (100 microM) pretreatment or to a Ca(2+)-free sOlution. These data show that Terpinen-4-Ol relaxes intestinal smooth muscle and suggest that this effect is myogenic in nature and depends on calcium antagonism.

Jader S. Cruz - One of the best experts on this subject based on the ideXlab platform.

  • (-)-Terpinen-4-Ol changes intracellular Ca2+ handling and induces pacing disturbance in rat hearts
    European journal of pharmacology, 2017
    Co-Authors: Antonio Nei Santana Gondim, Aline Lara, Artur Santos-miranda, Danilo Roman-campos, Sandra Lauton-santos, José Evaldo Rodrigues De Menezes-filho, Carla Maria Lins De Vasconcelos, Eduardo Antonio Conde-garcia, Silvia Guatimosim, Jader S. Cruz
    Abstract:

    (-)-Terpinen-4-Ol is a naturally occurring plant monoterpene and has been shown to have a plethora of biOlogical activities. The objective of this study was to investigate the effects of (-)-Terpinen-4-Ol on the rat heart, a key player in the contrOl and maintenance of arterial blood pressure. The effects of (-)-Terpinen-4-Ol on the rat heart were investigated using isOlated left atrium isometric force measurements, in vivo electrocardiogram (ECG) recordings, patch clamp technique, and confocal microscopy. It was observed that (-)-Terpinen-4-Ol reduced contraction force in an isOlated left atrium at millimOlar concentrations. Conversely, it induced a positive inotropic effect and extrasystOles at micromOlar concentrations, suggesting that (-)-Terpinen-4-Ol may have arrhythmogenic activity on cardiac tissue. In anaesthetized animals, (-)-Terpinen-4-Ol also elicited rhythm disturbance, such as supraventricular tachycardia and atrioventricular block. To investigate the cellular mechanism underlying the dual effect of (-)-Terpinen-4-Ol on heart muscle, experiments were performed on isOlated ventricular cardiomyocytes to determine the effect of (-)-Terpinen-4-Ol on L-type Ca2+ currents, Ca2+ sparks, and Ca2+ transients. The arrhythmogenic activity of (-)-Terpinen-4-Ol in vitro and in vivo may be explained by its effect on intracellular Ca2+ handling. Taken together, our data suggest that (-)-Terpinen-4-Ol has cardiac arrhythmogenic activity.

  • Investigation of Terpinen-4-Ol effects on vascular smooth muscle relaxation.
    Life Sciences, 2014
    Co-Authors: Rebeca Peres Moreno Maia-joca, Francisca Jéssica Penha Ribeiro, Kerly Shamyra Da Silva-alves, Andrelina Noronha Coelho-de-souza, Renata Vieira Do Nascimento, Humberto Cavalcante Joca, Jader S. Cruz, José Henrique Leal-cardoso
    Abstract:

    Abstract Aims This study investigated the mechanisms underlying the vascular effects of Terpinen-4-Ol in isOlated rat aortic ring preparations. Main methods The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Key findings Terpinen-4-Ol reversibly relaxed endothelium-containing preparations pre-contracted with high K+ and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca2 +-free and high K+ (80 mM) medium, the contractions produced by Ba2 + were reduced by Terpinen-4-Ol (100–1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca2 +-free conditions, Terpinen-4-Ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbOl 12,13-dibutyrate (1 μM). Terpinen-4-Ol (10–1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by Terpinen-4-Ol exposure. Significance The present results suggest that Terpinen-4-Ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through vOltage-operated calcium channels.

  • Investigation of Terpinen-4-Ol effects on vascular smooth muscle relaxation.
    Life sciences, 2014
    Co-Authors: Rebeca Peres Moreno Maia-joca, Francisca Jéssica Penha Ribeiro, Kerly Shamyra Da Silva-alves, Andrelina Noronha Coelho-de-souza, Renata Vieira Do Nascimento, Humberto Cavalcante Joca, Jader S. Cruz, José Henrique Leal-cardoso
    Abstract:

    This study investigated the mechanisms underlying the vascular effects of Terpinen-4-Ol in isOlated rat aortic ring preparations. The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Terpinen-4-Ol reversibly relaxed endothelium-containing preparations pre-contracted with high K(+) and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca(2+)-free and high K(+) (80 mM) medium, the contractions produced by Ba(2+) were reduced by Terpinen-4-Ol (100-1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca(2+)-free conditions, Terpinen-4-Ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbOl 12,13-dibutyrate (1 μM). Terpinen-4-Ol (10-1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by Terpinen-4-Ol exposure. The present results suggest that Terpinen-4-Ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through vOltage-operated calcium channels. Copyright © 2014 Elsevier Inc. All rights reserved.

Rebeca Peres Moreno Maia-joca - One of the best experts on this subject based on the ideXlab platform.

  • Investigation of Terpinen-4-Ol effects on vascular smooth muscle relaxation.
    Life Sciences, 2014
    Co-Authors: Rebeca Peres Moreno Maia-joca, Francisca Jéssica Penha Ribeiro, Kerly Shamyra Da Silva-alves, Andrelina Noronha Coelho-de-souza, Renata Vieira Do Nascimento, Humberto Cavalcante Joca, Jader S. Cruz, José Henrique Leal-cardoso
    Abstract:

    Abstract Aims This study investigated the mechanisms underlying the vascular effects of Terpinen-4-Ol in isOlated rat aortic ring preparations. Main methods The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Key findings Terpinen-4-Ol reversibly relaxed endothelium-containing preparations pre-contracted with high K+ and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca2 +-free and high K+ (80 mM) medium, the contractions produced by Ba2 + were reduced by Terpinen-4-Ol (100–1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca2 +-free conditions, Terpinen-4-Ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbOl 12,13-dibutyrate (1 μM). Terpinen-4-Ol (10–1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by Terpinen-4-Ol exposure. Significance The present results suggest that Terpinen-4-Ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through vOltage-operated calcium channels.

  • Investigation of Terpinen-4-Ol effects on vascular smooth muscle relaxation.
    Life sciences, 2014
    Co-Authors: Rebeca Peres Moreno Maia-joca, Francisca Jéssica Penha Ribeiro, Kerly Shamyra Da Silva-alves, Andrelina Noronha Coelho-de-souza, Renata Vieira Do Nascimento, Humberto Cavalcante Joca, Jader S. Cruz, José Henrique Leal-cardoso
    Abstract:

    This study investigated the mechanisms underlying the vascular effects of Terpinen-4-Ol in isOlated rat aortic ring preparations. The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Terpinen-4-Ol reversibly relaxed endothelium-containing preparations pre-contracted with high K(+) and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca(2+)-free and high K(+) (80 mM) medium, the contractions produced by Ba(2+) were reduced by Terpinen-4-Ol (100-1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca(2+)-free conditions, Terpinen-4-Ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbOl 12,13-dibutyrate (1 μM). Terpinen-4-Ol (10-1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by Terpinen-4-Ol exposure. The present results suggest that Terpinen-4-Ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through vOltage-operated calcium channels. Copyright © 2014 Elsevier Inc. All rights reserved.

Denise Madalena Palomari Spolidorio - One of the best experts on this subject based on the ideXlab platform.

  • Terpinen 4 Ol and nystatin co loaded precursor of liquid crystalline system for topical treatment of oral candidiasis
    Scientific Reports, 2020
    Co-Authors: Renata Serignoli Francisconi, Giovana Calixto, Patricia Milagros Maquerahuacho, Caroline Coradi Tono, Janaina De Cassia Orlandi Sardi, Marlus Chorilli, Denise Madalena Palomari Spolidorio
    Abstract:

    This study was performed to develop a liquid crystalline system (LCS) incorporated with Terpinen-4-Ol and nystatin to evaluate its antifungal, antibiofilm, and synergistic/modulatory activity against Candida albicans. The LCS was composed of a dispersion containing 40% propoxylated and ethoxylated cetyl alcohOl, 40% Oleic acid, and 0.5% chitosan dispersion. According to analysis by pOlarized light microscopy, rheOlogy, and mucoadhesion studies, the incorporation of 100% artificial saliva increased the pseudoplasticity, consistency index, viscosity, and mucoadhesion of the formulation. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity; the LCS containing Terpinen-4-Ol and nystatin effectively inhibited C. albicans growth at a lower concentration, displaying a synergistic action. Therefore, LCS incorporated with Terpinen-4-Ol and nystatin is a promising alternative for preventing and treating infections and shows potential for the development of therapeutic strategies against candidiasis.

  • Antibiofilm efficacy of tea tree oil and of its main component Terpinen-4-Ol against Candida albicans.
    Brazilian oral research, 2020
    Co-Authors: Renata Serignoli Francisconi, Janaina De Cassia Orlandi Sardi, Caroline Coradi Tonon, Ester Alves Ferreira Bordini, Patricia Milagros Maquera Huacho, Marília Ferreira Correia, Denise Madalena Palomari Spolidorio
    Abstract:

    Candida infection is an important cause of morbidity and mortality in immunocompromised patients. The increase in its incidence has been associated with resistance to antimicrobial therapy and biofilm formation. The aim of this study was to evaluate the efficacy of tea tree oil (TTO) and its main component - Terpinen-4-Ol - against resistant Candida albicans strains (genotypes A and B) identified by mOlecular typing and against C. albicans ATCC 90028 and SC 5314 reference strains in planktonic and biofilm cultures. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity. Results were obtained from analysis of the biofilm using the cell prOliferation assay 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazOlium-5-carboxanilide (XTT) and confocal laser scanning microscopy (CLSM). Terpinen-4-Ol and TTO inhibited C. albicans growth. CLSM confirmed that 17.92 mg/mL of TTO and 8.86 mg/mL of Terpinen-4-Ol applied for 60 s (rinse simulation) interfered with biofilm formation. Hence, this in vitro study revealed that natural substances such as TTO and Terpinen-4-Ol present promising results for the treatment of oral candidiasis.

  • Terpinen-4-Ol and carvacrOl affect multi-species biofilm composition.
    Biofouling, 2019
    Co-Authors: Patricia Milagros Maquera Huacho, Denise Madalena Palomari Spolidorio, Esteban Rodriguez Herrero, Tim Verspecht, Martine Pauwels, Elcio Marcantonio, Wim Teughels
    Abstract:

    AbstractThe aim of this study was to investigate the cytotoxic activity and inhibitory effect of Terpinen-4-Ol (T4Ol) and carvacrOl against single- and multi-species biofilms. The toxicity of each ...

  • Antimicrobial effects of Terpinen-4-Ol against oral pathogens and its capacity for the modulation of gene expression.
    Biofouling, 2018
    Co-Authors: Ester Alves Ferreira Bordini, Renata Serignoli Francisconi, Caroline Coradi Tonon, Patricia Milagros Maquera Huacho, Fernando Augusto Cintra Magalhães, Telma Blanca Lombardo Bedran, Sebastião Pratavieira, Luis Carlos Spolidório, Denise Madalena Palomari Spolidorio
    Abstract:

    AbstractThis study evaluated the antibacterial activity of Terpinen-4-Ol against Streptococcus mutans and Lactobacillus acidophilus and its influence on gbpA (S. mutans) and slpA (L. acidophilus) gene expression. As measured by XTT assay, the concentrations of Terpinen-4-Ol that effectively inhibited the biofilm were 0.24% and 0.95% for S. mutans and L. acidophilus, respectively. Confocal microscopy revealed the presence of a biofilm attached to the enamel and dentin block surfaces with significant Terpinen-4-Ol effects against these microorganisms. The expression of the gbpA and slpA genes invOlved in adherence and biofilm formation was investigated using RT-PCR. Expression of these genes decreased after 15 min with 0.24% and 0.95% Terpinen-4-Ol in S. mutans and L. acidophilus, respectively. These findings demonstrate the antimicrobial activity of Terpinen-4-Ol and its ability to modulate the expression of gbpA and slpA genes, emphasizing the therapeutic capacity of Terpinen-4-Ol as an alternative to inh...

  • In vitro antibacterial and cytotoxic activities of carvacrOl and Terpinen-4-Ol against biofilm formation on titanium implant surfaces.
    Biofouling, 2018
    Co-Authors: Patricia Milagros Maquera-huacho, Renata Serignoli Francisconi, Caroline Coradi Tonon, Ester Alves Ferreira Bordini, Elcio Marcantonio, Marília Ferreira Correia, Denise Madalena Palomari Spolidorio
    Abstract:

    This study evaluated the antibacterial properties of carvacrOl and Terpinen-4-Ol against Porphyromonas gingivalis and Fusobacterium nucleatum and its cytotoxic effects on fibroblast cells. The mini...

Francisca Jéssica Penha Ribeiro - One of the best experts on this subject based on the ideXlab platform.

  • Investigation of Terpinen-4-Ol effects on vascular smooth muscle relaxation.
    Life Sciences, 2014
    Co-Authors: Rebeca Peres Moreno Maia-joca, Francisca Jéssica Penha Ribeiro, Kerly Shamyra Da Silva-alves, Andrelina Noronha Coelho-de-souza, Renata Vieira Do Nascimento, Humberto Cavalcante Joca, Jader S. Cruz, José Henrique Leal-cardoso
    Abstract:

    Abstract Aims This study investigated the mechanisms underlying the vascular effects of Terpinen-4-Ol in isOlated rat aortic ring preparations. Main methods The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Key findings Terpinen-4-Ol reversibly relaxed endothelium-containing preparations pre-contracted with high K+ and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca2 +-free and high K+ (80 mM) medium, the contractions produced by Ba2 + were reduced by Terpinen-4-Ol (100–1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca2 +-free conditions, Terpinen-4-Ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbOl 12,13-dibutyrate (1 μM). Terpinen-4-Ol (10–1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by Terpinen-4-Ol exposure. Significance The present results suggest that Terpinen-4-Ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through vOltage-operated calcium channels.

  • Investigation of Terpinen-4-Ol effects on vascular smooth muscle relaxation.
    Life sciences, 2014
    Co-Authors: Rebeca Peres Moreno Maia-joca, Francisca Jéssica Penha Ribeiro, Kerly Shamyra Da Silva-alves, Andrelina Noronha Coelho-de-souza, Renata Vieira Do Nascimento, Humberto Cavalcante Joca, Jader S. Cruz, José Henrique Leal-cardoso
    Abstract:

    This study investigated the mechanisms underlying the vascular effects of Terpinen-4-Ol in isOlated rat aortic ring preparations. The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Terpinen-4-Ol reversibly relaxed endothelium-containing preparations pre-contracted with high K(+) and phenylephrine with IC50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca(2+)-free and high K(+) (80 mM) medium, the contractions produced by Ba(2+) were reduced by Terpinen-4-Ol (100-1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca(2+)-free conditions, Terpinen-4-Ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbOl 12,13-dibutyrate (1 μM). Terpinen-4-Ol (10-1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by Terpinen-4-Ol exposure. The present results suggest that Terpinen-4-Ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through vOltage-operated calcium channels. Copyright © 2014 Elsevier Inc. All rights reserved.