125 research outputs found

    Plan de mercadeo estratégico para incrementar las ventas de productos integrales de la empresa Pani Ltda

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    Pasantía (Profesional en Mercadeo y Negocios Internacionales)-- Universidad Autónoma de Occidente, 2008PregradoProfesional en Mercadeo y Negocios Internacionale

    Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell penetrating peptides

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    Recent molecular dynamics simulations (Herce and Garcia, PNAS, 104: 20805 (2007)) have suggested that the arginine-rich HIV Tat peptides might be able to translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, arginine residues play a fundamental role not only in the binding of the peptide to the surface of the membrane but also in the destabilization and nucleation of transient pores across the bilayer, despite being charged and highly hydrophilic. Here we present a molecular dynamics simulation of a peptide composed of nine arginines (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test this hypothesis experimentally by measuring ionic currents across phospholipid bilayers and cell membranes through the pores induced by Arg-9 peptides. We find that Arg-9 peptides, in the presence of an electrostatic potential gradient, induce ionic currents across planar phospholipid bilayers, as well as in cultured osteosarcoma cells and human smooth muscle cells freshly isolated from the umbilical artery. Our results suggest that the mechanism of action of Arg-9 peptide involves the creation of transient pores in lipid bilayers and cell membranes.Comment: This is an extended version of the published manuscript, which had to be shortened before publication to fit within the number of pages required by the journa

    Investigating users' preferences for Low Emission Buses : Experiences from Europe's largest hydrogen bus fleet

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    The Health Economics Research Unit is funded by the Chief Scientists Office (CSO) of the Scottish Government Health and Social Care Directorate. The views expressed paper in this paper are those of the authors and not necessarily those of the CSO. Data collection for this study was funded by the Henderson Economics Research Fund. The funders had no role in study design, data collection and analysis, or preparation of the manuscript.Peer reviewedPostprin

    Musculoskeletal patients’ preferences for care from physiotherapists or support workers : a discrete choice experiment

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    Acknowledgements The authors would like to thank the study participants, members of the study’s Patient and Public Involvement and Engagement (PPIE) group and members of the study’s Clinical Advisory group for their valuable input and advice.Peer reviewe

    Bupivacaine inhibits large conductance, voltage- and Ca2+- activated K+ channels in human umbilical artery smooth muscle cells

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    Bupivacaine is a local anesthetic compound belonging to the amino amide group. Its anesthetic effect is commonly related to its inhibitory effect on voltage-gated sodium channels. However, several studies have shown that this drug can also inhibit voltage-operated K+ channels by a different blocking mechanism. This could explain the observed contractile effects of bupivacaine on blood vessels. Up to now, there were no previous reports in the literature about bupivacaine effects on large conductance voltage- and Ca2+-activated K+ channels (BKCa). Using the patch-clamp technique, it is shown that bupivacaine inhibits single-channel and whole-cell K+ currents carried by BKCa channels in smooth muscle cells isolated from human umbilical artery (HUA). At the single-channel level bupivacaine produced, in a concentration- and voltage-dependent manner (IC50 324 μM at +80 mV), a reduction of single-channel current amplitude and induced a flickery mode of the open channel state. Bupivacaine (300 μM) can also block whole-cell K+ currents (∼45% blockage) in which, under our working conditions, BKCa is the main component. This study presents a new inhibitory effect of bupivacaine on an ion channel involved in different cell functions. Hence, the inhibitory effect of bupivacaine on BKCa channel activity could affect different physiological functions where these channels are involved. Since bupivacaine is commonly used during labor and delivery, its effects on umbilical arteries, where this channel is highly expressed, should be taken into account.Facultad de Ciencias Exacta

    Using a discrete choice experiment to develop a decision aid tool to inform the management of persistent pain in pharmacy : – a protocol for a randomised feasibility study

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    Acknowledgments The authors thank participants from previous stages that helped design the decision aid tool and study procedures for this feasibility study. They also thank Amanda Cardy and the NHS Research Scotland Primary Care (NRS Primary Care) network for their help recruiting healthcare professionals and patients in this and previous stages of the project, and members of the Patient Advisory Group whose input throughout has helped guide the study. The authors thanks internal reviewers whose comments helped improve this Protocol. The authors also thank Dr Gin Nie Chua for her work in the grant awarding and literature review process. Funding This work was funded by Pharmacy Research UK (Grant PRUK-2016-PG57-1). Additional funding has been granted by the University of Aberdeen. The Health Economics Research Unit is supported by the Scottish Government Health and Social Care Directorate. The funders had no input to the study design, collection, management, analysis or interpretation of the data and will have no input to the writing of the report or decision to submit for publication.Peer reviewedPublisher PD

    Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels

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    After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca2+-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca2+-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.Facultad de Ciencias ExactasFacultad de Ciencias MédicasCentro de Endocrinología Experimental y AplicadaGrupo de Investigación en Fisiología Vascula

    Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels

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    After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca2+-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca2+-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.Facultad de Ciencias ExactasFacultad de Ciencias MédicasCentro de Endocrinología Experimental y AplicadaGrupo de Investigación en Fisiología Vascula

    Cambio de uso del suelo: el caso del borde costero de la Araucanía, sur de Chile: evolución y situación actual

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    En esta investigación, se evidencian las implicancias ambientales de los procesos de transformación del paisaje sobre el territorio del borde costero de La Araucanía en Chile, el cual se caracteriza por cinco aspectos: (1) altos niveles de pobreza y de ruralidad, (2) una importante consolidación y expansión de asentamientos agregados, (3) presencia de elementos singulares dados por condiciones naturales (humedales, bosques pantanosos, estuarios), (4) pueblos originarios (mapuche) y (5) procesos de colonización tardía. La investigación muestra inicialmente una revisión exploratoria de los hitos históricos más relevantes que han determinado los procesos de transformación del paisaje. Luego se evalúa geoespacialmente el cambio de uso del suelo entre los años 1980 y 2004, lo que permite precisar las principales categorías de cambio del uso del suelo y el estado actual del paisaje ecológico. Este análisis se complementó con la revisión de indicadores demográficos y socioeconómicos que permite visualizar los efectos del cambio de uso del suelo en la población. Los resultados mostraron que la irrupción de la agroganadería hispano-mediterránea y la posterior desforestación por parte de los colonos tuvo graves efectos en el paisaje. Más recientemente, la dinámica de transformación en la matriz agropecuaria dominante hacia la actividad forestal (pasando de 1% en 1980 a 19% en 2004), ocasionó un retroceso de 8.762 ha de la matriz agropecuaria y una disminución general de todas las coberturas naturales. De este modo, se cuantificó una redistribución de los usos del suelo, aumento de la fragmentación del paisaje y pérdida de conectividad espacial de los sistemas naturales. A su vez, se constató un desplazamiento de la población rural y la consolidación de centros urbanos como Nueva Toltén, Hualpín, Teodoro Schmidt y Saavedra, lo cual se relaciona con la disminución de la natalidad, el incremento de la tasa de envejecimiento y la falta de empleo. Se concluye que la interfaz de relaciones socio-culturales, físico-ambientales y económicas en el área, dan cuenta de la necesidad de nuevos enfoques e instrumentos de planificación que permitan potenciar el desarrollo local.This research makes evident the environmental implications of the process of transforming the landscape in the territory of the coastal strip of La Araucania in Chile, which is characterized by five aspects: (1) high level of poverty and rurality, (2) a major consolidation and expansion of aggregate settlements, (3) the presence of singular elements due to natural conditions (wetlands, swamp forests, estuaries), (4) aboriginal people (mapuche) and, (5) late colonization process. The research shows initially an exploratory revision of the more relevant historical milestones, which have determined the process of transforming the landscape. Then, the change in land use between 1980 and 2004 it is geospatial rated, which allows to specify the main categories of change in land use and the current status of the ecological landscape. This analysis was complemented with the revision of demographic and socioeconomic indicators which permits to view the effects of the change in land use in the population. The results showed that the irruption of the spanish agriculture and and the subsequent deforestation by the settlers had severe effects on the landscape. More recently, the dynamics of transformation in the matrix to the dominant agricultural towards forestry (from 1% in 1980 to 19% in 2004), caused a decrease of 8.762 hectares of the agricultural matrix and a general decline of all natural coverage. Thus, a redistribution of the land use, an increased fragmentation of the landscape and a loss of spatial connectivity of natural systems was quantified. Besides, there was a movement of the rural population and a consolidation of urban centers like Nueva Toltén, Hualpin, Teodoro Schmidt y Saavedra, which it is related to falling of birth rate, increasing of rate of aging and lack of employment. We conclude that the interface of socio-cultural relations, economic and physical environment in the area, reveals the need for new approaches and planning tools for enhancing local development.Peer Reviewe
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