NEW BUTYROLACTONE FROM A MARINE-DERIVED FUNGUS ASPERGILLUS SP

Indexación: Web of Science; ScieloFour compounds that belong to two structure types, namely dibenzylbutyrolactone and sesterterpenoids, were obtained from the extract of the strain Aspergillus sp. (2P-22), isolated from a marine sponge, Cliona chilensis. Among them, compound 1 was identified as new, namely butylrolactone-VI. The structures of these compounds were characterized on the basis of spectroscopic data. Biological activities of these fungal metabolites, are described.http://ref.scielo.org/kbf7v

Effects of trans- and cis-resveratrol on Ca2+ handling in A7r5 vascular myocytes

Although the natural polyphenol resveratrol posses a direct vasorelaxant effect, its effects on cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in vascular cells remain still unclear. Here, we have investigated the effects of the isomers trans- and cis-resveratrol on agonist- and high-K(+)-induced [Ca(2+)](i) increases and on voltage-activated transmembrane Ca(2+) fluxes using imaging and patch-clamp techniques in vascular A7r5 myocytes. Arginine vasopressin (AVP) or angiotensin II caused a biphasic increase in [Ca(2+)](i) that was reduced by preincubation with trans-resveratrol and cis-resveratrol. Both isomers also reduced the agonist-induced increase in [Ca(2+)](i) in absence of extracellular Ca(2+). In high-K(+) Ca(2+)-free solution, reintroduction of Ca(2+) caused a sustained rise in [Ca(2+)](i) that was reduced by preincubation with trans-resveratrol or cis-resveratrol. When the isomers were applied during the plateau phase of the agonist- or the high-K(+)-induced response, a biphasic change in [Ca(2+)](i) was observed: a transient reduction of the plateau (10 min). Finally, trans-resveratrol and cis-resveratrol inhibited voltage-dependent L-type Ca(2+) currents (I(Ca(L))). In conclusion, resveratrol isomers exert a dual effect on [Ca(2+)](i) handling in A7r5 myocytes: 1) a blockade of I(Ca(L)) and 2) an increase in [Ca(2+)](i) by depletion of intracellular Ca(2+) stores (which interferes with the agonist-induced release of intracellular Ca(2+)) and influx of Ca(2+), mainly due to activation of capacitative Ca(2+) entry, although other Ca(2+)-permeable channels are also involved. Taken together, these effects may explain, in part, the endothelium-independent vasorelaxant effects of resveratrol in rat aorta

Synthesis and pharmacological evaluation of coumarins as new scaffold on the Parkinson´s disease

The 13th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic Chemistry and Natural ProductsWith the aim to find out the structural features for the MAO inhibitory activity and selectivity, in the present communication we report the design, synthesis and pharmacological evaluation of a new series of 8-bromo-6-methyl-3-phenylcoumarin derivatives without substituent and with different number of methoxy substituent in the 3-phenyl ring. The substituent in this new scaffold was introduced in the 3', 4' and/or 5' positions of the 3-phenyl ring of the coumarin moiety. The synthesized compounds 3-6 were evaluated as MAO A and B inhibitors using R-(-)-deprenyl (selegiline) and Iproniazide as reference inhibitors, showing, most of them, MAO-B inhibitory activities in the nanomolar range. Compounds 3 (11.05±0.81 nM), 4 (3.23±0.49 nM) and 5 (7.12±0.01 nM) show higher activity than selegiline (IC50 = 19.60 nM), and high MAO-B selectivity with 9,050- fold, 30,960-fold and 14,045-fold inhibition levels, with respect to the MAO-A isoformWe are grateful to the Spanish Ministerio de Sanidad y Consumo (PI061457 and PI061537) and to Xunta da Galicia (BTF20303PR, PXIB203022PR and CSA019203PR) and Fondazione Banco Sardegna (Italy) for financial support. M.J.M. also thanks MIUR for a PhD gran

Synthesis and vasorelaxant and platelet antiaggregatory activities of a new series of 6-Halo-3-phenylcoumarins

A series of 6-halo-3-hydroxyphenylcoumarins (resveratrol-coumarins hybrid derivatives) was synthesized in good yields by a Perkin reaction followed by hydrolysis. The new compounds were evaluated for their vasorelaxant activity in intact rat aorta rings pre-contracted with phenylephrine (PE), as well as for their inhibitory effects on platelet aggregation induced by thrombin in washed human platelets. These compounds concentration-dependently relaxed vascular smooth muscle and some of them showed a platelet antiaggregatory activity that was up to thirty times higher than that shown by trans-resveratrol and some other previously synthesized derivativesWe thank Progetto di Ricerca Scientifica 2007-Università di Cagliari and Fondazione del Banco di Sardegna, Spanish Ministerio de Sanidad y Consumo (FISS PI061537, PI061457), Xunta de Galicia (Spain; INCITE08PXIB203022PR) and Spanish Ministerio de Ciencia e Innovación (FISS PS09/00618). D. Vina acknowledges sponsorships for a tenure-track research position at the University of Santiago de Compostela from the Isidro Parga Pondal Programme of the “Dirección Xeral de Investigación e Desenvolvemento, Xunta de Galicia”. E. Quezada thanks for a postdoctoral grant from FCT (Portugal). Verónica García-Morales thanks for a predoctoral grant (FPU, AP2008-02609, Spanish Ministerio de Ciencia e Innovación). C. Picciau thanks for a predoctoral grant Master & Back-Regione SardegnaS

Selecting cash management models from a multiobjective perspective

[EN] This paper addresses the problem of selecting cash management models under different operating conditions from a multiobjective perspective considering not only cost but also risk. A number of models have been proposed to optimize corporate cash management policies. The impact on model performance of different operating conditions becomes an important issue. Here, we provide a range of visual and quantitative tools imported from Receiver Operating Characteristic (ROC) analysis. More precisely, we show the utility of ROC analysis from a triple perspective as a tool for: (1) showing model performance; (2) choosingmodels; and (3) assessing the impact of operating conditions on model performance. We illustrate the selection of cash management models by means of a numerical example.Work partially funded by projects Collectiveware TIN2015-66863-C2-1-R (MINECO/FEDER) and 2014 SGR 118.Salas-Molina, F.; Rodríguez-Aguilar, JA.; Díaz-García, P. (2018). Selecting cash management models from a multiobjective perspective. Annals of Operations Research. 261(1-2):275-288. https://doi.org/10.1007/s10479-017-2634-9S2752882611-2Ballestero, E. (2007). Compromise programming: A utility-based linear-quadratic composite metric from the trade-off between achievement and balanced (non-corner) solutions. European Journal of Operational Research, 182(3), 1369–1382.Ballestero, E., & Romero, C. (1998). Multiple criteria decision making and its applications to economic problems. Berlin: Springer.Bi, J., & Bennett, K. P. (2003). Regression error characteristic curves. In Proceedings of the 20th international conference on machine learning (ICML-03), pp. 43–50.Bradley, A. P. (1997). The use of the area under the roc curve in the evaluation of machine learning algorithms. Pattern Recognition, 30(7), 1145–1159.da Costa Moraes, M. B., Nagano, M. S., & Sobreiro, V. A. (2015). Stochastic cash flow management models: A literature review since the 1980s. In Decision models in engineering and management (pp. 11–28). New York: Springer.Doumpos, M., & Zopounidis, C. (2007). Model combination for credit risk assessment: A stacked generalization approach. Annals of Operations Research, 151(1), 289–306.Drummond, C., & Holte, R. C. (2000). Explicitly representing expected cost: An alternative to roc representation. In Proceedings of the sixth ACM SIGKDD international conference on Knowledge discovery and data mining (pp. 98–207). New York: ACM.Drummond, C., & Holte, R. C. (2006). Cost curves: An improved method for visualizing classifier performance. Machine Learning, 65(1), 95–130.Elkan, C. (2001). The foundations of cost-sensitive learning. In International joint conference on artificial intelligence (Vol. 17, pp. 973–978). Lawrence Erlbaum associates Ltd.Fawcett, T. (2006). An introduction to roc analysis. Pattern Recognition Letters, 27(8), 861–874.Flach, P. A. (2003). The geometry of roc space: understanding machine learning metrics through roc isometrics. In Proceedings of the 20th international conference on machine learning (ICML-03), pp. 194–201.Garcia-Bernabeu, A., Benito, A., Bravo, M., & Pla-Santamaria, D. (2016). Photovoltaic power plants: a multicriteria approach to investment decisions and a case study in western spain. Annals of Operations Research, 245(1–2), 163–175.Glasserman, P. (2003). Monte Carlo methods in financial engineering (Vol. 53). New York: Springer.Gregory, G. (1976). Cash flow models: a review. Omega, 4(6), 643–656.Hernández-Orallo, J. (2013). Roc curves for regression. Pattern Recognition, 46(12), 3395–3411.Hernández-Orallo, J., Flach, P., & Ferri, C. (2013). Roc curves in cost space. Machine Learning, 93(1), 71–91.Hernández-Orallo, J., Lachiche, N., & Martınez-Usó, A. (2014). Predictive models for multidimensional data when the resolution context changes. In Workshop on learning over multiple contexts at ECML, volume 2014.Metz, C. E. (1978). Basic principles of roc analysis. In Seminars in nuclear medicine (Vol. 8, pp. 283–298). Amsterdam: Elsevier.Miettinen, K. (2012). Nonlinear multiobjective optimization (Vol. 12). Berlin: Springer.Ringuest, J. L. (2012). Multiobjective optimization: Behavioral and computational considerations. Berlin: Springer.Ross, S. A., Westerfield, R., & Jordan, B. D. (2002). Fundamentals of corporate finance (sixth ed.). New York: McGraw-Hill.Salas-Molina, F., Pla-Santamaria, D., & Rodriguez-Aguilar, J. A. (2016). A multi-objective approach to the cash management problem. Annals of Operations Research, pp. 1–15.Srinivasan, V., & Kim, Y. H. (1986). Deterministic cash flow management: State of the art and research directions. Omega, 14(2), 145–166.Steuer, R. E., Qi, Y., & Hirschberger, M. (2007). Suitable-portfolio investors, nondominated frontier sensitivity, and the effect of multiple objectives on standard portfolio selection. Annals of Operations Research, 152(1), 297–317.Stone, B. K. (1972). The use of forecasts and smoothing in control limit models for cash management. Financial Management, 1(1), 72.Torgo, L. (2005). Regression error characteristic surfaces. In Proceedings of the eleventh ACM SIGKDD international conference on Knowledge discovery in data mining (pp. 697–702). ACM.Yu, P.-L. (1985). Multiple criteria decision making: concepts, techniques and extensions. New York: Plenum Press.Zeleny, M. (1982). Multiple criteria decision making. New York: McGraw-Hill

Design, Synthesis and Pharmacological Evaluation of New Coumarin Derivatives as Monoamine Oxidase A and B Inhibitors

The 12th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic Chemistry and Natural ProductsWith the aim to find out the structural features for the MAO inhibitory activity and selectivity, in the present communication we report the design, synthesis and pharmacological evaluation of a new series of coumarin derivatives with 4-methyl or cycloalkene or benzene ring condensed in the 3,4 position. The substituents in this new scaffold were introduced in the 5, 7 and/or 8 positions of the coumarin moiety. The synthesized compounds 1-13 were evaluated as MAO A and B inhibitors using clorgyline and selegiline, respectively, as reference inhibitors, showing, most of them, activities in the nanomolar range. Compounds 6 (IC50 = 1.18 nM) and 10 (IC50 = 1.48 nM), show higher activity than selegiline (IC50 = 19.60 nM), and high MAO-B selectivity with 100-fold and 1600-fold inhibition levels, with respect to the MAO-A isoformWe are grateful to the Xunta de Galicia (INCITE07PXI203030ES, PGIDIT05BTF20302PR and INCITE08PXIB203022PR) and Ministerio de Sanidad y Consumo (FIS PI061537 and PI061457) for financial support

Results of Pregnancy Control before and during the COVID-19 Pandemic: A Comparison of Two Cohorts

The COVID-19 pandemic placed pregnant women at high risk, but behavioural changes have also led to lower rates of preterm births in high-income countries. The main goal of this article is to study the ongoing impact of the COVID-19 pandemic on pregnancy control and outcomes; this is a joint analysis of two cohorts. The pre-pandemic cohort includes 969 pregnant women recruited in 2018. The pandemic cohort comprises 1168 pregnant women recruited in 2020. Information on demographic and socioeconomic characteristics, reproductive history, characteristics of the current pregnancy and its outcome were obtained from medical records. Birth by Caesarean section was more frequent in the pre-pandemic cohort (adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI): 0.55-0.92). A birth weight lower than 2500 g and higher than 4000 g occurred more frequently in the pre-pandemic cohort (adjusted OR = 0.62, 95% CI: 0.41-0.93 for lower than 2500 g and adjusted OR = 0.30, 95% CI: 0.20-0.46 for higher than 4000 g). Exclusive breastfeeding upon hospital discharge was more frequent in the pandemic cohort than in the pre-pandemic cohort (60% vs. 54%, p = 0.005), with adjusted OR = 0.67, 95% CI: 0.52-0.86 for mixed breastfeeding and infant formula. In conclusion, we report reductions in Caesarean sections and reduced numbers of low birth weight babies during the pandemic in a hospital located in northern Spain. Further analysis will clarify if these reductions are related to changes in health-related behaviour or healthcare operation

Educación para el desarrollo en Castilla y León: cómo vemos el mundo

439 p.Quienes creemos que son necesarios cambios en el sistema económico, político y financiero mundial que permitan avanzar en el desarrollo humano sostenible de los pueblos, superando las injusticias y las brechas de desigualdad en el acceso a los recursos, siempre hemos considerado la educación como una pieza clave para conducir ese cambio, y a la universidad como un agente fundamental que puede y debe desarrollarla. Es difícil reflexionar sobre la “Educación para el Desarrollo” distanciándose de los acontecimientos que durante los últimos meses están ocurriendo en Europa y España. Estamos viendo y viviendo cómo la crisis financiera y económica es utilizada para justificar decisiones políticas que reducen nuestro nivel de bienestar. Es inevitable la comparación con los planes de ajuste estructural (PAE) que desde los años 80 se impusieron al dictado del FMI y el BM a los países empobrecidos como respuesta a la crisis de la Deuda Externa, así como sus nefastas consecuencias sociales y económicas para los pueblos afectado

Study of the in vivo and in vitro cardiovascular effects of a hydralazine-like vasodilator agent (HPS-10) in normotensive rats

1. In this work, the cardiovascular effects of HPS-10, a new vasodilator agent, were studied in rats. 2. In conscious normotensive rats, oral administration of HPS-10 (4–9 mg kg(−1)) produced a dose-related and long-lasting fall in systolic arterial blood pressure (ED(30) of 5.32 mg kg(−1)), accompanied by an increase in heart rate (ED(30) of 8.43 mg kg(−1)). This tachycardia was totally inhibited by pretreatment with (±)-propranolol (10 mg kg(−1), p.o.). 3. In anaesthetized normotensive rats, HPS-10 (0.3–0.6 mg kg(−1), i.v.) produced a gradual, dose-dependent and sustained decrease in systolic, diastolic and mean arterial pressure (MAP) (ED(30) for MAP of 0.41 mg kg(−1), i.v.), accompanied by a significant bradycardia at high doses (>0.4 mg kg(−1); ED(20) of 0.61 mg kg(−1), i.v.). HPS-10 (0.5 mg kg(−1), i.v.) did not modify the positive chronotropic effects induced by intravenous administration of noradrenaline (NA; 5 μg kg(−1)), angiotensin II (AII; 0.2 μg kg(−1)) and nicotine (200 μg kg(−1)) but markedly inhibited the hypertensive response produced by these agents. 4. In rat isolated rubbed aorta, HPS-10 (0.1–1 mM) non-competitively and with almost equal effectiveness antagonized the contractions induced by NA, AII (in normal Krebs solution) and Ca(2+) (in depolarizing Ca(2+)-free high-K(+) 50 mM solution). In the experiments in Ca(2+)-free medium, HPS-10 (1 mM) considerably inhibited the contractions induced by NA, AII and caffeine in rat aorta. 5. Furthermore, in the studies with radioactive Ca(2+), HPS-10 (1 mM) did not modify the basal uptake of (45)Ca(2+) but strongly decreased the influx of (45)Ca(2+) induced by NA, AII and K(+) in rat aortic rings. 6. In rat isolated atria, HPS-10 (1 mM) produced a positive inotropic/negative chronotropic effect. 7. HPS-10 (0.3 mM) significantly inhibited the sustained and transient Ba(2+) inward current (I(Ba)) recorded in whole-cell clamped rat aortic myocytes. 8. These results indicate that the non-selective vasorelaxant effects of HPS-10 in rat aortic rings can be attributed to transmembrane Ca(2+)-antagonist activity and an intracellular action on smooth muscle cells. The direct vasodilator action of HPS-10 observed in rat isolated aorta may be responsible for the HPS-10 hypotensive activity in anaesthetized normotensive rats

Efecto del endotelio sobre las contracciones inducidas por noradrenalina y K+ en aortas de rata genéticamente hipertensa y rata normotensa

Desde que Furchgott (1, 2) descubrió que la presencia de endotelio era imprescindible para la acción relajante vascular de la acetilcolina, han aparecido diversos y variados estudios que demuestran su participación en la relajación provocada por diversos agentes (ATP, serotonina, histamina, ...) (3. 4, 5, 6). Es mas, se han descrito diversos mecanismos en células del endotelio vascular que, al ser activados, pueden estimular la liberación de varios factores endoteliales (7). También se ha demostrado la existencia de una posible disfunción o mal funcionamiento del sistema endotelial en procesos de hipertensión, debido. bien a una dificultad en la liberación de EDRF (endothelium derived relaxing factor)(8), o bien a un aumento en la liberación de EDCF (endothelium derived contracting factor)(9. 10). Con el objeto de confirmar la Influencia de los procesos de hipertensión sobre el estado del endotelio, en el presente trabajo se estudia la posible modulación por el sistema endotelial de las contracciones inducidas por noradrenalina y. CaCI2 (en media despolarizante) en aorta de rata normotensa e hipertensa