Synergistic Activity of Thymol with Commercial Antibiotics against Critical and High WHO Priority Pathogenic Bacteria.

The use of synergistic combinations between natural compounds and commercial antibiotics may be a good strategy to fight against microbial resistance, with fewer side effects on human, animal and environmental, health. The antimicrobial capacity of four compounds of plant origin (thymol and gallic, salicylic and gentisic acids) was analysed against 14 pathogenic bacteria. Thymol showed the best antimicrobial activity, with MICs ranging from 125 µg/mL (for Acinetobacter baumannii, Pasteurella aerogenes, and Salmonella typhimurium) to 250 µg/mL (for Bacillus subtilis, Klebsiella aerogenes, Klebsiella pneumoniae, Serratia marcescens, Staphylococcus aureus, and Streptococcus agalactiae). Combinations of thymol with eight widely used antibiotics were studied to identify combinations with synergistic effects. Thymol showed synergistic activity with chloramphenicol against A. baumannii (critical priority by the WHO), with streptomycin and gentamicin against Staphylococcus aureus (high priority by the WHO), and with streptomycin against Streptococcus agalactiae, decreasing the MICs of these antibiotics by 75% to 87.5%. The kinetics of these synergies indicated that thymol alone at the synergy concentration had almost no effect on the maximum achievable population density and very little effect on the growth rate. However, in combination with antibiotics at the same concentration, it completely inhibited growth, confirming its role in facilitating the action of the antibiotic. The time-kill curves indicated that all the combinations with synergistic effects were mainly bactericidal.

Supercritical Antisolvent Fractionation of Antioxidant Compounds from Salvia officinalis.

The increasing interest towards greener antioxidants obtained via natural sources and more sustainable processes encourages the development of new theoretical and experimental methods in the field of those compounds. Two advanced separation methods using supercritical CO2 are applied to obtain valuable antioxidants from Salvia officinalis, and a first approximation to a QSAR model relating molecular structure with antioxidant activity is explored in order to be used, in the future, as a guide for the preselection of compounds of interest in these processes. Separation experiments through antisolvent fractionation with supercritical CO2 were designed using a Response Surface Methodology to study the effect of pressure and CO2 flow rate on both mass yields and capability to obtain fractions enriched in three antioxidant compounds: chlorogenic acid, caffeic acid and rosmarinic acid which were tracked using HPLC PDA. Rosmarinic acid was completely retained in the precipitation vessel while chlorogenic and caffeic acids, though distributed between the two separated fractions, had a major presence in the precipitation vessel too. The conditions predicted for an optimal overall yield and enrichment were 148 bar and 10 g/min. Although a training dataset including much more compounds than those now considered can be recommended, descriptors calculated from the σ-profiles provided by COSMO-RS model seem to be adequate for estimating the antioxidant activity of pure compounds through QSAR.

Concentration of Antioxidant Compounds from Calendula officinalis through Sustainable Supercritical Technologies, and Computational Study of Their Permeability in Skin for Cosmetic Use.

The growing interest in the cosmetic industry in using compounds of natural and sustainable origin that are safe for humans is encouraging the development of processes that can satisfy these needs. Chlorogenic acid (CHA), caffeic acid (CAF) and ferulic acid (FA) are three compounds widely used within the cosmetic industry due to their functionalities as antioxidants, collagen modifiers or even as radiation protectors. In this work, two advanced separation techniques with supercritical CO2 are used to obtain these three compounds from Calendula officinalis, and these are then evaluated using a computational skin permeability model. This model is encompassed by the COSMO-RS model, the calculations of which make it possible to study the behaviour of the compounds in the epidermis. The results show that both CAF and FA are retained in the stratum corneum, while CHA manages to penetrate to the stratum spinosum. These compounds were concentrated by antisolvent fractionation with super-critical CO2 using a Response Surface Methodology to study the effect of pressure and CO2 flow rate. CHA, CAF and FA were completely retained in the precipitation vessel, with concentrations between 40% and 70% greater than in the original extract. The conditions predicted that the optimal overall yield and enrichment achieved would be 153 bar and 42 g/min.

Impact of Artemisia absinthium hydrolate extracts with nematicidal activity on non-target soil organisms of different trophic levels.

Natural pesticides are considered a good alternative to synthetic pesticides to reduce environmental impacts. However, biopesticides may have unknown effects on the environment, and can affect non-target organisms. In this study, the ecotoxicological effects of an aqueous extract (hydrolate) from Spanish populations of Artemisia absinthium (var. Candial) showing a promising biopesticide activity, were evaluated on non-target soil organisms from different trophic levels (natural microbial communities characterized through 16S rRNA gene sequencing, the earthworm Eisenia fetida and the plant Allium cepa). The hydrolate usually was considered as a by-product of the distillation to obtain essential oils. However, recently has been found to have nematicide properties. The hydrolate caused acute toxicity at values of LC50 of 3.87% v/v for A. cepa and 0.07 mL/g for E. fetida. All the concentrations except for the most diluted (1% v/v) reduced the bacterial physiological activity compared to controls (LC50 = 25.72% v/v after 24 h of exposure). The hydrolate also slightly altered the ability of the microbial community to degrade carbon substrates. These results indicate that the hydrolate from A. absinthium may affect the survival and metabolic abilities of key soil organisms.

Determinación de zonas isotérmicas y selección de estaciones meteorológicas representativas en Aragón como base para la estimación del impacto del cambio climático sobre la posible relación entre mortalidad y temperatura / Determination of isothermal Areas and selection of representative weather stations in Aragon as a basis for estimating the impact of climate change on the possible relationship between mortality and temperature

Fundamento: En regiones extensas y diversificadas, como Aragón, se cree la necesidad de dividirlas en áreas en función de las variables atmosféricas disponibles, para seleccionar una estación meteorológica representativa. El objeto de este artículo es determinar la existencia de regiones isotérmicas y seleccionar las estaciones representativas con el fin de estudiar la correlación entre variables de temperatura y mortalidad diaria. Métodos: Se seleccionaron datos diarios de temperatura máxima y mínima para el periodo comprendido entre enero de 1987 y diciembre de 2006. Para determinar las zonas isotérmicas se realizó un análisis de conglomerados jerárquicos y un análisis factorial discriminante, así como un tratamiento previo de datos de relleno de lagunas y detección de heterogeneidades en las series climáticas. Se analizaron datos de 93 estaciones (44 en Huesca, 15 en Teruel y 34 en Zaragoza). Resultados: De los resultados del análisis para la regionalización de Aragón extrajimos que un solo factor explica la varianza de cada serie. En temperaturas máximas ese único factor explicó el 93,43% de la varianza y la estación que representó un mayor factor de correlación fue Huesca-Monflorite (correlación=0,984). Para temperaturas mínimas un único factor explicó el 90,88% de la varianza, siendo la estación con mayor factor de correlación Pallaruelo de Monegros (correlación= 0,976). Conclusiones: Se consideró queAragón es una única región isotérmica con una única estación representativa de la variabilidad de las temperaturas, Zaragoza-Aeropuerto, con una correlación en temperaturas máximas de 0,980 y en mínimas de 0,974(AU)

Background: In extensive and diversified regions, such as Aragon, it is believed the need to divide them into areas in terms of the available atmospheric variables with a view to select a representative weather station. The objective of this study was to determine the existence of isothermal regions and select representative stations forAragon in order to carry out further study on the correlation between variables of temperature and daily mortality. Methods: Daily data on maximum and minimum temperature for the period between January 1987 and December 2006 was selected. In order to determine the isothermal areas a cluster analysis and a discriminate factor analysis were carried out along with a data pretreatment of filled gaps and detection of inhomogeneities in the climatic series. We analyzed data from 93 stations (44 in Huesca, 15 in Teruel and 34 in Zaragoza). Results: The results of the analysis for the regionalization ofAragon lead us to conclude that a unique factor explains the variance of each series; at high temperatures one factor explains 93.43% of the variance and the station with the highest correlation factor is Monflorite-Huesca (correlation = 0.984).At lowtemperatures one factor explains 90.88%of the variance, with Monegros-Pallaruelo being the station that presents the greatest correlation factor (correlation = 0.976). Conclusions: It was felt thatAragon was a unique isothermal region with one unique representative station of the temperature variability, Zaragoza-Airport with a correlation of 0.980 in maximum temperatures and 0.974 minimum(AU)