Dietary curcumin : correlation between bioavailability and health potential

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake

Addressing Critical Shortages: An Examination of Supports For Early Career Special Educators in Maine

Alarming percentages of early career special educators, as many as 50%, leave education within five years (Edgar & Pair, 2005; Menlove, Games, & Salzberg, 2004; Plash & Piotrowski, 2006). These statistics are cause for grave concern. The purpose of this survey research study was to discover early career special educators\u27 perceptions of the induction support they received

Submarine Volcanism of the Cabo de Gata Magmatic Arc in the Betic-Rif Orogen, SE Spain: Processes and Products

Volcanic eruptions in subaqueous settings have been traditionally characterized by the study of ancient deposits and, more recently, by indirect observation of the sea floor with different geophysical means. Subaqueous volcanism is largely governed by the physical properties of water and the way water interacts with magma. Among the characteristic products of subaqueous volcanism are hyaloclastite breccias of dense clasts and of pumiceous clasts produced by the quench fragmentation of hot magma in effusive eruptions. Pumice breccias driven by fragmentation of magma in explosive eruptions are not infrequent. The Miocene volcanic zone of Cabo de Gata in southeastern Spain provides excellent exposures where to test the current understanding on subaqueous volcanism. In particular, submarine lavas with a coherent core and an outer carapace of vesicular hyaloclastite together with pumice breccias and crystal tuffs of the El Barronal Formation provide clues to understand transient conditions during explosive and effusive eruptions. Debris avalanches deposits are rather common in Cabo de Gata, such as those of the Los Frailes Formation and the Cerro Estorvillas Formation, and help to understand the instability processes of submarine volcanic edifices and the resultant mass flows. Interbedding of volcanic rocks with shallow water sedimentary rocks allows inferring water depth conditions for volcanism and the subsidence history of the volcano-sedimentary basin

Discovery of unexpected sphingolipids in almonds and pistachios with an innovative use of triple quadrupole tandem mass spectrometry

The densely packed storage of valuable nutrients (carbohydrates, lipids, proteins, micronutrients) in the endosperm of nuts and seeds makes the study of their complex composition a topic of great importance. Ceramides in the total lipid extract of some ground almonds and pistachios were searched with a systematic innovative discovery precursor ion scan in a triple quadrupole tandem mass spectrometry, where iso-energetic collision activated dissociation was performed. Five descriptors were used to search components with different C18 long chain bases containing different structural motifs (d18:0, d18:1, d18:2, t18:0, t18:1). The presence of hexoside unit was screened with a specific neutral loss experiment under iso-energetic collision activated dissociation conditions. The discovery scans highlighted the presence of two specific hexosyl-ceramides with a modified sphingosine component (d18:2) and C16:0 or C16:0 hydroxy-fatty acids. The hexosyl-ceramide with the non-hydroxylated fatty acid seemed specific of pistachios and was undetected in almonds. The fast and comprehensive mass spectrometric method used here can be useful to screen lipid extracts of several more seeds of nutraceutical interest, searching for unusual and/or specific sphingosides with chemically decorated long chain bases

A Multiple Classifier System Identifies Novel Cannabinoid CB2 Receptor Ligands

open access articleDrugs have become an essential part of our lives due to their ability to improve people’s health and quality of life. However, for many diseases, approved drugs are not yet available or existing drugs have undesirable side effects, making the pharmaceutical industry strive to discover new drugs and active compounds. The development of drugs is an expensive process, which typically starts with the detection of candidate molecules (screening) for an identified protein target. To this end, the use of high-performance screening techniques has become a critical issue in order to palliate the high costs. Therefore, the popularity of computer-based screening (often called virtual screening or in-silico screening) has rapidly increased during the last decade. A wide variety of Machine Learning (ML) techniques has been used in conjunction with chemical structure and physicochemical properties for screening purposes including (i) simple classifiers, (ii) ensemble methods, and more recently (iii) Multiple Classifier Systems (MCS). In this work, we apply an MCS for virtual screening (D2-MCS) using circular fingerprints. We applied our technique to a dataset of cannabinoid CB2 ligands obtained from the ChEMBL database. The HTS collection of Enamine (1.834.362 compounds), was virtually screened to identify 48.432 potential active molecules using D2-MCS. This list was subsequently clustered based on circular fingerprints and from each cluster, the most active compound was maintained. From these, the top 60 were kept, and 21 novel compounds were purchased. Experimental validation confirmed six highly active hits (>50% displacement at 10 μM and subsequent Ki determination) and an additional five medium active hits (>25% displacement at 10 μM). D2-MCS hence provided a hit rate of 29% for highly active compounds and an overall hit rate of 52%

Field Emission Dark Current of Technical Metallic Electrodes

In the framework of the Low Emittance Gun (LEG) project, high gradient acceleration of a low emittance electron beam will be necessary. In order to achieve this acceleration a -500 kV, 250 ns FWHM, pulse will be applied in between two electrodes. Those electrodes should sustain the pulsed field without arcing, must not outgass and must not emit electrons. Ion back bombardment, and dark current will be damageable to the electron source as well as for the low emittance beam. Electrodes of commercially available OFE copper, aluminium, stainless steel, titanium and molybdenum were tested following different procedures including plasma glow discharge cleaning.Comment: 22 pages, 6 tables, 10 figures Vs 2 : graphics more readable, enhanced content Vs 3 : typo correcte

LC-MS/MS-Based Profiling of Tryptophan-Related Metabolites in Healthy Plant Foods

Food plants contain hundreds of bioactive phytochemicals arising from different secondary metabolic pathways. Among these, the metabolic route of the amino acid Tryptophan yields a large number of plant natural products with chemically and pharmacologically diverse properties. We propose the identifier "indolome" to collect all metabolites in the Tryptophan pathway. In addition, Tryptophan-rich plant sources can be used as substrates for the fermentation by yeast strains to produce pharmacologically active metabolites, such as Melatonin. To pursue this technological development, we have developed a UHPLC-MS/MS method to monitor 14 Tryptophan, Tryptamine, amino-benzoic, and pyridine metabolites. In addition, different extraction procedures to improve the recovery of Tryptophan and its derivatives from the vegetal matrix were tested. We investigated soybeans, pumpkin seeds, sesame seeds, and spirulina because of their botanical diversity and documented healthy effects. Four different extractions with different solvents and temperatures were tested, and water extraction at room temperature was chosen as the most suitable procedure to extract the whole Tryptophan metabolites pattern (called by us "indolome") in terms of ease, high efficiency, short time, low cost, and sustainability. In all plant matrices, Tryptophan was the most abundant indole compound, while the pattern of its metabolites was different in the diverse plants extracts. Overall, 5-OH Tryptamine and Kynurenine were the most abundant compounds, despite being 100-1000-fold lower than Tryptophan. Melatonin was undetected in all extracts, but sesame showed the presence of a Melatonin isomer. The results of this study highlight the variability in the occurrence of indole compounds among diverse food plants. The knowledge of Tryptophan metabolism in plants represents a relevant issue for human health and nutrition

An Innovative Lipidomic Workflow to Investigate the Lipid Profile in a Cystic Fibrosis Cell Line

Altered lipid metabolism has been associated to cystic fibrosis disease, which is characterized by chronic lung inflammation and various organs dysfunction. Here, we present the validation of an untargeted lipidomics approach based on high-resolution mass spectrometry aimed at identifying those lipid species that unequivocally sign CF pathophysiology. Of n.13375 mass spectra recorded on cystic fibrosis bronchial epithelial airways epithelial cells IB3, n.7787 presented the MS/MS data, and, after software and manual validation, the final number of annotated lipids was restricted to n.1159. On these lipids, univariate and multivariate statistical approaches were employed in order to select relevant lipids for cellular phenotype discrimination between cystic fibrosis and HBE healthy cells. In cystic fibrosis IB3 cells, a pervasive alteration in the lipid metabolism revealed changes in the classes of ether-linked phospholipids, cholesterol esters, and glycosylated sphingolipids. Through functions association, it was evidenced that lipids variation involves the moiety implicated in membrane composition, endoplasmic reticulum, mitochondria compartments, and chemical and biophysical lipids properties. This study provides a new perspective in understanding the pathogenesis of cystic fibrosis and strengthens the need to use a validated mass spectrometry-based lipidomics approach for the discovery of potential biomarkers and perturbed metabolism

Facies architecture, emplacement mechanisms and eruption style of the submarine andesite El Barronal complex, Cabo de Gata, SE Spain

El Barronal complex consists of a succession of andesite lavas and andesite volcaniclastic facies interbedded with carbonate and siliciclastic sedimentary rocks. Carbonate and siliciclastic rocks were deposited in a shallow-marine environment during periods of volcanic quiescence. Lavas consist of an inner coherent core grading outward into hyaloclastite breccia made of dense clasts that in turn grade into hyaloclastite breccia made of vesicular clasts, in massive to layered zones. Volcaniclastic facies contain clasts produced during explosive eruptions and reworked clasts from sources above wave base. Volcaniclastic facies were deposited from cold granular flows with different grain size populations. Stratigraphy and facies architecture at El Barronal suggest that a succession of several discrete eruptive events occurred with a similar cyclic pattern made of an initial explosive phase followed by effusive emplacement of lavas, in turn followed by a period of quiescence of volcanic activity. Hyaloclastic fragmentation of magma took place in the final stages of lava emplacement, allowing only for local disorganization of the jigsaw-fit texture. © 2013 Elsevier B.V.This research has been funded by projects CGL2005-03511/BTE and HI2006-0073Peer Reviewe