Bioavailability of Echinacea Constituents: Caco-2 Monolayers and Pharmacokinetics and the Alkylamides and Caffeic Acid Conjugates

Many studies have been done over the years to assess the effectiveness of Echinacea as an immunomodulator. We have assessed the potential bioavailability of alkylamides and caffeic acid conjugates using Caco-2 monolayers and compared it to their actualbioavailability in a Phase I clinical trial. The caffeic acid conjugates permeated poorly through the Caco-2 monolayers. Alkylamides were found to diffuse rapidly through Caco-2 monolayers. Differences in diffusion rates for each alkylamide correlated to structural variations, with saturation and N-terminal methylation contributing to decreases in diffusion rates. Alkylamide diffusion is not affected by the presence of other constituents and the results for a synthetic alkylamide were in line with those for alkylamides found in an ethanolic Echinacea preparation. We examined plasma from healthy volunteers for 12 hours after ingestion of Echinacea tablets manufactured from an ethanolic liquid extract. Caffeic acid conjugates could not be identified in any plasma sample at any time after tablet ingestion. Alkylamides were detected in plasma 20 minutes after tablet ingestion and for each alkylamide, pharmacokinetic profiles were devised. The data are consistent with the dosing regimen of one tablet three times daily and supports their usage as the primary markers for quality Echinacea preparations

The European Registered Toxicologist (ERT) : Current status and prospects for advancement

Acknowledgements We would like to thank the participants of the five workshops in which the issues presented in this paper were discussed and the revised guidelines prepared, as well as the EUROTOX Executive Committee and the societies of toxicology of Sweden, the Netherlands, Switzerland, Austria and France for their support which allowed the workshops to take place.Peer reviewedPostprin

Влияние дисперсности порошка, давления и температуры спекания на микроструктуру и физико-механические свойства керамики из карбида бора

Основной целью настоящей работы было получение высокоплотного сверхтвердого керамического материала на основе карбида бора спеканием под высоким давлением без использования активирующих добавок. Исследованы микроструктура, плотность и твердость по Виккерсу образцов, спеченных из порошков карбида бора различной дисперсности при давлении 4 ГПа в интервале температур 1200 – 2000 °С.Основною метою цієї роботи було отримання високоякісного надтвердого керамічного матеріалу на основі карбіду бору спіканням під високим тиском без використання активуючих добавок. Досліджені мікроструктура, щільність і твердість по Віккерсу зразків, спечених з порошків карбіду бору різної дисперсності при тиску 4 ГПа в інтервалі температур 1200–2000 °С.The main purpose of this work was to obtain a high-density superhard ceramic material based on boron carbide by sintering under high pressure without the use of activating additives. The microstructure, density and Vickers hardness of samples sintered from boron carbide powders of various dispersities at a pressure of 4 GPa in the temperature interval 1200–2000 °C were investigated

Exploring the Biochemical Foundations of a Successful GLUT1-Targeting Strategy to BNCT: Chemical Synthesis and In Vitro Evaluation of the Entire Positional Isomer Library of ortho-Carboranylmethyl-Bearing Glucoconjugates

Boron neutron capture therapy (BNCT) is a noninvasive binary therapeutic modality applicable to the treatment of cancers. While BNCT offers a tumor-targeting selectivity that is difficult to match by other means, the last obstacles preventing the full harness of this potential come in the form of the suboptimal boron delivery strategies presently used in the clinics. To address these challenges, we have developed delivery agents that target the glucose transporter GLUT1. Here, we present the chemical synthesis of a number of ortho-carboranylmethyl-substituted glucoconjugates and the biological assessment of all positional isomers. Altogether, the study provides protocols for the synthesis and structural characterization of such glucoconjugates and insights into their essential properties, for example, cytotoxicity, GLUT1-affinity, metabolism, and boron delivery capacity. In addition to solidifying the biochemical foundations of a successful GLUT1-targeting approach to BNCT, we identify the most promising modification sites in d-glucose, which are critical in order to further develop this strategy toward clinical use.Peer reviewe

The ADMORPH approach for Adaptively Morphing Embedded Systems

peer reviewedDue to the increasing performance demands of missionand safety-critical Cyber-Physical Systems (of Systems), these systems exhibit a rapidly growing complexity, manifested by an increasing number of (distributed) computational cores and application components connected via complex networks. However, with these systems’ growing complexity and interconnectivity, the chances of hardware failures and disruptions due to cyber-attacks will also quickly increase. In the ADMORPH project we explore system adaptivity, in terms of dynamically remapping application components to processing cores, to fuse fault- and intrusion tolerance with the increasing performance requirements of mission- and safety-critical CPS(oS). This paper describes the overall ADMORPH architecture and provides an overview of the developed methodologies, methods and tools for the specification, design, analysis and runtime deployment of adaptive mission- and safetycritical CPS(oS) that are robust against both component failures and cyber-attacks

A decade of sulfite control in Serbian meat industry and the effect of HACCP

In total 7,351 meat preparations and fresh processed meat products were analyzed from 555 different Serbian meat producers over a 10 year period, 4½ years before and 5½ years after mandatory HACCP implementation. From the obtained results, it could be concluded that HACCP has contributed to a better alignment of practices with the legal provisions. The share of non-compliant samples dropped from 18.6% before HACCP to 8.3% after its mandatory implementation. Average sulfite concentrations for all categories of meat preparations and fresh processed meat products decreased by 43%, declining from 33.6 mg kg-1 to 19.3 mg kg-1. Typical misuse and frequent abuse of sulfites was independent of a season. Application of HACCP principles in the Serbian meat industry raised awareness about the misuse of sulfites and contributed to a better control, minimizing exposure to sulfites

Growth and yield of mixed versus pure stands of Scots pine (Pinus sylvestris L. ) and European beech (Fagus sylvatica L.) analysed along a productivity gradient through Europe

Mixing of complementary tree species may increase stand productivity, mitigate the effects of drought and other risks, and pave the way to forest production systems which may be more resource-use efficient and stable in the face of climate change. However, systematic empirical studies on mixing effects are still missing for many commercially important and widespread species combinations. Here we studied the growth of Scots pine (Pinus sylvestris L.) and European beech (Fagus sylvatica L.) in mixed versus pure stands on 32 triplets located along a productivity gradient through Europe, reaching from Sweden to Bulgaria and from Spain to the Ukraine. Stand inventory and taking increment cores on the mainly 60-80 year-old trees and 0.02-1.55 ha sized, fully stocked plots provided insight how species mixing modifies the structure, dynamics and productivity compared with neighbouring pure stands. In mixture standing volume (+12 %), stand density (+20 %), basal area growth (+12 %), and stand volume growth (+8 %) were higher than the weighted mean of the neighbouring pure stands. Scots pine and European beech contributed rather equally to the overyielding and overdensity. In mixed stands mean diameter (+20 %) and height (+6 %) of Scots pine was ahead, while both diameter and height growth of European beech were behind (−8 %). The overyielding and overdensity were independent of the site index, the stand growth and yield, and climatic variables despite the wide variation in precipitation (520-1175 mm year−1), mean annual temperature (6-10.5 °C), and the drought index by de Martonne (28-61 mm °C−1) on the sites. Therefore, this species combination is potentially useful for increasing productivity across a wide range of site and climatic conditions. Given the significant overyielding of stand basal area growth but the absence of any relationship with site index and climatic variables, we hypothesize that the overyielding and overdensity results from several different types of interactions (light-, water-, and nutrient-related) that are all important in different circumstances. We discuss the relevance of the results for ecological theory and for the ongoing silvicultural transition from pure to mixed stands and their adaptation to climate change.The networking in this study has been sup-ported by COST Action FP1206 EuMIXFOR. All contributors thanktheir national funding institutions to establish, measure, and analysedata from the triplets. The first author also thanks the BayerischenStaatsforsten (BaySF) for supporting the establishment of the plots,the Bavarian State Ministry for Nutrition, Agriculture, and Forestryfor permanent support of the project W 07 ‘‘Long-term experimentalplots for forest growth and yield research’’ (# 7831-22209-2013) andthe German Science Foundation for providing the funds for the pro-jects PR 292/12-1 ‘‘Tree and stand-level growth reactions on droughtin mixed versus pure forests of Norway spruce and European beech’’.Thanks are also due to Ulrich Kern for the graphical artwork, and totwo anonymous reviewers for their constructive criticism

Maternal cadmium, iron and zinc levels, DNA methylation and birth weight

Background Cadmium (Cd) is a ubiquitous and environmentally persistent toxic metal that has been implicated in neurotoxicity, carcinogenesis and obesity and essential metals including zinc (Zn) and iron (Fe) may alter these outcomes. However mechanisms underlying these relationships remain limited. Methods We examined whether maternal Cd levels during early pregnancy were associated with offspring DNA methylation at regulatory sequences of genomically imprinted genes and weight at birth, and whether Fe and Zn altered these associations. Cd, Fe and Zn were measured in maternal blood of 319 women ≤12 weeks gestation. Offspring umbilical cord blood leukocyte DNA methylation at regulatory differentially methylated regions (DMRs) of 8 imprinted genes was measured using bisulfite pyrosequencing. Regression models were used to examine the relationships among Cd, Fe, Zn, and DMR methylation and birth weight. Results Elevated maternal blood Cd levels were associated with lower birth weight (p = 0.03). Higher maternal blood Cd levels were also associated with lower offspring methylation at the PEG3 DMR in females (β = 0.55, se = 0.17, p = 0.05), and at the MEG3 DMR in males (β = 0.72, se = 0.3, p = 0.08), however the latter association was not statistically significant. Associations between Cd and PEG3 and PLAGL1 DNA methylation were stronger in infants born to women with low concentrations of Fe (p < 0.05). Conclusions Our data suggest the association between pre-natal Cd and offspring DNA methylation at regulatory sequences of imprinted genes may be sex- and gene-specific. Essential metals such as Zn may mitigate DNA methylation response to Cd exposure. Larger studies are required