Structure-activity relationship study of 16 a-thiocamptothecins: an integrated in vitro and in silico approach

The instability of the hydroxylactone E ring represents a critical drawback of camptothecins, because the lactone ring is recognized to be essential for stabilization of topoisomerase I‐mediated DNA cleavage. In an attempt to investigate the effect of the thiopyridone pharmacophofore on the molecular and pharmacological features of the drug, we prepared a series of novel 16 a‐thiocamptothecin analogues. Due to the sulfur atom, a destabilization of the hydrogen bond between the hydroxy group in position 17 of the opened E ring and the carbonyl of the pyridone moiety is predicted, thus shifting the equilibrium toward the closed lactone form and increasing the lipophilic properties of the compounds. This feature was associated with superior antiproliferative potency, with reduced interaction with the human serum albumin and with substantial increase of the persistence of the topoisomerase I–DNA cleavable complex. These effects were prominent for thio‐SN38, the most active compound of the series. The favorable interactions at the molecular and cellular level of the reported thiocamptothecins confer promising features, and these compounds warrant preclinical development.     

In vitro fermentation characteristics of diets with different forage/concentrate ratios: comparison of rumen and faecal inocula

BACKGROUND: The aim of this trial was to evaluate the replacement of rumen fluid with faeces as inoculum in studying the in vitro fermentation characteristics of diets for ruminants using the in vitro gas production technique. Six iso‐protein diets with different forage/concentrate ratios were incubated with rumen fluid (RI) or faeces (FI) collected from sheep. RESULTS: Most of the fermentation parameters were influenced by diet and inoculum (P < 0.01). With both inocula, organic matter degradability (dOM), cumulative gas production (OMCV) and maximum fermentation rate (R_max) increased as the amount of concentrate in the diet increased. R_max was lower with FI vs RI (P < 0.01); dOM was higher with FI vs RI and the diet × inoculum interaction was significant. As expected, with both inocula, R_max increased as the neutral detergent fibre content of the diet decreased. Significant correlations were obtained using both inocula between OMCV/dOM and gas/volatile fatty acid (VFA), while the correlation VFA/dOM was significant only with FI. The microbial biomass yield calculated by stoichiometric analysis for all diets was higher with FI vs RI. With FI the organic matter used for microbial growth showed an overall decreasing trend as the amount of concentrate in the diet increased. CONCLUSION: The results indicate that both faeces and rumen fluid from sheep have the potential to be used as inoculum for the in vitro gas production technique. Copyright © 2011 Society of Chemical Industry     

Determination of Lutein from Fruit and Vegetables Through an Alkaline Hydrolysis Extraction Method and HPLC Analysis

A simple and rapid analytical method for the determination of lutein content, successfully used for cereal matrices, was evaluated in fruit and vegetables. The method involved the determination of lutein after an alkaline hydrolysis of the sample matrix, followed by extraction with solvents and analysis by normal phase HPLC. The optimized method was simple, precise, and accurate and it was characterized by few steps that could prevent loss of lutein and its degradation. The optimized method was used to evaluate the lutein amounts in several fruit and vegetables. Rich sources of lutein were confirmed to be green vegetables such as parsley, spinach, chicory, chard, broccoli, courgette, and peas, even if in a range of variability. Taking into account the suggested reference values these vegetables can be stated as good sources of lutein.     

Mass spectrometry detection of egg proteins in red wines treated with egg white

The need of label declaration for egg proteins is temporarily suspended when they are used as a processing aid in winemaking, because of a lack of scientific data concerning their actual permanence as residual proteins in fined wines.The possibility to detect residual egg proteins in red wines treated with a commercial egg white preparation was studied. By using an immunochemical method residual egg proteins were detected in the experimental red wines only for doses of fining agent of 50 g/hL or higher, whereas no residual proteins were detected by this system in a commercial red wine.A simple method based on the recovery and identification of the wine fining proteins by liquid chromatography coupled with tandem MS (LC-MS/MS) in a gel-free approach was developed. This allowed the detection of egg proteins in red wines fined down to 5 g/hL of commercial egg white preparation and also in the commercial red wine. These results indicate that the analytical approach here suggested is superior to the immunochemical methods in detecting egg proteins in wines. Therefore hypersensitivity reactions after consumption of wines treated with egg proteins can be a real risk for egg-allergic people.     

Effect of Silicon Substitution on the Sintering and Microstructure of Hydroxyapatite

The substitution of between 0 and 1.6 wt% silicon (Si-HA) in hydroxyapatite (HA) inhibited densification at low temperatures (1000°–1150°C), with these effects being more significant as the level of silicon substitution was increased. For higher sintering temperatures (1200°–1300°C), the sintered densities of HA and Si-HA compositions were comparable. Examination of the ceramic microstructures by scanning electron microscopy (SEM) showed that silicon substitution also inhibited grain growth at higher sintering temperatures (1200°–1300°C). The negative effect of silicon substitution on the sintering of HA at low temperatures (1000°–1150°C) was reflected in the hardness values of the ceramics. However, for higher sintering temperatures, e.g., 1300°C, where sintered densities were comparable, the hardness values of Si-HA compositions were equal to or greater than that of HA, reflecting the smaller grain sizes observed for the former.     

Etiological Contributions to Heavy Drinking From Late Adolescence to Young Adulthood.

The authors examined genetic and environmental contributions to stability and change in heavy drinking from late adolescence to young adulthood in a sample of 1,152 twin pairs. In men, heavy drinking was similarly heritable at ages 17 (h2 = .57) and 20 (h2 = .39), and its stability owed primarily to common genetic factors. In women, heavy drinking was less heritable than in men at ages 17 (h2 = .18) and 20 (h2 = .30) and its stability was primarily due to enduring shared environmental influences. P3 amplitude, an event-related brain potential marker of alcoholism risk, was less predictive of heavy drinking in women than in men, providing further support for the proposition that biological factors have less impact on heavy drinking in young adult women than in young adult men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fabrication of Copper Nanowire Films and their Incorporation into Polymer Matrices for Antibacterial and Marine Antifouling Applications

With the ban of tributyltin, copper‐based biocides are now widely used in antifouling coatings as the major active ingredients. Given the past experience of heavy‐metal accumulation in harbors with limited water exchange, there is a significant interest in developing copper materials that greatly reduce the amount of copper ions released into marine surroundings. In this paper, copper nanowires (NWs) encapsulated in polymer matrices are investigated as the means to control the release of copper ions and to achieve a long‐lasting antifouling effect. Very long CuNWs with high aspect ratio in organic solution are drop‐coated onto substrates to fabricate uniform thin films. They are then incorporated into an elastomeric polydimethylsiloxane (PDMS) matrix. A small amount of CuNWs in PDMS can inhibit barnacle cyprid settlement, while it exhibits low mortality to cyprids and nauplii present in the surrounding seawater environment. The low levels of copper released after 50 days suggest that the intersecting and interconnected CuNWs embedded in PDMS could potentially release copper ions continuously over a few years in seawater. This approach provides a novel platform to use hybrid materials as effective marine antifouling coatings, and may be applied to fouling release materials to enhance their antifouling properties.