Toward the first nonpeptidic molecular tong inhibitor of wild-type and mutated HIV-1 protease dimerization

Herein we describe the synthesis and HIV-1 protease (PR) inhibitory activity of 16 new peptidomimetic molecular tongs with a naphthalene scaffold. Their peptidic character was progressively decreased. Two of these molecules exhibited the best dimerization inhibition activity toward HIV-1 wild-type and multimutated ANAM-11 proteases obtained to date for this class of molecules (～40?nM for wild-type PR and 100?nM for ANAM-11 PR). Although the peptidic character of one molecular tong was completely suppressed, the mechanism of inhibition and inhibitory potency toward both proteases were maintained.     

Permeability of low molecular weight organics through nanofiltration membranes

The removal of natural organic matter (NOM) using nanofiltration (NF) is increasingly becoming an option for drinking water treatment. Low molecular weight (LMW) organic compounds are nevertheless only partially retained by such membranes. Bacterial regrowth and biofilm formation in the drinking water distribution system is favoured by the presence of such compounds, which in this context are considered as the assimilable organic carbon (AOC). In this study, the question of whether NF produces microbiologically stable water was addressed. Two NF membranes (cut-off of about 300 Da) were tested with different natural and synthetic water samples in a cross-flow filtration unit. NOM was characterised by liquid chromatography with organic carbon detection (LC-OCD) using a size-exclusion column in addition to specific organic acid measurements, while AOC was measured in a batch growth bioassay.Similarly to high molecular weight organic compounds like polysaccharides or humic substances that have a permeability lower than 1%, charged LMW organic compounds were efficiently retained by the NF membranes tested and showed a permeability lower than 3%. However, LMW neutrals and hydrophobic organic compounds permeate to a higher extent through the membranes and have a permeability of up to 6% and 12%, respectively. Furthermore, AOC was poorly retained by NF and the apparent AOC concentration measured in the permeated water was above the proposed limit for microbiologically stable water. This indicates that the drinking water produced by NF might be biologically unstable in the distribution system. Nevertheless, in comparison with the raw water, NF significantly reduced the AOC concentration.     

GC–MS analysis of oxysterols and their formation in cultivated liver cells (HepG2)

Oxysterols play a key role in many (patho)physiological processes and they are potential biomarkers for oxidative stress in several diseases. Here we developed a rapid gas chromatographic-mass spectrometry-based method for the separation and quantification of 11 biologically relevant oxysterols bearing hydroxy, epoxy, and dihydroxy groups. Efficient chromatographic separation (resolution ≥ 1.9) was achieved using a medium polarity 35%-diphenyl/65%-dimethyl polysiloxane stationary phase material (30 m × 0.25 mm inner diameter and 0.25 μm film thickness). Based on thorough analysis of the fragmentation during electron ionization we developed a strategy to deduce structural information of the oxysterols. Optimized sample preparation includes (i) extraction with a mixture of n-hexane/iso-propanol, (ii) removal of cholesterol by solid phase extraction with unmodified silica, and (iii) trimethylsilylation. The method was successfully applied on the analysis of brain samples, showing consistent results with previous studies and a good intra- and interday precision of ≤20%. Finally, we used the method for the investigation of oxysterol formation during oxidative stress in HepG2 cells. Incubation with tert-butyl hydroperoxide led to a massive increase in free radical formed oxysterols (7-keto-chol > 7β-OH-chol >> 7α-OH-chol), while 24 h incubation with the glutathione peroxidase 4 inhibitor RSL3 showed no increase in oxidative stress based on the oxysterol pattern. Overall, the new method described here enables the robust analysis of a biologically meaningful pattern of oxysterols with high sensitivity and precision allowing us to gain new insights in the biological formation and role of oxysterols.     

Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats

The purpose of this study was to investigate the implications of selected chemopreventive parameters and metabolic conversion of resveratrol in vivo. In two 8-week long feeding experiments with rats, a low-resveratrol diet containing 50 mg resveratrol per kg body weight (bw) and day and a high-resveratrol diet with 300 mg per kg bw and day were administered. For chemopreventive evaluation selected phase I and phase II enzymes of the biotransformation system, the total antioxidant activity, and the vitamin E status of the animals were determined. The level of resveratrol and its metabolites in the feces, urine, plasma, liver, and kidneys was identified and quantitated by high-performance liquid chromatography-diode array detection (HPLC-DAD) using synthesized resveratrol conjugate standards. Feeding of different dosages of resveratrol revealed no effect on the different chemopreventive parameters, except for the total antioxidant activity, which was elevated in plasma by 19% after feeding 50 mg resveratrol per kg bw and day. The formation of trans-resveratrol-3-sulfate, trans-resveratrol-4'-sulfate, trans-resveratrol-3,5-disulfate, trans-resveratrol-3,4'-disulfate, trans-resveratrol-3,4',5-trisulfate, trans-resveratrol-3-O-beta-D-glucuronide, and resveratrol aglycone was detected by HPLC analysis, depending on the biological material. Total resveratrol recovery in urine and feces of rats fed on 50 mg resveratrol per kg bw and day was 15% and 13%, respectively. For rats fed the higher dosage of 300 mg resveratrol per kg bw and day recovery was 54% and 17%, respectively. This is the first study performed with synthesized standards of relevant resveratrol conjugates. The lack of effect on the chemopreventive parameters is probably due to the formation of various resveratrol conjugates reducing its bioavailability in the rat.     

Microbial degradation of rice and barley straws in the sheep rumen and the donkey caecum

The chemical composition, intake, digestibility, ultrastructure and microbial degradation of rice straw from Camargue were compared with barley straw. These variables were observed in two different herbivore digestive ecosystems: the sheep rumen and the donkey caecum. The two straws differed essentially in their ash content, which was three times higher in rice, owing to its silica content. Other chemical components were comparable, except a higher phenolic acids‐to‐lignin ratio in rice. Rice straw was better ingested than barley straw. Organic matter and neutral detergent fibre digestibilities were the same in both straws. Dry matter and cell wall disappearances could be adjusted to the exponential modelling equation with lag time, and differed between animals but not between straws. The sheep rumen had a higher extent of degradation, but the donkey caecum had a higher degradation rate. Statistical analysis revealed that cell‐wall components degradation was similar in the two straws except for ferulic acid, which was more degraded in rice straw. Scanning electron microscopy showed important differences in parenchyma degradation, which was much more effective in rice. Copyright © 2003 Society of Chemical Industry     

Immunological Response to Biodegradable Magnesium Implants

The use of biodegradable magnesium implants in pediatric trauma surgery would render surgical interventions for implant removal after tissue healing unnecessary, thereby preventing stress to the children and reducing therapy costs. In this study, we report on the immunological response to biodegradable magnesium implants—as an important aspect in evaluating biocompatibility—tested in a growing rat model. The focus of this study was to investigate the response of the innate immune system to either fast or slow degrading magnesium pins, which were implanted into the femoral bones of 5-week-old rats. The main alloying element of the fast-degrading alloy (ZX50) was Zn, while it was Y in the slow-degrading implant (WZ21). Our results demonstrate that degrading magnesium implants beneficially influence the immune system, especially in the first postoperative weeks but also during tissue healing and early bone remodeling. However, rodents with WZ21 pins showed a slightly decreased phagocytic ability during bone remodeling when the degradation rate reached its maximum. This may be due to the high release rate of the rare earth-element yttrium, which is potentially toxic. From our results we conclude that magnesium implants have a beneficial effect on the innate immune system but that there are some concerns regarding the use of yttrium-alloyed magnesium implants, especially in pediatric patients.     

Studies of the pulse charge of lead-acid batteries for photovoltaic applications: Part IV. Pulse charge of the negative plate

The paper discusses the influence of the state of charge and pulse charge frequency on the mechanism of the lead-acid battery recharge with pulse current. The data from the pulse charge transients of the negative plate potential at various frequencies show that a decrease of the pulse charge frequency keeping constant average pulse current can impede the charge reaction leading to earlier start of the hydrogen evolution reaction. The dependence of the electrochemical double layer (EDL) capacitance on the state of charge was estimated both during the charge and the discharge using electrochemical impedance spectroscopy measurements at open circuit, followed by equivalent circuit modelling. These data were used to derive the dependence of the average double layer current on SOC and pulse charge frequency. The results show that in the end of the charge almost all of the charge proceeds with the participation of EDL in a certain pulse frequency domain. Using the data from the impedance measurements the optimal pulse charge frequencies were predicted, considering the existence of “electrochemical resonance”. The latter appears when the pulse charge frequency approaches the characteristic frequency of the Pb electrodeposition process, given by the product between EDL capacitance and the charge transfer resistance.     

Flow behaviour of carrot puree: modelling the influence of time,temperature and potato flakes addition

Rheological properties of carrot puree were investigated in the 1–1000 s^?1 shear rate range with the objective of modelling the influence of time, temperature and addition of potato flakes on the flow behaviour. Carrot puree exhibited a shear‐thinning behaviour that was well described by the Ostwald‐de Waele (Power Law) model with a flow behaviour index of 0.34 (±0.02) at 20 °C. The time‐dependent behaviour was characterised by a second‐order Structural Kinetic Model. The decay of the structural parameter with time was found to be independent of shear rate. The Arrhenius model was used to explain the effect of temperature in the range from 4 to 60 °C. The dry matter was increased by adding potato flakes (0–5%). A power law model (for the concentration) and the Arrhenius relationship (for the temperature) were combined to simultaneously describe the effects of temperature and concentration. This study provides essential data for equipment and process design.     

Synthese du furyl-2 oxiranne en milieu hétérogène solide-liquide faiblement hydrate: Determination du régime de production,expression de la loi cinétique

Optimum conditions for scaling up the synthesis of furyl-2 oxyrane from furfural have been determined. A continuous stirred tank reactor proved the most efficient configuration for the production of the oxirane. The kinetic model makes it possible to predict the yields of epoxide per unit volume and unit time.     

Environmental life cycle assessment of a pre‐fragmented high explosive grenade

Organisations today face increasing environmental constraints, e.g. in the form of legal and customer requirements; the defence sector is no exception. There is a need to evaluate and limit environmental effects of defence activities and materiel. In this study we used quantitative Life Cycle Assessment (LCA) and a method for simplified LCA (the Material, Energy, Chemicals and Others (MECO) method) to assess the environmental impacts of a grenade. The aims of the study are to identify aspects in the grenade's life‐cycle that have the largest environmental impact, suggest improvement possibilities, make a comparison between different approaches for waste management of munitions, and to perform a demonstrative case for the application of LCA to munitions. Significant environmental aspects of the grenade's life‐cycle include use of metals, use of fossil fuels, and detonation outdoors. The study shows that an LCA can be used to analyse environmental impacts from munitions. The simplified LCA gave information that is complementary to the quantitative LCA. Copyright © 2005 Society of Chemical Industry