Effects of Ospemifene on Drug Metabolism Mediated by Cytochrome P450 Enzymes in Humans in Vitro and in Vivo

The objective of these investigations was to determine the possible effects of the novel selective estrogen receptor modulator, ospemifene, on cytochrome P450 (CYP)-mediated drug metabolism. Ospemifene underwent testing for possible effects on CYP enzyme activity in human liver microsomes and in isolated human hepatocytes. Based on the results obtained in vitro, three Phase 1 crossover pharmacokinetic studies were conducted in healthy postmenopausal women to assess the in vivo effects of ospemifene on CYP-mediated drug metabolism. Ospemifene and its main metabolites 4-hydroxyospemifene and 4′-hydroxyospemifene weakly inhibited a number of CYPs (CYP2B6, CYP2C9, CYP2C19, CYP2C8, and CYP2D6) in vitro. However, only CYP2C9 activity was inhibited by 4-hydroxyospemifene at clinically relevant concentrations. Induction of CYPs by ospemifene in cultured human hepatocytes was 2.4-fold or less. The in vivo studies showed that ospemifene did not have significant effects on the areas under the plasma concentration-time curves of the tested CYP substrates warfarin (CYP2C9), bupropion (CYP2B6) and omeprazole (CYP2C19), demonstrating that pretreatment with ospemifene did not alter their metabolism. Therefore, the risk that ospemifene will affect the pharmacokinetics of drugs that are substrates for CYP enzymes is low.     

Testing activity‐based costing to large‐scale combined heat and power plant using bioenergy

This paper deals with the energy production and economics of a large‐scale biomass‐based combined heat and power (CHP) plant. An activity‐based costing model was developed for estimating the production costs of the heat and power of the bio‐CHP. A 100 MW plant (58 MW heat, 29 MW electricity) was used as reference. The production process was divided into four stages: fuel handling, fluidized bed boiler, turbine plant, and flue gas cleaning. The boiler accounted for close to 50% of the production costs. The interest rates and the utilization rate of the CHP had a significant effect on the profitability. We found that below 4000–4500 h per year utilization, the electricity production turned unprofitable. However, the heat production remained profitable with high interest rate (10%) and a low utilization rate (4000 h). The profitability also depended on the type of biomass used. We found that, e.g. with moderate interest rates and high utilization rate of the plant, the bio‐CHP plant could afford wood and Reed canary grass as fuel sources. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparison of the characteristics of bottom ash and fly ash from a medium-size (32 MW) municipal district heating plant incinerating forest residues and peat in a fluidized-bed boiler

In this study, the physical and chemical properties of bottom ash and fly ash originating from the co-combustion of biomass-derived fuels (i.e. wood chips, sawdust, bark, and peat) from a 32 MW fluidized bed boiler at a municipal district heating plant were investigated. Silicate minerals were predominant in the bottom ash and calcium minerals in the fly ash, with most of the inorganic nutrients and heavy metals being enriched in the fly ash. The enrichment factors for heavy metals in the fly ash varied between 0.2 for silicon and 16.3 for lead, and for plant nutrients, between 1.5 for phosphorous and 108 for potassium. However, all heavy metal concentrations in both the bottom ash and fly ash were significantly lower than the current Finnish limit for maximum allowable heavy metal concentrations for forest fertilizers, which came into force in March 2007. According to the particle size distribution, the mass loadings of heavy metals in the fly ash were more than 90% contributed by the smallest particle size fraction lower than 0.074 mm. In the bottom ash, between 83.6 and 91.9% of the mass loadings of heavy metals were contributed by the particle size fraction between 0.5 and 2.0 mm.     

Usability of low temperature waste heat for sea water desalination

Waste heat - energy that is cooled away from a process - appears at two very different temperature levels. The waste heat that is 50° C warmer than the ambience, can be utilized by a multi-effect-distillation process, and it is competitive to utilize it at least as thoroughly as the first-rate energy.At low temperatures, less than 20 °C above the ambient temperature, waste heat can be technically, and economically utilized, if the temperature difference is 7... 15 °C, depending on the pumping energy cost.     

Foreperiod and simple reaction time.

Reviews studies of simple visual and auditory reaction processes published since W. H. Teicher (1954), with emphasis on the preparatory phase of these processes, particularly the foreperiod (FP). The 1st section consists of the analysis of actual FP variables; duration, regularity, range, distribution, and preceding FPs. The 2nd section deals with factors affecting the relation between FP and reaction time (RT): (a) the modality, intensity, probability, and duration of the warning signal and reaction stimulus (RS) and (b) the speed–accuracy trade-off. It is suggested that the S's expectancy (momentary probability of the immediate delivery of the RS) is the most important determinant of the preparation to respond to the RS at any moment during a trial and, hence, of RT. Many factors exert their influence on preparation through their effect on expectancy. Other factors have a direct influence on preparation: short-term exhaustion and fatigue, immediate arousal evoked by intense auditory stimuli, the S's stimulus criterion, the speed–accuracy trade-off, and fluctuation in motor preparedness owing to inaccuracies in the control of motor preparation. (4? p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microchip atmospheric pressure chemical ionization source for mass spectrometry

A novel microchip heated nebulizer for atmospheric pressure chemical ionization mass spectrometry is presented. Anisotropic wet etching is used to fabricate the flow channels, inlet, and nozzle on a silicon wafer. An integrated heater of aluminum is sputtered on a glass wafer. The two wafers are jointed by anodic bonding, creating a two-dimensional version of an APCI source with a sample channel in the middle and gas channels symmetrically on both sides. The ionization is initiated with an external corona-discharge needle positioned 2 mm in front of the microchip heated nebulizer. The microchip APCI source provides flow rates down to 50 nL/min, stable long-term analysis with chip lifetime of weeks, good quantitative repeatability (RSD < 10%) and linearity (r(2) > 0.995) with linear dynamic rage of at least 4 orders of magnitude, and cost-efficient manufacturing. The limit of detection (LOD) for acridine measured with microchip APCI at flow rate of 6.2 muL/min was 5 nM, corresponding to a mass flow of 0.52 fmol/s. The LOD with commercial macro-APCI at a flow rate of 1 mL/min for acridine was the same, 5 nM, corresponding to a significantly worse mass flow sensitivity (83 fmol/s) than measured with microchip APCI. The advantages of microchip APCI makes it a very attractive new microfluidic detector.     

Drought Stress Alters the Concentration of Wood Terpenoids in Scots Pine and Norway Spruce Seedlings

Drought is known to have an impact on the resistance of conifers to various pests, for example, by affecting resin flow in trees. Little is known, however, about the quantitative and qualitative changes in resin when trees are growing in low moisture conditions. We exposed Scots pine (Pinus sylvestris L.) and Norway spruce (Picea abies (L.) Karst.) seedlings to medium and severe drought stress for two growing seasons and analyzed the monoterpenes and resin acids in the main stem wood after two years of treatment. In addition to secondary chemistry, we measured the level of nutrients in the needles and the growth response of seedlings. After the first year of treatment, drought stress did not affect the growth of seedlings, but in the second year, shoot growth was retarded, especially in Scots pine. In both conifer species, severe drought increased the concentrations of several individual monoterpenes and resin acids. Total monoterpenes and resin acids were 39 and 32% higher in severe drought-treated Scots pine seedlings than in the controls, and 35 and 45% higher in Norway spruce seedlings. In Scots pine needles, the concentrations of nitrogen and phosphorus increased, while magnesium and calcium decreased compared to controls. In Norway spruce needles, nutrient concentrations were not affected. The results suggest that drought stress substantially affects both the growth of conifers and the chemical quality of the wood. We discuss the potential trade-off in growth and defense of small conifer seedlings.     

Development of LC/MS/MS methods for cocktail dosed Caco-2 samples using atmospheric pressure photoionization and electrospray ionization

Good reliability of Caco-2 permeability studies requires competent sampling and analytical methods to ensure the comparability of day-to-day experiments. In this work, two n-in-one LC/MS/MS methods based on two different ionization techniques were developed and validated for a group of reference compounds; eight of them are recommended by the Food and Drug Administration (FDA) for the evaluation of oral drug permeability. The performance of a new ionization technique, atmospheric pressure photoionization (APPI), as an interface for quantitative LC/MS analysis was evaluated in comparison to the electrospray ionization (ESI). Generally, the validation parameters, including sensitivity, accuracy, and repeatability, were comparable for the APPI and ESI methods. The main difference was that the linear quantitative range of APPI was 3-4 orders of magnitude (r(2) >/= 0.998) whereas in ESI it was typically 2-3 orders of magnitude (r(2) >/= 0.990). By the APPI and ESI methods, the simultaneous analysis of nine highly heterogeneous compounds was achieved within 5.5-7 min, which leads to significant savings in time and cost of the analyses. The successful validation data indicate the usefulness of both the methods for the rapid and sensitive (LOD values typically 相似文献   

Selection of NF membrane to improve quality of chemically treated surface water

The requirement for higher quality drinking water necessitates the application of more efficient water treatment techniques. Nanofiltration is one promising option for enhanced water treatment, for example, in enhanced organic matter removal. The characteristics of different nanofiltration membranes vary remarkably, and the selection of a membrane has to be made according to the requirements of an application. In this study six nanofiltration membranes (NF70, NF255, NTR-7450, NTR-7410, Desal-5 and TFC-S) were evaluated in improving the quality of chemically pre-treated surface water in a pilot-scale process. The results indicate that the membrane with high organics removal and slightly reduced ion removal characteristics (NF255) performed best in terms of product water quality as well as membrane productivity and fouling. The most permeable membrane (NTR-7410) suffered intensive fouling and insufficient product water quality. An interesting finding was that the permeates of all the tested membranes possessed a significant potential for microbial growth, despite the low nutrient contents.     

Measuring the Size Distribution of Atmospheric Organic and Black Carbon Using Impactor Sampling Coupled with Thermal Carbon Analysis: Method Development and Uncertainties

A method for determining the mass size distribution of organic and black carbon (OC and BC) in atmospheric aerosols is introduced. The method relies on a particle sampling with 2 parallel size-segregating devices, a 12-stage Small Deposit area low pressure impactor (SDI) and a virtual impactor (VI), and the subsequent analysis of the samples with thermal and thermal-optical methods, respectively. The method development revealed that SDI is, like other sampling methods, susceptible to serious sampling artifacts and OC pyrolysis during thermal analysis. However, some of the SDI's limitations can be overcome by parallel VI measurements. The good correlation between the SDI and the VI data for most of the samples collected here indicates that under most conditions, the lack of the pyrolysis correction for the SDI samples does not cause significant errors in the OC/BC split. Valuable features of this method are that it offers a good size resolution in both sub- and supermicron size fractions, indicates if there has been serious positive or negative artifacts for OC during sampling, reveals if the samples have been affected by OC pyrolysis during thermal analysis, and provides semiquantitative means by which the OC and BC size distributions can be corrected for the samples being affected by OC pyrolysis. Application of the method to real atmospheric samples is demonstrated, and the major areas requiring further research and/or method development are identified.