The basel cocktail for simultaneous phenotyping of human cytochrome P450 isoforms in plasma, saliva and dried blood spots.

BACKGROUND AND OBJECTIVE Phenotyping cocktails use a combination of cytochrome P450 (CYP)-specific probe drugs to simultaneously assess the activity of different CYP isoforms. To improve the clinical applicability of CYP phenotyping, the main objectives of this study were to develop a new cocktail based on probe drugs that are widely used in clinical practice and to test whether alternative sampling methods such as collection of dried blood spots (DBS) or saliva could be used to simplify the sampling process. METHODS In a randomized crossover study, a new combination of commercially available probe drugs (the Basel cocktail) was tested for simultaneous phenotyping of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Sixteen subjects received low doses of caffeine, efavirenz, losartan, omeprazole, metoprolol and midazolam in different combinations. All subjects were genotyped, and full pharmacokinetic profiles of the probe drugs and their main metabolites were determined in plasma, dried blood spots and saliva samples. RESULTS The Basel cocktail was well tolerated, and bioequivalence tests showed no evidence of mutual interactions between the probe drugs. In plasma, single timepoint metabolic ratios at 2 h (for CYP2C19 and CYP3A4) or at 8 h (for the other isoforms) after dosing showed high correlations with corresponding area under the concentration-time curve (AUC) ratios (AUC0-24h parent/AUC0-24h metabolite) and are proposed as simple phenotyping metrics. Metabolic ratios in dried blood spots (for CYP1A2 and CYP2C19) or in saliva samples (for CYP1A2) were comparable to plasma ratios and offer the option of minimally invasive or non-invasive phenotyping of these isoforms. CONCLUSIONS This new combination of phenotyping probe drugs can be used without mutual interactions. The proposed sampling timepoints have the potential to facilitate clinical application of phenotyping but require further validation in conditions of altered CYP activity. The use of DBS or saliva samples seems feasible for phenotyping of the selected CYP isoforms.

Proximity of premolar roots to maxillary sinus: a radiographic survey using cone-beam computed tomography.

INTRODUCTION The proximity of the roots of the posterior maxillary teeth to the maxillary sinus is a constant challenge to the dental practitioner. Because the majority of studies have assessed the relationship regarding molars, the present study focused on premolars. METHODS Cone-beam computed tomographic images of 192 patients were reconstructed in sagittal, coronal, and axial planes to quantify the distances between the root apices of the maxillary premolars and the adjacent maxillary sinus. Measurements were taken for each root, and data were correlated with age, sex, side, and presence of both or absence of 1 of the 2 premolars. RESULTS A total of 296 teeth (177 first and 119 second premolars) were evaluated. The mean distances from buccal roots of the first premolars to the border of the maxillary sinus in the sagittal, coronal, and axial planes ranged from 5.15 ± 2.99 to 8.28 ± 6.27 mm. From palatal roots, the mean distances ranged from 4.20 ± 3.69 to 7.17 ± 6.14 mm. The mean distances of second premolars were markedly shorter in buccal roots between 2.32 ± 2.19 and 3.28 ± 3.17 mm and in palatal roots between 2.68 ± 3.58 and 3.80 ± 3.71 mm, respectively. The frequency of a premolar root protrusion into the maxillary sinus was very low in first premolars (0%-7.2%) but higher in second premolars (2.5%-13.6%). Sex, age, side, and presence/absence of premolars failed to significantly influence the mean distances between premolar roots and the maxillary sinus. CONCLUSIONS Based on the calculated mean distances of the present study, only few premolars (and if so second premolars) would present a risk of violating the border of the maxillary sinus during conventional or surgical endodontic treatment or in case of tooth extraction.

Immediate implant placement in mandible and prosthetic rehabilitation by means of all-zirconium oxide restorations: case report of a woman with a history of periodontitis.

Owing to its single surgical intervention, immediate implant placement has the advantage of shortening treatment time, and thus positively affects patient morbidity. According to the bone resorption pattern after tooth extraction, bone loss should be anticipated if immediate implant placement is considered. The present case report aims to present a possible treatment option and to demonstrate that a partially edentulous arch may be rehabilitated esthetically by immediate implant placement and by corresponding anticipatory measures.

Land based mesocosm experiment studying the simultaneous impact of warming and acidification on the planktonic food web of the Eastern Mediterranean

A land based mesocosm experiment focusing on the study of the simultaneous impact of warming and acidification on the planktonic food web of the Eastern Mediterranean took place in August-September 2013 at the mesocosm facilities of HCMR in Crete (CRETACOSMOS). Two different pCO2 (present day and predicted for year 2100) were applied in triplicate mesocosms of 3 m**3. This was tested in two different temperatures (ambient seawater T and ambient T plus 3°C). Twelve mesocosms in total were incubated in two large concrete tanks. Temperature was controlled by sophisticated, automated systems. A large variety of chemical, biological and biochemical variables were studied, including salinity, temperature, light and alkalinity measurements, inorganic and organic, particulate and dissolved, nutrient analyses, biological stock (Chla concentration, enumeration and community composition of microbial, phyto- and zooplankton organisms) and rate (primary, bacterial, viral production, copepod egg production, zooplankton grazing, N2 fixation, P uptake) measurements, bacterial DNA extraction and phytoplankton transcriptomics, calcifiers analyses. Twenty three scientists from 6 Institutes and 5 countries participated in this experiment.

Identification procedure of mealy apples by instrumental means. Extraction of storage features.

Mealiness is a negative attribute of sensory texture that combines the sensation of a disaggregated tissue with the sensation of lack of juiciness. Since January 1996, a wide EC Project entitled : "Mealiness in fruits. Consumers perception and means for detection'" is being carried out. Within it, three sensory panels have been trained at : the Institute of Food Research (IFR, United Kingdom), the Instituto de Agroquímica y Tecnología de los Alimentos (IATA, Spain) and the Institut voor Agrotechnologisch Onderzoek (ATO-DLO, Netherlands) to assess mealiness in apples. In all three cases, mealiness has been described as a multidimensional sensory descriptor capable of gathering the loss of consistency (of crispness and of hardness) and of juiciness. Also within the EC Project several instrumental procedures have been tested for mealiness assessment. In this sense the Physical Properties Laboratory (ETS1A-UPM) has focused its aims in a first stage on performing instrumental tests for assessing some textural descriptors as crispiness, hardness and juiciness. The results obtained within these tests have shown to correlate well with the sensory measurements (Barreiro et Ruiz-Altisent, 1997) in apples, but also have succeed when trying to generate several texture degradation levels on peaches from which mealiness appears to be the last stage (Ortiz et al. 1997).

Root Xylem Embolisms and Refilling. Relation to Water Potentials of Soil, Roots, and Leaves, and Osmotic Potentials of Root Xylem Sap1

Embolism and refilling of vessels was monitored directly by cryomicroscopy of field-grown corn (Zea mays L.) roots. To test the reliability of an earlier study showing embolism refilling in roots at negative leaf water potentials, embolisms were counted, and root water potentials (Ψroot) and osmotic potentials of exuded xylem sap from the same roots were measured by isopiestic psychrometry. All vessels were full at dawn (Ψroot −0.1 MPa). Embolisms were first seen in late metaxylem vessels at 8 am. Embolized late metaxylem vessels peaked at 50% at 10 am (Ψroot −0.1 MPa), fell to 44% by 12 pm (Ψroot −0.23 MPa), then dropped steadily to zero by early evening (Ψroot −0.28 MPa). Transpiration was highest (8.5 μg cm−2 s−1) between 12 and 2 pm when the percentage of vessels embolized was falling. Embolized vessels were refilled by liquid moving through their lateral walls. Xylem sap was very low in solutes. The mechanism of vessel refilling, when Ψroot is negative, requires further investigation. Daily embolism and refilling in roots of well-watered plants is a normal occurrence and may be a component of an important hydraulic signaling mechanism between roots and shoots.

Enhancing the catalytic repertoire of nucleic acids. II. Simultaneous incorporation of amino and imidazolyl functionalities by two modified triphosphates during PCR

The incorporation of potentially catalytic groups into DNA is of interest for the in vitro selection of novel deoxyribozymes. We have devised synthetic routes to a series of three C7 modified 7-deaza-dATP derivatives with pendant aminopropyl, Z-aminopropenyl and aminopropynyl side chains. These modified triphosphates have been tested as substrates for Taq polymerase during PCR. All the modifications are tolerated by this enzyme, with the aminopropynyl side chain giving the best result. Most protein enzymes have more than one type of catalytic group located in their active site. By using C5-imidazolyl-modified dUTPs together with 3-(aminopropynyl)-7-deaza-dATP in place of the natural nucleotides dTTP and dATP, we have demonstrated the simultaneous incorporation of both amino and imidazolyl moieties into a DNA molecule during PCR. The PCR product containing the four natural bases was fully digested by XbaI, while PCR products containing the modified 7-deaza-dATP analogues were not cleaved. Direct evidence for the simultaneous incorporation during PCR of an imidazole-modified dUTP and an amino-modified 7-deaza-dATP has been obtained using mass spectrometry.

Simultaneous implementation of the Bachelor, Masters and PhD degrees in nursing in the Universidad Jaume I. Castellón de la Plana, Spain

We present an experience in Nursing Education, accredited and implemented under the Spanish University System Reform in a Public University (Jaume I, Castellón) which had no previous nursing studies. The academics offered included all three educational levels (Bachelor, Master's and Doctorate), with an integrated theoretical-practical-clinical teaching methodology for the Bachelor Degree, competence acquisition in research in the Master's degree, and a doctorate formed by lines of research in the field of Nursing. Studies are accredited by the National Agency for Quality Assessment, which were authorized by the Spanish Ministry of Education and implanted between 2009 and 2011.

Simultaneous synthesis of work exchange networks with heat integration

The optimal integration of work and its interaction with heat can represent large energy savings in industrial plants. This paper introduces a new optimization model for the simultaneous synthesis of work exchange networks (WENs), with heat integration for the optimal pressure recovery of process gaseous streams. The proposed approach for the WEN synthesis is analogous to the well-known problem of synthesis of heat exchanger networks (HENs). Thus, there is work exchange between high-pressure (HP) and low-pressure (LP) streams, achieved by pressure manipulation equipment running on common axes. The model allows the use of several units of single-shaft-turbine-compressor (SSTC), as well as stand-alone compressors, turbines and valves. Helper motors and generators are used to respond to any demand and excess of energy. Moreover, between the WEN stages the streams are sent to the HEN to promote thermal recovery, aiming to enhance the work integration. A multi-stage superstructure is proposed to represent the process. The WEN superstructure is optimized in a mixed-integer nonlinear programming (MINLP) formulation and solved with the GAMS software, with the goal of minimizing the total annualized cost. Three examples are conducted to verify the accuracy of the proposed method. In all case studies, the heat integration between WEN stages is essential to improve the pressure recovery, and to reduce the total costs involved in the process.

Microwave-Assisted Extraction of Phenolic Compounds from Almond Skin Byproducts (Prunus amygdalus): A Multivariate Analysis Approach

A microwave-assisted extraction (MAE) procedure to isolate phenolic compounds from almond skin byproducts was optimized. A three-level, three-factor Box–Behnken design was used to evaluate the effect of almond skin weight, microwave power, and irradiation time on total phenolic content (TPC) and antioxidant activity (DPPH). Almond skin weight was the most important parameter in the studied responses. The best extraction was achieved using 4 g, 60 s, 100 W, and 60 mL of 70% (v/v) ethanol. TPC, antioxidant activity (DPPH, FRAP), and chemical composition (HPLC-DAD-ESI-MS/MS) were determined by using the optimized method from seven different almond cultivars. Successful discrimination was obtained for all cultivars by using multivariate linear discriminant analysis (LDA), suggesting the influence of cultivar type on polyphenol content and antioxidant activity. The results show the potential of almond skin as a natural source of phenolics and the effectiveness of MAE for the reutilization of these byproducts.

Solvent extraction of uranium : a literature search /

"March 1957."

The solvent-solvent extraction of uranium from sulfuric acid solutions with oil soluble amines /

Fifty oil soluble amines were screened for possible use as extractants for uranium from sulfuric acid solutions. The most promising of these were studied further to obtain the optimum conditions for operation of such a process. Kerosene was used as the diluent.

Reduced hepatic extraction of palmitate in steatosis correlated to lower level of liver fatty acid binding protein

Nonalcoholic fatty liver disease is the most common of all liver diseases. The hepatic disposition [H-3]palmitate and its low-molecular-weight metabolites in perfused normal and steatotic rat liver were studied using the multiple indicator dilution technique and a physiologically based slow diffusion/bound pharmacokinetic model. The steatotic rat model was established by administration of 17alpha-ethynylestradiol to female Wistar rats. Serum biochemistry markers and histology of treated and normal animals were assessed and indicated the presence of steatosis in the treatment group. The steatotic group showed a significantly higher alanine aminotransferase-to-aspartate aminotransferase ratio, lower levels of liver fatty acid binding protein and cytochrome P-450, as well as microvesicular steatosis with an enlargement of sinusoidal space. Hepatic extraction for unchanged [H-3]palmitate and production of low-molecular-weight metabolites were found to be significantly decreased in steatotic animals. Pharmacokinetic analysis suggested that the reduced extraction and sequestration for palmitate and its metabolites was mainly attributed to a reduction in liver fatty acid binding protein in steatosis.

Transcriptional response of sugarcane roots to methyl jasmonate

The effect of methyl jasmonate treatment on gene expression in sugarcane roots signalling between roots and shoots was studied. A collection of 829 ESTs were obtained from sugarcane roots treated with the defence-regulator methyl jasmonate (MJ) treatment. A subset of 747 of these were combined with 4793 sugarcane ESTs obtained from stem tissues in a cDNA microarray and experiments undertaken to identify genes that were induced in roots 24-120 h following treatment with MJ. Two data analysis systems (t-statistic and tRMA) were used to analyse the microarray results and these methods identified a common set of 21 ESTs corresponding to transcripts significantly induced by MJ in roots and 23 that were reduced in expression following MJ treatment. The induction of six transcripts identified in the microarray analysis was tested and confirmed using northern blotting. Homologues of genes encoding lipoxygenase and PR-10 proteins were induced 824 It after MJ treatment while the other four selected transcripts were induced at later time points. Following treatment of roots with MJ, the lipoxygenase homologue, but not the PR-10 homologue, was induced in untreated stem and leaf tissues. The PR-10 homologue and a PR-1 homologue, but not the lipoxygenase homologue, were induced in untreated tissues after the application of SA to roots. Repeated foliar application of MJ had no apparent effects on plant growth and was demonstrated to increase lipoxygenase transcripts in roots, but did not increase transcript levels-of other genes tested. These results lay a foundation for further studies of induced pest and disease resistance in sugarcane roots. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Conventional detection methodology is limiting our ability to understand the roles and functions of fine roots

We lack a thorough conceptual and functional understanding of fine roots. Studies that have focused on estimating the quantity of fine roots provide evidence that they dominate overall plant root length. We need a standard procedure to quantify root length/biomass that takes proper account of fine roots. Here we investigated the extent to which root length/biomass may be underestimated using conventional methodology, and examined the technical reasons that could explain such underestimation. Our discussion is based on original X-ray-based measurements and on a literature review spanning more than six decades. We present evidence that root-length recovery depends strongly on the observation scale/spatial resolution at which measurements are carried out; and that observation scales/resolutions adequate for fine root detection have an adverse impact on the processing times required to obtain precise estimates. We conclude that fine roots are the major component of root systems of most (if not all) annual and perennial plants. Hence plant root systems could be much longer, and probably include more biomass, than is widely accepted.