Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles

The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45 min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC–MS/MS. All dogs appeared sedated after each treatment without complication. Plasma concentrations of levomedetomidine were measured only in the racemic group and were 51.4% (51.4%–56.1%) lower than dexmedetomidine. Non-compartmental analysis (NCA) was performed for both drugs, while dexmedetomidine data were further described using a population pharmacokinetic approach. A standard two-compartment mammillary model with linear elimination with combined additive and multiplicative error model for residual unexplained variability was established for dexmedetomidine. An exponential model was finally retained to describe inter-individual variability on parameters of clearance (Cl1) and central and peripheral volumes of distribution (V1, V2). No effect of occurrence, levomedetomidine or atipamezole could be observed on dexmedetomidine PK parameters. Dexmedetomidine did not undergo significantly different PK when administered alone or as part of the racemic mixture in otherwise unmedicated dogs

Remineralization of demineralized dentin using a dual analog system.

ObjectiveImproved methods are needed to remineralize dentin caries in order to promote conservation of dentin tissue and minimize the surgical interventions that are currently required for clinical treatment. Here, we test the hypothesis that bulk substrates can be effectively mineralized via a dual analog system proposed by others, using a tripolyphosphate (TPP) "templating analog" and a poly(acrylic acid) (PAA) or poly(aspartic acid) (pAsp) "sequestration analog," the latter of which generates the polymer-induced liquid-precursor (PILP) mineralization process studied in our laboratory.Material & methodsDemineralized human dentin slices were remineralized with and without pre-treatment with TPP, using either PAA or pAsp as the PILP process-directing agent. A control experiment with no polymer present was used for comparison.ResultsNo mineralization was observed in any of the PAA groups. In both the pAsp and no polymer groups, TPP inhibited mineralization on the surfaces of the specimens but promoted mineralization within the interiors. Pre-treatment with TPP enhanced overall mineralization of the pAsp group. However, when analysed via TEM, regions with little mineral were still present.ConclusionPoly(acrylic acid) was unable to remineralize demineralized dentin slices under the conditions employed, even when pre-treated with TPP. However, pre-treatment with TPP enhanced overall mineralization of specimens that were PILP-remineralized using pAsp

Complex, but not quite complex enough : The turn to the complexity sciences in evaluation scholarship

This document is the Accepted Manuscript version of the following article: Chris Mowles, ‘Complex, but not quite complex enough: The turn to the complexity sciences in evaluation scholarship’. The final, definitive version of this paper has been published in Evaluation, Vol. 20 (2): 160-175, April 2014, doi: https://doi.org/10.1177/1356389014527885 , published by SAGE Publishing. All rights reserved.This article offers a critical review of the way in which some scholars have taken up the complexity sciences in evaluation scholarship. I argue that there is a tendency either to over-claim or under-claim their importance because scholars are not always careful about which of the manifestations of the complexity sciences they are appealing to, nor do they demonstrate how they understand them in social terms. The effect is to render ‘complexity’ just another volitional tool in the evaluator’s toolbox subsumed under the dominant understanding of evaluation, as a logical, rational activity based on systems thinking and design. As an alternative I argue for a radical interpretation of the complexity sciences, which understands human interaction as always complex and emergent. The interweaving of intentions in human activity will always bring about outcomes that no one has intended including in the activity of evaluation itself.Peer reviewe

Characterization of TiO2 nanoparticles in langmuir-blodgett films

In this work we have synthesized TiO2 nanoparticles, using either a sol–gel base catalysed process in the interior of CTAB reversed micelles (TiO2 CTAB sol), or the neutralization of a TiO2/H2SO4 solution in the interior of AOT reversed micelles. From the absorption and emission data of the TiO2 nanoparticles it is possible to conclude that in the sol–gel route there remains alkoxide groups in the structure, originating transitions lower than the energy gap of TiO2 semiconductor. These transitions disappear in the neutralization procedure, where the alkoxide groups are absent in the structure. We have assigned the observed indirect and direct optical transitions according to the anatase band structure. TiO2 Langmuir-Blodgett (LB) films were prepared either by direct deposition of titanium isopropoxide or by deposition of the TiO2 CTAB sol. These films showed photoluminescence, which was attributed to band-gap emission and to surface recombination of defect states

Mapping patterns of complementary and alternative medicine use in cancer: An explorative cross-sectional study of individuals with reported positive "exceptional" experiences

<p>Abstract</p> <p>Background</p> <p>While the use of complementary and alternative medicine (CAM) among cancer patients is common and widespread, levels of commitment to CAM vary. "Committed" CAM use is important to investigate, as it may be associated with elevated risks and benefits, and may affect use of biomedically-oriented health care (BHC). Multiple methodological approaches were used to explore and map patterns of CAM use among individuals postulated to be committed users, voluntarily reporting exceptional experiences associated with CAM use after cancer diagnosis.</p> <p>Method</p> <p>The verbatim transcripts of thirty-eight unstructured interviews were analyzed in two steps. First, manifest content analysis was used to elucidate and map participants' use of CAM, based on the National Center for Complementary Medicine (NCCAM)'s classification system. Second, patterns of CAM use were explored statistically using principal component analysis.</p> <p>Findings</p> <p>The 38 participants reported using a total of 274 specific CAM (median = 4) consisting of 148 different therapeutic modalities. Most reported therapies could be categorized using the NCCAM taxonomy (n = 224). However, a significant number of CAM therapies were not consistent with this categorization (n = 50); consequently, we introduced two additional categories: <it>Spiritual/health literature </it>and <it>Treatment centers</it>. The two factors explaining the largest proportion of variation in CAM usage patterns were a) number of CAM modalities used and b) a category preference for <it>Energy therapies </it>over the categories <it>Alternative Medical Systems </it>and <it>Treatment centers </it>or vice versa.</p> <p>Discussion</p> <p>We found considerable heterogeneity in patterns of CAM use. By analyzing users' own descriptions of CAM in relation to the most commonly used predefined professional taxonomy, this study highlights discrepancies between user and professional conceptualizations of CAM not previously addressed. Beyond variations in users' reports of CAM, our findings indicate some patterns in CAM usage related to number of therapies used and preference for different CAM categories.</p

Oxidative stress and adrenocortical insufficiency

This work has been supported by the Wellcome Trust (Clinical Research Training Fellowship grant number WT095984AIA to R P) and the Medical Research Council UK (project grant number MR/K020455/1 to L A M

Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model

Thirty-five percent of patients with Rett syndrome carry nonsense mutations in the MECP2 gene. We have recently shown in transfected HeLa cells that readthrough of nonsense mutations in the MECP2 gene can be achieved by treatment with gentamicin and geneticin. This study was performed to test if readthrough can also be achieved in cells endogenously expressing mutant MeCP2 and to evaluate potentially more effective readthrough compounds. A mouse model was generated carrying the R168X mutation in the MECP2 gene. Transfected HeLa cells expressing mutated MeCP2 fusion proteins and mouse ear fibroblasts isolated from the new mouse model were treated with gentamicin and the novel aminoglycosides NB30, NB54, and NB84. The localization of the readthrough product was tested by immunofluorescence. Readthrough of the R168X mutation in mouse ear fibroblasts using gentamicin was detected but at lower level than in HeLa cells. As expected, the readthrough product, full-length Mecp2 protein, was located in the nucleus. NB54 and NB84 induced readthrough more effectively than gentamicin, while NB30 was less effective. Readthrough of nonsense mutations can be achieved not only in transfected HeLa cells but also in fibroblasts of the newly generated Mecp2R168X mouse model. NB54 and NB84 were more effective than gentamicin and are therefore promising candidates for readthrough therapy in Rett syndrome patients

Enhancement of fluoride release from glass ionomer cement following a coating of silver fluoride

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.BACKGROUND: This study investigated the extent to which a coating of 10% silver fluoride (AgF) on discs of glass jonomer cements (GIGs) would enhance the release of fluoride ion into eluting solutions at varying pH. MATERIALS AND METHODS: Forty discs each of Fuji LX, Fuji VII and of Vitrebond were prepared in a plastic mould. Twenty discs of each material were coated for 30 seconds with a 10% solution of AgF. Five discs each of coated and uncoated material were placed individually in 4m1 of differing eluant solutions. The eluant solutions comprised deionized distilled water (DDW) and three separate acetate buffered solutions at pH 7, pH 5 and pH 3. After 30 minutes the discs were removed and placed in five vials containing 4m1 of the various solutions for a further 30 minutes. This was repeated for further intervals of time up to 216 hours, and all eluant solutions were stored. Fluoride concentrations in the eluant solutions were estimated using a fluoride specific electrode, with TISAB IV as a metal ion complexing and ionic concentration adjustment agent. Cumulative fluoride release patterns were determined from the incremental data. RESULTS: The coating of AgF greatly enhanced the level of fluoride ion release from all materials tested. Of the uncoated samples, Vitrehond released the greater concentrations of fluoride ion, followed by Fuji VII. However, cumulative levels of fluoride released from coated samples of the GICs almost matched those from coated Vitrebond. CONCLUSIONS: It was concluded that a coating of 10% AgF on GICs and a resin modified GIC greatly enhanced the concentration of fluoride released from these materials. This finding might be applied to improving protection against recurrent caries, particularly in high caries risk patients, and in the atraumatic restorative technique (ART) of restoration placement