Determination of the Enantiomers of Mianserin and its Metabolites in Plasma by Capillary Electrophoresis After Liquid—Liquid Extraction and On-Column Sample Preconcentration

Capillary electrophoresis has drawn considerable attention in the past few years, particularly in the field of chiral separations because of its high separation efficiency. However, its routine use in therapeutic drug monitoring is hampered by its low sensitivity due to a short optical path. We have developed a capillary zone electrophoresis (CZE) method using 2mM of hydroxypropyl-β-cyclodextrin as a chiral selector, which allows base-to-base separation of the enantiomers of mianserin (MIA), desmethylmianserin (DMIA), and 8-hydroxymianserin (OHMIA). Through the use of an on-column sample concentration step after liquid-liquid extraction from plasma and through the presence of an internal standard, the quantitation limits were found to be 5 ng/mL for each enantiomer of MIA and DMIA and 15 ng/mL for each enantiomer of OHMIA. To our knowledge, this is the first published CE method that allows its use for therapeutic monitoring of antidepressants due to its sensitivity down to the low nanogram range. The variability of the assays, as assessed by the coefficients of variation (CV) measured at two concentrations for each substance, ranged from 2 to 14% for the intraday (eight replicates) and from 5 to 14% for the interday (eight replicates) experiments. The deviations from the theoretical concentrations, which represent the accuracy of the method, were all within 12.5%. A linear response was obtained for all compounds within the range of concentrations used for the calibration curves (10-150 ng/mL for each enantiomer of MIA and DMIA and 20-300 ng/mL for each enantiomer of OHMIA). Good correlations were calculated between [(R) + (S)]-MIA and DMIA concentrations measured in plasma samples of 20 patients by a nonchiral gas chromatography method and CZE, and between the (R)- and (S)-concentrations of MIA and DMIA measured in plasma samples of 37 patients by a previously described chiral high-performance liquid chromatography method and CZE. Finally, no interference was noted from more than 20 other psychotropic drugs. Thus, this method, which is both sensitive and selective, can be routinely used for therapeutic monitoring of the enantiomers of MIA and its metabolites. It could be very useful due to the demonstrated interindividual variability of the stereoselective metabolism of MI

A simple label-free method reveals bacterial growth dynamics and antibiotic action in real-time

Funding: The authors gratefully acknowledge the financial support of Scottish Enterprise, NESTA Longitude Prize and the University of St Andrews.Understanding the response of bacteria to environmental stress is hampered by the relative insensitivity of methods to detect growth. This means studies of antibiotic resistance and other physiological methods often take 24 h or longer. We developed and tested a scattered light and detection system (SLIC) to address this challenge, establishing the limit of detection, and time to positive detection of the growth of small inocula. We compared the light-scattering of bacteria grown in varying high and low nutrient liquid medium and the growth dynamics of two closely related organisms. Scattering data was modelled using Gompertz and Broken Stick equations. Bacteria were also exposed meropenem, gentamicin and cefoxitin at a range of concentrations and light scattering of the liquid culture was captured in real-time. We established the limit of detection for SLIC to be between 10 and 100 cfu mL−1 in a volume of 1–2 mL. Quantitative measurement of the different nutrient effects on bacteria were obtained in less than four hours and it was possible to distinguish differences in the growth dynamics of Klebsiella pneumoniae 1705 possessing the BlaKPC betalactamase vs. strain 1706 very rapidly. There was a dose dependent difference in the speed of action of each antibiotic tested at supra-MIC concentrations. The lethal effect of gentamicin and lytic effect of meropenem, and slow bactericidal effect of cefoxitin were demonstrated in real time. Significantly, strains that were sensitive to antibiotics could be identified in seconds. This research demonstrates the critical importance of improving the sensitivity of bacterial detection. This results in more rapid assessment of susceptibility and the ability to capture a wealth of data on the growth dynamics of bacteria. The rapid rate at which killing occurs at supra-MIC concentrations, an important finding that needs to be incorporated into pharmacokinetic and pharmacodynamic models. Importantly, enhanced sensitivity of bacterial detection opens the possibility of susceptibility results being reportable clinically in a few minutes, as we have demonstrated.Publisher PDFPeer reviewe

Upgrading a ColdFusion-Based Academic Medical Library Staff Intranet

This article details the process of upgrading and expanding an existing academic medical library intranet to include a wiki, blog, discussion forum, and photo collection manager. The first version of the library\u27s intranet from early 2002 was powered by ColdFusion software and existed primarily to allow staff members to author and store minutes of library team meetings. Other ColdFusion-based applications and functions were subsequently added, as were various other library documents and procedures. As a follow-up to the library\u27s strategic plan, a library Staff Intranet Team was organized in early 2008 to reorganize the content of the intranet and to identify software tools that would allow greater staff participation in maintaining and updating intranet content. Early steps in the process included brainstorming, a card-sorting exercise, product research, a staff survey, and paper prototyping. The team focused on implementing various open-source, ColdFusion-based tools in order to accommodate existing technology, available budget, and time constraints. Challenges in implementing the tools included bypassing or modifying existing authentication systems and applying modifications that led to loss of native functionality. Despite usability testing and staff training, library staff have not universally welcomed or adopted all the new tools. Notwithstanding these challenges, the renovated staff intranet has shown promise in furthering the goals in the library\u27s strategic plan to improve communication and facilitate collaboration among library staff

Vilanterol and fluticasone furoate for chronic asthma in adults and children

Background Vilanterol (VI) is a long-acting beta2-agonist (LABA) that binds to the beta2-adrenoceptor on the airway smooth muscle, producing bronchodilation. LABA therapy, which is well established in adults as part of the British Thoracic Society (BTS) Guidelines for the Management of Asthma, leads to improvement in symptoms and lung function and reduction in exacerbations. At present, the commonly used LABAs licensed for use in asthma management (formoterol and salmeterol) require twice-daily administration, whereas VI is a once-daily therapy. Fluticasone furoate (FF) is an inhaled corticosteroid (ICS), and ICS therapy is recommended by the BTS asthma guidelines. ICSs, the mainstay of asthma treatment, lead to a reduction in both airway inflammation and airway hyper-responsiveness. Regular use leads to improvement in symptoms and lung function. ICSs are currently recommended as 'preventer' therapy for patients who use a 'reliever' medication (e.g. short-acting beta2 agonist (SABA), salbutamol) three or more times per week. Most of the commonly used ICS treatments are twice-daily medications, although two once-daily products are currently licensed (ciclesonide and mometasone). At the present time, only one once-daily ICS/LABA combination (FF/VI) is available, and several other combination inhalers are recommended for twice-daily administration

Technical and Economic Feasibility of Rabbiteye Blueberry Production East Texas.

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MammoSapiens: eResearch of the lactation program.

Delivering bioinformatics power to life science researchers inevitably runs into problems of limited computing resources in the context of exponentially increasing data sources, access time, costs, lack of skills and, rapidly evolving technology and software tools with poorly defined standards. In this context the development of e-facilities to best enable collaborative research often needs to be customized to specific project applications in close cooperation with the experimentalist users and, to be concerned with the storage and management of results to allow more consistency and traceability of e-results on a broad access data mining platform. Here we showcase an internet based eResearch platform using the PHP/MySQL paradigm for the collaborative, integrative and comparative analysis of lactation related gene sequences and gene expression experiments to support lactation research. We also illustrate how these resources are used, how they enable research by allowing meta-analysis of data and results and, how the bottom-up development of customized eResearch components can lead to the production of more generic functional software tools and eResearch environments for deployment to a larger number of biological research users working on other bio-systems.<br /

MammoSapiens: eResearch of the lactation program. Building online facilities for collaborative molecular and evolutionary analysis of lactation and other biological systems from gene sequences and gene expression data.

Delivering bioinformatics power to life science researchers inevitably runs into problems of limited computing resources in the context of exponentially increasing data sources, access time, costs, lack of skills and, rapidly evolving technology and software tools with poorly defined standards. In this context the development of online facilities to best enable collaborative research often needs to be customized to specific project applications in close cooperation with the experimentalist users and, to be concerned with the storage and management of results to allow more consistency and traceability of results on a broad access data mining platform. Here we showcase an Internet based research platform using the PHP/MySQL paradigm for the collaborative, integrative and comparative analysis of lactation related gene sequences and gene expression experiments to support lactation research. We also illustrate how these resources are used, how they enable research by allowing meta-analysis of data and results and, how the bottom-up development of customized eResearch components can lead to the production of more generic functional software tools and eResearch environments for deployment to a larger number of biological researchers working on other bio-systems

Global health and foreign policy.

Health has long been intertwined with the foreign policies of states. In recent years, however, global health issues have risen to the highest levels of international politics and have become accepted as legitimate issues in foreign policy. This elevated political priority is in many ways a welcome development for proponents of global health, and it has resulted in increased funding for and attention to select global health issues. However, there has been less examination of the tensions that characterize the relationship between global health and foreign policy and of the potential effects of linking global health efforts with the foreign-policy interests of states. In this paper, the authors review the relationship between global health and foreign policy by examining the roles of health across 4 major components of foreign policy: aid, trade, diplomacy, and national security. For each of these aspects of foreign policy, the authors review current and historical issues and discuss how foreign-policy interests have aided or impeded global health efforts. The increasing relevance of global health to foreign policy holds both opportunities and dangers for global efforts to improve health

The Victorian Newsletter (Spring 1985)

The Victorian Newsletter is sponsored for the Victorian Group of Modern Language Association by the Western Kentucky University and is published twice annually.Aubrey Beardsley Counts the Ways / Linda Gertner Zatlin -- Domesticating the Brutal Passion in Nineteenth-Century Fiction / Harriet Farwell Adams -- Tennyson's Courtship of Sorrow / Sylvia Manning -- "Love in a Life": The Case of Nietzsche and Lou Salomé / William Beatty Warner -- Wilde's Closet Self: A Solo at One Remove / Nathan Cervo -- "When Critics Disagree" / Kerry Powell -- Physical Opposition in Barnaby Rudge / Brian Rosenberg -- Herbert Spencer and the Study of Laughter / Michael S. Kearns -- Robert Browning and Aurora Leigh / George M. Ridenour -- Books Receive