59 research outputs found

    Recurrent Recruitment Manoeuvres Improve Lung Mechanics and Minimize Lung Injury during Mechanical Ventilation of Healthy Mice

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    INTRODUCTION: Mechanical ventilation (MV) of mice is increasingly required in experimental studies, but the conditions that allow stable ventilation of mice over several hours have not yet been fully defined. In addition, most previous studies documented vital parameters and lung mechanics only incompletely. The aim of the present study was to establish experimental conditions that keep these parameters within their physiological range over a period of 6 h. For this purpose, we also examined the effects of frequent short recruitment manoeuvres (RM) in healthy mice. METHODS: Mice were ventilated at low tidal volume V(T) = 8 mL/kg or high tidal volume V(T) = 16 mL/kg and a positive end-expiratory pressure (PEEP) of 2 or 6 cm H(2)O. RM were performed every 5 min, 60 min or not at all. Lung mechanics were followed by the forced oscillation technique. Blood pressure (BP), electrocardiogram (ECG), heart frequency (HF), oxygen saturation and body temperature were monitored. Blood gases, neutrophil-recruitment, microvascular permeability and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) and blood serum as well as histopathology of the lung were examined. RESULTS: MV with repetitive RM every 5 min resulted in stable respiratory mechanics. Ventilation without RM worsened lung mechanics due to alveolar collapse, leading to impaired gas exchange. HF and BP were affected by anaesthesia, but not by ventilation. Microvascular permeability was highest in atelectatic lungs, whereas neutrophil-recruitment and structural changes were strongest in lungs ventilated with high tidal volume. The cytokines IL-6 and KC, but neither TNF nor IP-10, were elevated in the BAL and serum of all ventilated mice and were reduced by recurrent RM. Lung mechanics, oxygenation and pulmonary inflammation were improved by increased PEEP. CONCLUSIONS: Recurrent RM maintain lung mechanics in their physiological range during low tidal volume ventilation of healthy mice by preventing atelectasis and reduce the development of pulmonary inflammation

    Applying physical science techniques and CERN technology to an unsolved problem in radiation treatment for cancer: the multidisciplinary ‘VoxTox’ research programme

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    The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose.JES was supported by Cancer Research UK through the Cambridge Cancer Centre. NGB, ASP and MG are supported by the National Institute of Health Research Cambridge Biomedical Research Centre. KH, MR AMB, EW and SJB were supported by the VoxTox Research Programme, funded by Cancer Research UK. DJN is supported by Addenbrooke’s Charitable Trust and Cancer Research UK through the Cambridge Cancer Centre. FMB was supported by the Science and Technology Facilities Council. MPDS was part supported by the VoxTox Research Programme, funded by Cancer Research UK. RJ was part supported by the VoxTox Research Programme, funded by Cancer Research UK. LS is supported by the Armstrong Trust. XC was supported by the Isaac Newton Trust. CBS acknowledges support from the EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging, the Leverhulme Trust, the EU-RISE project CHiPS and the Cantab Capital Institute for the Mathematics of Information. NT was supported by a Gates-Cambridge Scholarship, funded by the Bill and Melinda Gates Foundation, PLY and SYKS by the Singapore Government

    Approaches to analyzing insulators with Auger electron spectroscopy: Update and overview

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    This paper provides an updated overview, intended to be of practical value to analysts, of methods that can be applied to minimize or control the build-up of near-surface electrical charge during electron-induced Auger electron spectroscopy (AES). Although well-developed methods can be highly effective, dealing with insulating or ungrounded samples for which high spatial resolution is needed remains a challenge. Examples of the application of methods involving low-energy ion sources and sample thinning using a focused ion beam that can allow high-resolution measurements on a variety of samples are highlighted. The physical bases of newer and traditional methods are simply described along with strengths and limitations of the methods. Summary tables indicate methods that can be applied to most AES spectrometers, methods that require special instrumental capabilities and methods that require special sample preparation or mounting

    Approaches to analyzing insulators with Auger electron spectroscopy: Update and overview

    Get PDF
    This paper provides an updated overview, intended to be of practical value to analysts, of methods that can be applied to minimize or control the build-up of near-surface electrical charge during electron-induced Auger electron spectroscopy (AES). Although well-developed methods can be highly effective, dealing with insulating or ungrounded samples for which high spatial resolution is needed remains a challenge. Examples of the application of methods involving low-energy ion sources and sample thinning using a focused ion beam that can allow high-resolution measurements on a variety of samples are highlighted. The physical bases of newer and traditional methods are simply described along with strengths and limitations of the methods. Summary tables indicate methods that can be applied to most AES spectrometers, methods that require special instrumental capabilities and methods that require special sample preparation or mounting

    Macrocyclic Dual-Locked “Turn-On” Drug for Selective and Traceless Release in Cancer Cells

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    Drug safety and efficacy due to premature release into the bloodstream and poor biodistribution remains a problem despite seminal advances in this area. To circumvent these limitations, we report drug cyclization based on dynamic covalent linkages to devise a dual lock for the small molecule anticancer drug, camptothecin (CPT). Drug activity is "locked" within the cyclic structure by the redox responsive disulfide and pH-responsive boronic acid-salicylhydroxamate and turns on only in the presence of acidic pH, reactive oxygen species and glutathione through traceless release. Notably, the dual-responsive CPT is more active (100-fold) than the non-cleavable (permanently closed) analogue. We further include a bioorthogonal handle in the backbone for functionalization to generate cyclic-locked, cell-targeting peptide- and protein-CPTs, for targeted delivery of the drug and traceless release in triple negative metastatic breast cancer cells to inhibit cell growth at low nanomolar concentrations
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