Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we will assume that you are happy to receive all cookies and you will not see this message again. Click 'Find out more' for information on how to change your cookie settings.
  • Implementation of a modified version of NICE CG95 on chest pain of recent onset: Experience in a DGH

    15 October 2018

    National Institute for Health and Care Excellence (NICE) clinical guideline 95 (CG95) was introduced to rapidaccess chest pain clinics (RACPC) to aid investigation of possible stable angina based on pretest probability of coronary artery disease (CAD). Following a six-month audit of its implementation we introduced a modified version: patients with low/ moderate risk of CAD were referred for computed tomography coronary angiography (CTCA), while those at high/ very high risk were referred for invasive angiography. Patient records of 546 patients referred to our RACPC over a six-month period were retrospectively analysed. Pretest probability of CAD, referral for initial investigation, and outcomes at a minimum follow-up time of six months were documented. Incidence of CAD correlated well with pretest probability. Moderaterisk patients had a low incidence of CAD and revascularisation. High/ very high-risk patients had a high incidence of revascularisation, and this was predominantly for prognostically significant disease. In conclusion, low rates of CAD in lowand moderate-risk groups justifies the use of CTCA as a first-line investigation in these patients. Routine investigation of very high-risk patients allows a high proportion to undergo revascularisation for prognostically significant disease. Strict adherence to NICE CG95 could lead to these patients being missed.

  • The whole cell Ca2+ release-activated Ca2+ current ICRAC is regulated by the mitochondrial Ca2+ uniporter channel and is independent of extracellular and cytosolic Na.

    31 December 2018

    KEY POINTS: Ca2+ entry through Ca2+ release-activated Ca2+ channels activates numerous cellular responses. Under physiological conditions of weak intracellular Ca2+ buffering, mitochondrial Ca2+ uptake regulates CRAC channel activity. Knockdown of the mitochondrial Ca2+ uniporter channel prevented the development of ICRAC in weak buffer but not when strong buffer was used instead. Removal of either extracellular or intra-pipette Na+ had no effect on the selectivity, kinetics, amplitude, rectification or reversal potential of whole cell CRAC current Knockdown of the mitochondrial Na+ -Ca2+ exchanger did not prevent the development of ICRAC in strong or weak Ca2+ buffer. Whole cell CRAC current is Ca2+ -selective Mitochondrial Ca2+ channel and not Na+ -dependent transport regulates CRAC channels under physiological conditions. Ca2+ entry through store-operated Ca2+ release-activated Ca2+ (CRAC) channels plays a central role in activation of a range of cellular responses over broad spatial and temporal bandwidths. Mitochondria, through their ability to take up cytosolic Ca2+ , are important regulators of CRAC channel activity under physiological conditions of weak intracellular Ca2+ buffering. The mitochondrial Ca2+ transporter(s) that regulates CRAC channels is unclear and could involve the 40 KDa mitochondrial Ca2+ uptake channel MCU or the Na+ -Ca2+ -Li+ exchanger (NCLX). Here, we have investigated the involvement of these mitochondrial Ca2+ transporters in supporting the CRAC current ICRAC under a range of conditions in RBL mast cells. Knockdown of the MCU impaired the activation of ICRAC under physiological conditions of weak intracellular Ca2+ buffering. In strong Ca2+ buffer, knockdown of the MCU channel did not inhibit ICRAC development demonstrating that mitochondria regulate CRAC channels under physiological conditions by buffering of cytosolic Ca2+ via the MCU channel. Surprisingly, manipulations that altered extracellular Na+ , cytosolic Na+ or both failed to inhibit the development of ICRAC in either strong or weak intracellular Ca2+ buffer. Knockdown of NCLX also did not affect ICRAC . Prolonged removal of external Na+ also had no significant effect on store-operated Ca2+ entry, on cytosolic Ca2+ oscillations generated by receptor stimulation or on CRAC channel-driven gene expression. In the RBL mast cell, Ca2+ flux through the MCU but not NCLX is indispensable for activation of ICRAC . This article is protected by copyright. All rights reserved.

  • de Wet Group

    16 December 2013

    Role of ABC transporters in gut endocrine K-and L-cells

  • Bajo Lorenzana Group

    26 May 2015

    Hearing Loss and Tinnitus

  • Kohl Group

    10 July 2016

    Information encoding in the brain

  • Booth Group

    14 March 2014

    Optical engineering and microscopy for neuroscience and biomedical imaging

  • Ashcroft Group

    10 July 2016

    ATP-sensitive potassium (K-ATP) channels, insulin secretion and diabetes

  • Wade-Martins Group

    10 July 2016

    Understanding molecular mechanisms of age-related neurodegenerative diseases to generate novel molecular therapies

  • Walker Group

    16 September 2013

    We investigate how the activity of neurons in the brain give rise to our perception of sound.

  • Webber Group

    10 July 2016

    Computational Disease Genomics and Networks

  • Wilkins Group

    10 July 2016

    Membrane transport in cartilage and cancer cells

  • Wilson Group

    10 July 2016

    Cell Biology of Exosome Signalling, Secretion and Growth in Normal and Cancer Cells at Super-Resolution