57 research outputs found
Ultrafast Magnetic Resonance Imaging for Iron Quantification in Thalassemia Participants in the Developing World The TIC-TOC Study (Thailand and UK International Collaboration in Thalassaemia Optimising Ultrafast CMR)
Thalassemia is the most common monogenetic disorder worldwide, with 60 000
infants with thalassemia major born annually.1 Survival often depends on regular
blood transfusions to correct anemia and to reduce ineffective erythropoiesis, but
these transfusions can result in iron overload and organ failure unless chelation therapy
is undertaken. Serum ferritin levels continue to be used as a guide to chelation but are
unreliable, and the availability of cardiovascular magnetic resonance (CMR) T2* imaging
has transformed patient management by allowing organ-specific quantification of
iron content.
Countries with a high prevalence of thalassemia major have CMR, but magnet
time is expensive and analytic expertise lacking. The aim of TIC-TOC (Thailand and
UK International Collaboration in Thalassaemia Optimising Ultrafast CMR) was to
investigate whether ultrafast CMR mapping could provide reliable immediate diagnoses
of heart and liver iron content, eliminating the need for complex analysis, thus
reducing costs to a level within local resources. The research received approval by
the Institutional Review Board of the Faculty of Medicine at Chulalongkorn University.
All participants provided written informed consent.</p
Nicotine exploits a COPI-mediated process for chaperone-mediated up-regulation of its receptors
Chronic exposure to nicotine up-regulates high sensitivity nicotinic acetylcholine receptors (nAChRs) in the brain. This up-regulation partially underlies addiction and may also contribute to protection against Parkinson’s disease. nAChRs containing the α6 subunit (α6* nAChRs) are expressed in neurons in several brain regions, but comparatively little is known about the effect of chronic nicotine on these nAChRs. We report here that nicotine up-regulates α6* nAChRs in several mouse brain regions (substantia nigra pars compacta, ventral tegmental area, medial habenula, and superior colliculus) and in neuroblastoma 2a cells. We present evidence that a coat protein complex I (COPI)-mediated process mediates this up-regulation of α6* or α4* nAChRs but does not participate in basal trafficking. We show that α6β2β3 nAChR up-regulation is prevented by mutating a putative COPI-binding motif in the β3 subunit or by inhibiting COPI. Similarly, a COPI-dependent process is required for up-regulation of α4β2 nAChRs by chronic nicotine but not for basal trafficking. Mutation of the putative COPI-binding motif or inhibition of COPI also results in reduced normalized Förster resonance energy transfer between α6β2β3 nAChRs and εCOP subunits. The discovery that nicotine exploits a COPI-dependent process to chaperone high sensitivity nAChRs is novel and suggests that this may be a common mechanism in the up-regulation of nAChRs in response to chronic nicotine
Reference values of myocardial native T1 and extracellular volume in patients without structural heart disease and had negative 3T cardiac magnetic resonance adenosine stress test
Background: To establish the reference values of native T1 and extracellular volume (ECV) in patients without structural heart disease and had a negative adenosine stress 3T cardiac magnetic resonance. Methods: Short-axis T1 mapping images were acquired using a modified Look-Locker inversion recovery technique before and after administration of 0.15 mmol/kg gadobutrol to calculate both native T1 and ECV. To compare the agreement between measurement strategies, regions of interest (ROI) were drawn in all 16 segments then averaged to represent mean global native T1. Additionally, an ROI was drawn in the mid-ventricular septum on the same image to represent the mid-ventricular septal native T1. Results: Fifty-one patients (mean 65 years, 65 % women) were included. Mean global native T1 averaged from all 16 segments and a mid-ventricular septal native T1 were not significantly different (1221.2 ± 35.2 vs 1228.4 ± 43.7 ms, p = 0.21). Men had lower mean global native T1 (1195 ± 29.8 vs 1235.5 ± 29.4 ms, p < 0.001) than women. Both mean global and mid-ventricular septal native T1 were not correlated with age (r = 0.21, p = 0.13 and r = 0.18, p = 0.19, respectively). The calculated ECV was 26.6 ± 2.7 %, which was not influenced by either gender or age. Conclusions: We report the first study to validate the native T1 and ECV reference ranges, factors influencing T1, and the validation across measurement methods in older Asian patients without structural heart disease and had a negative adenosine stress test. These references allow for better detection of abnormal myocardial tissue characteristics in clinical practice
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