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H and P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID.
Radiology
December 2024
From the Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK (L.E.M.F., M.P.C., M.J., A.S., Z.A., S.N., D.J.T., B.R., L.V.); Oncology and Haematology Centre, Churchill Hospital, Oxford, UK (A.S.); Axcella Therapeutics, Cambridge, Mass (K.A.); and Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia (L.V.).
Background Emerging evidence suggests mitochondrial dysfunction may play a role in the fatigue experienced by individuals with post-COVID-19 condition (PCC), commonly called long COVID, which can be assessed using MR spectroscopy. Purpose To compare mitochondrial function between participants with fatigue-predominant PCC and healthy control participants using MR spectroscopy, and to investigate the relationship between MR spectroscopic parameters and fatigue using the 11-item Chalder fatigue questionnaire. Materials and Methods This prospective, observational, single-center study (June 2021 to January 2024) included participants with PCC who reported moderate to severe fatigue, with normal blood test and echocardiographic results, alongside control participants without fatigue symptoms.
View Article and Find Full Text PDFInstationary metabolic flux analysis reveals that NPC1 inhibition increases glycolysis and decreases mitochondrial metabolism in brain microvascular endothelial cells.
Neurobiol Dis
December 2024
Department of Bioengineering, University of Maryland, College Park, MD 20742, United States of America. Electronic address:
Niemann Pick Disease Type C (NP-C), a rare neurogenetic disease with no known cure, is caused by mutations in the cholesterol trafficking protein NPC1. Brain microvascular endothelial cells (BMEC) are thought to play a critical role in the pathogenesis of several neurodegenerative diseases; however, little is known about how these cells are altered in NP-C. In this study, we investigated how NPC1 inhibition perturbs BMEC metabolism in human induced pluripotent stem cell-derived BMEC (hiBMEC).
View Article and Find Full Text PDFSubcellular NAD pools are interconnected and buffered by mitochondrial NAD.
Nat Metab
December 2024
Department of Biomedicine, University of Bergen, Bergen, Norway.
The coenzyme NAD is consumed by signalling enzymes, including poly-ADP-ribosyltransferases (PARPs) and sirtuins. Ageing is associated with a decrease in cellular NAD levels, but how cells cope with persistently decreased NAD concentrations is unclear. Here, we show that subcellular NAD pools are interconnected, with mitochondria acting as a rheostat to maintain NAD levels upon excessive consumption.
View Article and Find Full Text PDFValidation and Optimization of a Stable Isotope-Labeled Substrate Assay for Measuring AGAT Activity.
Int J Mol Sci
November 2024
Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A1, Canada.
L-arginine: glycine amidinotransferase (AGAT) gained academic interest as the rate-limiting enzyme in creatine biosynthesis and its role in the regulation of creatine homeostasis. Of clinical relevance is the diagnosis of patients with AGAT deficiency but also the potential role of AGAT as therapeutic target for the treatment of another creatine deficiency syndrome, guanidinoacetate N-methyltransferase (GAMT) deficiency. Applying a stable isotope-labeled substrate method, we utilized ARG 15N (ARG-δ2) and GLY 13C15N (GLY-δ3) to determine the rate of 1,2-13C,15N guanidinoacetate (GAA-δ5) formation to assess AGAT activity in various mouse tissue samples and human-derived cells.
View Article and Find Full Text PDFObjective: The aim of this study is to evaluate the cost-effectiveness, diagnostic accuracy, clinical outcomes, and radiation exposure associated with rubidium-82 chloride perfusion PET.
Methods: A comprehensive literature search up to October 2024 was conducted to identify key studies assessing the use of rubidium-82 chloride perfusion PET/CT in ischemic heart disease (IHD). These studies included economic analyses, evaluations of diagnostic accuracy, and comparisons with other imaging modalities such as single-photon emission computed tomography (SPECT), stress echocardiography, and invasive coronary angiography.
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