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      Urinary lumirubin excretion in jaundiced preterm neonates during phototherapy with blue light-emitting diode vs. green fluorescent lamp

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          Abstract

          Phototherapy converts lipophilic unconjugated bilirubin to hydrophilic bilirubin photoisomers, such as lumirubin. We comparatively used a blue light-emitting diode (LED) and a green fluorescent lamp (FL) as light sources for phototherapy of hyperbilirubinemic preterm neonates with the aim of examining potential differences in urinary lumirubin excretion between these two wavelengths. Urinary lumirubin levels were measured using a fluorescence assay with blue light exposure in the presence of the unconjugated bilirubin-inducible fluorescent protein UnaG, and denoted as urinary UnaG-bound bilirubin (UUB)/creatinine (Cr) (μg/mg Cr). Preterm neonates born at ≤ 33 weeks gestational age and treated with phototherapy were subjected to this study. The maximum UUB/Cr level during phototherapy per device intensity was compared between neonates treated with the blue LED and the green FL. A total of 61 neonates were examined to determine the maximum UUB/Cr levels. The median of maximum UUB/Cr excretion per light intensity of each device (μg/mg Cr/μW/cm 2/nm) was 0.83 for the blue LED and 1.29 for the green FL ( p = 0.01). Green light was found to be more effective than blue one for bilirubin excretion via urinary lumirubin excretion. This is the first spectroscopic study to compare the efficacy of phototherapy at different wavelengths using fluorescence assay.

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          Most cited references20

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          A bilirubin-inducible fluorescent protein from eel muscle.

          The fluorescent protein toolbox has revolutionized experimental biology. Despite this advance, no fluorescent proteins have been identified from vertebrates, nor has chromogenic ligand-inducible activation or clinical utility been demonstrated. Here, we report the cloning and characterization of UnaG, a fluorescent protein from Japanese eel. UnaG belongs to the fatty-acid-binding protein (FABP) family, and expression in eel is restricted to small-diameter muscle fibers. On heterologous expression in cell lines or mouse brain, UnaG produces oxygen-independent green fluorescence. Remarkably, UnaG fluorescence is triggered by an endogenous ligand, bilirubin, a membrane-permeable heme metabolite and clinical health biomarker. The holoUnaG structure at 1.2 Å revealed a biplanar coordination of bilirubin by reversible π-conjugation, and we used this high-affinity and high-specificity interaction to establish a fluorescence-based human bilirubin assay with promising clinical utility. UnaG will be the prototype for a versatile class of ligand-activated fluorescent proteins, with applications in research, medicine, and bioengineering. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study.

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              Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

              It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.) 2008 Massachusetts Medical Society
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                Author and article information

                Contributors
                rmbsh274@yahoo.co.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                26 October 2023
                26 October 2023
                2023
                : 13
                : 18359
                Affiliations
                [1 ]GRID grid.474851.b, ISNI 0000 0004 1773 1360, Division of Neonatal Intensive Care, Maternal, Fetal and Neonatal Medical Center, , Nara Medical University Hospital, ; 840 Shijo-Cho, Kashihara-City, Nara 634-8521 Japan
                [2 ]Central Clinical Laboratory, Nara Medical University Hospital, ( https://ror.org/01wvy7k28) Kashihara-City, Nara Japan
                [3 ]GRID grid.471270.7, ISNI 0000 0004 1808 0424, R&D Division, , Ushio Inc, ; Himeji-City, Hyogo Japan
                [4 ]SANKEN, Osaka University, ( https://ror.org/035t8zc32) Ibaraki-City, Osaka Japan
                [5 ]Laboratory for Cell Function Dynamics, RIKEN Center for Brain Science, ( https://ror.org/04j1n1c04) Wako-City, Saitama Japan
                [6 ]Biotechnological Optics Research Team, RIKEN Center for Advanced Photonics, ( https://ror.org/05vmjks78) Wako-City, Saitama Japan
                Article
                45147
                10.1038/s41598-023-45147-7
                10603030
                37884564
                d0017981-797f-4772-b88f-c933d0e83a64
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 August 2023
                : 16 October 2023
                Funding
                Funded by: JSPS KAKENHI grant
                Award ID: 21K15886
                Award Recipient :
                Categories
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                © Springer Nature Limited 2023

                Uncategorized
                biomarkers,diseases
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                biomarkers, diseases

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