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https://www.readbyqxmd.com/read/29657736/a-new-mutation-of-congenital-methemoglobinemia-exacerbated-after-methylene-blue-treatment
#1
Fuminori Yamaji, Akio Soeda, Hiroki Shibata, Takuya Morikawa, Kodai Suzuki, Shozo Yoshida, Shinji Ogura
Case: Methylene blue is useful for the treatment of methemoglobinemia. However, even after the patient's methemoglobin (metHb) rate has improved, careful observation is important because they could have undiagnosed congenital methemoglobinemia. In this case, a 67-year-old man underwent gastrointestinal endoscopy with the use of lidocaine for local anesthesia. During the examination, he complained of dyspnea and had low SpO2 despite normal PaO2 and SaO2 . He was transferred to our department as a suspected case of acquired methemoglobinemia...
April 2018: Acute Medicine & Surgery
https://www.readbyqxmd.com/read/29482478/novel-mutation-r192c-in-cyb5r3-gene-causing-nadh-cytochrome-b5-reductase-deficiency-in-eight-indian-patients-associated-with-autosomal-recessive-congenital-methemoglobinemia-type-i
#2
Prabhakar S Kedar, Vinod Gupta, Prashant Warang, Ashish Chiddarwar, Manisha Madkaikar
OBJECTIVE: To investigate the cause of recessive congenital methemoglobinemia (RCM) in Indian families and to identify molecular defect associated with RCM. METHODS: Eight cases of RCM have been addressed to our laboratory in order to investigate the cause of cyanosis associated with genetic disorders. NADH-cytochrome b5 reductase (cytb5r) enzyme activities were measured by standard methods, and molecular analysis was performed by polymerase chain reaction (PCR) followed by DNA sequencing...
February 27, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29375859/congenital-methemoglobinemia-type-ii-in-a-5-year-old-boy
#3
Elizabeth A Mannino, Thomas Pluim, Jacob Wessler, Megan T Cho, Jane Juusola, Samantha A Schrier Vergano
Congenital Methemoglobinemia is a rare neurologic condition which can mimic other diseases such as epilepsy syndromes and leukodystrophies. The responsible gene, CYB5R3, is not typically included on commonly order neurologic and epilepsy panels. We recommend that laboratories include this gene on these tests which often precede larger-scale genetic studies.
January 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29356095/familial-congenital-methemoglobinemia-in-pomeranian-dogs-caused-by-a-missense-variant-in-the-nadh-cytochrome-b5-reductase-gene
#4
H Shino, Y Otsuka-Yamasaki, T Sato, K Ooi, O Inanami, R Sato, M Yamasaki
BACKGROUND: In veterinary medicine, congenital methemoglobinemia associated with nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) deficiency is rare. It has been reported in several breeds of dogs, but little information is available about its etiology. OBJECTIVES: To analyze the NADH-cytochrome b5 reductase gene, CYB5R3, in a Pomeranian dog family with methemoglobinemia suspected to be caused by congenital b5R deficiency. ANIMALS: Three Pomeranian dogs from a family with methemoglobinemia were analyzed...
January 2018: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29336038/a-single-nucleotide-polymorphism-in-the-canine-cytochrome-b-5-reductase-cyb5r3-gene-is-associated-with-sulfonamide-hypersensitivity-and-is-overrepresented-in-doberman-pinschers
#5
J M Reinhart, J Ekena, A C Cioffi, L A Trepanier
Canine sulfonamide hypersensitivity (HS) has been associated with a variant in the cytochrome b5 reductase gene (CYB5R3 729A>G), which encodes a drug-detoxifying enzyme. Study objectives were to determine variant allele frequency in Doberman Pinschers (DOBE), a breed which may be predisposed to sulfonamide HS, and to characterize the effects of CYB5R3 729G on gene expression and function. CYB5R3 729A>G allele frequencies were compared between DOBE (n = 24) vs. non-Doberman (non-DOBE; n = 60) dogs...
January 15, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28963729/long-term-treatment-with-methylene-blue-in-a-dog-with-hereditary-methemoglobinemia-caused-by-cytochrome-b5-reductase-deficiency
#6
J A Jaffey, M R Harmon, N A Villani, E K Creighton, G S Johnson, U Giger, J R Dodam
A juvenile male mixed breed dog was presented for lethargy, exercise intolerance, and aggression when touched on the head. Cyanosis, tachycardia, and tachypnea were observed and persisted during oxygen supplementation. Arterial blood gas analysis by co-oximetry identified an increased methemoglobin concentration (27%; normal, <2%) with normal arterial oxygen tension. The methemoglobinemia and associated clinical signs resolved after administration of methylene blue (1 mg/kg) IV, and the dog was discharged...
November 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28939879/differential-expression-and-co-expression-gene-networks-reveal-candidate-biomarkers-of-boar-taint-in-non-castrated-pigs
#7
Markus Drag, Ruta Skinkyté-Juskiené, Duy N Do, Lisette J A Kogelman, Haja N Kadarmideen
Boar taint (BT) is an offensive odour or taste observed in pork from a proportion of non-castrated male pigs. Surgical castration is effective in avoiding BT, but animal welfare issues have created an incentive for alternatives such as genomic selection. In order to find candidate biomarkers, gene expression profiles were analysed from tissues of non-castrated pigs grouped by their genetic merit of BT. Differential expression analysis revealed substantial changes with log-transformed fold changes of liver and testis from -3...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28603631/hepatic-expression-profiles-in-retroviral-infection-relevance-to-drug-hypersensitivity-risk
#8
Yat Yee Wong, Brian Johnson, Thomas C Friedrich, Lauren A Trepanier
HIV-infected patients show a markedly increased risk of delayed hypersensitivity (HS) reactions to potentiated sulfonamide antibiotics (trimethoprim/sulfamethoxazole or TMP/SMX). Some studies have suggested altered SMX biotransformation in HIV infection, but hepatic biotransformation pathways have not been evaluated directly. Systemic lupus erythematosus (SLE) is another chronic inflammatory disease with a higher incidence of sulfonamide HS, but it is unclear whether retroviral infection and SLE share risk factors for drug HS...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28584062/cytochrome-b5-reductase-3-modulates-soluble-guanylate-cyclase-redox-state-and-cgmp-signaling
#9
Mizanur M Rahaman, Anh T Nguyen, Megan P Miller, Scott A Hahn, Courtney Sparacino-Watkins, Soma Jobbagy, Nolan T Carew, Nadiezhda Cantu-Medellin, Katherine C Wood, Catherine J Baty, Francisco J Schopfer, Eric E Kelley, Mark T Gladwin, Emil Martin, Adam C Straub
RATIONALE: Soluble guanylate cyclase (sGC) heme iron, in its oxidized state (Fe(3+)), is desensitized to NO and limits cGMP production needed for downstream activation of protein kinase G-dependent signaling and blood vessel dilation. OBJECTIVE: Although reactive oxygen species are known to oxidize the sGC heme iron, the basic mechanism(s) governing sGC heme iron recycling to its NO-sensitive, reduced state remain poorly understood. METHODS AND RESULTS: Oxidant challenge studies show that vascular smooth muscle cells have an intrinsic ability to reduce oxidized sGC heme iron and form protein-protein complexes between cytochrome b5 reductase 3, also known as methemoglobin reductase, and oxidized sGC...
July 7, 2017: Circulation Research
https://www.readbyqxmd.com/read/27863456/a-microplate-reader-based-method-to-quantify-nadh-cytochrome-b5-reductase-activity-for-diagnosis-of-recessive-congenital-methaemoglobinemia
#10
Prabhakar Kedar, Anand Desai, Prashant Warang, Roshan Colah
OBJECTIVES: Congenital methemoglobinemia due to NADH-cytochrome b5 reductase 3 (CYB5R3) deficiencies is an autosomal recessive disorder that occurs sporadically worldwide, A sensitive, accurate, and rapid analysis of NADH-CYB5R enzyme concentrations is necessary for the diagnosis of RCM. Here we present an alternative microplate method that is based on a standard 96-well microplate format and microplate reader that simplify the quantification of NADH-CYB5R activity. METHODS: TECAN (Infinite 200 PRO series) microplate reader with Tecan's proven Magellan™ software measured the NADH-CYB5R enzyme activity in 250 normal controls and previously diagnosed 25 cases of RCM due to NADH-CYB5R deficiency in the Indian population using 96-well microplates using 200 μl of total reaction mixture and also compared with standard spectrophotometric assay...
May 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27469001/defining-the-role-of-the-nadh-cytochrome-b5-reductase-3-in-the-mitochondrial-amidoxime-reducing-component-enzyme-system
#11
Birte Plitzko, Antje Havemeyer, Bettina Bork, Florian Bittner, Ralf Mendel, Bernd Clement
The importance of the mitochondrial amidoxime reducing component (mARC)-containing enzyme system in N-reductive metabolism has been studied extensively. It catalyzes the reduction of various N-hydroxylated compounds and therefore acts as the counterpart of cytochrome P450- and flavin-containing monooxygenase-catalyzed oxidations at nitrogen centers. This enzyme system was found to be responsible for the activation of amidoxime and N-hydroxyguanidine prodrugs in drug metabolism. The synergy of three components (mARC, cytochrome b5, and the appropriate reductase) is crucial to exert the N-reductive catalytic effect...
October 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27323405/suppression-of-abhd2-identified-through-a-functional-genomics-screen-causes-anoikis-resistance-chemoresistance-and-poor-prognosis-in-ovarian-cancer
#12
Koji Yamanoi, Noriomi Matsumura, Susan K Murphy, Tsukasa Baba, Kaoru Abiko, Junzo Hamanishi, Ken Yamaguchi, Masafumi Koshiyama, Ikuo Konishi, Masaki Mandai
Anoikis resistance is a hallmark of cancer, and relates to malignant phenotypes, including chemoresistance, cancer stem like phenotypes and dissemination. The aim of this study was to identify key factors contributing to anoikis resistance in ovarian cancer using a functional genomics screen. A library of 81 000 shRNAs targeting 15 000 genes was transduced into OVCA420 cells, followed by incubation in soft agar and colony selection. We found shRNAs directed to ABHD2, ELAC2 and CYB5R3 caused reproducible anoikis resistance...
July 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/26351264/nadh-cytochrome-b5-reductase-3-promotes-colonization-and-metastasis-formation-and-is-a-prognostic-marker-of-disease-free-and-overall-survival-in-estrogen-receptor-negative-breast-cancer
#13
Rikke R Lund, Rikke Leth-Larsen, Tina Di Caterino, Mikkel G Terp, Jeanette Nissen, Anne-Vibeke Lænkholm, Ole N Jensen, Henrik J Ditzel
Metastasis is the main cause of cancer-related deaths and remains the most significant challenge to management of the disease. Metastases are established through a complex multistep process involving intracellular signaling pathways. To gain insight to proteins central to specific steps in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using stable isotopic labeling by amino acids in cell culture and subcellular fractionation, the nuclear, cytosol, and mitochondria proteomes were analyzed by LC-MS/MS, identifying a number of proteins that exhibited altered expression in isogenic metastatic versus nonmetastatic cancer cell lines, including NADH-cytochrome b5 reductase 3 (CYB5R3), l-lactate dehydrogenase A (LDHA), Niemann-pick c1 protein (NPC1), and nucleolar RNA helicase 2 (NRH2)...
November 2015: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/26291966/congenital-recessive-methemoglobinemia-revealed-in-adulthood-description-of-a-new-mutation-in-cytochrome-b5-reductase-gene
#14
Alexandra Forestier, Serge Pissard, Justine Cretet, Adeline Mambie, Laurent Pascal, Manuel Cliquennois, Nathalie Cambier, Christian Rose
Methemoglobinemia can be acquired (oxidizing drugs or chemicals products) or inherited either by mutations affecting globin chains [M hemoglobins (M Hbs)] or by defects in the enzymatic system involved in the reduction of spontaneous Hb oxidation: nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase. It is encoded by the CYB5R3 gene: there are two phenotypes of autosomal recessive congenital methemoglobinemia, in type II CYB5R deficiency is generalized and affects all cells, leading to an early onset, whereas in type I, the enzyme deficiency is restricted to erythrocytes, usually discovered in infancy but not exclusively...
2015: Hemoglobin
https://www.readbyqxmd.com/read/26226898/congenital-recessive-methemoglobinemia-revealed-in-adulthood-description-of-a-new-mutation-in-cytochrome-b5-reductase-gene
#15
Alexandra Forestier, Serge Pissard, Justine Cretet, Adeline Mambie, Laurent Pascal, Manuel Cliquennois, Nathalie Cambier, Christian Rose
Methemoglobinemia can be acquired (oxidizing drugs or chemicals products) or inherited either by mutations affecting globin chains [M hemoglobins (M Hbs)] or by defects in the enzymatic system involved in the reduction of spontaneous Hb oxidation: nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase. It is encoded by the CYB5R3 gene: there are two phenotypes of autosomal recessive congenital methemoglobinemia, in type II CYB5R deficiency is generalized and affects all cells, leading to an early onset, whereas in type I, the enzyme deficiency is restricted to erythrocytes, usually discovered in infancy but not exclusively...
July 31, 2015: Hemoglobin
https://www.readbyqxmd.com/read/26001785/structure-guided-chemical-modifications-of-propylthiouracil-reveal-novel-small-molecule-inhibitors-of-cytochrome-b5-reductase-3-that-increase-nitric-oxide-bioavailability
#16
Md Mizanur Rahaman, Fabio G Reinders, David Koes, Anh T Nguyen, Stephanie M Mutchler, Courtney Sparacino-Watkins, Roger A Alvarez, Megan P Miller, Dongmei Cheng, Bill B Chen, Edwin K Jackson, Carlos J Camacho, Adam C Straub
NADH cytochrome b5 reductase 3 (CYB5R3) is critical for reductive reactions such as fatty acid elongation, cholesterol biosynthesis, drug metabolism, and methemoglobin reduction. Although the physiological and metabolic importance of CYB5R3 has been established in hepatocytes and erythrocytes, emerging investigations suggest that CYB5R3 is critical for nitric oxide signaling and vascular function. However, advancement toward fully understanding CYB5R3 function has been limited due to a lack of potent small molecule inhibitors...
July 3, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25521918/genetic-variation-in-cyb5r3-is-associated-with-methemoglobin-levels-in-preterm-infants-receiving-nitric-oxide-therapy
#17
Tyson D Fuller, Cassandra N Spracklen, Kelli K Ryckman, Lindsey A Knake, Tamara D Busch, Allison M Momany, Jeffrey C Murray, John M Dagle
BACKGROUND: In recent years, increasing numbers of preterm infants have been exposed to inhaled nitric oxide (iNO). This population has decreased methemoglobin (MetHb) reductase activity in their erythrocytes, which may increase the risk of MetHb toxicity. We sought to determine if genetic factors are associated with the observed variance in MetHb levels. METHODS: A population of 127 preterm infants was genotyped for five single-nucleotide polymorphisms (SNPs) in the CYB5A and CYB5R3 genes...
March 2015: Pediatric Research
https://www.readbyqxmd.com/read/25225034/polymorphisms-in-the-carcinogen-detoxification-genes-cyb5a-and-cyb5r3-and-breast-cancer-risk-in-african-american-women
#18
Kristina L Blanke, James C Sacco, Robert C Millikan, Andrew F Olshan, Jingchun Luo, Lauren A Trepanier
PURPOSE: Cytochrome b 5 (encoded by CYB5A) and NADH cytochrome b 5 reductase (encoded by CYB5R3) detoxify aromatic and heterocyclic amine mammary carcinogens found in cigarette smoke. We hypothesized that CYB5A and CYB5R3 polymorphisms would be associated with breast cancer risk in women. METHODS: We characterized the prevalence of 18 CYB5A and CYB5R3 variants in genomic DNA from African American (AfrAm) and Caucasian (Cauc) women from the Carolina Breast Cancer Study population (1,946 cases and 1,747 controls) and determined their associations with breast cancer risk, with effect modification by smoking...
November 2014: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/25130546/identification-of-one-electron-reductases-that-activate-both-the-hypoxia-prodrug-sn30000-and-diagnostic-probe-ef5
#19
Jingli Wang, Chris P Guise, Gabi U Dachs, Yen Phung, Annie Huai-Ling Hsu, Neil K Lambie, Adam V Patterson, William R Wilson
SN30000 is a second-generation benzotriazine-N-oxide hypoxia-activated prodrug scheduled for clinical trial. Previously we showed that covalent binding of the hypoxia probe EF5 predicts metabolic activation of SN30000 in a panel of cancer cell lines under anoxia, suggesting that they are activated by the same reductases. However the identity of these reductases is unknown. Here, we test whether forced expression of nine oxidoreductases with known or suspected roles in bioreductive prodrug metabolism (AKR1C3, CYB5R3, FDXR, MTRR, NDOR1, NOS2A, NQO1, NQO2 and POR) enhances oxic or anoxic reduction of SN30000 and EF5 by HCT116 cells...
October 15, 2014: Biochemical Pharmacology
https://www.readbyqxmd.com/read/24945955/external-mitochondrial-nadh-dependent-reductase-of-redox-cyclers-vdac1-or-cyb5r3
#20
Anna B Nikiforova, Nils-Erik L Saris, Alexey G Kruglov
It was reported that VDAC1 possesses an NADH oxidoreductase activity and plays an important role in the activation of xenobiotics in the outer mitochondrial membrane. In the present work, we evaluated the participation of VDAC1 and Cyb5R3 in the NADH-dependent activation of various redox cyclers in mitochondria. We show that external NADH oxidoreductase caused the redox cycling of menadione ≫ lucigenin>nitrofurantoin. Paraquat was predominantly activated by internal mitochondria oxidoreductases. An increase in the ionic strength stimulated and suppressed the redox cycling of negatively and positively charged acceptors, as was expected for the Cyb5R3-mediated reduction...
September 2014: Free Radical Biology & Medicine
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