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Methylmalonic Acid

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https://www.readbyqxmd.com/read/28447237/effects-of-metformin-versus-placebo-on-vitamin-b12-metabolism-in-non-diabetic-breast-cancer-patients-in-cctg-ma-32
#1
Ana Elisa Lohmann, Mira F Liebman, William Brien, Wendy R Parulekar, Karen A Gelmon, Lois E Shepherd, Jennifer A Ligibel, Dawn L Hershman, Priya Rastogi, Ingrid A Mayer, Timothy J Hobday, Julie Lemieux, Alastair Mark Thompson, Kathleen I Pritchard, Timothy Joseph Whelan, Som D Mukherjee, Haji I Chalchal, Vanessa Bernstein, Vuk Stambolic, Bingshu E Chen, Pamela Jean Goodwin
BACKGROUND: Metformin is associated with low levels of vitamin B12 (VitB12) in patients with diabetes. The CCTG/MA.32 trial investigates the effects of metformin vs placebo on breast cancer (BC) outcomes in non-diabetic high-risk BC patients. We analyzed VitB12 at baseline and after 6 months of metformin (versus placebo) in the first 492 patients with paired blood samples. METHODS: VitB12 was analyzed centrally in baseline and 6-month fasting plasma. Levels <181 pmol/L were considered deficient, 181-221 pmol/L borderline, and ≥222 pmol/L sufficient...
April 26, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28441332/pregnant-sheep-in-a-farm-environment-did-not-develop-anaemia
#2
Gabrielle C Musk, Amanda James, Matthew W Kemp, Sara Ritchie, Andrew Ritchie, Michael Laurence
The aim of this study was to document the haematological profile of pregnant ewes throughout gestation. Sheep were divided into three groups (n = 8 per group): non-pregnant, singleton, or twin pregnancy. Blood samples were collected every 14 days from day 55 of gestation for haemoglobin concentration; packed cell volume; total protein; and albumin concentration. On days 55 and 125 of gestation blood was collected for trace element estimation: soluble copper and zinc; glutathione peroxidase (GSHPx); and methylmalonic acid (MMA)...
April 25, 2017: Animals: An Open Access Journal From MDPI
https://www.readbyqxmd.com/read/28421567/early-biomarker-response-and-patient-preferences-to-oral-and-intramuscular-vitamin-b12-substitution-in-primary-care-a-randomised-parallel-group-trial
#3
Corina Metaxas, Deborah Mathis, Cyrill Jeger, Kurt Eduard Hersberger, Isabelle Arnet, Philipp Walter
BACKGROUND: Vitamin B12 (VB12) deficiency can be treated with oral high-dose substitution or intramuscular (i.m.) injection of VB12. Whenever alternative routes of administration exist, patient preferences should be considered when choosing the treatment. We aimed to assess outpatient preferences towards oral or IM VB12 substitution and confirm noninferiority of early biomarker response with oral treatment, in a typical primary care population. METHODS: Prospective randomised nonblinded parallel-group trial...
April 19, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28402324/vitamin-b12-status-in-pregnant-women-and-their-infants-in-south-india
#4
J L Finkelstein, A V Kurpad, T Thomas, K Srinivasan, C Duggan
BACKGROUND/OBJECTIVES: Vitamin B12 deficiency during pregnancy has been associated with increased risk of adverse perinatal outcomes. However, few studies have investigated the burden and determinants of vitamin B12 status in young infants. This study was conducted to determine the associations between maternal and infant vitamin B12 status. SUBJECTS/METHODS: Pregnant women participating in a vitamin B12 supplementation trial in Bangalore, India, were randomized to receive vitamin B12 (50 μg) or placebo supplementation daily during pregnancy through 6 weeks postpartum...
April 12, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28395089/methylmalonate-induces-inflammatory-and-apoptotic-potential-a-link-to-glial-activation-and-neurological-dysfunction
#5
Patricia Gabbi, Leandro Rodrigo Ribeiro, Gutierres Jessié Martins, Alexandra Seide Cardoso, Fernanda Haupental, Fernanda Silva Rodrigues, Alencar Kolinski Machado, Juliana Sperotto Brum, M M Medeiros Frescura Duarte, Maria Rosa Chitolina Schetinger, Ivana Beatrice Mânica da Cruz, Ana Flávia Furian, Mauro Schneider Oliveira, Adair Roberto Soares Dos Santos, Luiz Fernando Freire Royes, Michele Rechia Fighera, Mayara Lutchemeyer de Freitas
Methylmalonic acid (MMA) accumulates in tissues in methylmalonic acidemia, a heterogeneous group of inherited childhood diseases characterized by neurological dysfunction, oxidative stress and neuroinflammation; it is associated with degeneration of striatal neurons and cerebral cortical atrophy. It is presently unknown, however, whether transient exposure to MMA in the neonatal period is sufficient to trigger inflammatory and apoptotic processes that lead to brain structural damage. Here, newborn mice were given a single intracerebroventricular dose of MMA at 12 hours after birth...
March 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28381531/ratios-of-one-carbon-metabolites-are-functional-markers-of-b-vitamin-status-in-a-norwegian-coronary-angiography-screening-cohort
#6
Arve Ulvik, Steinar Hustad, Adrian McCann, Øivind Midttun, Ottar K Nygård, Per M Ueland
Background: Functional (metabolic) markers of B-vitamin status, including plasma total homocysteine (tHcy) for folate and plasma methylmalonic acid (MMA) for vitamin B-12, suffer from moderate sensitivity and poor specificity. Ratios of metabolites belonging to the same pathway may have better performance characteristics.Objective: We evaluated the ratios of tHcy to total cysteine (tCys; Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to tCys to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status represented by a summary score composed of folate, cobalamin, betaine, pyridoxal 5'-phosphate (PLP), and riboflavin concentrations measured in plasma...
April 5, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28363510/x-linked-cobalamin-disorder-hcfc1-mimicking-nonketotic-hyperglycinemia-with-increased-both-cerebrospinal-fluid-glycine-and-methylmalonic-acid
#7
Emmanuel Scalais, Elise Osterheld, Christiane Weitzel, Linda De Meirleir, Frederic Mataigne, Geert Martens, Tamim H Shaikh, Curtis R Coughlin, Hung-Chun Yu, Michael Swanson, Marisa W Friederich, Gunter Scharer, Daniel Helbling, Jamie Wendt-Andrae, Johan L K Van Hove
BACKGROUND: Autosomal recessive or X-linked inborn errors of intracellular cobalamin metabolism can lead to methylmalonic aciduria and homocystinuria. In neonates, both increased cerebrospinal fluid glycine and cerebrospinal fluid/plasma glycine ratio are biochemical features of nonketotic hyperglycinemia. METHODS: We describe a boy presenting in the neonatal period with hypotonia, tonic, clonic, and later myoclonic seizures, subsequently evolving into refractory epilepsy and severe neurocognitive impairment...
January 7, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28333089/south-asian-ethnicity-is-related-to-the-highest-risk-of-vitamin-b12-deficiency-in-pregnant-canadian-women
#8
Marta Jeruszka-Bielak, Carly Isman, Theresa H Schroder, Wangyang Li, Tim J Green, Yvonne Lamers
Vitamin B12 (B12) adequacy during pregnancy is crucial for maternal health and optimal fetal development; however, suboptimal B12 status has been reported in pregnant Canadian women. Methylmalonic acid (MMA) is a sensitive indicator of B12 status. Since few studies have measured MMA during pregnancy in Canadian women, the objective of this study was to evaluate B12 status in pregnant women living in Metro Vancouver, using both plasma total B12 and MMA. We recruited a convenience sample of 320 pregnant women between 20 and 35 gestational weeks from local healthcare facilities...
March 23, 2017: Nutrients
https://www.readbyqxmd.com/read/28330909/vitamin-b-12-status-in-infancy-is-positively-associated-with-development-and-cognitive-functioning-5-y-later-in-nepalese-children
#9
Ingrid Kvestad, Mari Hysing, Merina Shrestha, Manjeswori Ulak, Andrew L Thorne-Lyman, Sigrun Henjum, Per M Ueland, Øyvind Midttun, Wafaie Fawzi, Ram K Chandyo, Prakash S Shrestha, Tor A Strand
Background: Poor vitamin B-12 (cobalamin) status is widespread in South Asia. Insufficient vitamin B-12 status has been linked to poor neurodevelopment in young children.Objective: We measured the associations between vitamin B-12 status in infancy (2-12 mo) and the development and cognitive functioning in Nepalese children 5 y later.Design: Vitamin B-12 status was assessed in infancy with the use of plasma cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). At 5 y of age, we measured development with the use of the Ages and Stages Questionnaire, 3rd edition (ASQ-3), and cognitive functioning by using the Developmental Neuropsychological Assessment, 2nd edition (NEPSY II), in 320 children...
March 22, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28321931/disruptions-in-valine-degradation-affect-seed-development-and-germination-in-arabidopsis
#10
Andrew B Gipson, Kyla J Morton, Rachel J Rhee, Szabolcs Simo, Jack A Clayton, Morgan E Perrett, Christiana G Binkley, Erika L Jensen, Dana L Oakes, Matthew F Rouhier, Kerry A Rouhier
We have functionally characterized the role of two putative mitochondrial enzymes in valine degradation using insertional mutants. Prior to this study, the relationship between branched-chain amino acid degradation (named for leucine, valine, and isoleucine) and seed development was limited to leucine catabolism. Using a reverse genetics approach we show that disruptions in the mitochondrial valine degradation pathway affect seed development and germination in Arabidopsis thaliana. A null mutant of 3-hydroxyisobutyryl-CoA hydrolase (CHY4, At4g31810) resulted in an embryo lethal phenotype, while a null mutant of methylmalonate semialdehyde dehydrogenase (MMSD, At2g14170) resulted in seeds with wrinkled coats, decreased storage reserves, elevated valine and leucine, and reduced germination rates...
March 20, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28315235/identification-and-quantitation-of-malonic-acid-biomarkers-of-in-born-error-metabolism-by-targeted-metabolomics
#11
Chandra Shekar R Ambati, Furong Yuan, Lutfi A Abu-Elheiga, Yiqing Zhang, Vivekananda Shetty
Malonic acid (MA), methylmalonic acid (MMA), and ethylmalonic acid (EMA) metabolites are implicated in various non-cancer disorders that are associated with inborn-error metabolism. In this study, we have slightly modified the published 3-nitrophenylhydrazine (3NPH) derivatization method and applied it to derivatize MA, MMA, and EMA to their hydrazone derivatives, which were amenable for liquid chromatography- mass spectrometry (LC-MS) quantitation. 3NPH was used to derivatize MA, MMA, and EMA, and multiple reaction monitoring (MRM) transitions of the corresponding derivatives were determined by product-ion experiments...
March 17, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28237602/effects-of-intramuscular-injections-of-folic-acid-vitamin-b12-or-both-on-lactational-performance-and-energy-status-of-multiparous-dairy-cows
#12
M Duplessis, H Lapierre, D Pellerin, J-P Laforest, C L Girard
The purpose of this experiment was to gain understanding on changes in energy partitioning when folic acid and vitamin B12 supplements, alone or combined, were given by weekly intramuscular injections from 3 wk before the expected calving date until 7 wk postpartum. Twenty-four multiparous cows were assigned to 6 blocks of 4 cows each according to previous 305-d lactation yield to either 0 or 320 mg of folic acid and 0 or 10 mg of vitamin B12 in a 2 × 2 factorial arrangement. Plasma concentration of folates was increased by folic acid supplement, and this increase was greater with the combined supplement...
May 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28236717/efficient-automated-synthesis-of-2-5-18-f-fluoropentyl-2-methylmalonic-acid-18-f-ml-10-on-a-commercial-available-18-f-fdg-synthesis-module
#13
Shaoyu Liu, Dahong Nie, Shende Jiang, Ganghua Tang
[(18)F]ML-10 (2-(5-[(18)F]fluoro-pentyl)-2-methylmalonic acid) is a small molecule positron emission tomography (PET) probe for apoptosis imaging. Automated synthesis of [(18)F]ML-10 was developed by using two different purification methods through a direct saponification procedure on a modified commercial [(18)F]Fluoro-2-Deoxyglucose ([(18)F]FDG) synthesizer. C18 purification method 1: The final [(18)F]ML-10 solution containing ethanol was obtained with radiochemical yields of 60±5% (n=5) at the end of bombardment (EOB) and radiochemical purity of 98% in 35min...
February 20, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/28101778/eight-novel-mut-loss-of-function-missense-mutations-in-chinese-patients-with-isolated-methylmalonic-academia
#14
Lian-Shu Han, Zhuo Huang, Feng Han, Yu Wang, Zhu-Wen Gong, Xue-Fan Gu
BACKGROUND: Isolated methylmalonic acidemia is a rare autosomal recessive metabolic disorder mostly caused by mutations in the methylmalonyl coenzyme A mutase (MCM) gene (MUT). This study aimed to verify whether missense mutations in MUT in Chinese patients affect the stability and enzymatic activity of MCM. METHODS: Eight Chinese patients were identified with novel mutations. Plasmids carrying the wild-type and mutated MUT cDNA were constructed and transfected into HEK293T cells for functional analyses...
January 19, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28070528/methylmalonic-acidemia-diagnosis-by-laboratory-methods
#15
Keyfi Fatemeh, Talebi Saeed, Varasteh Abdol-Reza
Methylmalonic acidemia (MMA) is usually caused by a deficiency of the enzyme methylmalonyl-CoA mutase (MCM), a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, cblC, cblF, cblD, and cblX), or deficiency of the enzyme methylmalonyl-CoA epimerase. A comprehensive diagnostic approach involves investigations of metabolites with tandem mass spectrometry, organic acid analysis with gas chromatography, enzymatic studies with fibroblast cell culture, and finally, mutation analysis...
October 2016: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28060111/frequent-infections-hypotonia-and-anemia-in-a-breastfed-infant
#16
Fatma Kamoun, Rime Guirat, Fatma Megdich, Salma Ben Ameur, Choumous Kallel, Mongia Hachicha
Vitamin B12 deficiency may be responsible of serious hematologic and neurodevelopmental abnormalities. We report the case of an infant who was hospitalized because of recurrent infections, failure to thrive, hypotonia, and weakness. He was 8 months old and had been exclusively breastfed. Blood cell count showed pancytopenia with megaloblastic bone marrow. The serum IgG concentration was low. Vitamin B12 level was very low and associated with increased urinary methylmalonic acid. Cobalamin deficiency was caused by mother's unrecognized pernicious anemia...
March 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28057043/rapid-healing-of-a-patient-with-dramatic-subacute-combined-degeneration-of-spinal-cord-a-case-report
#17
Florian C Roessler, Stephanie Wolff
BACKGROUND: Prevalence of cobalamin deficiency is high especially in older patients and an immediate therapy start is necessary to prevent irreversible neurological damages. Unfortunately, the diagnosis of cobalamin deficiency is difficult and at present, there is no consensus for diagnosis of this deficiency. Therefore, we aim to elucidate a meaningful diagnostic pathway by a case report with an initially misleading medical history. CASE PRESENTATION: A 57 year-old Caucasian man suffering from dramatic myelosis of the cervical posterior columns...
January 3, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28052884/vitamin-b-12-fortified-toothpaste-improves-vitamin-status-in-vegans-a-12-wk-randomized-placebo-controlled-study
#18
Anne-Kathrin Siebert, Rima Obeid, Stine Weder, Hussain M Awwad, Andreas Sputtek, Juergen Geisel, Markus Keller
Background: The oral application of vitamin B-12 may prevent its deficiency if the vitamin is absorbed via the mucosal barrier.Objectives: We studied the effect of the use of a vitamin B-12-fortified toothpaste on vitamin-status markers in vegans and assessed the efficiency of markers in the identification of vitamin-augmentation status.Design: In this 12-wk, double-blinded, randomized, placebo-controlled study, 76 vegans received either a placebo (n = 34) or vitamin B-12 (n = 42) toothpaste. Sixty-six subjects (n = 30 in the placebo arm; n = 36 in the vitamin B-12 arm) completed the intervention...
March 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28029114/folate-and-vitamin-b12-related-biomarkers-in-relation-to-brain-volumes
#19
Nikita L van der Zwaluw, Elske M Brouwer-Brolsma, Ondine van de Rest, Janneke P van Wijngaarden, Paulette H In 't Veld, Daniella I Kourie, Karin M A Swart, Anke W Enneman, Suzanne C van Dijk, Nathalie van der Velde, Roy P C Kessels, Paul A M Smeets, Frans J Kok, Rosalie A M Dhonukshe-Rutten, Lisette C P G M de Groot
AIM: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not. METHODS: Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T₁-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV)...
December 24, 2016: Nutrients
https://www.readbyqxmd.com/read/27981743/whey-protein-isolate-improves-vitamin-b12-and-folate-status-in-elderly-australians-with-subclinical-deficiency-of-vitamin-b12
#20
Varinderpal S Dhillon, Dimitrios Zabaras, Theodora Almond, Paul Cavuoto, Genevieve James-Martin, Michael Fenech
SCOPE: Whey protein isolate (WPI) contains vitamin B12 and folate. However, the efficacy of WPI as a bioavailable source of these vitamins in the elderly with low vitamin B12 was not previously tested. We investigated the effects of WPI supplementation on vitamin B12 and folate status in blood and measured changes in homocysteine (HCY), methylmalonic acid (MMA), and genome integrity biomarkers in elderly individuals with low vitamin B12 status. The effect of WPI was compared to soy protein isolate (SPI)...
December 16, 2016: Molecular Nutrition & Food Research
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