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J Hara, W R Shankle, L W Barrentine, M V Curole
OBJECTIVES: Studies have produced conflicting results assessing hyperhomocysteinemia (HYH) treatment with B vitamins in patients with normal cognition, Alzheimer's disease and related disorders (ADRD). This study examined the effect of HYH management with L-methylfolate (LMF), methylcobalamin (MeCbl; B12), and N-acetyl-cysteine (CFLN: Cerefolin®/Cerefolin-NAC®) on cognitive decline. DESIGN: Prospective, case-control study of subjects followed longitudinally. SETTING: Outpatient clinic for cognitive disorders...
2016: Journal of Nutrition, Health & Aging
Tejas Shah, Kalpana Joshi, Sanjay Mishra, Suhas Otiv, Vijay Kumbar
Folic acid (FA) and iron are essential supplements during pregnancy. Similarly effects of vitamin B12 (B12) inadequacy and high folate and low B12 status, on pregnancy outcome are available. However there are no mandatory recommendations for B12. There are many forms of B12 viz. Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl), and Hydroxycobalamin (HCbl) though there is limited consensus on which form has better efficacy. In the present study we have determined effect of various forms of B12 in the presence of two FA concentrations namely normal physiological (20ng/mL; NPFA) and supra-physiological (2000ng/mL; SPFA) concentration to mimic real time situation where FA is in excess due to supplementation...
September 28, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Mitra Naseri, Gholam-Reza Sarvari, Mohammad Esmaeeli, Anoush Azarfar, Zahra Rasouli, Giti Moeenolroayaa, Shohre Jahanshahi, Simin Farhadi, Zohreh Heydari, Narges Sagheb-Taghipoor
INTRODUCTION: Folic acid and vitamin B12, alone or in combination have been used to reduce homocysteine (Hcy) levels in dialysis patients. OBJECTIVES: We aimed to assess the efficacy of high doses of oral folate and vitamin B12 in reducing plasma Hcy levels after a 12-week treatment. PATIENTS AND METHODS: Thirty-two dialysis patients aged 10-324 months screened for hyperhomocysteinuria. Then cases with hyperhomocysteinemia received oral folate 10 mg/day with sublingual methylcobalamin 1 mg/day for 12 weeks...
2016: Journal of Renal Injury Prevention
William R Shankle, Junko Hara, Lori W Barrentine, Melanie V Curole
We examined whether using a medical food therapy for hyperhomocysteinemia (HHcy) in patients with Alzheimer's disease (AD) or cognitive impairment due to cerebrovascular disease (CVD) with Cerefolin®/CerefolinNAC® (CFLN: L-methylfolate, methylcobalamin, and N-acetyl-cysteine) slowed regional brain atrophy. Thirty HHcy patients with AD and related disorders (ADRD) received CFLN (HHcy+CFLN: duration [μ ±  σ] = 18.6±16.1 months); a sub-sample of this group did not receive CFLN for varying periods of time (HHcy+NoCFLN: duration [μ ±  σ] = 12...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Hongping Yao, Juanyi Feng, Qiaowei Zheng, Youxia Wei, Shixiang Wang, Weiyi Feng
AIMS: This study investigated the efficacies of gliclazide (GLZ), methylcobalamin (MCA), and GLZ+MCA combination therapy on DPN by evaluating the treatment-related changes in peripheral nerve function, the polyol pathway, and oxidative stress in the sciatic nerve of streptozotocin-induced diabetic rats. MATERIALS AND METHODS: The rat model of streptozotocin-induced diabetes was orally given GLZ (25mg/kg/day), MCA (175μg/kg/day), and GLZ+MCA (25mg/kg/day+175μg/kg/day) combination therapy for 8weeks, in order to observe its effects on the motor nerve conduction velocity (MNCV), on the activities of Na(+), K(+)-ATPase, aldose reductase(AR), AR mRNA expression, on the polyol contents, antioxidative enzyme activities and peroxidation products in the sciatic never tissue...
September 15, 2016: Life Sciences
Amber Parry-Strong, Fali Langdana, Sylvan Haeusler, Mark Weatherall, Jeremy Krebs
UNLABELLED: MAIM: To compare a single 1mg intramuscular hydroxocobalamin injection with a 3-month course of 1mg/day sublingual methylcobalamin supplements on serum vitamin B12 concentrations in participants withtype 2 diabetes treated with metformin. METHOD: Participants on metformin treatment with vitamin B12 concentrations below 220pmol/L were recruited through hospital diabetes clinics and primary care practices. They were randomised to receive either the injection or sublingual treatment...
2016: New Zealand Medical Journal
Mihaela Pupavac, David Watkins, Francis Petrella, Somayyeh Fahiminiya, Alexandre Janer, Warren Cheung, Anne-Claude Gingras, Tomi Pastinen, Joseph Muenzer, Jacek Majewski, Eric A Shoubridge, David S Rosenblatt
Vitamin B12 (cobalamin, Cbl) cofactors adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl) are required for the activity of the enzymes methylmalonyl-CoA mutase (MCM) and methionine synthase (MS). Inborn errors of Cbl metabolism are rare Mendelian disorders associated with hematological and neurological manifestations, and elevations of methylmalonic acid and/or homocysteine in the blood and urine. We describe a patient whose fibroblasts had decreased functional activity of MCM and MS and decreased synthesis of AdoCbl and MeCbl (3...
September 2016: Human Mutation
G Guo, S Xu, L-D Cao, Q-Y Wu
OBJECTIVE: This study aims to investigate hyperhomocysteinemia (HHcy) resulted from treatment in patients with Parkinson's disease (PD) and to evaluate the therapeutic outcome of HHcy. PATIENTS AND METHODS: Ninety-three newly diagnosed PD patients were divided into Madopar group (treated with Madopar) and non-Madopar group (not treated with Madopar). Plasma Hcy levels were measured. Five months later, 67 patients presenting with HHcy were randomly divided into treatment group (n = 34) (receiving methylcobalamin 500 µg, tid, and folic acid 50 mg, tid, orally) and control group (n = 33)...
June 2016: European Review for Medical and Pharmacological Sciences
Jing Xu, Wei Wang, Xiong-Xiong Zhong, Yiwei Feng, Xuhong Wei, Xian-Guo Liu
BACKGROUND: Vincristine, a widely used chemotherapeutic agent, often induces painful peripheral neuropathy and there are currently no effective drugs to prevent or treat this side effect. Previous studies have shown that methylcobalamin has potential analgesic effect in diabetic and chronic compression of dorsal root ganglion model; however, whether methylcobalamin has effect on vincristine-induced painful peripheral neuropathy is still unknown. RESULTS: We found that vincristine-induced mechanical allodynia and thermal hyperalgesia, accompanied by a significant loss of intraepidermal nerve fibers in the plantar hind paw skin and an increase in the incidence of atypical mitochondria in the sciatic nerve...
2016: Molecular Pain
Sheyu Li, Xiang Chen, Qianrui Li, Juan Du, Zhimin Liu, Yongde Peng, Mian Xu, Qifu Li, Minxiang Lei, Changjiang Wang, Shaoxiong Zheng, Xiaojuan Zhang, Hongling Yu, Jinyu Shi, Shibing Tao, Ping Feng, Haoming Tian
AIMS/INTRODUCTION: To assess the efficacy and safety of acetyl-L-carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC). MATERIALS AND METHODS: This was a multicenter, randomized, parallel-group, double-blind, double-dummy, positive-controlled, non-inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks...
September 2016: Journal of Diabetes Investigation
Dominic J Harrington
The detection and correction of vitamin B12 (B12) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B12 status is commonly estimated using the abundance of the vitamin in serum, with ∼148 pmol/L (200 ng/L) typically set as the threshold for diagnosing deficiency. Serum B12 assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B12 It is only holotranscobalamin that is taken up by cells to meet metabolic demand...
May 11, 2016: Journal of Clinical Pathology
(no author information available yet)
No abstract text is available yet for this article.
May 5, 2016: New England Journal of Medicine
Yiting Zhang, Nathaniel Hodgson, Malav Trivedi, Richard Deth
Neuregulin 1 (NRG-1) is a key neurotrophic factor involved in energy homeostasis and CNS development, and impaired NRG-1 signaling is associated with neurological disorders. Cobalamin (Cbl), also known as vitamin B12, is an essential micronutrient which mammals must acquire through diet, and neurologic dysfunction is a primary clinical manifestation of Cbl deficiency. Here we show that NRG-1 stimulates synthesis of the two bioactive Cbl species adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl) in human neuroblastoma cells by both promoting conversion of inactive to active Cbl species and increasing neuronal Cbl uptake...
2016: Oxidative Medicine and Cellular Longevity
Tadeusz Andruniów, Piotr Lodowski, Brady D Garabato, Maria Jaworska, Pawel M Kozlowski
The photolysis of the methylcobalamin cofactor (MeCbl) in its base-off form was investigated by considering the extent of spin-orbit coupling (SOC). Triplet Co-C photodissociation pathways previously invoked at the density functional theory level using Landau-Zener theory were further validated with ab initio calculations that combine SOC based on multi-state second order perturbation theory. It was determined that SOC is feasible between singlet and triplet states at elongated Co-C distances, leading to photodissociation from the state having dominant σ(dz(2)) character, by either direct coupling with the lowest singlet states or by crossing with SOC mixed triplets...
March 28, 2016: Journal of Chemical Physics
Mostafa Waly, Verna-Ann Power-Charnitsky, Nathaniel Hodgson, Alok Sharma, Tapan Audhya, Yiting Zhang, Richard Deth
The folate and cobalamin (Cbl-) dependent enzyme methionine synthase (MS) is highly sensitive to oxidation and its activity affects all methylation reactions. Recent studies have revealed alternative splicing of MS mRNA in human brain and patient-derived fibroblasts. Here we show that MS mRNA in SH-SY5Y human neuroblastoma cells is alternatively spliced, resulting in three primary protein species, thus providing a useful model to examine cofactor dependence of these variant enzymes. MS activity was dependent upon methylcobalamin (MeCbl) or the combination of hydroxocobalamin (OHCbl) and S-adenosylmethionine (SAM)...
2016: Oxidative Medicine and Cellular Longevity
Pawel M Kozlowski, Brady D Garabato, Piotr Lodowski, Maria Jaworska
This Perspective Article highlights recent theoretical developments, and summarizes the current understanding of the photolytic properties of cobalamins from a computational point of view. The primary focus is on two alkyl cobalamins, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), as well as two non-alkyl cobalamins, cyanocobalamin (CNCbl) and hydroxocobalamin (HOCbl). Photolysis of alkyl cobalamins involves low-lying singlet excited states where photodissociation of the Co-C bond leads to formation of singlet-born alkyl/cob(ii)alamin radical pairs (RPs)...
March 21, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Gang X, Site Xu, Wei-Zhen Tang, Gang Xú, Chao Cheng, Jie Xu
OBJECTIVE: . To determine the efficacy of methylcobalamin combined with lidocaine for acute herpetic neuralgia. DESIGN: . Randomized controlled trial with longitudinal analysis. SUBJECTS: . The authors recruited 204 patients (>50 years) with T5-10 dermatomal acute herpetic neuralgia with rash onset within 7 days. Patients were divided into two groups based on the time of onset: immediate-early (IE, 1-3 days) and early stage (ES, 4-7 days) groups and then subdivided randomly into control (IE-Ctl, ES-Ctl) and treatment (IE-Tr, ES-Tr) groups...
December 7, 2015: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Yiting Zhang, Nathaniel W Hodgson, Malav S Trivedi, Hamid M Abdolmaleky, Margot Fournier, Michel Cuenod, Kim Quang Do, Richard C Deth
Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects...
2016: PloS One
Yoshitsugu Morita, Koji Oohora, Eiichi Mizohata, Akiyoshi Sawada, Takashi Kamachi, Kazunari Yoshizawa, Tsuyoshi Inoue, Takashi Hayashi
Myoglobins reconstituted with aqua- and cyano-Co(III) tetradehydrocorrins, rMb(Co(III)(OH2)(TDHC)) and rMb(Co(III)(CN)(TDHC)), respectively, were prepared and investigated as models of a cobalamin-dependent enzyme. The former protein was obtained by oxidation of rMb(Co(II)(TDHC)) with K3[Fe(CN)6]. The cyanide-coordinated Co(III) species in the latter protein was prepared by ligand exchange of rMb(Co(III)(OH2)(TDHC)) with exogenous cyanide upon addition of KCN. The X-ray crystallographic study reveals the hexacoordinated structures of rMb(Co(III)(OH)(TDHC)) and rMb(Co(III)(CN)(TDHC)) at 1...
February 1, 2016: Inorganic Chemistry
Juan Wang, Mingyin Wu, Gan Lu, Youbin Si
The resistance of Shewanella oneidensis MR-1 to toxic arsenic was investigated by measuring the growth of the bacteria in the presence of As(III) and As(V) in different growth media. The bacteria were shown to biotransform arsenic through the partial methylation of inorganic arsenic into methylated metabolites. This biotransformation of inorganic arsenic by S. oneidensis MR-1 was affected by the methyl donor, the composition of the medium, and the presence of Fe(III). The relative content of methylated arsenic in the medium containing S-adenosyl methionine as the methyl donor was greater than that in the medium containing methylcobalamin...
February 2016: Chemosphere
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